Melatonin: reproductive effects.
N-acetyl-5-methoxytryptamine, melatonin, is synthesized within and secreted from the pineal gland. Although the concentration of this constituent in the blood is diminished after surgical removal of the pineal gland it does not completely disappear. Other potential contributors to blood titers of melatonin include the retinas, the Harderian glands and the gastro-intestinal tract. Melatonin has a potent antigonadotrophic action in the Syrian hamster ( a highly photosensitive species) provided the indole is given during a restricted portion of the light phase of the light-dark cycle. This so-called sensitive period falls late in the light phase; melatonin acutely administered at other times has virtually no inhibitory influence on the reproductive physiology of hamsters. When melatonin is continuously available (from a subcutaneous deposit) it counteracts the antigonadotrophic influence of the pineal gland in light restricted or blinded hamsters, i.e., it causes a "functional pinealectomy". Furthermore, chronically available melatonin negates the antigonadotrophic capability of acute melatonin injections.


Further characterization of subunit III of bovine procarboxypeptidase A-S6 as a non activatable zymogen.
The homology of Subunit III of bovine procarboxypeptidase A-S6 (EC 3.4.12.-) with Subunit II (bovine chymotrypsinogen C) of the same complex, already reported in a previous publication (Puigserver, A. and Desnuelle, P. (1975) Proc. Natl. Acad. Sci. U.S. 72, 2442-2445) has been extended to the position of the single methionine of the chains. The sequence linked by 4 disulfide bridges out of 5 are also probably homologous in the 2 proteins. The last bridge is displaced in Subunit III as a consequence of the deletion of the N-terminal half-cystine. Subunit II, which is not activatable by trypsin, due to the loss of essential residues in the N-terminal region, has conserved a weakly functional active site reacting with concentrated diisopropylfluorophosphate at exactly the same rate as that of Subunit II.


Effects of verapamil on histamine-induced changes in lung mechanics.
The effects of verapamil on airway resistance and total thoracic compliance were studied in 15 rabbits with histamine-induced changes in lung mechanics. The animals, after being tracheotomized under anaesthesia, were subjected to mechanical ventilation in a time-cycled, volume-limited mode. Airway pressure and gas flow signals measured by a pneumotachograph and integrated for volume, were registered on a recorder. Each animal was given histamine hydrochloride in an isotonic solution of sodium chloride at a rate of 0.05 micrograms.kg-1.min-1 through a peripheral venous line. Verapamil was infused intravenously in an isotonic solution of sodium chloride at a rate of 20 micrograms.kg-1.min-1 after the initiation of histamine. Verapamil reduced the histamine-induced increase in airway resistance by 20% at 20 min after the start of administration.


Dye-sensitized solar cells based on multiwalled carbon nanotube-titania/titania bilayer structure photoelectrode.
Dye-sensitized solar cells (DSSCs) were fabricated using multiwalled carbon nanotube (MWCNT)-TiO(2) nanocomposite as a light scattering layer. Morphology of the MWCNT-TiO(2) film was investigated by field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). FESEM and TEM images demonstrate that MWCNTs and TiO(2) nanoparticles can be dispersed with chitosan. Internal resistance in the DSSC was characterized by electrochemical impedance spectroscopy (EIS). EIS results reveal a decrease in the charge resistance of electrolyte/dye/MWCNT-TiO(2)/TiO(2) interface with increasing MWCNT content up to 3 wt% which leads to an improvement in the photovoltaic performance. Compare with a nanocrystalline TiO(2) single-layer cell, the DSSC based on the MWCNT (3 wt%)-TiO(2)/TiO(2) bilayer structure photoelectrode shows ~100% increase in solar-to-electric energy conversion efficiency, which is attributed to the inclusion of MWCNTs in TiO(2) matrix.


Evaluation of the indicative roles of seven potential biomarkers on hepato-nephrotoxicity induced by Genkwa Flos.
Genkwa Flos, a classical traditional Chinese medicine, is used for the definite antitumor activity and tends to be taken overdose or long term in these years. While the excessive application can result in damage to liver and kidney. In this study, the indicative roles of seven potential biomarkers were evaluated to investigate hepato-nephrotoxicity in the early stages after oral administration of Genkwa Flos for 14 days. Histopathology, serum biochemistry and seven potential biomarkers in serum or urine from male Sprague-Dawley rats were monitored. Hepatic and renal tissues were histopathologically examined to identify specific changes occurring. Routine serum biochemical parameters were tested by using standard clinical laboratory methods. Seven biomarkers including cholic acid, taurine, 5-oxoproline, hippuric acid, uric acid, 3-indoxyl sulfate and kynurenic acid were detected by a developed LC-MS method. The histopathological alterations and the increased levels of serum biochemistry were detected on the 8th day after Genkwa Flos treated. The seven analytes were also found significantly changed in Genkwa Flos treated group, especially cholic acid, taurine, 5-oxoproline and hippuric acid which were changed on the 2nd or 4th day. Although serum biochemistry and histopathology suggested that Genkwa Flos was responsible for the hepato-nephrotoxicity that occurred following the ingestion of this medicinal herb, evaluation of these biomarkers might be more beneficial for the early detection of liver and kidney injuries. This study could be further used in hepatic and renal failures caused by other reasons in the following research works.


Quantification of blue carbon in tropical salt marshes and their role in climate change mitigation.
Vegetated coastal ecosystems (VCE) display a promising potential to act as natural carbon sinks in climate change mitigation. Although growing interest in wetland carbon has intensified the global level carbon stock estimation studies, large knowledge gaps and uncertainties remain, particularly in tropical salt marshes in the South and Southeast Asian regions. Therefore, the current study aims to quantify the organic carbon stocks in the salt marsh habitats on the Northwest coast of Sri Lanka and to showcase the relevance of salt marsh carbon in local and regional contexts. Vegetation and soil up to a depth of 50 cm were sampled from four sites representing the Wedithalathive Nature Reserve (WNR). Species-specific allometric relationships developed for the major succulent halophytic species indicated a significant positive correlation between dry biomass and plant height. The loss-on-ignition (LOI) technique was applied in combination with a carbon conversion factor to calculate the soil organic carbon (SOC) content across 4 depth intervals. The study provided an average total organic carbon (TOC) storage of 73 ± 14.47 Mg C ha-1 up to a depth of 50 cm, in which the aboveground vegetation accounted for ~2% share. Sri Lankan salt marshes hold 2.01 Tg of organic carbon and directly reflect their potential for inclusion in Nationally Determined Contributions (NDCs) under the Paris Agreement. This has been the first comprehensive study on salt marsh blue carbon stocks in Sri Lanka and the findings of this study will strengthen the knowledge base on regional and global saltmarsh carbon stocks and their potential role in climate change mitigation.


Distinguishing the optimal binding mechanism through reversible and irreversible inhibition analysis of HSP72 protein in cancer therapy.
Over the past two decades, covalent inhibitors have gained much interest and are living up to their reputation as a powerful tool in drug discovery. Covalent inhibitors possess several significant advantages, including increased biochemical efficiency, prolonged duration and the ability to target shallow, solvent-exposed substrate-binding domains. One of the enzymes that have been both covalently and non-covalently targeted is the heat shock protein 72 (HSP72). This elevated enzyme expression in cancer cells may be responsible for tumorigenesis and tumor progression by providing chemotherapy resistance. A critical gap remains in the molecular understanding of the structural mechanism's covalent and non-covalent binding to HSP72. In this study, we explore the most optimal binding mechanism in the inhibition of the HSP72. Based on the molecular dynamic analyses, it was evident that the non-covalent complex showed more stability than the covalent complex. The covalent ligand, however, was more able to induce and stabilize the sealed conformation of the HSP72-NBD ATP binding domain throughout the. Also, the non-covalent ligand does not induce any significant conformational change as it remained close to the shape of the unbound complex; and the affinity is only dependent on the multiple hydrogen bonds in contrast to the covalent ligand. This is supported by the secondary structure elements and principal component analysis that was more dominant in the covalently inhibited complex. Covalent bond induced the α-helices sealed conformation of the HSP72-NBD; based on our findings, this will prevent other small molecules from interacting at the ATP binding site domain. Moreover, inhibition of the ATP binding domain can directly affect the ATPs protein folding mechanism of the HSP72 enzyme. The essential dynamic analysis presented in this report compliments the binding mechanism of HSP72, establishing covalent inhibition as the preferred method of inhibiting the HSP72 protein. The findings from this study may assist in the design of more target-specific HSP72 covalent inhibitors exploring the surface-exposed lysine residues.


Adriamycin alone or combined with vincristine in the treatment of advanced breast cancer.
One hundred and nineteen women with advanced breast cancer treated previously by endocrine therapy but no prior chemotherapy were given adriamycin 70 mg/m2 i.v. on day 1 of a 3-weekly cycle for 8 courses, followed by a regimen of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) until relapse. They were allocated randomly to receive either no treatment (group A) or vincristine 1.4 mg/m2 i.v. on days 1 and 8 during treatment with adriamycin (group AV). In 107 evaluable patients objective responses were seen in 30/53 patients (57%) in group A and in 28/54 patients (52%) in group AV. The projected dose of adriamycin received was 78% in group A and 75% in group AV; and 60% for vincristine in group AV. The subjective and haematological toxicity for adriamycin was similar in both groups, but 65% of patients treated with vincristine developed neurotoxicity. The median duration of objective regressions was the same for both groups (7 months), and the median time to failure was 5 months for group A and 6 months for group AV respectively. The median survival of the responders tended to be longer in group AV (17.5 months) than in group A (13 months), but this difference was not statistically significant (P = 0.112). It is concluded that there is no advantage therapeutically in combining vincristine and adriamycin in patients with advanced breast cancer.


[Determination of the histostructure of cutaneous melanoblastomas by cytologic study of smears].
The work was undertaken to reveal the opportunities of cytological investigations of smears for recognition of the skin melanoblastoma histostructure. Three variants of smear cytograms corresponding to histological types of melanoblastomas were differentiated: epithelioid-cellular, spindle-cell and mixed. In 167 patients press-smears from the tumor surface were studied cytologically with subsequent pathomorphological assay of radically removed neoplasms. Skin melanoblastomas were revealed in all these patients, an epithelioid-cell type - in 119, mixed - in 37, spindle-cell - in 11.


Electrophysiological studies on ciguatera poisoning in man (Part II).
Fifteen cases of acute ciguatera poisoning were subjected to electrical studies on the sural and common peroneal nerves. Significant slowing of sensory conduction velocity and prolongation of the absolute refractory, relative refractory and supernormal periods were recorded. These findings indirectly suggest that ciguatoxin causes an abnormally prolonged sodium channel opening in nerve membranes.


Evaluating the effects of socioeconomic status on stroke and bleeding risk scores and clinical events in patients on oral anticoagulant for new onset atrial fibrillation.
The risk of thromboembolism and bleeding before initiation of oral anticoagulant (OAC) in atrial fibrillation patients is estimated by CHA2DS2-VASc and HAS-BLED scoring system, respectively. Patients' socioeconomic status (SES) could influence these risks, but its impact on the two risk scores' predictive performance with respect to clinical events remains unknown. Our objective was to determine if patient SES defined by area deprivation index (ADI), in conjunction with CHA2DS2-VASc and HAS-BLED scores, could guide oral anticoagulation therapy. The study cohort included newly diagnosed patients with AF who were treated with warfarin. The cohort was stratified by the time in therapeutic range of INR (TTR), ADI, CHA2DS2-VASc, and HAS-BLED risk scores. TTR and ischemic and bleeding events during the first year of therapy were compared across subpopulations. Among 7274 patients, those living in the two most deprived quintiles (ADI ≥60%) had a significantly higher risk of ischemic events and those in the most deprived quintile (ADI≥80%) had a significantly increased risk of bleeding events. ADI significantly improved the predictive performance of CHA2DS2-VASc but not HAS-BLED risk scores. ADI can predict increased risk for ischemic and bleeding events in the first year of warfarin therapy in patients with incident AF.


Prognostic importance of visit-to-visit blood pressure variability for micro- and macrovascular outcomes in patients with type 2 diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study.
The prognostic importance of an increased visit-to-visit blood pressure variability (BP-VVV) for the future development of micro- and macrovascular complications in type 2 diabetes has been scarcely investigated and is largely unsettled. We aimed to evaluate it in a prospective long-term follow-up study with 632 individuals with type 2 diabetes. BP-VVV parameters (systolic and diastolic standard deviations [SD] and variation coefficients) were measured during the first 24-months. Multivariate Cox analysis, adjusted for risk factors and mean BP levels, examined the associations between BP-VVV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications (total cardiovascular events [CVEs], major adverse CVEs [MACE] and cardiovascular and all-cause mortality). Improvement in risk discrimination was assessed by the C-statistic and integrated discrimination improvement (IDI) index. Over a median follow-up of 11.3 years, 162 patients had a CVE (132 MACE), and 212 patients died (95 from cardiovascular diseases); 153 newly-developed or worsened diabetic retinopathy, 193 achieved the renal composite outcome (121 newly-developed microalbuminuria and 95 deteriorated renal function), and 171 newly-developed or worsened peripheral neuropathy. Systolic BP-VVV was an independent predictor of MACE (hazard ratio: 1.25, 95% CI 1.03-1.51 for a 1-SD increase in 24-month SD), but not of total CVEs, cardiovascular and all-cause mortality, and of any microvascular outcome. However, no BP-VVV parameter significantly improved cardiovascular risk discrimination (increase in C-statistic 0.001, relative IDI 0.9%). Systolic BP-VVV was an independent predictor of MACE, but it did not improve cardiovascular risk stratification. The goal of anti-hypertensive treatment in patients with type 2 diabetes shall remain in controlling mean BP levels, not on decreasing their visit-to-visit variability.


Enabling long-lived organic room temperature phosphorescence in polymers by subunit interlocking.
Long-lived room temperature phosphorescence (LRTP) is an attractive optical phenomenon in organic electronics and photonics. Despite the rapid advance, it is still a formidable challenge to explore a universal approach to obtain LRTP in amorphous polymers. Based on the traditional polyethylene derivatives, we herein present a facile and concise chemical strategy to achieve ultralong phosphorescence in polymers by ionic bonding cross-linking. Impressively, a record LRTP lifetime of up to 2.1 s in amorphous polymers under ambient conditions is set up. Moreover, multicolor long-lived phosphorescent emission can be procured by tuning the excitation wavelength in single-component polymer materials. These results outline a fundamental principle for the construction of polymer materials with LRTP, endowing traditional polymers with fresh features for potential applications.


Temporal and spatial multiplexed infrared single-photon counter based on high-speed avalanche photodiode.
We report on a high-speed temporal and spatial multiplexed single-photon counter with photon-number-resolving capability up to four photons. The infrared detector combines a fiber loop to split, delay and recombine optical pulses and a 200 MHz dual-channel single-photon detector based on InGaAs/InP avalanche photodiode. To fully characterize the photon-number-resolving capability, we perform quantum detector tomography and then reconstruct its positive-operator-valued measure and the associated Wigner functions. The result shows that, despite of the afterpulsing noise and limited system detection efficiency, this temporal and spatial multiplexed single-photon counter can already find applications for large repetition rate quantum information schemes.


Differences in Hearing, Balance, and Quality-of-Life Outcomes in Petroclival Versus Nonpetroclival Posterior Fossa Meningiomas.
To compare hearing, tinnitus, balance, and quality-of-life treatment outcomes of petroclival meningioma and nonpetroclival cerebellopontine angle meningioma cohorts. A retrospective cohort study of 60 patients with posterior fossa meningiomas, 25 petroclival and 35 nonpetroclival, who were treated at a single tertiary care center between 2000 and 2020. A survey battery that included the Hearing Effort of the Tumor Ear, Speech and Spatial Qualities of Hearing, Tinnitus Functional Index, Dizziness Handicap Inventory (DHI), and Short Form Health Survey. Petroclival and nonpetroclival cohorts were matched for tumor size and demographic features. Differences between groups in hearing, balance outcomes, and quality of life and patient factors that influence posttreatment quality of life. Petroclival meningioma patients reported poorer audiovestibular outcomes with a higher rate of deafness in the tumor ear (36.0% versus 8.6%, p = 0.032) and lower functional hearing by the Hearing Effort of the Tumor Ear, Speech and Spatial Qualities of Hearing (76.6 [6.1] versus 82.0 [4.4], p < 0.001). Current dizziness rate was higher (48.0% versus 23.5%, p = 0.05), with more severe dizziness by DHI (18.4 [4.8] versus 5.7 [2.2], p < 0.001). Both cohorts had similar high quality of life and low tinnitus severity indices. Quality-of-life Short Form Health Survey predictors were tumor size ( p = 0.012) and DHI ( p = 0.005) in multivariable analysis. Hearing and dizziness treatment outcomes of petroclival meningioma are poorer relative to other posterior fossa meningiomas. Despite audiovestibular outcome distinctions, the overall posttreatment quality of life was high for both petroclival and nonpetroclival meningioma.


Molecular and functional analysis of a novel MEK2 mutation in cardio-facio-cutaneous syndrome: transmission through four generations.
Cardio-facio-cutaneous (CFC) syndrome is one of the RASopathies and is caused by alteration of activity through the Ras/mitogen-activated protein kinase (MAPK) pathway due to heterozygous de novo mutations in protein kinases BRAF, MEK1, or MEK2. CFC is a rare multiple congenital anomaly disorder in which individuals have characteristic dysmorphic features, cardiac defects, ectodermal anomalies and developmental delay.We report a 7(1/2)-month-old boy with a clinical diagnosis of CFC. Bidirectional sequence analysis of MEK2 revealed a novel c.383C-->A transversion in exon 3 resulting in a nonsynonymous missense substitution, p.P128Q. Other family members, including the proband's mother and half-sibling, displayed phenotypic features of CFC and were also screened for the MEK2 mutation identified in the proband. Sorting Intolerant From Tolerant (SIFT) analysis determined the novel MEK2 p.P128Q to be deleterious. To corroborate the functional alteration of the novel mutant protein, transient transfection of HEK 293T cells with subsequent Western analysis was used to demonstrate increased kinase activity, as measured by ERK phosphorylation. This first reported case of a vertically transmitted functional CFC MEK mutation further expands our understanding of germline mutations within the Ras/MAPK pathway.


A safety and feasibility trial of 131 I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study.
131 I-meta-iodobenzylguanidine (131 I-MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by 131 I- MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high-risk neuroblastoma. Patients with MIBG-avid high-risk neuroblastoma were eligible. After the first two patients to receive protocol therapy developed severe sinusoidal obstruction syndrome (SOS), the trial was re-designed to include an 131 I-MIBG dose escalation (12, 15, and 18 mCi/kg), with a required 10-week gap before Bu/Mel administration. Patients who completed induction chemotherapy were evaluable for assessment of 131 I-MIBG feasibility; those who completed 131 I-MIBG therapy were evaluable for assessment of 131 I-MIBG + Bu/Mel feasibility. Fifty-nine of 68 patients (86.8%) who completed induction chemotherapy received 131 I-MIBG. Thirty-seven of 45 patients (82.2%) evaluable for 131 I-MIBG + Bu/Mel received this combination. Among those who received 131 I-MIBG after revision of the study design, one patient per dose level developed severe SOS. Rates of moderate to severe SOS at 12, 15, and 18 mCi/kg were 33.3%, 23.5%, and 25.0%, respectively. There was one toxic death. The 131 I-MIBG and 131 I-MIBG+Bu/Mel feasibility rates at the 15 mCi/kg dose level designated for further study were 96.7% (95% CI: 83.3%-99.4%) and 81.0% (95% CI: 60.0%-92.3%). This pilot trial demonstrated feasibility and tolerability of administering 131 I-MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children with high-risk neuroblastoma in a cooperative group setting, laying the groundwork for a cooperative randomized trial (NCT03126916) testing the addition of 131 I-MIBG during induction therapy.


RGS14 is a mitotic spindle protein essential from the first division of the mammalian zygote.
Heterotrimeric G protein alpha subunits, RGS proteins, and GoLoco motif proteins have been recently implicated in the control of mitotic spindle dynamics in C. elegans and D. melanogaster. Here we show that "regulator of G protein signaling-14" (RGS14) is expressed by the mouse embryonic genome immediately prior to the first mitosis, where it colocalizes with the anastral mitotic apparatus of the mouse zygote. Loss of Rgs14 expression in the mouse zygote results in cytofragmentation and failure to progress to the 2-cell stage. RGS14 is found in all tissues and segregates to the nucleus in interphase and to the mitotic spindle and centrioles during mitosis. Alteration of RGS14 levels in exponentially proliferating cells leads to cell growth arrest. Our results indicate that RGS14 is one of the earliest essential product of the mammalian embryonic genome yet described and has a general role in mitosis.


Long noncoding RNA SOX2OT silencing alleviates cerebral ischemia-reperfusion injury via miR-135a-5p-mediated NR3C2 inhibition.
This study is aimed to investigate the role of the long noncoding RNA SOX2 overlapping transcript (SOX2OT) in cerebral ischemia-reperfusion injury (CIRI) and the underlying regulatory mechanisms. The oxygen-glucose deprivation/reoxygenation (OGD/R)-treated PC12 cells and middle cerebral artery occlusion/reperfusion (MCAO/R)-treated rats were established to simulate CIRI condition in vitro and in vivo. Quantitative real-time polymerase chain reaction was performed to detect the expression of SOX2OT, microRNA-135a-5p (miR-135a-5p), and nuclear receptor subfamily 3 group C member 2 (NR3C2). The cell viability and apoptosis were analyzed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) or interleukin (IL)-1β and IL-6 were used to evaluate the oxidative stress or inflammation. Dual-luciferase reporter assay was conducted to validate the interactions among SOX2OT, miR-135a-5p, and NR3C2. Additionally, neurological deficit scores (NDS), infarct volume, and brain edema were used to assess brain impairments in vivo. The expression of SOX2OT and NR3C2 was increased, while miR-135a-5p was decreased in OGD/R-treated PC12 cells. SOX2OT silencing repressed the levels of LDH, MDA, ROS, IL-1β, IL-6, reduced the numbers of TUNEL positive cells, and elevated viability and SOD level in OGD/R-treated PC12 cells. Besides, SOX2OT targeted miR-135a-5p, and miR-135a-5p targeted NR3C2. Both miR-135a-5p downregulation and NR3C2 upregulation reversed the suppressive effects of SOX2OT knockdown on oxidative stress, apoptosis, and inflammation of OGD/R-treated PC12 cells. Furthermore, injection of sh-SOX2OT reduced the NDS, cerebral infarct, and cerebral edema in MCAO/R-treated rats. Silencing of SOX2OT attenuated CIRI via regulation of the miR-135a-5p/NR3C2 axis, which may provide a novel therapeutic target for CIRI.


Limitations to the adoption of a standardized Strongyloides stercoralis diagnostic method: Case study in the Caribbean.
Strongyloides stercoralis is frequently under-diagnosed due to the low sensitivity of common faecal diagnostic methods used in clinical laboratories. This leads to a belief that prevalence is low and that S. stercoralis is not an important soil-transmitted helminth (STH). S. stercoralis diagnostic methods with higher sensitivity are available but often not used. Reasons for their lack of use need to be identified and addressed in order to increase awareness of this neglected parasite. A survey was conducted with public health (14) and private laboratories (15) within the Caribbean region to determine current diagnostic methods used and technological capabilities within the laboratories. Formal-ether concentration and direct smears were the primary methods used. Five of the laboratories used a specific method for S. stercoralis (Baermann and/or agar plate culture). A Standard Operating Procedure (SOP) for a modified Baermann tailored to be compatible with the technological capabilities of the laboratories was developed and demonstrated at ten laboratories to determine limitations to adopting a S. stercoralis specific method. The primary limitations were: cost of using two diagnostic methods for one submitted sample; lack of communication with the physician regarding the reason for the faecal analysis; general lack of awareness of S. stercoralis; and lack of awareness of differences in sensitivity of diagnostic methods. Changing diagnostic methods involves more than ensuring the method fits within the technological capabilities of the laboratories. Several factors that influence the method used are external to the laboratory. To improve diagnosis of any of the STHs, these external factors must be addressed. Within the laboratory, more education on the sensitivity of diagnostic methods, differences in excretion levels of diagnostic stages with low infection, and increased awareness of S. stercoralis is required.


Marsupials have monoallelic MEST expression with a conserved antisense lncRNA but MEST is not imprinted.
The imprinted isoform of the Mest gene in mice is involved in key mammalian traits such as placental and fetal growth, maternal care and mammary gland maturation. The imprinted isoform has a distinct differentially methylated region (DMR) at its promoter in eutherian mammals but in marsupials, there are no differentially methylated CpG islands between the parental alleles. Here, we examined similarities and differences in the MEST gene locus across mammals using a marsupial, the tammar wallaby, a monotreme, the platypus, and a eutherian, the mouse, to investigate how imprinting of this gene evolved in mammals. By confirming the presence of the short isoform in all mammalian groups (which is imprinted in eutherians), this study suggests that an alternative promoter for the short isoform evolved at the MEST gene locus in the common ancestor of mammals. In the tammar, the short isoform of MEST shared the putative promoter CpG island with an antisense lncRNA previously identified in humans and an isoform of a neighbouring gene CEP41. The antisense lncRNA was expressed in tammar sperm, as seen in humans. This suggested that the conserved lncRNA might be important in the establishment of MEST imprinting in therian mammals, but it was not imprinted in the tammar. In contrast to previous studies, this study shows that MEST is not imprinted in marsupials. MEST imprinting in eutherians, therefore must have occurred after the marsupial-eutherian split with the acquisition of a key epigenetic imprinting control region, the differentially methylated CpG islands between the parental alleles.


Is sport the brain's biggest challenge?
Sport is a demanding activity requiring more cognitive skills than is often appreciated. By trying to understand the sporting brain, in particular that of elite athletes, we may learn something about behaviour relevant to the normal population. We may also be confronted by the limits of current cognitive neuroscience. Here I outline some of the key areas where engaging with the cognitive aspects of sport will help cognitive neuroscientists to confront the application of their science outside the laboratory.


Terminal deoxynucleotidyl transferase activity in lymphoma.
Terminal deoxynucleotidyl transferase (TdT) was estimated in the tissues of 42 patients with lymphoma, whose cells were also typed by the use of surface markers. Four of the 8 patients with T-cell lymphoma were TdT+ including patients whose lymph nodes showed an undifferentiated or poorly differentiated appearance. The TdT- T-cell lymphomas included cases with diffuse histiocytic Sezary cell, diffuse, poorly differentiated and angio-immunoblastic histology. The tissues of 31 patients with B-cell lymphoma were invariably TdT-, whether the histology was poorly differentiated, well differentiated, nodular, diffuse, histiocytic or Burkitt type, and including cases with about equal proportions of T and B cells, and those whose cells showed non-capping and capping surface immunoglobulin. Hodgkin's tissue was also invariably TdT-. We conclude that estimation of TdT in tissues of patients with malignant lymphoma may be a useful test in diagnosing the T-cell lymphoma, particularly in patients with tumours of undifferentiated or poorly differentiated histology.


Release of activatable kallikrein by isolated rat kidneys.
Rat isolated kidneys were perfused for 60 minutes with a modified Krebs-Henseleit bicarbonate solution. Perfusate and urine samples showed kininogenase activity (active kallikrein) which could be enhanced by activation with trypsin (activatable kallikrein). Identification of the kininogenase activity generated by trypsin was made with rat renal kallikrein antiserum, aprotinin, lima bean trypsin inhibitor (LBTI), soybean trypsin inhibitor (SBTI), and ovomucoid. A sample of perfusate was partially purified through DEAD-Sephacel chromatography. Intraarterial injection of this fraction decreased blood pressure in the perfused hind limb of a rat.


Characterization of two divergent beta-tubulin genes from Colletotrichum graminicola.
We have cloned and sequenced two beta-tubulin genes, TUB1 and TUB2, from the phytopathogenic fungus, Colletotrichum graminicola. The nucleotide sequences of the coding regions of the two genes are only 72.8% homologous. This divergence is reflected in the deduced amino acid (aa) sequences which differ at 94 aa residues. Comparison with the aa sequences of other fungal beta-tubulins indicates that the C. graminicola TUB2 gene encodes a conserved isotype, whereas the C. graminicola TUB1 product is highly divergent. Both genes contain six identically placed introns and the position of each intron is conserved in other fungal beta-tubulin genes. Also typical of other fungal beta-tubulin genes, there is a pronounced bias in codon usage in the C. graminicola TUB2 gene; there is a lesser codon bias in TUB1 from C. graminicola. Both C. graminicola beta-tubulin genes are transcribed and yield similar sized messages.


Intraoperative Neuromonitoring of Recurrent Laryngeal Nerve During Thyroidectomy with Adhesive Skin Electrodes.
Alternative methods to overcome limitations of electromyogram (EMG) tube applied for intraoperative neuromonitoring (IONM) of recurrent laryngeal nerve (RLN) during thyroidectomy have been introduced. In this study, we evaluated the feasibility of adhesive skin electrodes for IONM of RLN in patients who underwent thyroidectomy. A total of 39 nerves at risk were prospectively enrolled in this study. Twenty-five patients with papillary thyroid carcinoma, 3 patients with follicular neoplasm, and 2 patients with Graves' disease underwent thyroidectomy. All patients were intubated with EMG tube, and two disposable pre-gelled surface electrodes were attached to skin at both upper margins of thyroid cartilage. We followed the standard procedure of IONM, and the latency (msec) and amplitude (μV) of each signal were recorded prospectively. Intraoperative neuromonitoring using skin adhesive electrodes was successful in all nerves at risk. Amplitudes of the signals in IONM were significantly lower compared to those from EMG tube at each step of IONM, while no significant difference was identified in latency between two methods. Four nerves at risk (10.3%) showed loss of signal (<100 μV) during the steps of IONM from EMG tube, while all nerves at risk from adhesive skin electrodes showed acceptable biphasic EMG signal. We verified the usefulness of adhesive skin electrodes for IONM of RLN during thyroidectomy. Although lower amplitude remains the major limitation of this technique, adhesive skin electrodes may be considered an alternative method for IONM during thyroidectomy.


A cost benefit analysis of the Luminex xTAG Gastrointestinal Pathogen Panel for detection of infectious gastroenteritis in hospitalised patients.
Recent advances in the laboratory detection of infectious diarrhoea allow more rapid and sensitive identification of infected patients. Several commercial multiplex molecular panels are now available and may have significant advantages over culture based techniques. Faster and more sensitive testing of hospitalised patients with suspected infectious gastroenteritis could result in significant efficiencies in the utilisation of isolation facilities, however few studies have examined this potential benefit. We studied the potential clinical and cost benefits of a commercially available molecular panel. An eight-month parallel diagnostic study was conducted to measure potential economic benefits of testing hospitalised patients with the Luminex xTAG Gastrointestinal Pathogen Panel (GPP) compared with conventional laboratory testing (based on a combination of culture, microscopy and enzyme immunoassay). Laboratory testing costs and patient isolation costs were measured or estimated for 800 patients. Although costing an additional £22,283, use of GPP could enable a reduction in isolation time from 2202 to 1447 days, a saving of £66,765, which more than offsets the additional laboratory testing costs. Syndromic testing of patients against a broad panel of organisms using a multiplex molecular panel can both improve detection rates and allow better laboratory workflow practices. Removing patients testing negative using this panel could result in significant patient isolation savings.


Comparison of Magnetic Resonance Imaging and Transrectal Ultrasound Informed Prostate Biopsy for Prostate Cancer Diagnosis in Biopsy Naïve Men: A Systematic Review and Meta-Analysis.
Multiparametric magnetic resonance imaging with informed targeted biopsies has changed the paradigm of prostate cancer diagnosis. Randomized studies have demonstrated a diagnostic benefit of clinical significance for targeted biopsy compared to standard systematic biopsies. We evaluated whether multiparametric magnetic resonance imaging informed targeted biopsy has superior diagnosis rates of any, clinically significant, high grade and clinically insignificant prostate cancer compared to systematic biopsy in biopsy naïve men. Data were searched in Medline®, Embase®, Web of Science and Evidence-Based Medicine Reviews-Cochrane Database of Systematic Reviews from database inception until 2019. Studies were selected by 2 authors independently, with disagreements resolved by consensus with a third author. Overall 1,951 unique references were identified and 100 manuscripts underwent full-text review. Data were pooled using random effects models. The meta-analysis is reported according to the PRISMA statement and the study protocol is registered with PROSPERO (CRD42019128468). Overall 29 studies (13,845 patients) were analyzed. Compared to systematic biopsy, use of multiparametric magnetic resonance imaging informed targeted biopsy was associated with a 15% higher rate of any prostate cancer diagnosis (95% CI 10-20, p <0.00001). This relationship was not affected by the study methodology (p=0.11). Diagnoses of clinically significant and high grade prostate cancer were more common in the multiparametric magnetic resonance imaging informed targeted biopsy group (risk difference 11%, 95% CI 0-20, p=0.05 and 2%, 95% CI 1-4, p=0.005, respectively) while there was no difference in diagnosis of clinically insignificant prostate cancer (risk difference 0, 95% CI -3 to 3, p=0.96). Notably, the exclusion of systematic biopsy in the multiparametric magnetic resonance imaging informed targeted biopsy arm significantly modified the association between a multiparametric magnetic resonance imaging strategy and lower rates of clinically insignificant prostate cancer diagnosis (p=0.01) without affecting the diagnosis rates of clinically significant or high grade prostate cancer. Compared to systematic biopsy a multiparametric magnetic resonance imaging informed targeted biopsy strategy results in a significantly higher diagnosis rate of any, clinically significant and high grade prostate cancer. Excluding systematic biopsy from multiparametric magnetic resonance imaging informed targeted biopsy was associated with decreased rates of clinically insignificant prostate cancer diagnosis without affecting diagnosis of clinically significant or high grade prostate cancer.


Alpiniae oxyphyllae Fructus and Alzheimer's disease: An update and current perspective on this traditional Chinese medicine.
Alzheimer's disease (AD) is a common progressive neuro-degenerative disease, and the morbidity and mortality are still on the rise. In spite of recent advances in AD treatment, their clinical efficacy has been limited, non-curative and easy to drug resistance. Alpiniae oxyphyllae Fructus (AOF), derived from the dried and mature fruits of the Zingiberaceae plant Alpinia oxyphylla Miq, is a choice in traditional Chinese medicine to treat AD, which has a good effect and has been used for a long time. Recent studies have demonstrated its potent activities in modulating multiple signaling pathways associated with β-amyloid deposition, tau protein phosphorylation, chronic inflammation, oxidative stress. The neuropharmacological mechanism of AOF in AD have been fully illustrated in numerous studies. In this review, we first briefly described the active components of AOF and related mechanism for treating AD. And we also provide a systematic overview of recent progress on the pharmacokinetic characteristics of the active ingredients of AOF and analyzed their bioavailability differences in the development of AD. Thus, AOF hold a great therapeutic potential in the treatment of AD and is worthy of further research and promotion.


[Interpersonal differentiation of the enzymatic pattern in the polymorphic hydroidHydractinia echinata].
Interpersonal differentiation between gasterozooids and gonozooids, inHydractinia echinata, is reflected by the pattern of extractable enzyme activities. With regard to their activity levels in the different hydranths the enzymes can be arranged in two groups. In the first group the specific activities are highest in gasterozooids and decline in the order gasterozooids>male gonozooids>female gonozooids. This group includes GAPDH, LDH, ICDH, and GPT. The activities of the second group are highest in female polyps and display the inverse sequence. This group comprises CS, GOT, and GLDH. When the GAPDH levels, taken as 100 pc each, are chosen as point of reference only this second sequence can be established and is now represented by MDH, ICDH, and G-6-PDH as well. 6-PGDH activity could not be determined in adult hydranths.According to the ratio of GAPDH/CS and the LDH level the gasterozooids prefer the anaerobic glycolytic pathway whereas in the sexual hydranths relatively more substrate is supplied at the disposal of the citrate cycle. Two metabolites of the citrate cycle, ketoglutarate and succinate, are known to promote the transformation of nutritive zooids into sexual zooids. The differences observed in the activities of GOT, GLDH, and ICDH, therefore, may be correlated not only with the production of gonocytes but also with the specific type of differentiation which in sexual hydranths is governed by a specific morphogen.


Twitter and academic Urology in the United States and Canada: a comprehensive assessment of the Twitterverse in 2019.
To provide the first comprehensive analysis of the Twitterverse amongst academic urologists and programmes in North America. Using national accreditation and individual programme websites, all active urology residency programmes (USA and Canada) and academic Urology faculty at these programmes were identified. Demographic data for each programme American Urological Association [AUA] section, resident class size) and physician (title, fellowship training, Scopus Hirsch index [H-index] and citations) were documented. Twitter metrics (Twitter handle, date joined, # tweets, # followers, # following, likes) for programmes and physicians were catalogued (data capture: March-April 2019). Descriptive analyses and temporal trends in Twitter utilisation amongst programmes and physicians were assessed. Multivariable logistic regression was used to identify predictors of Twitter use. In all, 156 academic programmes (143 USA, 13 Canada) and 2214 academic faculty (2015 USA, 199 Canada) were identified. Twitter utilisation is currently 49.3% and 34.1% amongst programmes and physicians, respectively, and continues to increase. On multivariable analysis, programmes with 3-5 residents/year and programmes with a higher percentage of faculty Twitter engagement were more likely to have Twitter accounts. From a physician perspective, those with fellowship training, lower academic rank (Clinical Instructor, Assistant Professor, Associate Professor vs Professor) and higher H-indices were more likely to have individual Twitter accounts. There is a steady increase in Twitter engagement amongst Urology programmes and academic physicians. Faculty Twitter utilisation is an important driver of programme Twitter engagement. Twitter social media activity is strongly associated with academic productivity, and may in fact drive academic metrics. Within Urology, social media presence appears to be proportional to academic activity.


Smart and emerging nanomaterials-based biosensor for SARS-CoV-2 detection.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a primary cause of the COVID-19 pandemic. To date, various detection approaches are already present, and many other techniques are also being developed for the rapid and real-time detection of COVID-19 infection in the wake of this pandemic. Hence, this featured review will provide an overview of COVID-19, its biomarkers, current diagnostic techniques, and emerging smart nanomaterials-based biosensing approaches; apart from this, it will also extend some light on future perspectives of biosensing technologies for SARS-CoV-2 diagnosis.


Building a better preoperative assessment clinic.
In every surgical patient's journey, a well-run preoperative assessment clinic (PAC) is an essential first step in ensuring excellence in quality and patient safety. In 2007, the PAC at Victoria General Hospital, a busy community hospital, averaging more than 7,000 surgical procedures per year, struggled to support the volume of surgical patients. Processes were ill defined, staffing levels were suboptimal, and the physical space was inadequate. This hospital is one of seven acute care hospitals that provide surgical services within the city, under the umbrella of a regional health authority, and is the largest of 11 regional health authorities within the province. With support of the PAC team and administration, a commitment was made to embark on improvements with limited financial resources and space available. After implementing the proposed changes and evaluating the data, the evidence indicates that several small changes can make significant overall improvements in providing superior patient care, more efficient processes, and healthier work environments.


Evaluation of synthetic, M type-specific peptides as antigens in a multivalent group A streptococcal vaccine.
The recent development of emm gene sequence-based typing methodology has allowed group A streptococci (GAS) M serotype prevalence data to be determined. This information has been used to identify the components of a multivalent M protein peptide vaccine that could theoretically prevent most of the GAS-mediated diseases in the USA. In this study, we have evaluated in mice the immunogenicity and protective ability of multiple synthetic, M type-specific peptides, derived from the N-termini of three prevalent GAS serotypes (three peptides per serotype, total of nine peptides). At least one peptide, representing each of the three M types tested, was immunogenic. Five of the nine synthetic peptides tested, elicited an immune response in mice, and sera raised against four of the peptides, all possessed functional activity as demonstrated in a bactericidal assay. In vivo nasopharyngeal challenge experiments were carried out with peptides from the M1 (peptide M1-3) and M3 (peptide M3-2) proteins induced in vivo immune protection by reducing intranasal carriage. Reduction in colonization for M1-3 and M3-2 was 90% (P=0.02) and 66% (P<0.17), respectively. A reduction in colonization of 67% (P=0.03) was observed for M3-2 immunized mice when M43, a heterologous serotype, was used as the challenge strain. These results show the utility of synthetic, M type-specific peptides as antigens in a multivalent GAS vaccine.


PKCγ and PKCε are Differentially Activated and Modulate Neurotoxic Signaling Pathways During Oxygen Glucose Deprivation in Rat Cortical Slices.
Cerebral ischemia is known to trigger a series of intracellular events such as changes in metabolism, membrane function and intracellular transduction, which eventually leads to cell death. Many of these processes are mediated by intracellular signaling cascades that involve protein kinase activation. Among all the kinases activated, the serine/threonine kinase family, protein kinase C (PKC), particularly, has been implicated in mediating cellular response to cerebral ischemic and reperfusion injury. In this study, using oxygen-glucose deprivation (OGD) in acute cortical slices as an in vitro model of cerebral ischemia, I show that PKC family of isozymes, specifically PKCγ and PKCε are differentially activated during OGD. Detecting the expression and activation levels of these isozymes in response to different durations of OGD insult revealed an early activation of PKCε and delayed activation of PKCγ, signifying their roles in response to different durations and stages of ischemic stress. Specific inhibition of PKCγ and PKCε significantly attenuated OGD induced cytotoxicity, rise in intracellular calcium, membrane depolarization and reactive oxygen species formation, thereby enhancing neuronal viability. This study clearly suggests that PKC family of isozymes; specifically PKCγ and PKCε are involved in OGD induced intracellular responses which lead to neuronal death. Thus isozyme specific modulation of PKC activity may serve as a promising therapeutic route for the treatment of acute cerebral ischemic injury.


Malpractice Litigation Related to Diagnosis and Treatment of Intracranial Aneurysms.
Approaches to management of intracranial aneurysms are inconsistent, in part due to apprehension relating to potential malpractice claims. The purpose of this article was to review the causes of action underlying medical malpractice lawsuits related to the diagnosis and management of intracranial aneurysms and to identify the factors associated and their outcomes. We consulted 2 large legal databases in the United States to search for cases in which there were jury awards and settlements related to the diagnosis and management of patients with intracranial aneurysms in the United States. Files were screened to include only those cases in which the cause of action involved negligence in the diagnosis and management of a patient with an intracranial aneurysm. Between 2000 and 2020, two hundred eighty-seven published case summaries were identified, of which 133 were eligible for inclusion in the analysis. Radiologists constituted 16% of 159 physicians sued in these lawsuits. Failure to diagnose was the most common medical malpractice claim referenced (100/133 cases), with the most common subgroups being "failure to include cerebral aneurysm as a differential and thus perform adequate work-up" (30 cases), and "failure to correctly interpret aneurysm evidence on CT or MR imaging" (16 cases). Only 6 of these 16 cases were adjudicated at trial, with 2 decided in favor of the plaintiff (awarded $4,000,000 and $43,000,000, respectively). Incorrect interpretation of imaging is relatively infrequent as a cause of malpractice litigation compared with failure to diagnose aneurysms in the clinical setting by neurosurgeons, emergency physicians, and primary care providers.


Treatment of congestive heart failure: experience with fosinopril.
The prevalence of congestive heart failure (CHF), a debilitating condition associated with impaired quality of life and markedly shortened life expectancy, is increasing. The goals of therapy for CHF are reducing symptoms, improving functional capacity, and slowing the progression of the condition. In most cases, this is best achieved with a combination of diuretic and vasodilator therapy. Angiotensin-converting enzyme (ACE) inhibitors have several advantages over other vasodilatory agents and are becoming widely used for treating CHF. The most recently introduced ACE inhibitor, fosinopril, is at least as effective as enalapril, and its dual and compensatory route of excretion is particularly advantageous in patients with renal insufficiency. Fosinopril may also have particular benefits in the prevention of CHF, as it has beneficial effects on cardiac function that may help delay the onset of overt cardiac failure.


Genotyping Brucella canis isolates using a highly discriminatory multilocus variable-number tandem-repeat analysis (MLVA) assay.
Differentiation of Brucella canis from other Brucella species are mainly performed through PCR-based methods and multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) procedures. Both PCR-based and MLVA methods are limited in discriminating B. canis strains. A new MLVA-13Bc method for B. canis genotyping was established by combining eight newly-developed VNTRs with five published ones. During 2010 and 2016, 377 B. canis PCR-positives were identified from 6,844 canine blood samples from 22 U.S. states, resulting in 229 B. canis isolates. The MLVA-13Bc method was able to differentiate each of these 229 isolates. The Hunter-Gaston Discriminatory Index of the individual VNTR loci ranged from 0.516 to 0.934 and the combined discriminatory index reached 1.000. Three major clusters (A, B and C) and 10 genotype groups were identified from the 229 B. canis isolates. Cluster A mainly contains genotype groups 1 and 2, and a few group 3 isolates; nearly all Cluster B isolates were from group 6; other genotype groups were classified into Cluster C. Our newly developed MLVA-13Bc assay is a highly discriminatory assay for B. canis genotyping, and can serve as a useful molecular epidemiological tool, especially for tracing the source of contamination in an event of a B. canis outbreak.


Collagen biosynthesis in cultured rat testicular Sertoli and peritubular myoid cells.
The incorporation of 3H-proline into protein was regarded as a measure of total protein synthesis and the incorporation into hydroxyproline as indicative of collagen synthesis. Relative collagen synthesis (expressed as percent of total protein synthesized) by Sertoli and peritubular myoid cells cultured from 20-22 day old rat testis was estimated. In both secreted and cellular pools, relative collagen synthesis by Sertoli cells was significantly greater than by peritubular myoid cells. Coculture of Sertoli and myoid cells resulted in a significant increase in relative collagen synthesis when compared to monocultures of each cell type. Addition of serum to peritubular myoid cells resulted in a stronger stimulation of relative collagen production. Sertoli cell extracellular matrix inhibited relative collagen synthesis by peritubular myoid cells in the presence or absence of serum. Radioactivity into hydroxyproline as corrected per cellular DNA also showed similar results. Immunolocalization studies confirmed that both cell types synthesize type I and type IV collagens. These results indicate that stimulation of collagen synthesis observed in Sertoli-myoid cell cocultures is due to humoral interactions, rather than extracellular matrix, and Sertoli cell extracellular matrix regulates serum-induced increase in collagen synthesis by peritubular myoid cells.


Interventional cardiology audit report for 2011.
In 2011 there were 658 percutaneous coronary intervention cases performed with more than 60% of the patients presenting to the hospital as an acute coronary syndrome. Most procedures consisted of balloon dilatation followed by stent deployment, and 93% of these stents were drug-eluting stents. Procedural success was achieved in 93.3% of cases and an overall major adverse cardiac events rate of 3.6%. This includes a mortality rate of (0.5%). In addition, there were 25 Core Valve procedures carried out. This is more than twice the amount of patients who had a transcatheter aortic valve implantation in 2010, reflecting the changing direction of the management of structural heart disease.


A simple and high production rate manufacturing method for submicron polymer fibres.
The manufacturing technique for cotton-candy floss, heat-aided rotary jet-spinning, was used to produce submicron-scale fibrous meshes by using bioabsorbable thermoplastic polymers. The method was feasible for 100 wt% polymer concentrations functioning completely without solvents. It was possible to produce submicron diameter fibres using a simple device, which indicates that this manufacturing method is a very promising technique for obtaining high-throughput rates for submicron, and possibly nano-scale, fibrous meshes.


Stress thallium-201 myocardial scintigraphy for the detection of individual coronary arterial lesions in patients with and without previous myocardial infarction.
The value of stress thallium-201 scintigraphy for detecting individual coronary arterial stenoses was analyzed in 141 patients with angiographically proved coronary artery disease, 101 with and 40 without a previous myocardial infarction. In patients without infarction, the sensitivity for detecting greater than 50 percent narrowing in the left anterior descending, the right and the left circumflex coronary artery was 66, 53 and 24 percent, respectively. In those with a previous infarction, the sensitivity for demonstrating disease in the artery corresponding to the site of infarction was 100 percent for the left anterior descending, 79 percent for the right and 63 percent for the left circumflex coronary artery. In patients with a prior anterior infarction, concomitant right or left circumflex coronary arterial lesions were detected in only 1 of 12 cases, whereas in those with previous inferior or inferolateral infarction, the sensitivity for left anterior descending coronary artery disease was 69 percent. Because of the reasonably high sensitivity for detecting left anterior descending arterial disease, irrespective of the presence and location of previous infarction, myocardial scintigraphy was useful in identifying multivessel disease in patients with a previous inferior infarction. However, because of its relative insensitivity for right or left circumflex coronary artery disease, scintigraphy proved to be a poor predictor of multivessel disease in patients with a prior anterior infarction and in patients without previous myocardial infarction.


A rapid assessment of litter magnitudes and impacts along the Torre Guaceto marine protected area (Brindisi, Italy).
This study focuses on assessing litter magnitudes along the Torre Guaceto Marine Protected Area (Brindisi, Italy). Collected litter was grouped into twenty different types and classified into four litter typologies according to the Guidance on Monitoring of Marine Litter in European Seas. All data were analyzed using an index-based approach that allowed the classification of a coastal stretch in terms of cleanliness, and presence of plastics as well hazardous items. The average litter abundance in the study area was 0.5 items/m2, being plastics the most common litter item. Hazardous litter items were found along the study area, reaching 21.3% of the total collected items. The application of environmental indices allowed to define the study area with a "moderate cleanliness" and a "moderate" presence of hazardous litter items. Sampled litter typologies and related magnitudes suggest a combination of sources that mainly include direct activities on the nearby coastal zones and river basins (dumping).


User knowledge factors that hinder the design of new home healthcare devices: investigating thirty-eight devices and their manufacturers.
The demand for home healthcare devices arises; however, many home healthcare devices on the market are not designed to reflect the needs and features of the end-users. This study explored the user knowledge factors that hindered the design of new home healthcare devices and the interrelationships between the factors. The abovementioned factors were identified from analysing the project documents of thirty-eight carefully selected home healthcare devices produced by five manufacturers; followed by interviewing the thirty stakeholders playing key roles in developing the devices. The design of the home healthcare devices was influenced by (1) the user insights utilised in formulating project strategies; (2) the sources of user information; (3) the execution of user research; and (4) the formulation of the manufacturers' principal innovation processes. The users' characteristics and needs were not sufficiently reflected in developing new home healthcare devices. One root cause was that the end-users were not perceived by the manufacturers as a key success factor in most cases, given that most of the devices were initiated following the public sector's requests. Actual or potential applications of this study include the facilitation of the appropriate application of human factors methods in developing new home healthcare devices and the improvement of the user performance of the end-devices.


Ground versus air transport of trauma victims: medical and logistical considerations.
Emergency aeromedical transport for trauma victims varies widely, from 10% or less in some programs to more than 90% in others. There is the potential in all such programs for dramatic, lifesaving efforts as well as for costly and dangerous overuse. We propose the following preliminary guidelines for emergency aeromedical transport of trauma victims. Trauma scene flights should be dispatched only for seriously injured patients who are potentially salvageable. Trauma scene flights are not justified if the flight does not significantly reduce the interval between injury and patient arrival at an appropriate hospital (eg, from motor vehicle accident with entrapment) unless the flight delivers needed medical expertise or equipment to the scene. Critically injured patients should be returned to the closest hospital of appropriate capabilities and demonstrated expertise. Flight services should be a public service fully integrated into the metropolitan emergency medical services system. Scene flights should be dispatched within medical guidelines established by the regional emergency medical services system. Emergency aeromedical evacuation of trauma victims should assist the regionalization of trauma care to centers with special capabilities for the management of seriously injured patients. Promulgation of more detailed guidelines will depend on the accumulation of clinical experience and will be possible only if consistent efforts are made to obtain measures of injury severity, categories of injury, and long-term outcomes of management.


Polyamine profiles in human milk, infant artificial formulas, and semi-elemental diets.
Using a sensitive high-performance liquid chromatography method, we quantified the concentration of polyamines (putrescine, spermidine, and spermine) in human milk as well as in a representative group of commonly used artificial infant formulas. Variations in polyamine levels were also analyzed in human milk during the immediate postnatal period. During the first week postpartum, putrescine levels in human milk remained very low and varied little, while spermidine and spermine concentrations rose markedly during the first 3 days, reaching plateau levels that were 12 and eight times higher, respectively, than the values measured on day 0. The mean total polyamine concentration was 557 +/- 18 nmol/dl with the following profile: spermine, 313 +/- 16; spermidine, 220 +/- 20; and putrescine, 24 +/- 3.5. In artificial powdered formulas, the polyamine concentration was approximately 10 times lower than in human milk, with no difference in putrescine and spermine contents between first-age and second-age formulas. By contrast, semi-elemental diets prepared by hydrolytic procedures using crude extracts of pancreatic enzymes were shown to be major sources of polyamines with a profile similar to that of human milk. Compared with first-age formulas, mean concentrations in spermine and spermidine were 39 and six times higher, respectively, in these semi-elemental diets, whereas putrescine levels remained almost equivalent in all types of milk tested. These data indicate that human milk and some semi-elemental diets provide substantial amounts of spermine and spermidine to neonates and infants that could potentially modulate intestinal maturation.


Molecular cloning of rat amidophosphoribosyltransferase.
The cDNA of rat amidophosphoribosyltransferase (EC 184.108.40.206, ATase), which is the supposed regulatory allosteric enzyme of de novo purine nucleotide biosynthesis, has been cloned by polymerase chain reaction. The predicted open reading frame encodes a protein of 517 amino acids with a deduced molecular weight of 57,436 including a supposed 11-amino acid propeptide. The 16 amino acid residues next to the propeptide were identical to the N-terminal amino acid microsequence of a purified rat liver ATase, which is consistent with the cleavage of the propeptide from the proenzyme in rat liver. The derived amino acid sequence is the first sequence reported for a mammalian ATase and it exhibits 81, 41, 36, and 31% identity with the sequences of chicken, Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae ATases, respectively. The molecular weight (M(r)) of 57,436 suggests a tetrameric structure of native ATase with a M(r) of 240,000-248,000. Southern blot analysis suggested that the ATase gene exists as a single copy in the rat genome. Northern blot analysis revealed that ATase is expressed at a high level in brain, heart, liver, and stomach. The ATase mRNA in brain, heart, and stomach was 3.5 kilobases (kb) and in liver the 3.5-kb band was observed as well as an additional band of 4.2 kb. Reverse transcription-polymerase chain reaction analysis showed that ATase is ubiquitously expressed in all tissues examined. Comparison with chicken ATase showed that 2 cysteine residues for an iron-sulfur cluster were conserved. Three conserved and two non-conserved consensus phosphorylation sites for cAMP-dependent protein kinase were found.


Molecular cloning and characterization of a novel SGNH arylesterase from the goat rumen contents.
An esterase-encoding gene, estR5, was directly obtained from the genomic DNA of goat rumen contents. The 555-bp full-length gene encodes a 184-residue polypeptide (EstR5) without putative signal peptide. Deduced EstR5 shared the highest identity (50%) to a putative arylesterase from Ruminococcaceae bacterium D16. Phylogenetic analysis indicated that EstR5 was closely related with microbial esterases of gastrointestinal source. A comparison of the conserved motifs shared with GDSL proteins revealed that EstR5 could be grouped into the GDSL family and was further classified into the subfamily of SGNH hydrolases. The gene estR5 was expressed in Escherichia coli BL21 (DE3) and purified to electrophoretic homogeneity. Recombinant EstR5 exhibited highest catalytic efficiency towards α-naphthyl acetate followed by phenyl acetate and p-nitrophenyl acetate and had no activity towards PNP esters with acyl chains longer than C8. The enzyme exhibited optimal activity at around 60°C and pH 8.0, was stable at pH ranging from 6.0 to 11.0 and was slightly activated by detergent Tween, Nonidet P-40, and Triton X-100. These properties suggest that EstR5 has great potential for basic research and industrial applications. To our knowledge, this is the first arylesterase obtained from rumen microenvironment.


Renal Allograft Function Is a Risk Factor of Left Ventricular Remodeling After Kidney Transplantation.
Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplantation (KT) patients. The prevalence of left ventricular hypertrophy increases with the progression of renal insufficiency. We investigated the association between the progression of renal insufficiency and left ventricular hypertrophy after KT. We reviewed KT patients at Seoul National University Hospital from January 1973 to December 2009. The creatinine elevation ratio (CER, the percentage change in the creatinine level from 1 month to 5 years after transplant) was calculated as follows: (creatinine level at 5 years minus creatinine level at 1 month)/creatinine level at 1 month × 100. The study population was classified into a high-CER group (CER ≥25%) and low-CER group (CER <25%). Mean left ventricular mass index (LVMI) values were 135.7 and 134.7 g/m2 before KT and 101.7 and 123.7 g/m2 at 5 years after KT in the low-CER and high-CER groups, respectively. The LVMI before or 1 year after KT was not different between the 2 groups, but the LVMI at 5 years post-transplant was higher in the high-CER group than in the low-CER group. The LVMI increased after its initial decrease in the high-CER group, whereas its reduction was maintained in the low-CER group during the 5 years after KT (P = .009, repeated-measures analysis of variance). These data suggest that deterioration of renal allograft function is associated with left ventricular remodeling after KT.


Finding the optimal access for proximal upper limb artery (PULA) interventions: Lessons learned from the PULA multicenter registry.
The multicenter proximal upper limb artery (PULA) Registry was created to study the optimal puncture sites for the interventions involving the subclavian, axillary, and innominate arteries. Little is known about the optimal vascular access for PULA interventions, despite the well-known technical complexity of these procedures. We performed the retrospective analysis of consecutive patients treated for symptomatic steno-occlusive disease of the proximal upper limb arteries between January 2015 and December 2019 in three high-volume centers. Acute thrombotic occlusions were excluded from the study. Two hundred and seventy-two patients were treated for significant stenosis and 108 for total occlusion. The baseline patient's characteristics were similar, except for the higher median age of the stenotic patients: 68.5 years (31.1; 90.0) versus 64 years (38.0; 86.0) p = 0.0015. Successful revascularization rate was higher in the stenotic group 93.75% (255/272) versus 86.11% (93/108) p = 0.0230, while the procedure length 27 min (8; 133) versus 46 min (7; 140) p = 0.0001 and fluoroscopy times 439 s (92; 2993) versus 864 s (86; 4176) p = 0.0001 were higher in the occlusion group. The main adverse event rate was similarly low. Dual access was used more often to treat occlusions (60.19% (65/108) vs. 11.40% (31/272) p = 0.0001) without significantly increasing the complication rate. The safest access was ultrasound-guided distal radial artery puncture, significantly better than conventional radial access with 0% (0/31) versus 13.6% (18/131) p = 0.0253 complication. The percutaneous revascularization of proximal upper limb arteries is a safe and effective. Dual access can be applied to increase treatment efficacy, without significantly compromising safety.


Crystal packing in six crystal forms of pancreatic ribonuclease.
We compare the molecular packing of bovine pancreatic ribonuclease A (RNase A) in six crystal forms, two grown with alcohol, three with high salt and one with polyethylene glycol as a precipitant. The six packings differ in the number of molecules in contact and in the extent of the contacts, which bury 1570 A2 to 2790 A2 of the RNase surface. Regions of the protein surface involved in the six packings cover almost the whole RNase molecule. The abundance of polar interactions, about one per 200 A2, is the same in all types of precipitants. All molecule-to-molecule contacts are different in the six crystal forms, except for the one that forms a RNase dimer. The dimer has a large interface covering 1800 A2 and eight to ten polar interactions. Its presence in the three salt-grown crystal forms suggests that it is an intermediate in salt induced crystallization. In contrast, the two alcohol-grown forms contain only small interfaces, implying a different mechanism of nucleation.


Biogeography of Southern Ocean prokaryotes: a comparison of the Indian and Pacific sectors.
We investigated the Southern Ocean (SO) prokaryote community structure via zero-radius operational taxonomic unit (zOTU) libraries generated from 16S rRNA gene sequencing of 223 full water column profiles. Samples reveal the prokaryote diversity trend between discrete water masses across multiple depths and latitudes in Indian (71-99°E, summer) and Pacific (170-174°W, autumn-winter) sectors of the SO. At higher taxonomic levels (phylum-family) we observed water masses to harbour distinct communities across both sectors, but observed sectorial variations at lower taxonomic levels (genus-zOTU) and relative abundance shifts for key taxa such as Flavobacteria, SAR324/Marinimicrobia, Nitrosopumilus and Nitrosopelagicus at both epi- and bathy-abyssopelagic water masses. Common surface bacteria were abundant in several deep-water masses and vice-versa suggesting connectivity between surface and deep-water microbial assemblages. Bacteria from same-sector Antarctic Bottom Water samples showed patchy, high beta-diversity which did not correlate well with measured environmental parameters or geographical distance. Unconventional depth distribution patterns were observed for key archaeal groups: Crenarchaeota was found across all depths in the water column and persistent high relative abundances of common epipelagic archaeon Nitrosopelagicus was observed in deep-water masses. Our findings reveal substantial regional variability of SO prokaryote assemblages that we argue should be considered in wide-scale SO ecosystem microbial modelling.


Methods for investigating decision making in health care network meetings.
To demonstrate a method of describing and analysing the interactions between people engaged in decision making in health care network meetings. Analysis of the meeting interaction involved three steps: recording the meeting, annotating the verbal interactions of the meeting, and calculating various metrics from the annotations. Each annotation represented one utterance by one person. Annotations were assigned start and end times and an associated behaviour from four mutually exclusive behaviour categories. We used software and algorithms developed for this process at the Australian e-Health Research Centre. A meeting interaction fingerprint was produced from one meeting, which consisted of a set of metrics describing different aspects of the interaction between participants in the meeting. Creating meeting fingerprints and analysing the interactions between meeting participants has the potential to provide feedback to improve decision making in health care network teams.


Biochar and hydrochar derived from freshwater sludge: Characterization and possible applications.
Freshwater sludge (FS) is generated in large quantities during the production of drinking water every day. It is largely underutilized, and has long been filter pressed to sludge cake and then disposed of in landfills. The search for more economical and sustainable disposal or reuse options is urgently needed. Biochar and hydrochar are increasingly popular wastes derived materials with huge potential for soil improvement, environmental remediation, and mitigation of climate change, but there is a lack of research on the production of FS derived biochar and hydrochar. In this study, biochar was produced by pyrolysis at 300, 500 or 700 °C for 1 h, and hydrochar was produced by hydrothermal carbonization (HTC) at 140, 160, 180 or 200 °C for 4 h. Proximate analyses show that the biochar has a higher carbon stability and is possibly suitable for carbon sequestration, while the hydrochar contains more labile carbon structures. The ultimate analysis indicates that the surface hydrophobicity is in the order of: biochar > hydrochar > FS. The phytotoxicity tests indicate their positive effects on germination of wheat seeds. This study provides a new treatment to reuse numerous FS and put forward the possible applications of its carbonaceous products, which is expected to facilitate a circular economy and realize the zero-waste target.


DNA repair in primordial follicle oocytes following cisplatin treatment.
Genotoxic chemotherapy and radiotherapy can cause DNA double stranded breaks (DSBs) in primordial follicle (PMF) oocytes, which then undergo apoptosis. The development of effective new fertility preservation agents has been hampered, in part, by a limited understanding of DNA repair in PMF oocytes. This study investigated the induction of classical DSB repair pathways in the follicles of wild type (WT) and apoptosis-deficient Puma-/- mice in response to DSBs caused by the chemotherapy agent cisplatin. Adult C57BL/6 WT and Puma-/- mice were injected i.p. with saline or cisplatin (5 mg/kg); ovaries were harvested at 8 or 24 h. Follicles were counted, and H2A histone family member (γH2AX) immunofluorescence used to demonstrate DSBs. DNA repair protein RAD51 homolog 1 (RAD51) and DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) immunofluorescence were used to identify DNA repair pathways utilised. Puma-/- mice retained 100% of follicles 24 h after cisplatin treatment. Eight hours post-treatment, γH2AX immunofluorescence showed DSBs across follicular stages in Puma-/- mice; staining returned to control levels in PMFs within 5 days, suggesting repair of PMF oocytes in this window. RAD51 immunofluorescence eight hours post-cisplatin was positive in damaged cell types in both WT and Puma-/- mice, demonstrating induction of the homologous recombination pathway. In contrast, DNA-PKcs staining were rarely observed in PMFs, indicating non-homologous end joining plays an insignificant role. PMF oocytes are able to conduct high-fidelity repair of DNA damage accumulated during chemotherapy. Therefore, apoptosis inhibition presents a viable strategy for fertility preservation in women undergoing treatment.


The possible role of HSPs on Behçet's disease: a bioinformatic approach.
Current evidence lends increasing support to immunoinflammatory mechanisms as one of the prime pathogenic processes involved in the development and progression of Behçet's disease (BD). It has been observed that most human beings have cellular and humoral reactions against microbial heat shock proteins (HSPs). The observation that eukaryotic and prokaryotic HSPs have high sequence similarity promoted the hypothesis that HSPs might be potential candidates for molecular mimicry and could act as potentially dangerous autoantigens. In this study, using bioinformatics tools, we examined the hypothesis that HSPs (evolutionarily conserved proteins), which are present in pathogenic and commensal organisms and their hosts, provide the stimulus that initiates BD in susceptible individuals. In this regards, the nucleotide and amino acid sequences of the human HSP 60 kDa and bacterial HSP 60 kDa deposited in the NCBI and PDB databases were subjected to analysis using bioinformatics tools, including The CLC Sequence Viewer and MEGA softwares. These data showed that the sequence homology between bacterial and self HSPs (leading to cross-reactivity and molecular mimicry phenomenon) may be associated with the development of the disease; and suggesting that microbial HSPs, which cross-react with host tissues and elicit significant immune responses are possible pathogenetic agents involved in the development and progression of BD.


Toward the Existence of a Sympathetic Neuroplasticity Adaptive Mechanism Influencing the Immune Response. A Hypothetical View-Part I.
The nervous system exerts a profound influence on the function of the immune system (IS), mainly through the sympathetic arm of the autonomic nervous system. In fact, the sympathetic nervous system richly innervates secondary lymphoid organs (SLOs) such as the spleen and lymph nodes. For decades, different research groups working in the field have consistently reported changes in the sympathetic innervation of the SLOs during the activation of the IS, which are characterized by a decreased noradrenergic activity and retraction of these fibers. Most of these groups interpreted these changes as a pathological phenomenon, referred to as "damage" or "injury" of the noradrenergic fibers. Some of them postulated that this "injury" was probably due to toxic effects of released endogenous mediators. Others, working on animal models of chronic stimulation of the IS, linked it to the very chronic nature of processes. Unlike these views, this first part of the present work reviews evidence which supports the hypothesis of a specific adaptive mechanism of neural plasticity from sympathetic fibers innervating SLOs, encompassing structural and functional changes of noradrenergic nerves. This plasticity mechanism would involve segmental retraction and degeneration of these fibers during the activation of the IS with subsequent regeneration once the steady state is recovered. The candidate molecules likely to mediate this phenomenon are also here introduced. The second part will extend this view as to the potential changes in sympathetic innervation likely to occur in inflamed non-lymphoid peripheral tissues and its possible immunological implications.


Fatal generalized BCG histiocytosis.
An infant was vaccinated at the age of 3 days with BCG vaccine. At the age of 3 years 10 months he developed an infection by Salmonella typhimurium. The infection persisted with recurrent episodes of fever, peri-nephritic abscess, abscesses of lymph nodes, hepatomegaly, splenomegaly and paravertebral and retro-peritoneal abscesses, from which Salmonella were isolated. At the age of 6 years and 2 months later. At post-mortem examination there were widespread histiocytic nodules in many organs, from which Mycobacterium bovis BCG were cultured. One previous case has been reported from Czechoslovakia. The mother of that child was the sister of the father of the child reported here. It was not possible to investigate the possibility of abnormalities of humoral or cellular immunity in the family.


Advantages of nanomedicine over the conventional treatment in Acute myeloid leukemia.
Leukemia is a cancer of blood cells that mainly affects the white blood cells. In acute myeloid leukemia (AML) sudden growth of cancerous cells occurs in blood and bone marrow, and it disrupts normal blood cell production. Most patients are asymptomatic, but it spreads rapidly and can become fatal if left untreated. AML is the prevalent form of leukemia in children. Risk factors of AML include chemical exposure, radiation, genetics, etc. Conventional diagnostic methods of AML are complete blood count tests and bone marrow aspiration, while conventional treatment methods involve chemotherapy, radiation therapy, and bone marrow transplant. There is a risk of cancer cells spreading progressively to the other organs if left untreated, and hence, early diagnosis is required. The conventional diagnostic methods are time- consuming and have drawbacks like harmful side effects and recurrence of the disease. To overcome these difficulties, nanoparticles are employed in treating and diagnosing AML. These nanoparticles can be surface- modified and can be used against cancer cells. Due to their enhanced permeability effect and high surface-to-volume ratio they will be able to reach the tumour site which cannot be reached by traditional drugs. This review article talks about how nanotechnology is more advantageous over the traditional methods in the treatment and diagnosis of AML.


Adverse Events After Left Atrial Appendage Closure: Lessons Learned From the Manufacturer and User Facility Device Experience (MAUDE) Database.
Left atrial appendage (LAA) closure devices are alternative treatments recently approved for patients with atrial fibrillation. Due to the novelty of these devices, limited postapproval surveillance data on LAA closure devices have been published. Thus, we analyzed the United States Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database to report these findings. The primary endpoint was final event outcome, and secondary endpoints included management strategies of reported events.


Serum growth differentiation factor 15 is closely associated with metabolic abnormalities in Chinese pregnant women.
To explore the relationship between serum growth differentiation factor 15 (GDF15) and metabolic abnormalities in Chinese pregnant women. We recruited 200 patients with gestational diabetes mellitus (GDM) and 211 matched normal control within 24-28 weeks of pregnancy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum GDF15 levels of all participants. Then we grouped participants according to the number of metabolic abnormalities (including blood glucose, blood lipids and blood pressure), divided them into a normal metabolic group, one metabolic abnormality group, two or more metabolic abnormalities group. Finally, multinomial logistic regression analysis was used to estimate the odds radio (OR) and 95% CIs expressing the association between GDF15 and metabolic abnormalities in pregnant women. Through bivariate correlation analysis, we found that serum GDF15 is linearly correlated with glucose metabolism indices, such as 1h-PG, 2h-PG, HbA1c (all P < 0.05). In addition, serum GDF15 and triglycerides were linearly correlated (P < 0.05). Grouping by the number of metabolic abnormalities, we found that as GDF15 levels increased, the risk of metabolic abnormalities also increased (OR > 1), and the risk of multiple metabolic abnormalities was higher. As the number of metabolic abnormalities increased, serum GDF15 levels also were elevated (P < 0.001). The results suggest that serum GDF15 levels are closely associated with metabolic abnormalities in pregnant women and may be used as a predictor of metabolic abnormalities during pregnancy.


Deletion of a Histone Acetyltransferase Leads to the Pleiotropic Activation of Natural Products in Metarhizium robertsii.
Histone deacetylation normally decreases the gene expression in organisms. By genome-wide deletions of epigenetic regulators in entomopathogenic fungus Metarhizium robertsii, unexpected activations of orphan secondary metabolite genes have been found upon the disruption of a histone acetyltransferase (HAT) gene Hat1. This led to the characterization of 11 new natural products, including eight isocoumarin derivatives meromusides A-H and two nonribosomal peptides meromutides A and B. Therefore, disruption of HAT represents a new approach to mine chemical diversity from fungi.


Prediction of pKa values of phenolic and nitrogen-containing compounds by computational chemical analysis compared to those measured by liquid chromatography.
The pKa values of 64 phenolic and 50 nitrogen-containing compounds were obtained by reversed-phase liquid chromatography and computational chemical calculation. The chromatographically obtained values of phenolic compounds were equal to pKa values from references and Hammett's equation, and those of nitrogen-containing compounds were lower than the reference values. It appeared difficult to calculate the properties of the ortho effect and nitro group by the computational calculation method. However, the calculation was simpler than selecting different constants of Hammett's equation for a variety of compounds.


1D iron(II)-1,2,4-triazolic chains with spin crossover assembled from discrete trinuclear complexes.
We report on a molecular cationic iron(II) complex with a 4-amino-1,2,4-triazole ligand and a tetraiodomercurate anion exhibiting an incomplete spin crossover (SCO). The complex exhibits an unusual disordered structure with a linear arrangement of ligand and water molecules that can potentially accommodate up to four iron atoms, but both terminal metal positions have half chemical occupancies, while occupancies of all ligands are full. This corresponds to the crystallisation of disordered trinuclear complexes arranged into 1D supramolecular chains. Iron cations have different N6 or N3O3 coordination environments, leading to the thermally induced SCO in two thirds of the metal centres. This SCO behaviour was characterised by magnetic susceptibility measurements and Mössbauer spectroscopy.


Can Porphyromonas gingivalis Contribute to Alzheimer's Disease Already at the Stage of Gingivitis?
Alzheimer's disease (AD) has been associated with periodontitis, which starts as gingivitis. Similar to periodontitis, gingivitis bacteria, bacterial products, and inflammatory mediators can travel to the brain via the blood stream and promote brain inflammation. Periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, both associated with AD, have been found in dental plaque of children already at the age of 3. It is suggested that these bacteria during long-term exposure may drive microglia (brain resident macrophage cells) into a pro-inflammatory M1 phase where they contribute to AD rather than protect against it. This notion comes from studies in mice showing that microglia actually can "remember" previous inflammatory challenge and become "trained" or "tolerant" to toxins like lipopolysaccharide. If gingivitis has an impact on AD, which should be verified, AD prophylaxis should start already at this pre-periodontitis stage with removal of supragingival plaque.


The lambda sign in gallium-67 scintigraphy is a useful clue to the early diagnosis of sarcoidosis.
A 40-year-old man with bilateral hilar lymphadenopathy in chest X-ray and the λ-sign in gallium-67 scintigraphy was subsequently diagnosed with systemic sarcoidosis according to the findings of bronchoalveolar lavage and histopathological examinations of transbronchial lung biopsies. Identifying the λ-sign could be a valuable clue to the early diagnosis of sarcoidosis.


Physiological responses of Gracilariopsis longissima (S.G. Gmelin) Steentoft, L.M. Irvine and Farnham (Rhodophyceae) to sub-lethal copper concentrations.
Through a series of comparative experiments the relative effects of copper (Cu) exposure on the growth and physiology (chlorophyll fluorescence, ion leakage, O(2) evolution and pigmentation) of the red seaweed Gracilariopsis longissima was investigated. Of the various physiological end-points measured, growth proved to be the most sensitive with reductions in relative growth rate (RGR) observed at a concentration of 12.5 microg l(-1) Cu, with zero growth above about 300 microg l(-1). A significant increase in ion leakage and reduction in phycobiliprotein concentrations were evident, but only at the highest concentration tested (500 microg l(-1)), at which point shrinkage of apical tips also occurred. Photosynthetic rates, as measured by chlorophyll fluorescence and oxygen evolution, were first impaired at 250 microg l(-1), with a 30% reduction in photosynthetic efficiency (F(v)/F(m)) and a 60% reduction in oxygen evolution. There were no discernible effects on respiration rates or chlorophyll a and beta-carotene content over this concentration range. It was hypothesised that the observed uncoupling of growth and photosynthesis at low Cu concentrations might be explained by the release of dissolved organic matter (DOC), resulting in less available energy for growth. No such increase in DOC was apparent. Alternative explanations to account for the uncoupling, including the diversion of energy for maintenance of cell integrity and induction of protective mechanisms, are discussed.


U-2940, a human B-cell line derived from a diffuse large cell lymphoma sequential to Hodgkin lymphoma.
Several patterns of association between Hodgkin and non-Hodgkin lymphomas are recognized, some of which support a common cellular origin or shared transformation events for both malignancies. We describe the U-2940 cell line derived from a diffuse large B-cell lymphoma with some features consistent with mediastinal large B-cell lymphoma, clinically apparent 1 month after the initial course of chemotherapy for Hodgkin's disease, fulfilling the criteria for composite malignancies. U-2940 cells display a mature B phenotype with hypermutated IgH rearrangement typical of germinal/postgerminal center origin. The cell line is negative for Epstein-Barr virus and no evidence of t(14;18) was found. U-2940 cells display multiple chromosomal rearrangements similar to recurrent aberrations described in both Hodgkin and non-Hodgkin lymphomas, also partially shared by U-2932 derived from a B-cell lymphoma sequential to Hodgkin's disease. The original large B-cell lymphoma and the U-2940 cell line bear microsatellite instability, an abnormality associated with particular subtypes of non-Hodgkin lymphomas and found in tissues involved by Hodgkin lymphoma. Therefore, U-2940 cells bear several features known to occur in Hodgkin and in non-Hodgkin lymphomas, leading to the assumption that this cell line may constitute a useful tool to address elective pathways of lymphomagenesis and eventually the Hodgkin and non-Hodgkin lymphoma association.


A severity grading system of food-induced acute allergic reactions to avoid the delay of epinephrine administration.
Substantial discrepancies among anaphylaxis severity scores may delay epinephrine administration. The study aims to develop a transparent severity grading system of food-induced acute allergic reactions with a decision model for epinephrine use. The natural course of 315 acute food-induced allergic reactions in children hospitalized at the Allergology department between May 2016 and July 2019 owing to follow-up treatment and allergy diagnostics was evaluated. The severity of episodes was classified according to the 5 most accepted grading systems. The interrater reliability of classification between anaphylaxis severity scores was assessed. All symptoms were grouped into a heat map according to their real-life incidence and clinical relevance. Based on the heat map analysis, a severity grading system of food-induced acute allergic reactions in children with the epinephrine administration decision model was created. Data from 259 food-induced anaphylaxis episodes in 157 children were included in the analysis. Comparing the grading systems, we observed a 24.7% to 70.2% disagreement between severity scores. The heat map illustrated a strong association between 29 symptoms and their categorization. A new severity grading system was developed and a 2-stage decision model was proposed: "epinephrine yes" (any rapidly progressing symptoms, even mild ones or from 1 organ system; any symptoms from more than 1 organ system; or every grade of anaphylaxis), and "epinephrine available and prepared to use" (nonprogressing mild systemic allergic reaction from 1 system area only; no anaphylaxis). A new severity grading system of food-induced acute allergic reactions in children could serve as a clinical tool for health care professionals to avoid epinephrine administration delay.


[Remote results and critical review of the use of the Sparks-Mandril prosthesis].
Long-term clinical results and pathologic features, both macroscopic and microscopic, of 24 Sparks-Mandril grafts as femoro-popliteal substitutes are reviewed. High rate of complications and low percentage of patency are stressed. Further use of this graft is not recommended.


Quantitation of the nearest-neighbour effects of amino acid side-chains that restrict conformational freedom of the polypeptide chain using reversed-phase liquid chromatography of synthetic model peptides with L- and D-amino acid substitutions.
Side-chain backbone interactions (or "effects") between nearest neighbours may severely restrict the conformations accessible to a polypeptide chain and thus represent the first step in protein folding. We have quantified nearest-neighbour effects (i to i+1) in peptides through reversed-phase liquid chromatography (RP-HPLC) of model synthetic peptides, where L- and D-amino acids were substituted at the N-terminal end of the peptide sequence, adjacent to a L-Leu residue. These nearest-neighbour effects (expressed as the difference in retention times of L- and D-peptide diastereomers at pHs 2 and 7) were frequently dramatic, depending on the type of side-chain adjacent to the L-Leu residue, albeit such effects were independent of mobile phase conditions. No nearest-neighbour effects were observed when residue i is adjacent to a Gly residue. Calculation of minimum energy conformations of selected peptides supported the view that, whether a L- or D-amino acid is substituted adjacent to L-Leu, its orientation relative to this bulky Leu side-chain represents the most energetically favourable configuration. We believe that such energetically favourable, and different, configurations of L- and D-peptide diastereomers affect their respective interactions with a hydrophobic stationary phase, which are thus quantified by different RP-HPLC retention times. Side-chain hydrophilicity/hydrophobicity coefficients were generated in the presence of these nearest-neighbour effects and, despite the relative difference in such coefficients generated from peptides substituted with L- or D-amino acids, the relative difference in hydrophilicity/hydrophobicity between different amino acids in the L- or D-series is maintained. Overall, our results demonstrate that such nearest-neighbour effects can clearly restrict conformational space of an amino acid side-chain in a polypeptide chain.


Inhibition, post-hydroxymethylglutaryl-CoA regulation and relation to cell growth of cholesterol biosynthesis in cultured human skin fibroblasts.
Cholesterol biosynthesis in cultured human skin fibroblasts was studied by [14C]acetic acid incorporation into non-saponifiable lipids and quantification of labeled cholesterol among its precursors. Synthesis was slow, in spite of a high 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA) activity and led to an accumulation of unexpected non-polar metabolites identified as C-30 sterones, but not C-27 sterol precursors. This supports a post-HMG-CoA regulation at the lanosterol demethylation step. Cholesterol biosynthesis was stimulated by cell culture in lipid depleted medium and was inhibited by pentadecane-2-one which acts mainly at two post-HMG-CoA steps: lanosterol demethylation and lathosterol isomerisation to cholesterol. A parallel pentadecane-2-one inhibition of cell growth was also observed, even when cells were cultured in the presence of whole serum. This indicates the existence of a relationship between endogenous cholesterol synthesis and cell growth and sheds additional light on the role of post-HMG-CoA regulation in this phenomenon.