The computation of EEG bispectra.
This paper presents a FORTRAN program for computation of bispectra of multichannel EEG on a PDP-11/55 computer. Input data are already digitized and file-structured. Output of power spectra, bicoherence and biphases is produced in synoptic form on a line printer.


Intramolecular long-range electron transfer in the hemerythrin monomer: a pulse radiolysis study.
The single sulfhydryl group (Cys-50) of the methemerythrin from Phascolosoma gouldii reacts with 5,5'dithiobis(2-nitrobenzoic acid) to form a mixed disulfide. The pulse radiolytically generated formate radical reduces this mixed disulfide to its radical anion. In turn, the disulfide radical anion reduces the protein two-iron center over a nominal distance of 13 A. The rate constant for this intramolecular electron transfer is approximately 15 s-1 at room temperature, pH 7. Between the two redox centers there is an equilibrium driving force of 0.78 V, measured by differential pulsed polarography.


Differential diagnosis of chordoma, chondroid, and ependymal tumors as aided by anti-intermediate filament antibodies.
Six chordomas, nine chondrosarcomas, and three myxopapillary ependymomas of the filum terminale were evaluated immunohistochemically for the expression of intermediate filament proteins by the use of monospecific antibodies against intermediate filament proteins of keratin, vimentin, and glial fibrillary acidic protein (GFAP) type. All chordomas were positive for keratin but negative for GFAP, whereas chondrosarcomas and ependymomas were negative for keratin. Chondrosarcomas showed strong vimentin positivity, whereas ependymomas were positive for GFAP. Chordomas showed desmosomelike junctions by electron microscopy, whereas chondrosarcomas of different types showed no junctions or only primitive ones. By electron microscopy chordomas often showed prominent intermediate filaments also associated with desmosomes, and poorly differentiated chondrosarcomas also showed prominent intermediate filaments. Keratin positivity of chordomas suggests their epithelial nature, while vimentin positivity of chondrosarcomas is in line with their mesenchymal derivation. The results also show that antibodies against different intermediate filament proteins can be applied as diagnostic aids in making the distinction between chordomas, chondroid tumors, and ependymal tumors.


Lipid composition of the main fractions of rabbit semen.
Rabbit semen contains mature spermatozoa and several other fractions (seminal plasma, droplets and vesicles) which are separated by various procedures. These fractions have a variable lipid profile: spermatozoa contain the largest amount of phospholipids (PL), whereas seminal plasma, droplets and vesicles accounted for 49.8% of the total PLs. The cholesterol content in raw semen was 811 microg/10(9) but was only 21-23% in spermatozoa. The main PL classes of rabbit spermatozoa were PC, LPC, PE, PS, SM and PI, which varied according to the separation procedures used. Percoll-separated spermatozoa (Sp(p)) showed an increase of LPC, a higher LPC/PC ratio but a lower lipid content compared to the theoretical amount. This membrane modification did not affect the number of live cells but greatly influenced the functional properties of the rabbit spermatozoa, i.e. the HOS-test and induced acrosome reaction. PC, followed by PE and LPC were the most abundant PL classes of seminal plasma, droplets and vesicles. These fractions have higher PE and SM levels and lower PC/PE+PC ratios than in the germinal cells. Some physiological implications are discussed.


Airway macrophages from patients with asthma do not proliferate.
Macrophages are involved in asthma, but their pulmonary turnover is unknown. We compared the ability of bronchoalveolar lavage (BAL) and bronchial macrophages to proliferate in normal subjects and patients with asthma. BAL cells from eight patients with asthma and eight normal volunteers were separated with a discontinuous Percoll gradient (Pharmacia Fine Chemicals, Uppsala, Sweden). In a first experiment, nuclei of each alveolar macrophage (AM) fraction, stained with propidium iodide, were analyzed for DNA content with a flow cytometer, and the proportions of cells in the G0/G1, S, and G2 + M phases were determined. In a second experiment, expression of Ki-67-related antigen was sought on AMs by immunocytochemistry. Macrophages from 10 patients with asthma and 10 normal volunteers were studied in biopsy specimens by means of immunohistochemistry with a panmacrophage monoclonal antibody (HAM-56) and a monoclonal antibody against proliferating cell nuclear antigen. The proportions of BAL AMs in the different phases of the cell cycle were similar in normal subjects and patients with asthma for all fractions, and the percentage of cells in S and G2 +/- M phases ranged from 7.3% to 11.3%. Under 1% of BAL AMs expressed Ki-67-related antigen. None of the macrophages present in the biopsy specimens expressed proliferating cell nuclear antigen. This study does not indicate that an important source of airway macrophages is local proliferation.


Do Professionals Take Over? Professionalisation and Membership Influence in Civil Society Organisations.
While many scholars have postulated the decline of membership influence as an important consequence of the professionalisation of civil society organisations (CSOs), other analysts have argued that traditional membership-driven CSOs are resilient and that hiring professionals does not necessarily diminish membership influence. This study sheds light on this issue by analysing membership influence in a representative sample of approximately 2000 CSOs from five European countries and the European level. As members generally have a strong influence on CSOs' policy positions, our analysis demonstrates that the pessimistic tone in much contemporary scholarly work is largely unwarranted. On the contrary, hiring professionals does not invariably decrease membership influence and can, when members are closely engaged in advocacy work, even facilitate it.


A histopathologic study of oral mucosal lupus erythematosus.
Specimens representing 17 cases of each of oral mucosal lupus erythematosus (LE) and lichen planus were examined under the light microscope to establish a set of histopathologic criteria that would distinguish between the two. Statistical analysis showed that significant differences in histopathology exist between the two diseases. A classic case of LE was found to exhibit the following characteristics: vacuolization of keratinocytes, patchy PAS-positive deposits subepithelially, edema in the lamina propria, PAS-positive thickening of blood vessel walls, and the presence of a severe or perivascular inflammatory cell infiltrate. A number of other less significant alterations were also identified. It is concluded from this study that oral LE in most cases is characteristic enough to provide a definitive diagnosis at the light microscopic level.


Multidisciplinary out-patient treatment with monitoring by telemedicine for a large-volume multifocal pyogenic liver abscess in times of the pandemic.
Pyogenic liver abscesses represent one of the rarer, but potentially life-threatening diseases of the liver. The treatment for large-volume liver abscesses is usually multimodal with percutaneous drainage combined with several days of treatment in hospital. We are presenting a report on a male patient with type-2 diabetes mellitus who suffered from a multifocal liver abscess (>10 cm). Due to the exceptional situation caused by the corona pandemic, the patient was treated conservatively with non-standard treatment which involved a multidisciplinary team and out-patient visits. Follow-up to ensure the treatment would be successful was carried through dialogue with the GP responsible for the patient's care, as well as daily telemedicine visits. The daily telemedicine visits were supplemented by episodic follow-up testing of laboratory values and contrast-enhanced ultrasound scans (CEUS) of the liver. We show that purely conservative therapy can be successful in a case with a high risk of mortality by using a combination of close telemedical monitoring and proactive interdisciplinary collaboration with the GP.


Significance of Exercise-Related Ventricular Arrhythmias in Patients With Brugada Syndrome.
Background Sinus tachycardia during exercise attenuates ST-segment elevation in patients with Brugada syndrome, whereas ST-segment augmentation after an exercise test is a high-risk sign. Some patients have premature ventricular contractions (PVCs) related to exercise, but the significance of exercise-related PVCs in patients with Brugada syndrome is still unknown. The objective of this study was to determine the significance of exercise-related PVCs for predicting occurrence of ventricular fibrillation (VF) in patients with Brugada syndrome. Methods and Results The subjects were 307 patients with Brugada syndrome who performed a treadmill exercise test. We evaluated the occurrence of PVCs at rest, during exercise and at the peak of exercise, and during recovery after exercise (0-5 minutes). We followed the patients for 92±68 months and evaluated the occurrence of VF. PVCs occurred in 82 patients (27%) at the time of treadmill exercise test: PVCs appeared at rest in 14 patients (4%), during exercise in 60 patients (20%), immediately after exercise (0-1.5 minutes) in 28 patients (9%), early after exercise (1.5-3 minutes) in 18 patients (6%), and late after exercise (3-5 minutes) in 12 patients (4%). Thirty patients experienced VF during follow-up. Multivariable analysis including symptoms, spontaneous type 1 ECG, and PVCs in the early recovery phase showed that these factors were independently associated with VF events during follow-up. Conclusions PVCs early after an exercise test are associated with future occurrence of VF events. Rebound of vagal nerve activity at the early recovery phase would promote ST-segment augmentation and PVCs in high-risk patients with Brugada syndrome.


Logical thinking in pattern differentiation of traditional Chinese medicine.
To discuss the application of logic to pattern differentiation for treatment in Traditional Chinese Medicine (TCM). Comparing logic reasoning of syllogism with the logical thinking of TCM pattern differentiation for treatment. TCM logical thinking depends on symbolic and intuitive judgment with abstractive reasoning integrated into the process. Although it lacks quantitative measurement, it pays great attention to the comprehensive analysis of a disease's cause and its development patterns to get insight into the essence of illness. TCM diagnosis reasoning method may lack rigorousness, continuity, systematic induction and deduction, but its logical thinking still can attain its goal following a process with rigorous, regulated and scientific formal logic.


Therapeutic potential of furin inhibitors for the chronic infection of hepatitis B virus.
Hepatitis B e antigen (HBeAg) is essential for the development of chronic hepatitis B virus (HBV) infection. Furin, a proprotein convertase, plays a key role in processing of HBeAg precursor into maturated HBeAg. For these reasons, the therapeutic potential of furin inhibition for chronic HBV infection was studied. The effects of furin inhibitor I (decanoyl-RVKR-chloromethylketone, CMK) and furin inhibitor II (hexa-D-arginine, D6R) on HBeAg secretion, the destination of unprocessed precursor and cellular secretory functions were comparatively investigated. CMK and D6R significantly decreased the supernatant level of HBeAg and increased the intracellular level of HBeAg precursor in HepG2.2.15 cells in vitro. The accumulated HBeAg precursor was not found to be retro-transported into the cytosol to inhibit HBV replication as expected, but was found to be expressed on the cell surface, where it may be more convenient to mediate host immune responses. Furthermore, these inhibitors at effective concentrations were not found to interfere with the maturations of albumin and prothrombin. Compared with CMK, D6R was suboptimal in effectiveness; however, D6R neither enhanced HBV replication through the accumulation of cytosolic HBcAg nor did it cause severe cell damage in an elongated safety analyses. Furin inhibitors CMK and D6R reduce HBeAg secretion and increase cell surface expression of the HBeAg precursor in HepG2.2.15 cells. Novel furin inhibitors or modified forms of D6R may promote the reduction of immune tolerance and the elimination of infected hepatocytes in patients with chronic HBV infection.


Synergic influence of degrading mechanisms and induced loading by prestressing on the concrete: state of the art.
Since prestressed concrete is regarded as more durable and reliable than other construction materials, it is used in a variety of civil engineering applications, including nuclear plants, bridges, and concrete piles. However, as with other building structures, prestressed concrete structures are also subjected to different long-term environmental actions, which influence the durability and performance of prestressed concrete structures. Furthermore, it has been found that data on the effect of deteriorating environmental mechanisms on prestressed concrete is scarce. This state-of-the-art review attempts to provide a concise assessment of existing research on the effect of environmental actions such as freezing and thawing, carbonation, and chloride on prestressed concrete's durability. It can be summarised that continuous exposure of prestressed concrete to such aggressive environmental conditions reduces not only their mechanical properties, but also their durability performance is affected; the prestress losses increase rapidly and cause significant damage, and cracking occurs. Furthermore, if subjected to marine exposure, the microcracks and widened cracks may provide pathways for chlorides and other harmful agents to penetrate towards the prestress wires or tendons and subsequently cause corrosion.


Metatarsal osteotomy for relief of metatarsalgia.
If surgery is indicated for metatarsalgia, osteotomy of the metatarsals should be considered. In the years 1967-1977 we have operated on 35 feet. The first 17 we performed a proximal V-shaped osteotomy, the next 18 we performed a distal oblique osteotomy. The results were excellent in 18 cases, good in 13 cases and poor in 4 cases. We recommend the oblique distal osteotomy because the operation is simple, recovery is rapid and symptoms are well relieved.


A method for studying the mutagenicity of some gaseous compounds in Salmonella typhimurium.
A dynamic flow-through exposure system was designed for mutagenicity studies of gaseous compounds in Salmonella. Salmonella typhimurium strain TA100 was the primary tester strain. The dose ranges were 0.5-20% of vinyl chloride, ethene, propene, and 1,3-butadiene, 1-200 ppm of ethylene oxide, 0.5-20 ppm of nitrogen dioxide, and 0.1-3.5 ppm of ozone. The gas flow rate was 250, 500, or 1,000 ml/min, and the exposure time was 6 or 7 hours. Of the tested gases, vinyl chloride, ethylene oxide, and nitrogen dioxide were mutagenic. Ethene, propene, and 1,3-butadiene were not mutagenic in this system. Ozone is bacteriotoxic, and no mutagenic effect could be demonstrated in the nontoxic dose range. The exposure system was considered suitable for studies on gaseous chemicals.


Do pulse checks delay semiautomatic defibrillation by EMT-defibrillators?
Advanced cardiac life support (ACLS) guidelines from the American Heart Association (AHA) now recommend not checking for a pulse between the initial three defibrillations for pulseless patients in ventricular tachycardia or fibrillation. The AHA asserts that checking for a pulse needlessly delays defibrillation. This study was undertaken to determine if pulse checks delay defibrillation by EMT-Defibrillators (EMT-Ds) using a semiautomatic defibrillator (SAED). Twenty-seven EMT-Ds demonstrated delivery of three successive defibrillations during two test scenarios: once with and once without pulse checks after the first and second defibrillations. The time from the first to third defibrillation was recorded. The mean time to deliver the defibrillations was 60.2 +/- 6.2 seconds with pulse checks and 57.5 +/- 4.6 seconds without pulse checks. The difference, 2.7 +/- 5.9 seconds, was statistically significant (P = 0.026). Pulse checks by EMT-Ds do delay administration of defibrillations, but consideration should be given to reinstating pulse checks as a part of the AHA guidelines, since this delay is of questionable clinical significance.


Localization of hepatitis B surface antigen in hepatocellular carcinoma.
The author respectively examined the localization of hepatitis B surface antigen (HBsAg) in 150 autopsy cases of hepatocellular carcinoma (HCC) with particular attention to growth pattern of HCC. Varying numbers of orcein-positive cells were observed in 42 cases (28.0%) with various distribution patterns, and all the 42 cases were confirmed with immunoperoxidase technique for HBsAg. HBsAg-positive cells were detected in HCC tissue in 10 cases (6.6%) among the 150 cases. Regarding the growth pattern of HCC in the 10 cases, many HBsAg-positive cells were seen in HCCs of the sinusoidal and replacing types, in which the hepatocytes were frequently retained in the cancerous tissue, particularly around the tumor-nontumor boundary. On the other hand, there was no HBsAg-positive cell in the encapsulated type HCC which was the most common (approximately 50%) in the present study and in which the retained hepatocytes were hardly seen. Meticulous histological observation after decoloration of the positive reaction to HBsAg in the sections treated with immunoperoxidase technique and subsequent eosin stain disclosed that HBsAg-positive cells in HCC tissue were retained hepatocytes in 9 cases, and the possibility of HCC cell was not denied in one case. Moreover, HBsAg-positive cells were never detected in tumor thrombi of the portal vein branches and pulmonary metastases.


Endothelin-induced changes in intracellular calcium concentration in rat vascular smooth muscle cells: effects of extracellular calcium and atrial natriuretic factor.
The purpose of this study was to examine whether different mechanisms might underlie the changes in intracellular calcium concentration ([Ca2+]i) stimulated by high and low concentrations of endothelin, and whether atrial natriuretic factor (ANF) has an inhibitory effect on endothelin-induced [Ca2+]i changes in cultured rat vascular smooth muscle cells (VSMCs). In calcium-replete buffer, cultured monolayers of rat VSMCs superfused with endothelin at a high concentration (10 nM) exhibited a marked transient rise in [Ca2+]i, followed by a sustained elevation, whereas a low concentration of endothelin (0.1 nM) induced a sustained monophasic elevation. When calcium-free buffer was used, 10 nM endothelin induced a transient rise in [Ca2+]i of lesser amplitude, whereas 0.1 nM endothelin did not produce a significant rise. Pretreatment of VSMCs with ANF and cosuperfusion with endothelin failed to inhibit either transient or sustained endothelin-induced changes in [Ca2+]i in calcium-replete buffer.


Elevated early gastric carcinoma. Differential diagnosis as regards adenomatous polyps.
Differential diagnostic problems between gastric carcinomas and precancerous lesions with severe dysplasia have become more perceptible with the increasing number of resected early carcinomas. Although such problems come up for all macroscopic and histologic types of gastric cancer they are particularly marked between early carcinomas of the elevated type and adenomatous polyps. Elevated early carcinomas are usually highly differentiated adenocarcinomas with a morphology which often reminds of of adenomas. But sometimes the carcinomas also demonstrate convincing signs of being developed from adenomas. The criterion of distinction between intramucosal carcinomas and adenomas is invasion through the basal membrane, often difficult to evaluate. The morphological relation between elevated early gastric carcinomas and adenomas and the criterion of distinction between them were studied in 20 early gastric carcinomas of the Japanese types I and IIa, 6 intramucosal and 14 submucosal all highly differentiated adenocarcinomas, and in 42 polyps, of which 5 were of the adenomatous type. All lesions were taken from resection specimens. Among the carcinomas 5 demonstrated convincing signs of being malignant transformed adenomas. In addition, 6 carcinomas had a morphology which more or less reminded of adenomas, but their genetic origin was more uncertain. Nine carcinomas revealed no sign of an adenomatous origin. Among the 5 polyps diagnosed as adenomas 2 revealed an extraordinary degree of severe dysplasia which caused uncertainty on the benign diagnosis. The rest of the polyps were without dysplasia. The significance of invasion through the basal membrane as an indispensable factor of distinction between adenoma and carcinoma in the stomach is discussed. It is concluded that the degree of dysplasia can be so severe and the invasion so difficult to evaluate that the classification of some few tumours depends on the subjectivity of the single pathologist. Four of the tumours, 2 adenomas and 2 intramucosal carcinomas, having a remarkable macroscopic appearance like a large mucosal fold are especially mentioned. Their relation to gastric mucosal prolaps is discussed. Furthermore, a tumour apparently demonstrating only a moderate degree of dysplasia, but even so setting up metastases is mentioned in detail.


Analgesic effects of nonsteroidal antiinflammatory drugs, acetaminophen, and morphine in a mouse model of bone cancer pain.
Bone metastasis is one of the major causes of cancer-related pain, and not all bone cancer pain can be effectively treated. Recently, a mouse model of bone cancer pain was introduced. To test the analgesic effects of nonsteroidal antiinflammatory drugs on bone cancer pain, the authors examined the effects of oral administration of a cyclooxygenase-1 (COX-1) selective inhibitor (SC560), a COX-2 selective inhibitor (celecoxib), and a nonselective COX inhibitor (indomethacin) on bone cancer pain and compared these effects to the effect of orally administered acetaminophen and morphine. An animal model of bone cancer pain was induced by injecting osteolytic murine sarcoma cells in the mouse femur. Drugs were administered orally 2 weeks after tumor-cell implantation, and the level of bone cancer pain was assessed 30, 60, 90, 120, and 180 min after drug administration. Oral administration of acetaminophen, indomethacin, and morphine, but not of SC560 or celecoxib, produced an analgesic effect on bone cancer pain. Co-administration of a subanalgesic does of morphine with acetaminophen enhanced the analgesic effect of acetaminophen. These data suggest that bone cancer pain is effectively treated by oral administration of indomethacin, acetaminophen, and morphine and that the co-administration of acetaminophen and an opioid provides a beneficial effect when treating of bone cancer pain.


Functions of outer mitochondrial membrane proteins: mediating the crosstalk between mitochondrial dynamics and mitophagy.
Most cellular stress responses converge on the mitochondria. Consequently, the mitochondria must rapidly respond to maintain cellular homeostasis and physiological demands by fine-tuning a plethora of mitochondria-associated processes. The outer mitochondrial membrane (OMM) proteins are central to mediating mitochondrial dynamics, coupled with continuous fission and fusion. These OMM proteins also have vital roles in controlling mitochondrial quality and serving as mitophagic receptors for autophagosome enclosure during mitophagy. Mitochondrial fission segregates impaired mitochondria in smaller sizes from the mother mitochondria and may favor mitophagy for eliminating damaged mitochondria. Conversely, mitochondrial fusion mixes dysfunctional mitochondria with healthy ones to repair the damage by diluting the impaired components and consequently prevents mitochondrial clearance via mitophagy. Despite extensive research efforts into deciphering the interplay between fission-fusion and mitophagy, it is still not clear whether mitochondrial fission essentially precedes mitophagy. In this review, we summarize recent breakthroughs concerning OMM research, and dissect the functions of these proteins in mitophagy from their traditional roles in fission-fusion dynamics, in response to distinct context, at the intersection of the OMM platform. These insights into the OMM proteins in mechanistic researches would lead to new aspects of mitochondrial quality control and better understanding of mitochondrial homeostasis intimately tied to pathological impacts.


C1-inhibitor efficiently inhibits Escherichia coli-induced tissue factor mRNA up-regulation, monocyte tissue factor expression and coagulation activation in human whole blood.
Both the complement system and tissue factor (TF), a key initiating component of coagulation, are activated in sepsis, and cross-talk occurs between the complement and coagulation systems. C1-inhibitor (C1-INH) can act as a regulator in both systems. Our aim in this study was to examine this cross-talk by investigating the effects of C1-INH on Escherichia coli-induced haemostasis and inflammation. Fresh human whole blood collected in lepirudin was incubated with E. coli or ultrapurified E. coli lipopolysaccharide (LPS) in the absence or presence of C1-INH or protease-inactivated C1-INH. C3 activation was blocked by compstatin, a specific C3 convertase inhibitor. TF mRNA was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and TF surface expression was measured by flow cytometry. In plasma, the terminal complement complex, prothrombin F1·2 (PTF1·2) and long pentraxin 3 (PTX3) were measured by enzyme-linked immunosorbent assay (ELISA). Cytokines were analysed using a multiplex kit. C1-INH (1·25-5 mg/ml) reduced both LPS- and E. coli-induced coagulation, measured as a reduction of PTF1·2 in plasma, efficiently and dose-dependently (P < 0·05). Both LPS and E. coli induced marked up-regulation of TF mRNA levels and surface expression on whole blood monocytes. This up-regulation was reduced efficiently by treatment with C1-INH (P < 0·05). C1-INH reduced the release of PTX3 (P < 0·05) and virtually all cytokines measured (P < 0·05). Complement activation was inhibited more efficiently with compstatin than with C1-INH. C1-INH inhibited most of the other readouts more efficiently, consistent with additional non-complement-dependent effects. These results indicate that complement plays a role in activating coagulation during sepsis and that C1-INH is a broad-spectrum attenuator of the inflammatory and haemostatic responses.


Trajectories of Informal Caregiving to the Oldest-old: A One-year Follow-up Study.
This study aimed to analyze caregivers and care recipients' health characteristics and caregiving context changes during a one-year follow-up. A total of 204 informal caregivers and oldest-old care recipients ( ≥ 80 years) were assessed on two occasions, 12 months apart. Information was retrieved on the dyad's sociodemographic profile, caregiver's health/caregiving outcomes, care recipients' dependency level, and caregiving context. Descriptive analysis was performed for all variables and comparisons between the two moments using paired t tests or McNemar tests. Caregiving hours, caregiver burden, and negative aspects of caregiving got significantly worse over one year. The number of unmet needs, in-home services utilization, and self-perception of mental health improved. Care recipients declined in their functional and health status and on their cognitive performance. This study provides information about caregiving trajectory changes over one year and stresses a probable caregiver adaptation even when facing increasing caregiving demands.


Quality audit programme for (99m)Tc and (131)I radioactivity measurements with radionuclide calibrators.
The use of radiopharmaceuticals in nuclear medicine for diagnosis and therapy has increased over the years with (99m)Tc and (131)I being most widely used. Quality audit programmes for radioactivity measurements of (131)I have been ongoing and the 12th audit was recently conducted among seventy nuclear medicine centres (NMC) in India. An audit for the activity measurements of (99m)Tc was conducted for the first time among ten NMCs in Mumbai, India. These programmes for radioactivity measurements have become very important to establish traceability of measurements to national and international standards and ensure accurate calibration of radionuclide calibrators. The results of both the audits are very encouraging. Ninety-four percent of the NMCs for (131)I activity measurements were within a window of +/-10% and for (99m)Tc one NMC was deviating more than +/-10%. The methodology adopted for the audit and results are discussed in detail in this paper.


MSCs and inflammation: new insights into the potential association between ALCL and breast implants.
Possible association between anaplastic large cell lymphoma (ALCL) and breast implants has been suggested. In this context, formation of the periprosthetic capsule has been reported as a cause of inflammation, which plays a key role in tumor onset. Tumors take advantage of inflammation to influence and interfere with the host immune response by secreting multiple factors, and their onset and survival is in turn affected by the paracrine effects from mesenchymal stem cells (MSCs). In this study, we tried to clarify how inflammation can modify the immunobiology and the exerted paracrine effect of MSCs. MSCs derived from both inflamed (I-MSCs) and control (C-MSCs) tissues were isolated and co-cultured with an ALCL cell line. Proliferation rate and the expression of selected cytokines were tested. I-MSCs secrete higher levels of cytokine related to chronic inflammation than C-MSCs. After co-cultures with KI-JK cells, C- and I-MSCs show the same variation in the cytokine expression, with an increase of IL2, IL4, IL5, IL10, IL13, TNF-α, TGF-β, and G-CSF. Proliferation of ALCL cells was not influenced by co-cultures. Our results state that (i) inflamed microenvironment affects the immunobiology of MSCs modifying the profile of the expressed cytokines, and (ii) the paracrine effects exerted by MSCs on ALCL cells are not influenced by inflammation. Moreover, it seems that ALCL cells are able to manipulate MSCs' immunoregulatory properties to evade the host immune control. Nevertheless, this ability is not associated with inflammation and the question about BIA-ALCL is not proved by our experiments.


Influence of fungal elicitors on production of ajmalicine by cell cultures of Catharanthus roseus.
Suspension cultures of Catharanthus roseus (C. roseus) were elicited with fungal cell wall fragments of Aspergillus niger (A. niger), Fusarium moniliforme (F. moniliforme), and Trichoderma viride (T. viride). The effects of elicitor dosage, exposures time, and age of subculture on ajmalicine accumulation were studied. A higher concentration of elicitor extract responded positively to C. roseus suspension cultures. Ajmalicine accumulation increased by about 3-fold when cells were treated with A. niger, F.moniliforme, and T. viride. The maximum ajmalicine production (75 microg g(-1) dry weight (DW)) was observed in cells treated with T. viride. Cell cultures were elicited with 5% preparation of A. niger, F. moniliforme, and T. viride and exposed for 24, 48, 72, and 96 h. for elicitation. Suspension cultures elicited with T. viride for 48 h showed a 3-fold increase (87 microg g(-1) DW) in ajmalicine contents, whereas A. niger and F. moniliforme synthesized a 2-fold increase in alkaloid and yielded 52 and 56 microg g(-1) DW ajmalicine, respectively. C. roseus cells of different age (5,10, 15, 20, and 25 days old) were treated with a 5% elicitor of A. niger, F. moniliforme, and T. viride and investigated elicitors activity at different age of cell cultures. Maximum yield 166 microg g(-1) DW of ajmalicine was synthesized in 20 day old suspension cultures treated with T. viride. A longer period of incubation of cell cultures with elicitors adversely affected the ajmalicine synthesis.


The prevalence of tick-borne encephalitis in the region of West Bohemia (Czech Republic) between 1960-2005.
Between 1960-2005, 1,621 cases of tick-borne encephalitis were confirmed by laboratory testing in the region of West Bohemia (now the regions of Pilsen and Karlovy Vary) which represents a rate of infection of 4.1 per 100,000 inhabitants per year. The highest infection rate was established in men aged 20-24 and women aged 45-54. Over the monitored years, there was a significant shift of the maximum infection rate into an older age group. Currently, it is the 45-64 age group which carries the highest rate of infection. Of the identified disease cases, 12 were lethal, which represents 0.7% of the total. Over the years, the risks of transmission in particular areas of the region have changed. The highest infection rate is currently in the district of Klatovy (21.7 per 100,000 inhabitants per year). Of the total number, only two cases were contracted outside the Czech Republic (Slovakia and Austria). In 4.8% cases, the patient's anamnesis showed data on the consumption of non-pasteurized milk. 3.0% of infections probably originated as a result of professional exposure. Over the years, the season of infection has extended. Presently, the transmission can occur anytime between March and November. According to official data, only 6.7% of the population in the Pilsen district has been vaccinated so far. The low percentage of vaccinated cases may, however, in no way influence the unfavorable epidemiological situation regarding tick-borne encephalitis.


The impact of caring for those with chronic obstructive pulmonary disease (COPD) on carers' psychological well-being: a narrative review.
To identify and summarise studies of the psychological well-being of informal carers of people with chronic obstructive pulmonary disease. The review included studies if they reported the carers perspective of caregiving - studies that focused mostly on the person with chronic obstructive pulmonary disease were included only if the carers perspective of the caregiver role could be extracted. Electronic searches of MEDLINE, CINAHL, PsychInfo, Sociological Abstracts and The Cochrane Library were carried out between December 2008 and February 2009, with update searches undertaken in June 2011. A narrative approach was adopted to evaluate studies according to their contribution and drew together evidence from a range of methodologies, including qualitative and quantitative studies. Twenty studies were included in this review. Twelve studies focuses only on the caregiver (quantitative studies=7 and qualitative studies=5) and eight included caregivers and the person with chronic obstructive pulmonary disease (quantitative=6 and qualitative=2). Common methodological limitations of studies included in this review were a lack of non-caregiver age-matched comparison groups, focus on the experience of female carers, small sample sizes, and failure to follow-up caregivers longitudinally. Seven studies provided estimates of the prevalence of psychological distress among caregivers but no conclusions could be drawn from the current evidence base. The totality of the current evidence-base suggests that many factors are related to caregiver psychological distress, but it is not possible to gauge the prevalence of this at present. Further studies are needed to clarify the prevalence of chronic obstructive pulmonary disease caregivers' psychological comorbidity and disease specific factors that predict poorer carer health outcomes. That work will enable appropriate interventions to be developed and evaluated.


Electrochemical studies of S-nitrosothiols.
S-nitrosothiols (RSNO), such as SNAP, GSNO, and Glc-SNAP-1 exhibited a single, totally irreversible, diffusion controlled reduction peak at potentials of -0.97 V, -0.98 V and -0.91 V, respectively, vs. Ag/AgCl (3 M NaCl) reference electrode. This corresponded to the nitric oxide (NO) release from the S-nitrosothiols. A possible mechanism is proposed for the reduction process.


Case of chickenpox in which varicella zoster virus genotype E was identified for the first time in Japan.
Varicella zoster virus (VZV) is now classified into seven genotypes, and type J (clade 2) is known as an exclusively prevalent genotype in Japan. Here, we describe an adult Japanese patient who was suffering from chickenpox caused by VZV type E, the most prevalent genotype in Western Europe. Because the eruptions were distributed over the trunk and limbs and the patient had a high titer of immunoglobulin G against VZV, we diagnosed this case as secondary VZV infection. To investigate the current prevalence of VZV genotypes in Japan, we examined the genotype of VZV in an additional 49 Japanese varicella/zoster patients who visited our hospital during 2018-2019. We found that VZV type E was still an exceptionally rare genotype (1/50) in Japan. Because foreign nationals living in Japan who carry VZV genotypes other than type J are increasing in number, secondary chickenpox may increase in Japan in the near future, as well as in the USA where multiple VZV genotypes are distributed.


Correlation between the carcinogenicity of organic substances and their spectral characteristics.
A correlation between the carcinogenicity of organic substances and their UV-absorption characteristics has been established. It is found that chemical carcinogens have absorption maxima in the wavelength region of 206--248 nm. On the basis of revealed correlation, a mechanism of chemical carcinogenesis is proposed.


Spatial distribution of axon collaterals of single inferior olive neurons.
The aim of this study was to define the overall distribution pattern of the axon collaterals of single inferior olive (IO) neurons in relation to the multiple somatotopic maps defined by the climbing fiber (CF) input through the cerebellar cortex. In a previous study (Rosina and Provini: Brain Res. 289:45-63, '83), it was shown that the IO neurons supply interlobar collaterals to pairs of somatotopically related areas in the intermediate part of the anterior lobe (PIAL), in the paramedian lobule (PML), in crus II, and in the simple lobule, within strips C1 to D2. The residual branches then could either distribute within single folia or to adjacent folia within each somatotopically defined cerebellar area or both. We studied whether or not the IO axons branch over neighboring folia of the face-forelimb (FL) areas of PIAL and PML and how this interfolial branching relates to the interlobar collateralization by using the multiple fluorescent retrograde tracing technique. The main results of the study were as follows: the axons from neurons in IO subdivisions that are related to strips C1-C3 give off two interfolial branches in the FL area of PIAL and practically no interfolial collaterals are given in the FL area of PML; and the neurons that give off interfolial collaterals also give interlobar branches. From these data we have inferred the general branching pattern of the IO neurons that convey FL information to PIAL and PML. Each neuron gives off two interlobar collaterals: the branch directed to PIAL splits again into two interfolial collaterals, while each of these three collaterals should give off about three branches within each target folium to account for the ten collaterals estimated to be present in the cat. The distribution pattern of IO axon collaterals proposed here suggests that the same CF-relayed information may interact, at the Purkinje cell level, with different sets of mossy fiber inputs. The effect of this interaction would be to modulate the motor commands forwarded to specific muscle groups in relation to the different conditions under which a given movement is executed.


Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia.
To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients, a phase 3, multicenter, randomized, double-blind, study evaluated 945 patients. Coprimary end points were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure. Cure rates were 67.9% for tigecycline and 78.2% for imipenem (CE patients) and 62.7% and 67.6% (c-mITT patients), respectively. A statistical interaction occurred between ventilator-associated pneumonia (VAP) and non-VAP subgroups, with significantly lower cure rates in tigecycline VAP patients compared to imipenem; in non-VAP patients, tigecycline was noninferior to imipenem. Overall mortality did not differ between the tigecycline (14.1%) and imipenem regimens (12.2%), although more deaths occurred in VAP patients treated with tigecycline than imipenem. Overall, the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population; this difference appears to have been driven by results in VAP patients.


Enhanced Wnt signaling by methylation-mediated loss of SFRP2 promotes osteosarcoma cell invasion.
Wnt signaling is essential for the initiation and progression of osteosarcoma (OS) tumors and is suppressed by the secreted frizzled-related proteins (SFRPs). The methylation-induced protein degradation reduces the activity of SFRPs and subsequently increases the activity of Wnt signaling. However, whether the methylation of SFRP2, a member of SFRPs, may be involved in the pathogenesis of OS is not known. Here, we investigated the expression levels of SFRP2 in OS specimens. We found that SFRP2 mRNA was significantly decreased and methylation of SFRP2 gene was significantly increased in malignant OS tumors as compared to the paired adjacent non-tumor tissue. Moreover, SFRP2 expression was significantly decreased in the malignant OS cell lines, SAOS2, MG63, and U2OS, but not in the primary osteoblast cells. The demethylation of SFRP2 gene by 5'-aza-deoxycytidine (5-aza-dCyd) in OS cell lines restored SFRP2 expression, at both mRNA and protein levels, and suppressed cell invasion. Furthermore, the demethylation of SFRP2 gene appeared to inhibit nuclear retention of a key Wnt signaling factor, β-catenin, in OS cell lines. Together, these data suggest that SFRP2 may function as an OS invasion suppressor by interfering with Wnt signaling, and the methylation of SFRP2 gene may promote pathogenesis of OS.


The internalization of Helicobacter pylori plays a role in the failure of H. pylori eradication.
Helicobacter pylori (H. pylori) internalization involves invasion of cells by the bacterium. Several studies have shown that H. pylori can invade human gastric epithelial cells, immune cells, and Candida yeast in vivo and in vitro. Whether bacterial invasion plays a role in eradication failure is unclear. To investigate the relationship between H. pylori invasion of GES-1 cells and H. pylori eradication failure. Forty-two clinical strains isolated from H. pylori-positive patients with different outcomes after treatment with furazolidone-based therapy were examined (17 failures and 25 successes). The H. pylori strains were shown to be susceptible to amoxicillin and furazolidone, and the patients also exhibited good compliance. Genotyping was performed for cagA and vacA (s and m). The antibiotic susceptibility of the strains to amoxicillin, furazolidone, clarithromycin, metronidazole, and levofloxacin was determined by E-tests. The levels of H. pylori invasion of GES-1 cells were detected by gentamicin colony-forming unit assays. The internalization level in the eradication success group was 5.40±5.78 × 10-3 cfu/cell, and the median was 6.194 × 10-3 cfu/cell; the internalization level in the eradication failure group was 8.98±5.40 × 10-3 cfu/cell, and the median was 10.28 × 10-3 cfu/cell. The eradication failure group showed a greater invasion level than the eradication success group (P<.05). No significant difference was observed between the susceptible strains and the resistant strains when the internalization levels were compared (P>.05). The results showed that H. pylori invasion of the gastric epithelia might play a role in eradication failure.


Activation of protein kinase C is required for AMPA receptor GluR1 phosphorylation at serine 845 in the dorsal striatum following repeated cocaine administration.
Phosphorylation in the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors plays a crucial role in the regulation of AMPA receptor plasticity associated with drugs of abuse. It is well known that phosphorylation of AMPA receptor GluR1 subunit at serine 845 (S845) is regulated by protein kinase A downstream to dopamine D1 receptors in the striatum. This study was performed to determine whether GluR1-S845 phosphorylation in the rat dorsal striatum is altered by repeated cocaine via a signaling mechanism involving glutamate receptor-associated and Ca(2+)-dependent protein kinases. Systemic administration of cocaine (20 mg/kg, once a day for 7 days) upregulated GluR1-S845 phosphorylation. This upregulation was mediated via a mechanism involving stimulation of group I metabotropic glutamate receptor 1, N-methyl-D-aspartate receptors, and inositol 1,4,5-triphosphate-sensitive receptors. Interactions of several protein kinases, including protein kinase C, Ca(2+)/calmodulin-dependent protein kinase II, and extracellular signal-regulated kinases, are also involved in this event. Protein phosphatases further control S845 phosphorylation by dephosphorylating S845 and phosphorylated protein kinases. These findings suggest that phosphorylation of AMPA receptors at GluR1-S845 is upregulated by interactions of glutamate receptor-coupled Ca(2+)-dependent protein kinases following repeated cocaine administration in the dorsal striatum.


References Values of Soluble α-Klotho Serum Levels Using an Enzyme-Linked Immunosorbent Assay in Healthy Adults Aged 18-85 Years.
α-Klotho protein is a powerful predictor of the aging process and lifespan. Although lowered circulating soluble α-Klotho levels have been observed in aged non-healthy individuals, no specific reference values across a wide range of ages and sex using an enzyme-linked immunosorbent assay (ELISA) are available for larger cohorts of healthy individuals. The present analytical cross-sectional study was aimed to establish the reference values of soluble α-Klotho serum levels in healthy adults by age and sex groups. A total of 346 (59% women) healthy individuals aged from 18 to 85 years were recruited. Subjects were divided by sex and age as: (i) young (18−34.9 years), (ii) middle-aged (35−54.9 years), and (iii) senior (55−85 years) individuals. The soluble α-Klotho levels were measured in serum using ELISA. Senior adults were the age-group that presented the lowest soluble α-Klotho serum levels (p < 0.01), with age showing a negative association with soluble α-Klotho serum levels (p < 0.001). No differences between sexes were observed. Therefore, soluble α-Klotho levels were especially decreased—regardless of sex—in our cohort of healthy individuals because of the physiological decline derived from the aging process. We recommend routine assessments of soluble α-Klotho levels using ELISA as a simple and cheap detectable marker of aging that improves quality of life in the elderly.


Effects of the antibiotic growth promoters flavomycin and florfenicol on the autochthonous intestinal microbiota of hybrid tilapia (Oreochromis niloticus ♀ × O. aureus ♂).
The 16S rDNA PCR-DGGE and rpoB quantitative PCR (RQ-PCR) techniques were used to evaluate the effects of dietary flavomycin and florfenicol on the autochthonous intestinal microbiota of hybrid tilapia. The fish were fed four diets: control, dietary flavomycin, florfenicol and their combination. After 8 weeks of feeding, 6 fish from each cage were randomly chosen for the analysis. The total number of intestinal bacteria was determined by RQ-PCR. The results showed that dietary antibiotics significantly influenced the intestinal microbiota and dramatically reduced the intensity of total intestinal bacterial counts. The intensity of some phylotypes (EU563257, EU563262 and EU563255) were reduced to non-detectable levels by both dietary antibiotics, while supplementation of florfenicol to the diet also reduced the intensity of the phylotypes EU563242 and EU563262, uncultured Mycobacterium sp.-like, uncultured Cyanobacterium-like and uncultured Cyanobacterium (EU563246). Dietary flavomycin only reduced the OTU intensity of one phylotype, identified as a member of the phylum Fusobacteria. The antibiotic combination only reduced the phylotypes EU563242 and EU563262. Based on our results, we conclude that the reduced effect of florfenicol on intestinal microbiota was stronger than that of flavomycin, and when flavomycin and florfenicol were added in combination, the effect of florfenicol overshadowed that of flavomycin.


Headache after ischemic stroke: A systematic review and meta-analysis.
Headache associated with ischemic stroke is poorly understood. To gain further insight, we systematically reviewed studies examining the prevalence and characteristics of new-onset poststroke headache. Medline and PubMed databases were queried. A total of 1,812 articles were identified. Of these, 50 were included in this systematic review. Twenty were included in a meta-analysis and meta-regression. Headache occurred in 6%-44% of the ischemic stroke population. Most headaches had tension-type features, were moderate to severe, and became chronic in nature. Meta-analysis using an inverse-variance heterogeneity model revealed a pooled prevalence of 0.14 (95% confidence interval [CI] 0.07-0.23) with heterogeneity among studies. Metaregression revealed a significant association between prevalence and study location, the source population's national human development index (HDI), and study quality. We found higher prevalence in European (0.22, 95% CI 0.14-0.30) and North American (0.15, 95% CI 0.05-0.26) studies compared with Middle Eastern and Asian studies (0.08, 95% CI 0.01-0.18). However, within each region, populations from countries with higher HDI (p = 0.03) and studies with higher quality (p = 0.001) had lower prevalence. Calculated crude odds ratios (ORs) showed that posterior circulation stroke (pooled OR 1.92, 95% CI 1.4-2.64; n = 7 studies) and female sex (pooled OR 1.25, 95% CI 1.07-1.46; n = 11 studies) had greater odds of headache associated with ischemic stroke. Taken together, these data suggest that headache is common at the onset of or shortly following ischemic stroke and may contribute to poststroke morbidity. Better understanding of headache associated with ischemic stroke is needed to establish treatment guidelines and inform patient management.


MPTP lesions of the nigrostriatal dopaminergic projection decrease [3H]1-[1-(2-thienyl)cyclohexyl]piperidine binding to PCP site 2: further evidence that PCP site 2 is associated with the biogenic amine reuptake complex.
Our previous studies have demonstrated that, using membranes of guinea pig brain, [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) labels not only the phencyclidine binding site associated with the NMDA receptor (PCP site 1), but also a second high affinity binding site which is associated with the biogenic amine reuptake carrier (termed PCP site 2). To test this hypothesis, the binding of [3H]GBR12935 to the dopamine transporter, and [3H]TCP binding to PCP sites 1 and 2 were measured in caudates harvested from control, MPTP-treated and reserpine-treated dogs. MPTP treatment decreased dopamine levels by over 99%, decreased [3H]GBR12935 binding by over 90%, decreased [3H]TCP binding to PCP site 2 by about 50%, and had no significant effect on [3H]TCP binding to PCP site 1. These data are consistent with the hypothesis that a portion of PCP site 2 is associated with dopaminergic nerve terminals in dog caudate.


Antimicrobial drug-resistant microbes associated with hospitalized community-acquired and healthcare-associated pneumonia: a multi-center study in Taiwan.
Community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) may be caused by potential antimicrobial drug-resistant (PADR) microbes. The aims of this study were to evaluate the incidences and risk factors associated with PADR microbes observed in patients with pneumonia occurring outside the hospital setting in Taiwan. We conducted a retrospective study of patients with CAP or HCAP admitted to six medical centers in the northern, central, and southern regions of Taiwan in 2007. The pathogens were evaluated by microbiological specimens within 72 hours after admission. The patients' comorbidities, pathogens, and outcomes were evaluated. The risk factors of PADR microbes were identified by logistic regression analysis. The enrolled patients exhibited HCAP (n=713) and CAP (n=933). The pathogens associated with HCAP (n=383) and CAP (n=441) included Pseudomonas spp. (29%vs. 10%, p<0.001), Klebsiella spp. (24% vs. 25%, p=0.250), Escherichia coli (6% vs. 8%, p=0.369), Haemophilus influnezae (3% vs. 7%, p=0.041), Streptococcus pneumoniae (2% vs. 6%, p=0.003) and methicillin-resistant Staphylococcus aureus (MRSA) (8% vs. 4%, p=0.008). The core pathogens of CAP and HCAP differed among the three regions of Taiwan. PADR microbes, including Pseudomonas spp. (n=191), Acinetobacter spp. (n=41), MRSA (n=49) and cefotaxime- or ceftazidime-resistant Enterbacteriaceae (n=25), were isolated from 13% of patients with CAP and 23% of patients with HCAP. Previous hospitalization, and neoplastic and neurological diseases were significant risk factors for acquiring PADR microbes. PADR microbes were common in patients with HCAP and CAP in Taiwan. Broad-spectrum antibiotics targeting PADR microbes should be administered to patients who have undergone previous hospitalization and who exhibit neurological disorders and/or malignancies.


Retromer-mediated endosomal protein sorting: all WASHed up!
Endosomal protein sorting governs the fate of many physiologically important proteins involved in a panoply of cellular functions. Recent discoveries have revealed a vital role for endosomally localised branched actin patches in facilitating protein sorting. The formation of the actin patches has been shown to require the function of the WASH complex - the major endosomal actin polymerisation-promoting complex - which stimulates the activity of the ubiquitously expressed Arp2/3 complex. Another key component of the endosomal protein-sorting machinery is the retromer complex. Studies now show that retromer mediates the recruitment of the WASH complex and its regulators to endosomes. In this review, recent progress in understanding the role of the WASH complex along with retromer in endosomal protein sorting is discussed.


Sex-specific microRNAs in women with diabetes and left ventricular diastolic dysfunction or HFpEF associate with microvascular injury.
Left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction (HFpEF) are microcirculation defects following diabetes mellitus (DM). Unrecognized HFpEF is more prevalent in women with diabetes compared to men with diabetes and therefore sex-specific diagnostic strategies are needed. Previously, we demonstrated altered plasma miRs in DM patients with microvascular injury [defined by elevated plasma Angiopoietin-2 (Ang-2) levels]. This study hypothesized the presence of sex-differences in plasma miRs and Ang-2 in diabetic (female) patients with LVDD or HFpEF. After a pilot study, we assessed 16 plasma miRs in patients with LVDD (n = 122), controls (n = 244) and female diabetic patients (n = 10). Subsequently, among these miRs we selected and measured plasma miR-34a, -224 and -452 in diabetic HFpEF patients (n = 53) and controls (n = 52). In LVDD patients, miR-34a associated with Ang-2 levels (R2 0.04, R = 0.21, p = 0.001, 95% CI 0.103-0.312), with plasma levels being diminished in patients with DM, while women with an eGFR < 60 ml/min and LVDD had lower levels of miR-34a, -224 and -452 compared to women without an eGFR < 60 ml/min without LVDD. In diabetic HFpEF women (n = 28), plasma Ang-2 levels and the X-chromosome located miR-224/452 cluster increased compared to men. We conclude that plasma miR-34a, -224 and -452 display an association with the microvascular injury marker Ang-2 and are particularly targeted to women with LVDD or HFpEF.


High apolipoprotein E in cerebrospinal fluid of patients with Lewy body disorders is associated with dementia.
Apolipoprotein E ε4 allele (APOE ε4) increases the apolipoprotein E (apoE) protein levels in Alzheimer's disease (AD) cerebrospinal fluid (CSF). Thus, we hypothesized that apoE levels were also associated with the APOE genotype, and amyloid-β (Aβ)-associated clinical, functional, and imaging parameters in patients with Lewy body-associated disorders (LBD). Indeed, similar to AD, patients with LBD displayed high CSF apoE levels (greatest in patients with dementia with LBD), and this was linked to APOE ε4. High CSF apoE protein correlated positively with CSF soluble amyloid precursor protein, total tau, and cortical and striatal Pittsburgh compound B retention; and correlated negatively with CSF Aβ42, cognitive tests scores, and glucose uptake ratio in the temporal and parietal cortices. APOE ε4-triggered accumulation of apoE in CSF is related to Aβ-associated clinical and functional imaging parameters in LBD. Accordingly, therapeutic strategies aimed at reducing apoE levels in the brain should be explored not only in AD but also in LBD, particularly when accompanied with dementia.


Sister-chromatid exchange induction by sodium selenite: dependence on the presence of red blood cells or red blood cell lysate.
Sodium selenite (Na2SeO3) sister-chromatid exchange (SCE) induction was studied in both short-term and long-term cell cultures. The ability of Na2SeO3 to induce SCEs was found to depend on the culture conditions employed. Concentrations of Na2SeO3 (7.90 X 10(-6) M and greater) that produced elevated SCE frequencies in whole blood cultures resulted in control level SCE frequencies (6-8 SCEs/cell) in Ficoll-Hypaque--purified lymphocyte cultures. However, whole blood and purified lymphocyte cultures were equally sensitive to SCE induction by methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), and N-hydroxy-2-acetylaminofluorene (N-OH-AAF). Analysis of different whole blood components showed that the presence of red blood cells (RBCs), and specifically RBC lysate, was a prerequisite for Na2SeO3 SCE induction in purified lymphocyte cultures. The SCE frequencies of xeroderma pigmentosum (XP12RO) and normal human lymphoblastoid cell lines were also found to be unaffected by Na2SeO3 concentrations that produced elevated SCE frequencies in whole blood cultures. Incubation of these latter two cell types with Na2SeO3 and RBC lysate resulted in SCE frequencies comparable to those in Na2SeO3-exposed whole blood cultures.


Metformin Inhibits Multiple Myeloma Serum-induced Endothelial Cell Thrombosis by Down-Regulating miR-532.
Thrombotic complications in multiple myeloma (MM) impairs the quality of life in patients. Metformin has a certain effect on anti-thrombosis, but its role and mechanism in MM-induced thrombosis are still uncovered. Therefore, this study evaluated the effect of metformin on MM-induced thrombosis. Human umbilical vein endothelial cells (HUVECs) were exposed to normal serum (15%), MM serum (15%), metformin (0.01 mmol/L), or MM serum, and metformin simultaneously. The expression of tissue factor (TF) in HUVECs was detected by flow cytometry and quantitative real-time polymerase chain reaction PCR (qRT-PCR). QRT-PCR was also used to determine the expressions of endothelial protein C receptor (EPCR) and miR-532. The generation of thrombin and activated protein C was measured by thrombin generation and protein C activation assays. EPCR, extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathway related protein expressions were detected by western blot. MM serum increased the expressions of TF and miR-532, induced thrombin generation, inhibited EPCR and protein C activation in HUVECs. And metformin could reverse the effects of MM serum on the expressions of TF, EPCR and miR-532, thrombin generation, protein C activation in HUVECs. However, miR-532 mimic reversed the effects of metformin and promoted the levels of thrombosis-related indicators in HUVECs. Moreover, metformin activated the ERK 1/2, p38 MAPK, and NF-κB pathways but miR-532 mimic suppressed the pathway activation. Metformin played an inhibitory effect on MM serum-induced HUVEC thrombosis, suggesting that metformin could serve as a novel antithrombotic approach for MM patients.


Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab.
Bone is a complex tissue that provides mechanical support for muscles and joints, protection for vital organs, a mineral reservoir that is essential for calcium homeostasis, and the environment and niches required for haematopoiesis. The regulation of bone mass in mammals is governed by a complex interplay between bone-forming cells termed osteoblasts and bone-resorbing cells termed osteoclasts, and is guided physiologically by a diverse set of hormones, cytokines and growth factors. The balance between these processes changes over time, causing an elevated risk of fractures with age. Osteoclasts may also be activated in the cancer setting, leading to bone pain, fracture, spinal cord compression and other significant morbidities. This Review chronicles the events that led to an increased understanding of bone resorption, the elucidation of the signalling pathway mediated by osteoprotegerin, receptor activator of NF-κB (RANK) and RANK ligand (RANKL) and its role in osteoclast biology, as well as the evolution of recombinant RANKL antagonists, which culminated in the development of the therapeutic RANKL-targeted antibody denosumab.


Touch on predefined areas on the forearm can be associated with specific fingers: Towards a new principle for sensory feedback in hand prostheses.
Currently available hand prostheses lack sensory feedback. A "phantom hand map", a referred sensation, on the skin of the residual arm is a possible target to provide amputees with non-invasive somatotopically matched sensory feedback. How-ever, not all amputees experience a phantom hand map. The aim of this study was to explore whether touch on predefined areas on the forearm can be associated with specific fingers. A longitudinal cohort study. A total of 31 able-bodied individuals. A "tactile display" was developed consisting of 5 servo motors, which provided the user with mechanotactile stimulus. Predefined pressure points on the volar aspect of the forearm were stimulated during a 2-week structured training period. Agreement between the stimulated areas and the subjects' ability to discriminate the stimulation was high, with a distinct improvement up to the third training occasion, after which the kappa score stabilized for the rest of the period. It is possible to associate touch on intact skin on the forearm with specific fingers after a structured training period, and the effect persisted after 2 weeks. These results may be of importance for the development of non-invasive sensory feedback systems in hand prostheses.


The key role of transforming growth factor-beta receptor I and 15-lipoxygenase in hypoxia-induced proliferation of pulmonary artery smooth muscle cells.
Our laboratory has proved that 15-hydroxyeicosatetraenoic acid, a product of arachidonic acid catalyzed by 15-lipoxygenase (15-LO), plays a pivotal role in hypoxic pulmonary arterial hypertension. However, the mechanisms of how hypoxia regulates 15-LO expression are still unclear. As the formation of endogenous transforming growth factor-beta1 (TGF-β1), implicated in pulmonary arterial hypertension pathogenesis, was promoted by hypoxia, we suspect whether hypoxia-induced the expression of 15-LO is via the TGF-β1 pathway. We found that treatment of pulmonary artery smooth muscle cells with TGF-β1 significantly increased the expression of 15-LO and levels of 15-hydroxyeicosatetraenoic acid, product of 15-LO, which were inhibited by transforming growth factor-beta receptor I (TGFβRI) inhibitor, SD-208 and siRNA targeted to knockdown rat TGFβRI. Moreover, our results showed that TGF-β1 regulated the cell cycle progression and made more cells from the G(0)/G(1) phase to the G(2)/M+S phase and enhanced the microtubule formation in cell nucleus. Additionally, we found that the 15-LO pathway was involved in TGFβ-1-mediated cell viability, DNA synthesis and the cell cycle progression. Our data provide novel evidence that hypoxia induced 15-LO expression is through TGF-β1, and 15-LO pathway plays a critical role in TGFβRI mediated the proliferation of pulmonary artery smooth muscle cells induced by hypoxia. Thus, new strategies aimed at combined blockade of TGFβRI as well as 15-LO may yield optimal therapeutic benefits.


2-(Aryl)-3-furan-2-ylmethyl-thiazolidin-4-ones as selective HIV-RT inhibitors.
A series of 4-thiazolidinones were evaluated as selective inhibitors of the HIV-RT enzyme. Our attempt in correlating the derived physicochemical properties with the HIV-RT inhibitory activity resulted in some statistically significant QSAR models with good predictive ability. The QSAR studies indicated the role of lipophilicity, dipole moment and out-of-plane potential energy of the compounds in rationalizing the activity. One of the compounds, 1, inhibited the enzyme at 0.204 microM concentration with minimal toxicity to MT-4 cells.


Ferritin: another pregnancy-specific protein in human seminal plasma and amniotic fluid, as estimated by six methods.
Large quantities of ferritin were found in both seminal plasma and amniotic fluid, but there was a wide spread of results for each of six new non-radioactive monoclonal assays designed to give the same results for ferritin in blood serum. Correlation of values between the various assays was also poor, but after the exclusion of outliers it was possible to calculate approximate ratios for the concentrations. For seminal plasma, the Amersham 'Amerlite' luminescence immunoassay gave the lowest concentrations at 81 +/- 56 ng ml-1 WHO 80/602 (mean +/- SD, n = 43). Relative to this value as 100%, the other assays gave:Flow 'Monoscan' colorimetric IEMA = 161%; Pharmacia-LKB 'DELFIA' fluoroimmunoassay = 174%, Walker 'Synelisa' colorimetric ELISA = 182%; Abbott 'IMx' MEIA = 207%, while the results from the Ramco colorimetric ELISA were much higher and not parallel to the other assays. For amniotic fluid, the Amersham 'Amerlite' LIA gave 127 +/- 95 ng ml-1 (n = 38), taken as 100%, and the ratios for the other assays were:Abbott also approximately 100% but with a wide spread; Walker 43%, Pharmacia-LKB 22% and Ramco 148%. The Flow assay produced 15 zero values from 38 samples, and values were also very low in another 17 samples, so that no comparison with the other assays was possible. An attempt was made to determine the proportion of the different types of isoferritins being estimated. The Pharmacia-LKB assay estimated 90% of the theoretical concentration for pure liver ferritin, 42% of that from the placenta, 26% of that from the heart and 13% of that from the spleen. The other assays gave different proportions.


Physiology-guided revascularization versus optimal medical therapy of nonculprit lesions in elderly patients with myocardial infarction: Rationale and design of the FIRE trial.
Myocardial infarction (MI) in elderly patients is associated with unfavorable prognosis, and it is becoming an increasingly prevalent condition. The prognosis of elderly patients is equally impaired in ST-segment elevation (STE) or non-STE (NSTE), and it is markedly worsened by the common presence of multivessel disease (MVD). Given the limited evidence available for elderly patients, it has not yet been established whether, as for younger patients, a complete revascularization strategy in MI patients with MVD should be advocated. We present the design of a dedicated study that will address this research gap. The FIRE trial is a prospective, randomized, international, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients aged 75 years and older, with MI (either STE or NSTE), MVD at coronary artery angiography, and a clear culprit lesion will be randomized to culprit-only treatment or to physiology-guided complete revascularization. The primary end point will be the patient-oriented composite end point of all-cause death, any MI, any stroke, and any revascularization at 1 year. The key secondary end point will be the composite of cardiovascular death and MI. Quality of life and physical performance will be evaluated as well. All components of the primary and key secondary outcome will be tested also at 3 and 5 years. The sample size for the study is 1,400 patients. The FIRE trial will provide evidence on whether a specific revascularization strategy should be applied to elderly patients presenting MI and MVD to improve their clinical outcomes.


Acute Kidney Injury in Severe Preeclamptic Patients Admitted to Intensive Care Unit: Epidemiology and Role of Serum Neutrophil Gelatinase-associated Lipocalcin.
Patients with preeclampsia admitted to the intensive care unit (ICU) may have risk factors for acute kidney injury (AKI). Although the use of neutrophil gelatinase-associated lipocalcin (NGAL) to predict AKI is previously validated, we could locate only scanty data regarding the epidemiology of AKI and role of NGAL in preeclamptic patients admitted to ICU. Patients with preeclampsia admitted to our ICU were included. The incidence and severity of AKI during the entire ICU stay were assessed using kidney disease improving global outcomes criteria, while the a priori risk factors and serum NGAL were also evaluated. A total of 52 preeclamptic patients admitted to ICU were included, among whom the majority had eclampsia (75%). AKI developed in 25 (48.1%) patients with stages 1, 2, and 3 in 56, 36, and 8%, respectively. The incidence of sepsis (16 vs 0%), shock (40 vs 7.4%), and anemia (84 vs 59.3%) was significantly greater in patients with AKI (p < 0.05). ICU mortality (28 vs 3.7%), duration of ICU, and hospital stay were significantly higher in patients who developed AKI (p < 0.05). There was no association of serum NGAL [274 (240-335) ng/mL] with AKI or the mortality (p = 0.725, 0.861); there was, however, a significant discriminatory value for eclampsia [p = 0.019; area under curve = 0.736 (95% confidence interval: 0.569-0.904)]. Although AKI is common among patients with preeclampsia admitted to ICU, serum NGAL does not predict its occurrence. Tyagi A, Yadav P, Salhotra R, Das S, Singh PK, Garg D. Acute Kidney Injury in Severe Preeclamptic Patients Admitted to Intensive Care Unit: Epidemiology and Role of Serum Neutrophil Gelatinase-associated Lipocalcin. Indian J Crit Care Med 2021;25(9):1013-1019.


Temporal and spatial patterns of nitrogen wet deposition in different weather types in the Pearl River Delta (PRD), China.
The temporal and spatial patterns of nitrogen wet deposition were investigated in the Pearl River Delta (PRD) under different weather types. The study was carried out in 27 monitoring sites with reliable meteorological data from 2010 to 2017. Large spatial variation data showed that both annual volume weighted mean (VWM) concentrations and fluxes were higher in the central PRD while lower in the outer area. The annual mean concentrations and fluxes were in the range of 0.8-1.3 mg N L-1 and 10.9-20.6 kg N ha-1 yr-1, respectively. The monthly mean concentrations and fluxes ranged from 0.1 to 0.2 mg N L-1 and 0.4 to 2.4 kg N ha-1, respectively. Further the study data revealed that the ratio of NH4+/NO3- was 1.1 which was much lower than the ratio reported in other regions like Northern China, Sichuan Basin, the US and Europe. The flux of NH4+ in urban sites was comparable to rural sites, implying that potential non-agricultural NH3 emissions were likely to be high in the PRD. The top three weather types were E, C and SE, with the total contribution of more than a half to the flux. Multiple linear regression was used to set up an equation to predict the variation of annual fluxes under the changes in weather conditions. The result hints that the variation on annual fluxes in the PRD tends to be stable in the next 30 years. Considering the increasing impact on the ecosystem, more effort should be exerted to reduce nitrogen wet deposition in the future.


Thermoluminescence response of dysprosium doped strontium tetraborate glasses subjected to electron irradiations.
The paper presents the thermoluminescence (TL) response of strontium tetraborate glass subjected to electron irradiations at various Dy2O3 concentrations ranging from 0.00 to 1.00mol%. All glass samples exhibited single broad peak with maximum peak temperature positioned at 170-215°C. The optimum TL response was found at Dy2O3 concentration 0.75mol%. This glass showed good linearity and higher sensitivity for 7MeV compared to 6MeV electrons. Analysis of kinetic parameters showed that the glasses demonstrate second order kinetic.


Transient expression and sequence of the matrix (M1) gene of WSN influenza A virus in a vaccinia vector.
A cDNA encoding the entire amino acid sequence of the matrix (M1) protein of influenza A/WSN/33 virus was cloned, sequenced, and expressed in a vaccinia virus system consisting of the T7 bacteriophage RNA polymerase and a plasmid carrying the M1 gene flanked by T7 polymerase promoter and terminator sequences. The transiently expressed M1 gene product comigrated on SDS-polyacrylamide gels with the endogenous WSN virus M1 protein and was recognized in Western blot analysis by three epitope-specific monoclonal antibodies directed to the M1 protein. The nucleotide sequence and the predicted amino acid sequence of the cloned WSN virus M1 coding region was found to be more than 97% homologous to that of the M1 gene of influenza virus A/PR/8/34 reported by G. Winter and S. Fields (Nucleic Acids Res. 8, 1965-1974, 1980).


Effectiveness of perioperative anticoagulation interruption without heparin bridging on thromboembolic events in patients with atrial fibrillation undergoing elective invasive procedures: a systematic review protocol.
This review will determine whether withholding heparin bridging is superior to bridging in patients with atrial fibrillation requiring temporary interruption of anticoagulation therapy in the perioperative period of an elective invasive procedure. Atrial fibrillation is the most commonly diagnosed clinical arrhythmia. It is an important cause of cardioembolic events, requiring the use of oral anticoagulation in most patients. It is unclear whether heparin bridging during temporary interruption of anticoagulants has superior outcomes compared with no bridging in the perioperative setting. This review will consider studies that compare adults aged 18 years or older; diagnosed with atrial fibrillation; undergoing elective invasive procedures; and who have had oral anticoagulants temporarily withheld with heparin bridging with patients without heparin bridging. Participants will be excluded if they had an alternative reason for anticoagulation or were admitted for emergency surgery. Outcomes will include arterial or venous thromboembolism (including stroke, transient ischemic attack, systemic embolism), major bleeding events, non-major bleeding events, length of hospital stay, and all-cause mortality. The review will follow the JBI methodology for systematic reviews of effectiveness. Databases including MEDLINE, Embase, CINAHL, and CENTRAL will be searched for randomized and non-randomized trials from inception until the present. Two independent reviewers will screen citations by title and abstract, and again at full text. Risk of bias will be assessed using the JBI critical appraisal instrument, and data will be extracted using a modified extraction tool. Results will be synthesized using a random effects meta-analysis and presented in a forest plot. Heterogeneity will be tested for using the standard χ 2 and I2 tests. Overall certainty of evidence will be evaluated using the GRADE approach. PROSPERO CRD42022348538.


Effects of antimetabolites on the production of tubular structures in Vero cells infected with herpes simplex virus type 2.
Treatment of Vero cells infected with herpes simplex virus type 2 with the proper concentrations of hydroxyurea (HU) reduced the production of infectious virus and markedly increased the accumulation of tubular structures in the nuclei when the drug was added within 6 hours after infection. Similar accumulation of tubular structures in the infected nuclei was also observed when infected cells were treated with phosphonoacetic acid at proper concentrations. The release of HU-treated, herpes simplex virus type 2-infected cells from the drug-induced blocking of synthesis of infectious virus resulted in the marked decrease of tubular structures coincidentally with the beginning of production of infectious virus. The data suggest the possibility that the disappearance of tubular structures may be related to the active production of infectious virus.


Compulsory schooling system and equity in education: An analysis on intergenerational transmission of education.
This paper uses the China Family Panel Studies' micro-level data and the ordered logit model to study intergenerational transmission of education and examines whether the nine-year compulsory schooling system affects equity in education. The results show that when parents have higher educational attainments, their children will have higher educational attainments. Full-sample results show that when the mother has higher education, the probability that her children have higher education increases by 7.97%, whereas for the sub-sample after the compulsory schooling policy carried out, the probability increases by 22.42%. We find that the compulsory schooling system strengthens intergenerational transmission of education in the level of higher education. An implication is that the compulsory schooling system may promote equity in compulsory education but does not promote equity in higher education.


The Frequency of Routine Blood Sampling and Patient Outcomes Among Maintenance Hemodialysis Recipients.
Surveillance blood work is routinely performed in maintenance hemodialysis (HD) recipients. Although more frequent blood testing may confer better outcomes, there is little evidence to support any particular monitoring interval. Retrospective population-based cohort study. All prevalent HD recipients in Ontario, Canada, as of April 1, 2011, and a cohort of incident patients commencing maintenance HD in Ontario, Canada, between April 1, 2011, and March 31, 2016. Frequency of surveillance blood work, monthly versus every 6 weeks. The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events, all-cause hospitalization, and episodes of hyperkalemia. Cox proportional hazards with adjustment for demographic and clinical characteristics was used to evaluate the association between blood testing frequency and all-cause mortality. Secondary outcomes were evaluated using the Andersen-Gill extension of the Cox model to allow for potential recurrent events. 7,454 prevalent patients received care at 17 HD programs with monthly blood sampling protocols (n=5,335 patients) and at 8 programs with blood sampling every 6 weeks (n=2,119 patients). More frequent monitoring was not associated with a lower risk for all-cause mortality compared to blood sampling every 6 weeks (adjusted HR, 1.16; 95% CI, 0.99-1.38). Monthly monitoring was not associated with a lower risk for any of the secondary outcomes. Results were consistent among incident HD recipients. Unmeasured confounding; limited data for center practices unrelated to blood sampling frequency; no information on frequency of unscheduled blood work performed outside the prescribed sampling interval. Monthly routine blood testing in HD recipients was not associated with a lower risk for death, cardiovascular events, or hospitalizations as compared with testing every 6 weeks. Given the health resource implications, the frequency of routine blood sampling in HD recipients deserves careful reassessment.


Effect of fluctuating temperature on the duration of embryonic development in two Ecdyonurus spp. and Rhithrogena cf. hybrida (Ephemeroptera) from Austrian streams.
Eggs of Ecdyonurus picteti from the Herrnalmbach and Seebach, and E. venosus and Rhithrogena cf. hybrida from the Seebach were fertilized artificially and kept at fluctuating temperatures (range 2.8°-18.1° C) in the laboratory. The percentage of eggs that hatched at each sinusoidal temperature cycle ranged from 0 to 49% and values were similar to those obtained for eggs reared under constant temperature conditions. The hatching time (days after fertilization for 10, 50% and 90% of the eggs to hatch) decreased with increasing temperature and the relationship between the two variables was well described by a powerlaw within the range 2.8°-18.1° C for E. venosus. A similar relationship has been found for the effect of constant temperature on the hatching time of eggs of E. venosus. It appears that the effect of temperature on the rate of change in the hatching time and the rate of development is approximately similar for both constant and fluctuating temperatures.


Crystal structure of the complex of ribulose-1,5-bisphosphate carboxylase and a transition state analogue, 2-carboxy-D-arabinitol 1,5-bisphosphate.
The crystal structure of the binary complex of nonactivated ribulose-1,5-bisphosphate carboxylase/oxygenase from Rhodospirillum rubrum and a transition state analogue, 2-carboxy-D-arabinitol 1,5-bisphosphate has been determined to 2.6 A resolution with x-ray crystallographic methods. The transition state analogue binds in a rather extended conformation at the active site. The orientation of the transition state analogue within the active site could be determined from the electron density maps. The P1 phosphate group of the analogue binds at a site built up of residues from loops 5 and 6 of the alpha/beta-barrel. The phosphate group interacts with the side chains of the conserved residues Arg-288, His-321, and Ser-368 and with main chain nitrogens from residues Thr-322 and Gly-323. The second phosphate group of the transition state analogue binds at the opposite side of the barrel close to loops 1 and 8. Significant differences for the positions and interactions of the P2 phosphate group with the enzyme are found in the two subunits of the dimer. The different mode of binding for this phosphate group in the two subunits is interpreted as a consequence of different conformations of the polypeptide chain observed in loops 6 and 8. The P2 phosphate group interacts with the sidechains of Lys-166 and Lys-329. Loop 6, which is disordered in the nonactivated, nonliganded enzyme is considerably more ordered in one of the subunits, probably due to the interaction of the side chain of Lys-329 with the P2 phosphate group. Almost all oxygen atoms are hydrogen bonded to groups on the enzyme. The carboxyl group forms hydrogen bonds to the side chain of the conserved Asn-111. The binding of the transition state analogue to the nonactivated enzyme is different from the binding of the analogue to activated spinach ribulose-bisphosphate carboxylase.


Methicillin-resistant Macrococcus canis in a human wound.
A hemolytic Macrococcus canis strain (LI021) was isolated for the first time from a human skin infection. The complete genome of LI021 consisting of a 2,216,765-bp circular chromosome was obtained by de novo hybrid assembly of Illumina and Oxford Nanopore technology reads. Strain LI021 belonged to the new sequence type ST75 and was resistant to β-lactam antibiotics due to the presence of a methicillin resistance gene mecB. The mecB gene as well as putative hemolysin genes hlgB and hlgC were located on a novel composite pseudo (Ψ) SCCmec island. These findings show that a methicillin-resistant M. canis may be associated with human infection and indicate that this bacterium should be considered by human diagnostic laboratories.


A Comprehensive Review on COVID-19: Emphasis on Current Vaccination and Nanotechnology Aspects.
COVID-19, caused by the SARS-CoV-2 virus, has been expanding. SARS-CoV caused an outbreak in early 2000, while MERS-CoV had a similar expansion of illness in early 2010. Nanotechnology has been employed for nasal delivery of drugs to conquer a variety of challenges that emerge during mucosal administration. The role of nanotechnology is highly relevant to counter this "virus" nano enemy. This technique directs the safe and effective distribution of accessible therapeutic choices using tailored nanocarriers, as well as the interruption of virion assembly, by preventing the early contact of viral spike glycoprotein with host cell surface receptors. This study summarises what we know about earlier SARS-CoV and MERS-CoV illnesses, with the goal of better understanding the recently discovered SARS-CoV-2 virus. It also explains the progress made so far in creating COVID-19 vaccines/ treatments using existing methods. Furthermore, we studied nanotechnology- based vaccinations and therapeutic medications that are now undergoing clinical trials and other alternatives.


Genetic factors controlling inheritance of susceptibility to 1,2-dimethylhydrazine.
Reciprocal crosses were made between AKR/J, a 1,2-dimethylhydrazine (DMH)-resistant mouse strain, and SWR/J, a sensitive strain. The F1 hybrids were tested with DMH and methylazoxymethanol (MAM), two colon carcinogens. Either DMH (20 mg/kg body weight) or MAM (35 mg/kg body weight), a metabolic derivative of DMH, was injected weekly for 10 weeks. In each group of 35 mice, 10 were injected with tritiated thymidine (25 microCi) 1 week after the sixth injection of DMH and MAM for the evaluation of proliferative characteristics and the number of foci of dysplasia occurring in 325 microns of distal colonic mucosa. At 27 weeks after the first injection of the carcinogen, the colons of remaining mice were opened longitudinally and the number of tumors enumerated. Compared with DMH-treated mice, the number of foci of dysplasia per mouse, the percentage of tumor-bearing mice, the number of tumors per animal, and the number of tumors per tumor-bearing animal induced by MAM were severalfold higher. This would suggest the presence of a gene(s) repressing metabolism of DMH to MAM. Moreover, differences in response to the carcinogens were observed between the sexes. In contrast to males, females treated with both DMH and MAM had significantly greater numbers of tumors per animal, tumors per tumor-bearing mice, and a greater proliferative response with extension of S-phase cells to the upper third and luminal surface of crypts. Among males, those with the XAKR/YSWR heritage appeared more resistant than XSWR/YAKR males, particularly in their response to MAM. A twofold difference in the number of foci of dysplasia per mouse, tumors per animal, and the number of tumors per tumor-bearing animals was seen. Analyses of the response to DMH and MAM by F1 reciprocal hybrids of the AKR and SWR strains have shown a complex inheritance pattern governing susceptibility to DMH. Resistance to the carcinogen is provided by at least two specific repressor genes, one governing metabolism of carcinogen from DMH to MAM, and the other controlled by gender. Genetic factors contributed by the AKR female appear to convey additional resistance to male progeny, suggesting more than one gender-related gene.


Return to fertility after cessation of a continuous oral contraceptive.
To evaluate the return to fertility among women planning to become pregnant after the use of a continuous regimen of levonorgestrel 90 microg and ethinyl E(2) 20 microg. Descriptive analysis of pregnancy outcomes after participation in a contraceptive trial. Multicenter trial. Participants in a phase 3 contraceptive trial who discontinued to become pregnant. Eligible subjects were contacted at 3 and 12 months after treatment discontinuation to determine if and when they had conceived. Kaplan-Meier analysis displaying the time until conception after oral contraceptive discontinuation. In the phase 3 trial, 34 of 2,134 subjects cited a desire for pregnancy as a reason for discontinuation. Of these, 4 were already pregnant before stopping treatment, 4 initiated other contraception, and 5 were lost to follow-up. Of the remaining 21 subjects at risk of pregnancy, the pregnancy rate was 57% at 3 months, 81% at 12 months, and 86% (18 of 21) (95% confidence interval 64% to 97%) at 13 months after discontinuation of treatment. These findings suggest that a continuous oral contraceptive with levonorgestrel 90 microg and ethinyl E(2) 20 microg does not delay the return to fertility.


Periodontitis may increase the risk of peripheral arterial disease.
The aim of this case control study was to evaluate whether periodontitis was associated with peripheral arterial disease (PAD). Twenty-five patients diagnosed with aorto-iliac and/or femoro-popliteal occlusive disease and thirty-two generally healthy control subjects were enrolled in this study. Polymerase chain reaction (PCR) was used to identify Porphyromonas gingivalis, Treponema denticola, Actinobacillus actinomycetemcomitans, Prevotella intermedia, Cytomegalovirus (CMV), Chlamydia pneumoniae, and Helicobacter pylori in tissue specimens taken from the anastomotic site of distal bypasses. Periodontal status was evaluated; serum IgG titres against the four listed bacteria were measured. Periodontopathic bacteria were detected in 13/25 (52%) atherosclerotic specimens. CMV or C. pneumoniae was detected in 1/25 (4%) specimens; H. pylori was not detected from any of these specimens. Fontaine grade III or IV patients showed higher detection frequency of P. gingivalis than Fontaine grade II patients (57.1% vs 22.2%, P=0.09). After adjusting for age, gender, diabetes and smoking, periodontitis increased 5-fold the risk of having PAD (OR 5.45). There were preliminary indications that periodontitis was associated with increased serum IL-6 and TNF-alpha concentrations. This study suggests that periodontitis may be associated with an increased risk of PAD. This association could result from the increased concentration of serum inflammatory cytokines in those with periodontitis.


Fracture Epidemiology in Professional Baseball From 2011 to 2017.
Fractures are a significant cause of missed time in Major League Baseball (MLB) and Minor League Baseball (MiLB). MLB and the MLB Players Association recently instituted rule changes to limit collisions at home plate and second base. To evaluate the epidemiologic characteristics of fractures in professional baseball and to assess the change in acute fracture incidence secondary to traumatic collisions at home plate and second base after the recently instituted rule changes. Descriptive epidemiology study. The MLB Health and Injury Tracking System (HITS) database was used to access injury information on MLB and MiLB players to analyze fracture data from 2011 to 2017. Injuries were included if the primary diagnosis was classified as a fracture in the HITS system in its International Classification of Diseases, Ninth Revision, codes; injuries were excluded if they were not work related, if they occurred in the offseason, or if they were sustained by a nonplayer. The proportion of fractures occurring due to contact with the ground or another person in the relevant area of the field-home plate or second base-in the years before rule implementation was compared with the years after. A total of 1798 fractures were identified: 342 among MLB players and 1456 among MiLB players. Mean time missed per fracture was 56.6 ± 48.4 days, with significantly less time missed in MLB (46.8 ± 47.7 days) compared with MiLB (59.0 ± 48.3 days) (P < .0001). A 1-way analysis of variance with post hoc Bonferroni correction demonstrated that starting pitchers missed significantly more time due to fractures per injury than all other position groups (P < .0001). Acute fractures due to contact with the ground or with another athlete were significantly decreased after rule implementation at home plate in 2014 (22 [3.0%] vs 14 [1.3%]; P = .015) and at second base in 2016 (90 [7.0%] vs 23 [4.5%]; P = .045). The recently instituted rule changes to reduce collisions between players at home plate and at second base are associated with reductions in the proportion of acute fractures in those areas on the field.


Alternans of the ST segment in variant angina. Incidence, time course and relation to ventricular arrhythmias during ambulatory electrocardiographic recording.
The ST alternans was recorded during at least one ischemic attack with ST elevation in nine of 65 patients with variant angina. The magnitude and duration of ST elevation during ischemic attacks were significantly greater in patients with than in those without ST alternans. It always appeared during the occlusion phase and disappeared during the reperfusion phase of ischemic attacks. In patients with episodic ST alternans, the ischemic attacks showed a greater ST elevation and a longer duration in the presence of ST alternans than in its absence. The incidence of occlusion phase ventricular arrhythmias was greater in patients with than in those without ST alternans; the incidence of reperfusion phase ventricular arrhythmias was similar in the two groups. The ST alternans always preceded the onset of occlusion phase arrhythmias. Thus, in variant angina, ST alternans represents an index of the severity of ischemia and a precursor of ventricular arrhythmias.


Escape From Traumas: Emigration And Hungarian Jewish Identity After The Holocaust.
Unlike other European countries, at the turn of the 20th century, Hungary ensured complete legal and religious equality for Jews living in the country. As a result, they became strongly assimilated and identified themselves as Hungarian. Leading up to and during WWII, there was a gradual and steady deterioration of those legal and religious conditions, and the "betrayal" and persecution of Jews caused unspeakable trauma all over the world. After the defeat of the Nazis, only a small number of Holocaust survivors returned to their home country; the majority emigrated. This study provides a psychoanalytical analysis of the changes in Hungarian survivors' psychic realities and the construction of their new identities, depending on the survival strategy they chose. The hypothesis is that the rebuilding of the demolished identity and the level of trauma elaboration depend on whether this process was done at the place of the trauma or in a different society. The study uses psychoanalytic and social psychology literature to follow the impacts of the emigration process, to draw conclusions and apply them to trauma elaboration after the Holocaust.


Comprehensive assessment of metals and organic pollutants in pelagic fishing port sediments.
Fishing ports are among the environments that accumulate pollutants along the coast but often lack environmental data and scientific research. This study investigated 8 metals, 16 polycyclic aromatic hydrocarbons (PAHs), 10 phthalate esters (APs), and 2 alkylphenols (APs) in the surface sediments of Qianzhen Fishing Port, the largest pelagic fishing port in Taiwan. Indicator compounds, pollution hotspots, potential ecological risk levels, and pollution sources were evaluated. Results showed that copper, zinc, and bis(2-ethylhexyl) phthalate (DEHP) in surface sediments were pollution indicators posing potential toxicological risks. Metals and PAHs in sediments were mainly from ship-related sources, while PAEs and APs were related to dockland activities. Combining metal and organic pollutants, the sediments had a moderate potential ecological risk, with metals higher than organic pollutants. Cluster analysis and color geographic map of risks indicate sediment pollution hotspots and areas requiring immediate intervention. In the future, sustainable operation and management can be carried out by using metal-free antifouling paint, improving sewage treatment rate, and regular environmental dredging of fishing port.


Imaging of incoherent extended objects by a polarizing microscope with crossed polarizers.
Diffraction images of incoherent objects such as line, edge and disk have been evaluated by carrying out integration of the point spread function over appropriate limits. The resulting expressions have been computed numerically and the results are in agreement with those obtained previously using optical transfer function approach.


Metabolic syndrome is not only a risk factor for cardiovascular diseases in systemic lupus erythematosus but is also associated with cumulative organ damage: a cross-sectional analysis of 311 patients.
Patients with systemic lupus erythematosus (SLE) have increased rates of cardiovascular disease (CVD) that are one of the major causes of mortality. The aim of this study was to determine the frequencies of metabolic syndrome (MetS) and CVD in SLE patients and investigate the link between these and clinical features of SLE. A total of 311 SLE patients were consecutively assessed for cumulative organ damage (SDI/SLICC scores), history of CVD and MetS as defined by the National Cholesterol Educational Program Adult Treatment Panel III (NCEP ATP III). Clinical data of SLE patients were collected from the records. The mean age of the patients was 40.2 ± 13.4 years and 89% were female. The frequencies of CVD and MetS were 15.2% and 19%, respectively. In this SLE cohort increased age, cumulative damage, disease duration and CVD were associated with MetS. CVD was associated with disease duration, cumulative damage, pericarditis, hematologic involvement, lymphopenia, thrombocytopenia, neurological involvement and antiphospholipid antibody (aPL) positivity. Hydroxychloroquine (HCQ) use was found as a protective factor for CVD. In SLE patients, MetS was associated with CVD and both increased with disease duration. Patients who developed MetS and/or CVD had increased cumulative organ damage. Certain clinical features of SLE and the presence of aPL were also associated with CVD. There was a significant protective effect of HCQ from CVD. The prevention of MetS and long-term use of HCQ may be beneficial in improving the prognosis of SLE.