[Microscopic excision of a colloyd cyst of the third ventricle assisted by endoscopy. Case report and literature analysis.]
Colloid cysts are histologically benign lesions, probably derived from the endoderm, which represent 0.3-2% of brain tumors. They are usually attached to the roof of the third ventricle in direct relation to the foramen of Monro, which can cause a blockage to the circulation of cerebrospinal fluid, determining hydrocephalus and in some cases sudden death. Other more common symptoms are headache, nausea and vomiting, blurred vision, gait ataxia, and cognitive impairment. Treatment options include microsurgery, endoscopy, stereotaxic casting, or cerebrospinal fluid shunts for the treatment of hydrocephalus. The objective of surgery is the total excision of the lesion. It should be noted that the microsurgical technique allows total excision more frequently, but at the cost of greater manipulation and tissue trauma; on the contrary, endoscopic being minimally invasive, allows better tissue preservation, although the rates of complete tumor excision are usually lower due to the difficulties in dissecting the lesions densely adhered to the roof of the third ventricle. We present a clinical case of a patient with a third ventricle tumor compatible with a colloid cyst, with progressive hydrocephalus, operated with microsurgical technique and endoscopic assistance. Total excision of the colloid cyst with improvement of the symptoms. Antegrade memory disorder that resolved completely after 3 months. The endoscopy-assisted microsurgical technique is safe for the management of this pathology and provides intraoperative benefits.


[Diagnostic difficulties in cases of expanding intracranial lesions where the anterior cerebral artery does not fill in arteriograms (2 cases)].
The author describes two cases of frontal-lobe brain tumours which expanded compressing the anterior cerebral artery and closing its lumen which simulated on arteriography intravascular obliteration of the vessel.


Factors Affecting the Adsorption of Per- and Polyfluoroalkyl Substances (PFAS) by Colloidal Activated Carbon.
The immobilization of per- and polyfluoroalkyl substances (PFAS) by colloidal activated carbon (CAC) barriers has been proposed as a potential in-situ method to mitigate the transport of plumes of PFAS in the subsurface. However, if PFAS are continuously released from a source zone, the adsorptive sites on CAC will eventually become saturated, upon which point the breakthrough of PFAS in the barrier will occur. To predict the long-term effectiveness of CAC barriers, it is important to evaluate the factors that may affect the adsorption of PFAS on CAC. In this study, the adsorption of 7 PFAS on a polymer-stabilized CAC (i.e., PlumeStop®) and on a polymer-free CAC was investigated using batch experiments. The adsorption affinity of PFAS to CAC was in the following order: PFOS > 6:2 FTS > PFHxS > PFOA > PFBS > PFPeA > PFBA. This result indicates that hydrophobic interaction was the predominant adsorption mechanism, and that hydrophilic compounds such as PFBA and PFPeA will break through CAC barriers first. The partition coefficient Kd for the adsorption of PFAS on the polymer-stabilized CAC was 1.3 - 3.5 times smaller than the Kd for the adsorption of PFAS on the polymer-free CAC, suggesting that the polymers decreased the adsorption, presumably due to competitive sorption. Thus, the PFAS adsorption capacity of PlumeStop CAC barriers is expected to increase once the polymers are biodegraded and/or washed away. The affinity of PFOS and PFOA to CAC increased when the ionic strength of the solution increased from 1 to 100 mM, or when the concentration of Ca2+ increased from 0 to 2 mM. In contrast, less PFOS and PFOA were adsorbed in the presence of 1 - 20 mgC/L Suwannee River Fulvic Acid, which represented dissolved organic carbon, or in the presence of 10 - 100 mg/L diethylene glycol butyl ether (DGBE), which is an important component in some aqueous film-forming foam (AFFF) formulations. The presence of 0.5 - 4.8 mg/L benzene or 0.5 - 8 mg/L trichloroethylene, the co-contaminants that may comingle with PFAS at AFFF-impacted sites, diminished PFOS adsorption but had no effect or even slightly enhanced PFOA adsorption. When the initial concentration of TCE was 8 mg/L, the Kd (514 ± 240 L/g) for the adsorption of PFOS was approximately 20 times lower than that in the TCE-free system (Kd = 9,579 ± 829 L/g). The results of this study provided insights into some key factors that may affect the adsorption of PFAS in in-situ CAC barriers.


[Fibrodysplasia ossificans progressiva: orthopedic pitfalls and controversies].
Fibrodysplasia ossificans progressiva (FOP) is a rare disorder of the connective tissue associating malformation of the great toes and progressive heterotopic ossifications. Diagnosis is mostly clinical and currently no treatment is available. We report on the case of an 8 year old boy having an unusual form of FOP. We discuss clinical aspects of the disease and insist on the importance of early diagnosis, avoiding harmful events and therapeutic pitfalls.


Early Revision Rate Following Primary Carpal Tunnel Release.
The published revision rates after carpal tunnel release (CTR) vary from 0.3% to 7%. The explanation for this variation may not be fully apparent. The purpose of this study was to determine the rate of surgical revision within 1-5 years following primary CTR at a single academic institution, compare it with rates reported in the literature, and attempt to provide explanations for these differences. We identified all patients who underwent primary CTR at a single orthopedic practice by 18 fellowship-trained orthopedic hand surgeons from October 1, 2015, through October 1, 2020, using a combination of Current Procedural Terminology (CPT) and International Classification of Diseases (ICD), 10th Revision, codes. Patients who underwent CTR because of a diagnosis other than primary carpal tunnel syndrome were excluded. Patients who required revision CTR were identified using a practice-wide database query using a combination of CPT and ICD-10 codes. Operative reports and outpatient clinic notes were reviewed to determine the cause of revision. Data on patient demographics, surgical technique (open vs single-portal endoscopic), and medical comorbidities were collected. A total of 11,847 primary CTR procedures were performed during the 5-year period on 9,310 patients. We found 24 revision CTR procedures among 23 patients, resulting in a revision rate of 0.2%. Of 9,422 open primary CTRs performed, 22 cases (0.23%) went on to undergo revision. Endoscopic CTR was performed in 2,425 cases, with 2 cases (0.08%) ultimately undergoing revision. The average length of time from primary CTR to revision was 436 days (range, 11-1,647 days). We noted a substantially lower rate of revision CTR within 1-5 years of primary release (0.2%) in our practice than that noted in previously published studies, although we accept that this does not account for out-of-area migration. There was no significant difference in the revision rates between open and single-portal endoscopic primary CTR. Therapeutic III.


Anaplastic large cell lymphomas with equivocal DUSP22 FISH results: recommendations for clinical reporting and diagnostic evaluation.
Anaplastic large cell lymphoma (ALCL), one of the most common T-cell lymphomas, shows unifying pathological features but is clinically and genetically heterogeneous. One genetic subgroup, characterized by recurrent DUSP22 rearrangements (R), has distinct morphologic, immunophenotypic, and molecular features and can be identified in routine pathology practice using a breakapart (BAP) fluorescence in situ hybridization (FISH) probe. However, some cases show equivocal BAP-FISH findings (BAP-FISHEQ) and the features of these cases are poorly understood. Here, we sought to characterize DUSP22 BAP-FISHEQ ALCLs further. First, we applied an immunohistochemistry (IHC) algorithm using TIA1, pSTAT3Y705, and LEF1, which can predict DUSP22-R with high accuracy. Among 37 BAP-FISHEQ ALCLs, 18 (49%) were IHC-algorithm positive (IHCPOS), 8 (21%) were IHC-algorithm negative (IHCNEG), and 11 (30%) were IHCEQ. In 32 BAP-FISHEQ cases, we also applied a dual-color, dual-fusion (D-FISH) probe for t(6;7)(p25.3;q32.3), which accounts for 45% of DUSP22-R ALCLs. Among BAP-FISHEQ cases, D-FISH was positive in 10/18 IHCPOS cases (56%), 0/9 IHCEQ cases (0%), and 0/5 IHCNEG cases (0%). Median survival in BAP-FISHEQ ALCLs was 105 months, intermediate between BAP-FISHPOS ALCLs (median survival not reached) and BAP-FISHNEG ALCLs (19 months). Thus, DUSP22 BAP-FISHEQ ALCLs are clinicopathologically heterogeneous, likely due to an admixture of cases with an unbalanced DUSP22-R and cases with focal deletions without rearrangement. For clinical reporting, we recommend that DUSP22 BAP-FISHEQ ALCLs be reported as equivocal, and not be grouped with BAP-FISHPOS ALCLs. Clinical adoption of an IHC algorithm, possibly supplemented by t(6; 7) D-FISH, could facilitate genetic subtyping in about two-thirds of BAP-FISHEQ ALCLs.


Small-molecule discovery through DNA-encoded libraries.
The development of bioactive small molecules as probes or drug candidates requires discovery platforms that enable access to chemical diversity and can quickly reveal new ligands for a target of interest. Within the past 15 years, DNA-encoded library (DEL) technology has matured into a widely used platform for small-molecule discovery, yielding a wide variety of bioactive ligands for many therapeutically relevant targets. DELs offer many advantages compared with traditional screening methods, including efficiency of screening, easily multiplexed targets and library selections, minimized resources needed to evaluate an entire DEL and large library sizes. This Review provides accounts of recently described small molecules discovered from DELs, including their initial identification, optimization and validation of biological properties including suitability for clinical applications.


Opinion comparison concerning future information technology in Finnish community pharmacies.
To compare the opinions of community pharmacy owners, managers and personnel concerning the key features of the future information technology system needed in Finnish community pharmacies. The study was targeted to the pharmacists working in community pharmacies as managers (owners and staff pharmacists with M.Sc. degree) or personnel responsible for dispensing and patient counselling (pharmacists with B.Sc. degree). A national cross-sectional survey to all of Finnish community pharmacy owners (n = 580) and staff pharmacists (B.Sc. and M.Sc. degrees, n = 1709) working in community pharmacies, was conducted in order to determine differences in opinions between these occupation groups with different professional duties. The response rates were 53% for pharmacy owners (n = 308) and 22% for staff pharmacists (n = 373). The main outcome measure was the perceived importance of 89 potential features for a new IT system ranked by using a five-point Likert scale. The responding community pharmacy managers and staff pharmacists had differences in their ranking of more than half (52%) of the potential features listed in the survey questionnaire. The features related to the pharmacy's internal processes, such as financial management, sales and marketing management and stock holding, were ranked significantly higher by the managers, while the personnel prioritized the features supporting pharmaceutical service provision and personnel management. The managers and personnel shared their opinion on the importance of features supporting drug information and patient counselling, medication safety and interprofessional collaboration. The managers and staff pharmacists have different views of the importance of IT features, reflecting their different professional duties in the community pharmacy. A high priority was given for the features familiar to the users and needed in their daily practice. This indicates the need for involving different occupation groups in planning the new IT systems for community pharmacies.


Attenuated expression of DFFB is a hallmark of oligodendrogliomas with 1p-allelic loss.
Allelic loss of chromosome 1p is frequently observed in oligodendroglioma. We screened 177 oligodendroglial tumors for 1p deletions and found 6 tumors with localized 1p36 deletions. Several apoptosis regulation genes have been mapped to this region, including Tumor Protein 73 (p73), DNA Fragmentation Factor subunits alpha (DFFA) and beta (DFFB), and Tumor Necrosis Factor Receptor Superfamily Members 9 and 25 (TNFRSF9, TNFRSF25). We compared expression levels of these 5 genes in pairs of 1p-loss and 1p-intact tumors using quantitative reverse-transcriptase PCR (QRTPCR) to test if 1p deletions had an effect on expression. Only the DFFB gene demonstrated decreased expression in all tumor pairs tested. Mutational analysis did not reveal DFFB mutations in 12 tested samples. However, it is possible that DFFB haploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development.


Drivers of polar bear behavior and the possible effects of prey availability on foraging strategy.
Change in behavior is one of the earliest responses to variation in habitat suitability. It is therefore important to understand the conditions that promote different behaviors, particularly in areas undergoing environmental change. Animal movement is tightly linked to behavior and remote tracking can be used to study ethology when direct observation is not possible. We used movement data from 14 polar bears (Ursus maritimus) in Hudson Bay, Canada, during the foraging season (January-June), when bears inhabit the sea ice. We developed an error-tolerant method to correct for sea ice drift in tracking data. Next, we used hidden Markov models with movement and orientation relative to wind to study three behaviors (stationary, area-restricted search, and olfactory search) and examine effects of 11 covariates on behavior. Polar bears spent approximately 47% of their time in the stationary drift state, 29% in olfactory search, and 24% in area-restricted search. High energy behaviors occurred later in the day (around 20:00) compared to other populations. Second, olfactory search increased as the season progressed, which may reflect a shift in foraging strategy from still-hunting to active search linked to a shift in seal availability (i.e., increase in haul-outs from winter to the spring pupping and molting seasons). Last, we found spatial patterns of distribution linked to season, ice concentration, and bear age that may be tied to habitat quality and competitive exclusion. Our observations were generally consistent with predictions of the marginal value theorem, and differences between our findings and other populations could be explained by regional or temporal variation in resource availability. Our novel movement analyses and finding can help identify periods, regions, and conditions of critical habitat.


Detection of phosphorylated NF-H in the cerebrospinal fluid and blood of aneurysmal subarachnoid hemorrhage patients.
Blood and cerebrospinal fluid (CSF) of 30 Fisher grade 3 aneurysmal subarachnoid hemorrhage (ASAH) patients were analyzed for the presence of the phosphorylated axonal form of the major neurofilament subunit NF-H (pNF-H), a promising biomarker of axonal injury. Patient demographic data including development of vasospasm and outcome scores at 6 months after aneurysmal rupture (AR) were evaluated. Higher pNF-H blood levels in the first few days after AR were strongly predictive of a negative outcome. Blood pNF-H levels in most recovering patients showed a steady increase into the second week after AR, presumably reflecting axonal degeneration secondary to the original insult. Almost half of the patients studied showed sudden dramatic peaks of pNF-H protein release into CSF in the 3- to 14-day time period after AR, which must reflect profound, coordinated, and secondary loss of axons. Patients in whom vasospasm was detected had significantly more pNF-H in both blood and CSF compared with those in whom vasospasm was not detected. We conclude that the analysis of pNF-H levels in blood and CSF differentiates between patients with poor and favorable outcomes and also reveals several novel features of ASAH progression and recovery.


Viral vaccines under development: a third generation.
In summary then, my purpose has been two-fold: on the one hand, I have tried to highlight the kinds of basic science advances in both cellular and virologic research that can (and should) be focussed both on vaccines under development and, retrospectively, on those whose origins were strictly empiric. On the other hand, I have attempted a partial survey of some of the prominent members of a potential new generation of vaccines to point out areas where these advances can and should contribute either to progress or to a sense of caution about the further reliance on pure empiricism. It is clear that we are not finished with new viral vaccines. It is equally clear that narrowing the persistent gap between basic science and its application to public health needs will require much energy and attention as vaccine development progresses.


Fault mechanism analysis and diagnosis for closed-loop drive system of industrial robot based on nonlinear spectrum.
To solve the problem of nonlinear characteristics neglecting and fault mechanism analysis lacking in fault diagnosis research, a new method of fault mechanism analysis and diagnosis based on nonlinear spectrum is proposed. Firstly, based on the Permanent Magnet Synchronous Motor (PMSM) model of robot, the first 4-order spectrums based on nonlinear output frequency response function (NOFRF) in different states are obtained by batch calculation method. Secondly, the high-frequency spectrum distribution rule of NOFRF spectrum in different states are analyzed. Finally, in the closed-loop simulation environment of robot, the identification method based on data-driven is adopted for NOFRF spectrum calculation to verify power loss fault of PMSM. Meanwhile, the fault diagnosis experiment is also carried out. The experimental results indicate that the key characteristics distribution rule of NOFRF spectrums in the real environment is consistent with the theoretical analysis results, and compared with the traditional fault feature extraction methods by output signal, the diagnosis with fault feature of NOFRF spectrum for industrial robot closed-loop drive system has the highest accuracy, which verifies the validity of NOFRF spectrum as the fault feature.


Assessment of association between BRAF-V600E mutation status in melanomas and clinical response to ipilimumab.
Ipilimumab, a fully human monoclonal antibody against cytotoxic T lymphocyte antigen-4, has demonstrated significant improvement in overall survival in previously treated advanced melanoma patients. The BRAF inhibitor, vemurafenib, has shown up to 78% objective response rates in melanoma patients harboring the BRAF-V600E mutation but not in patients lacking the mutation. As an immune potentiator, the mechanism of action of ipilimumab may not be dependent of the activity of the BRAF pathway. To test this, we investigated whether the clinical activity of ipilimumab would be affected by the BRAF-V600E mutation status of the tumors. Thus, this retrospective analysis was carried using a set of tumor biopsies from a completed phase II clinical trial. CA184004 was a randomized, double-blind, multicenter trial of 82 previously treated or untreated patients with unresectable stage III/IV melanoma. Patients received ipilimumab 3 or 10 mg/kg every 3 weeks for four doses followed by maintenance dosing in eligible patients. The BRAF-V600E mutation status for 80 patients was determined in tumor biopsies by PCR-based assays. Data on disease control were available for 69 patients with evaluated BRAF-V600E mutation status. Rates of objective responses and stable disease in patients with BRAF-V600E mutation positive tumors (30%) were comparable to those in patients with the wild-type gene (~33%). Eleven patients displayed Durable Disease Control (DDC) of which 55% had BRAF-V600E mutation positive tumors and 45% did not. In the 48 patients showing no DDC, the mutation frequency was 50%. In this study, no association between BRAF-V600E mutation status of melanoma tumors and DDC after treatment with ipilimumab was detected.


Noncontact assessment for fatigue based on heart rate variability using IR-UWB radar.
Physical fatigue can be assessed using heart rate variability (HRV). We measured HRV at rest and in a fatigued state using impulse-radio ultra wideband (IR-UWB) radar in a noncontact fashion and compared the measurements with those obtained using electrocardiography (ECG) to assess the reliability and validity of the radar measurements. HRV was measured in 15 subjects using radar and ECG simultaneously before (rest for 10 min before exercise) and after a 20-min exercise session (fatigue level 1 for 0-9 min; fatigue level 2 for 10-19 min; recovery for ≥ 20 min after exercise). HRV was analysed in the frequency domain, including the low-frequency component (LF), high-frequency component (HF) and LF/HF ratio. The LF/HF ratio measured using radar highly agreed with that measured using ECG during rest (ICC = 0.807), fatigue-1 (ICC = 0.712), fatigue-2 (ICC = 0.741) and recovery (ICC = 0.764) in analyses using intraclass correlation coefficients (ICCs). The change pattern in the LH/HF ratios during the experiment was similar between radar and ECG. The subject's body fat percentage was linearly associated with the time to recovery from physical fatigue (R2 = 0.96, p < 0.001). Our results demonstrated that fatigue and rest states can be distinguished accurately based on HRV measurements using IR-UWB radar in a noncontact fashion.


Antibacterial Activity of Alanine-Derived Gemini Quaternary Ammonium Compounds.
The antibacterial activity of alanine-derived gemini quaternary ammonium salts (chlorides and bromides) with various spacer and alkyl chain lengths was investigated. The studied compounds exhibited a strong bactericidal effect, especially bromides with 10 and 12 carbon alkyl chains and 3 carbon spacer groups (TMPAL-10 Br and TMPAL-12 Br), with a short contact time. Both salts dislodged biofilms of Pseudomonas aeruginosa and Staphylococcus epidermidis, and were lethal to adherent cells of S. epidermidis. Bromide with 2 carbon spacer groups and 12 carbon alkyl chains (TMEAL-12 Br) effectively reduced microbial adhesion by coating polystyrene and silicone surfaces. The results obtained suggest that, after further studies, gemini QAS might be considered as antimicrobial agents in medicine or industry.


Standardization of BOD₅/COD ratio as a biological stability index for MSW.
The control of biodegradable substances is the key issue in evaluating the short and long-term emission potential and environmental impact of a landfill. Aerobic and anaerobic indices, such as respirometric index (RI) and biomethane potential production (GB21), can be used in the estimation of the stability of solid waste samples. Previous studies showed different degrees of relationship between BOD₅/COD ratio compared with RI4. Aim of this study is to standardize the parameter BOD₅/COD ratio and to test the methodology under different operating conditions (dynamic or static leaching and leaching duration, 6 and 24-h) keeping constant temperature and liquid/solid ratio (L/S=10 l/kg(TS)), with the introduction of a COD fractioning method. The COD fractioning is based on the differentiation between the soluble fraction (COD(sol)) and the colloidal fraction (COD(coll)) using a flocculation method. The BOD₅/COD and the BOD₅/COD(sol) indices are both consistent and significant and can be used as stability indices. The BOD₅/COD ratio does not seem to be influenced, for the same test duration, by the type of test, static or dynamic. In the same way the longer test duration (24-h) does not influence significantly the values of BOD₅/COD ratio. As a consequence a leaching test duration of 6-h is preferable to avoid the beginning of the hydrolysis and oxidation processes.


A young woman who did not awake after extensive surgery.
Cystic echinococcosis (CE) caused by Echinococcus granulosus, significantly impacts health globally, but is a rare disease in Norway. CE is treated with a combination of anthelmintics and surgery, or percutaneous drainage. A woman in her thirties underwent extensive surgery due to disseminated CE in the abdominal cavity and liver. Due to intraoperative cyst rupture with contamination of the abdominal cavity, peritoneal lavage with hypertonic saline (20 % NaCl), a scolicidal agent, was performed for ten minutes before irrigation with physiological saline. Immediately after surgery, the patient was haemodynamically unstable and did not awake. Blood level of sodium was found to be severely increased at 188 mmol/L (ref 137−144 mmol/L). Hypotonic fluids (5 % glucose) were immediately administered intravenously to correct the acute hypernatraemia. CT scan of the head did not show signs of bleeding or oedema. The sodium level was normalised on postoperative day three and the patient was discharged without any neurological sequelae. Our patient developed iatrogenic acute severe hypernatraemia following abdominal lavage with hypertonic saline. Acute severe hypernatraemia is potentially lethal. Hypertonic saline must be used intraoperatively with great caution. Regular blood tests to detect hypernatraemia and monitor other electrolyte disturbances should be mandatory.


Meperidine to control shivering associated with platelet transfusion reaction.
Shivering may be part of a febrile non-haemolytic reaction to blood product transfusion. Shivering can increase oxygen consumption up to 500 per cent which may be detrimental to patients with decreased myocardial reserve. A case is presented of a reaction to platelet transfusion characterized by shivering, tachycardia and hypertension in a patient with a recent myocardial infarction in whom the metabolic and haemodynamic effects were considered to be potentially disastrous. Intravenous injection of meperidine was rapidly effective in treating these changes.


Evaluating Quality and Adequacy of Gastrointestinal Samples Collected using Reusable or Disposable Forceps.
Sample quality of gastrointestinal endoscopic biopsies is of paramount importance for accurate histological diagnosis. Many veterinary practices use reusable forceps as a result of perceived decreased cost. With reusable forceps, it remains unknown whether sample quality declines with repeated use and becomes inferior to single-use forceps and is therefore more or less cost effective than single-use forceps. The study hypothesis was that reusable forceps sample quality would deteriorate after repeated use as compared to single-use forceps. Sixty-five dogs undergoing gastrointestinal endoscopy for diagnostic investigations at the Hospital for Small Animals, Edinburgh University. A prospective, pathologist-blinded study comparing single-use and reusable alligator standard cup biopsy forceps (Olympus 2.0 mm 1550 mm) with 5 randomized reusable forceps. Sample quality (stomach, duodenum, ileum, and colon) was assessed by a single pathologist using the WSAVA guidelines. There was no difference in the adequacy, depth, villi number, or crush artifact in the 4 intestinal areas between forceps type with at least 10, and up to 15, repeated uses of the reusable forceps. This study demonstrates that reusable cup biopsy forceps provide equivalent biopsy quality after repeated uses to single-use forceps and are cost effective at 10-case use.


The treatment effect of diazoxide on 44 patients with congenital hyperinsulinism.
To study the treatment effect and safety of diazoxide on patients with congenital hyperinsulinism (CHI). A total of 44 patients who have been hospitalized to our hospital and used diazoxide as a trial after diagnosis of CHI were chosen as research subjects. The clinical data of the patients were analyzed, and the treatment effects and safety of diazoxide on CHI were evaluated. In the 44 patients studied, the blood glucoses of 36 cases recovered to normal level after using diazoxide, indicating that the 36 patients respond to the treatment of diazoxide. Eight cases still showed severe hypoglycemia after using diazoxide for 10 days, which indicated that the eight patients were unresponsive to diazoxide treatment. Eighteen patients suffered the side effect of fluid retention, and 12 patients suffered transient gastrointestinal reactions. Diazoxide is a first-line treatment of CHI with high safety. Most of the patients with CHI were responsive to diazoxide treatment. Diazoxide should be used as a trial immediately after CHI diagnosis was made.


Synaptonemal complex karyotyping in spermatocytes of the Chinese hamster (Cricetulus griseus). II. Morphology of the XY pair in spread preparations.
The X and Y chromosome axes have a distinctive morphology at pachytene and are clearly distinguishable from autosomal SCs. The X and Y are totally unpaired at late zygotene when most of the autosomes are synapsed; however, their attachment points at the presumptive SC end are closely apposed. The X and Y axes pair to form a length of SC that is somewhat shorter than the unpaired portion of the Y. Unpaired axes may appear thin and sometimes double, or may thicken to form fusiform bulges that are sometimes hollow: two on the X and one on the Y. Discrete differentiations, tentatively identified as kinetochores, are often visible at the proximal end of the SC on the Y axis, and also between the fusiform differentiations on the X axis. Additional differentiations, in the form of loops and densely staining granular excrescences form on the X axis and sometimes on the Y. A further differentiation appears as a cloud-like sheath around the distal end of the X axis, often in association with a bi-lobed dense body. At late pachytene, the XY-SC remains intact, but the unpaired X and Y axes develop side branches. Just before diplotene, while the autosomal SCs are still intact, the XY-SC is lost, although the axes persist and remain together at the attachment point of the SC. The X and Y differentiations form a logical temporal sequence when grouped according to progressive structural complexity. The morphological types may serve as markers for the sub-stages of pachytene.


Comparative proteomic analysis of soluble and surface-enriched proteins from Acanthamoeba castellanii trophozoites.
Acanthamoeba castellanii is a free-living organism widely distributed in the environment that may cause disease. This protozoan exists in two forms, an infective trophozoite and a dormant cyst. The trophozoites are able to cause keratitis and granulomatous amoebic encephalitis in humans. Keratitis is an acute, sight threatening infection of cornea with potential to cause permanent blindness without prompt treatment. However, the lack of suspicion and the low awareness about these amoebae besides of the absence of commercially available immunodiagnostic tests may delay an accurate diagnosis. The identification of proteins with potential for use in immunodiagnosis may improve the parasite detection more quickly and specifically. The amoeba adhesion to the host cell is the primary step for infection but there is no full understanding of A. castellanii proteins relevant for host invasion or infection. In this study, an assessment of soluble and surface-enriched protein fractions expressed by A. castellanii trophozoites, based on complementary LC-MS/MS approach using peptides from SDS-PAGE excised bands, was performed. Our proteomic analysis allowed identification of a total of 503 proteins, of which 308 proteins were exclusively identified in the soluble fraction, 119 in surface-enriched fraction and 76 in both. In silico analysis of functional classification revealed several proteins involved in many biological mechanisms in A. castellanii, including pathogen survival and infection of mammalian hosts. The analysis of predicted antigenic peptides allowed the identification of proteins with potential for immunodiagnostic assays.


Weight gain after lung transplantation.
Weight gain is frequently observed after lung transplantation, but the magnitude, predictors and implications of weight gain after lung transplant are unknown. This retrospective cohort study included 826 lung transplant recipients randomly selected from 12 international transplant centers. We included adult patients with available weight data at baseline and 1 year post-transplant. We examined demographic and clinical predictors of first year weight gain using a multiple linear regression model (n = 579) with percent weight change as the dependent variable. To study the association between first year weight gain and subsequent survival, we performed a Cox proportional hazards analysis. p < 0.05 was considered statistically significant. The median weight change was 10% (range -32% to 84%). On multi-variate analysis, increasing age and prolonged mechanical ventilation were inversely associated with weight gain; obstructive disease, interstitial disease and increasing ischemic time were positively associated with weight gain. Increasing baseline weight was negatively associated with weight gain in patients with obstructive and interstitial disease. The model accounted for 14% of the variance in weight gain. Patients with weight gain above the median had better subsequent survival (adjusted hazard ratio 0.61, 95% confidence interval 0.41 to 0.90). Infection was a more common cause of death in these patients, whereas malignant deaths were more frequent in patients with below-median weight gain. Substantial weight gain occurs in the first year after lung transplantation. The predictors of weight gain may be used to target high-risk patients for early intervention. Higher weight gain is associated with better subsequent survival.


Eosinophilic appendicitis. Demonstration of Strongyloides stercoralis as a causative agent.
A 50-year-old man had severe ileus from strongyloidiasis. Pathologic examination of the appendix revealed the presence of an intact Strongyloides larva surrounded by an eosinophilic granuloma. This finding provides very strong evidence for Strongyloides as the causative agent of appendiceal eosinophilic granulomas previously only inferred to be due to Strongyloides in patients with evidence of strongyloidiasis.


Prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infection among Spanish drug users measured by HTLV-1 assay and HTLV-1 and -2 assay. HTLV-1 and HTLV-2 Spanish Study Group.
The prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infection in 1992 and 1993 was determined by testing 2,152 specimens from injection drug users living in 11 geographic areas in Spain. Results obtained by an authentic HTLV-1 and -2 test were compared with those obtained by an HTLV-1 assay. HTLV infection was identified in 7 of 11 regions, with an overall prevalence of 2.5% (range, 0.4 to 11.5%). Fourty-four (81%) of 54 subjects were infected with HTLV-2; the viral strains in the remaining 10 subjects could not be serologically typed. Underestimation of HTLV infection because of the low sensitivities of HTLV-1 enzyme immunoassays for HTLV-2 antibody was relatively low (< 20%). Therefore, previous epidemiologic findings generated with HTLV-1 enzyme immunoassays appear to be reasonably accurate. Our results suggest that the rate of HTLV infection may have been increasing recently among Spanish drug users.


Trends in Comprehensive Abortion Care (CAC) and characteristics of women receiving abortion care in a tertiary hospital in Nepal.
One of the leading cause of maternal mortality and morbidity is unsafe abortion. Globally 55.7million of abortions occurred each year between 2010 and 2014. In lower resource countries 24.3 million abortions were unsafe which is significantly higher. Nepal is one of the lower resource countries among others. Comprehensive abortion care (CAC) service can reduce this burden among women. A retrospective review of CAC service register at Tribhuvan University Teaching Hospital (TUTH) was conducted to collect data from 2006 to2015 with approval from the Nursing Department to identify the trends of CAC service delivery, client characteristics, category of service providers, and reason for seeking CAC services, its effectiveness and complications. The data was entered in SPSS software and descriptive analysis was performed. A total of 2367 women received CAC in ten years period showing similar trend as 272-275 cases per year. Women's mean age was 28.4 years, 34% attained secondary level education and 98.9% were married. 70% were house wives and 84% multi gravid. The gestational period varied from 5 to 12 weeks. 85.6% had Manual Vacuum Aspiration (MVA) and 14.4% had Medical Abortion (MA). Only 37.6% women used any method of post abortion contraception. Unwanted pregnancy was the commonest reason for CAC. A majority of service providers were doctors (62.4%). The nurses were equally competent to provide CAC service as doctors. The number of women receiving CAC was relatively constant over the ten-year period. Nurses should be promoted for providing CAC services to cover a larger population in need.


Pseudomonas aeruginosa biofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia.
Pseudomonas aeruginosa (PA) forms biofilms in lungs of cystic fibrosis (CF) patients, a process regulated by quorum-sensing molecules including N-(3-oxododecanoyl)-l-homoserine lactone (C12). C12 (10-100 µM) rapidly triggered events commonly associated with the intrinsic apoptotic pathway in JME (CF ΔF508CFTR, nasal surface) epithelial cells: depolarization of mitochondrial (mito) membrane potential (Δψ(mito)) and release of cytochrome C (cytoC) from mitos into cytosol and activation of caspases 3/7, 8 and 9. C12 also had novel effects on the endoplasmic reticulum (release of both Ca(2+) and ER-targeted GFP and oxidized contents into the cytosol). Effects began within 5 min and were complete in 1-2 h. C12 caused similar activation of caspases and release of cytoC from mitos in Calu-3 (wtCFTR, bronchial gland) cells, showing that C12-triggered responses occurred similarly in different airway epithelial types. C12 had nearly identical effects on three key aspects of the apoptosis response (caspase 3/7, depolarization of Δψ(mito) and reduction of redox potential in the ER) in JME and CFTR-corrected JME cells (adenoviral expression), showing that CFTR was likely not an important regulator of C12-triggered apoptosis in airway epithelia. Exposure of airway cultures to biofilms from PAO1wt caused depolarization of Δψ(mito) and increases in Ca(cyto) like 10-50 µM C12. In contrast, biofilms from PAO1ΔlasI (C12 deficient) had no effect, suggesting that C12 from P. aeruginosa biofilms may contribute to accumulation of apoptotic cells that cannot be cleared from CF lungs. A model to explain the effects of C12 is proposed.


Mucinous cyst exhibiting severe dysplasia in gastric heterotopic pancreas associated with gastrointestinal stromal tumour.
Heterotopic pancreatic tissue within the stomach is rare and dysplasia within heterotopic pancreatic tissue is very rare. We present the first report of a patient with concurrent occurrence of heterotopic pancreas in the stomach with a gastrointestinal stromal tumour.


Dimensional distribution of human erythrocytes obtained from electropermeabilization experiments.
Electropermeabilization of erythrocyte membrane was performed using square electric field pulses of 50 microseconds and 1 ms pulse length. The electrohemolysis efficiency has a sigmoid dependence on the electric field strength given mainly by the statistical distribution of erythrocytes radius. The normalized dimensional distribution function for a human erythrocyte population was determined from electropermeabilization data.


Cavin Family: New Players in the Biology of Caveolae.
Caveolae are specialized small plasma-membrane invaginations that play crucial cellular functions. Two essential protein families are required for caveola formation: membrane caveolin proteins and cytoplasmic cavin proteins. Each family includes members with specific tissue distribution, and their expression is altered under physiological and pathological conditions, implying highly specialized functions. Cavins not only stabilize caveolae, but modulate their morphology and functions as well. Before association with the plasma membrane, cavins form homo- and hetero-oligomers with strikingly strict stoichiometry in the cytosol. At the plasma membrane, they provide an outer peripheral cytosolic layer, necessary for caveola stability. Interestingly, upon stimulation, cavins can be released from caveolae into the cytoplasm in distinct subcomplexes, providing a rapid dynamic link between caveolae and cellular organelles including the nucleus. In this review, we detail the biology of cavins, their structural and functional roles, and their implication in pathophysiology.


Correction to: Les misérables: A Parallel Between Antimicrobial Resistance and COVID‑19 in Underdeveloped and Developing Countries.
[This corrects the article DOI: 10.1007/s11908-022-00788-z.].


The antidepressant-like effect of Hypericum caprifoliatum Cham & Schlecht (Guttiferae) on forced swimming test results from an inhibition of neuronal monoamine uptake.
A crude (ECH) and a purified cyclohexane extract (HCP) of Hypericum caprifoliatum and their main phloroglucinol derivative (HC1) were evaluated regarding their action on monoaminergic systems, more precisely on dopamine. In rats and mice forced swimming test, ECH and HCP dose-dependently reduced the immobility time. The effect of the highest dose was prevented by a prior administration of either sulpiride or SCH 23390 (D(2) and D(1) dopamine receptor antagonist, respectively). HCP (360 mg/kg) decreased the locomotor activity of mice. ECH (90 mg/kg) caused hypothermia and potentiated apomorphine-induced (16 mg/kg) hypothermia in mice. HCP and HC1 inhibited, in a concentration-dependent and monophasic manner, the [(3)H]-DA, [(3)H]-NA and [(3)H]-5HT synaptosomal uptakes, but did not prevent the binding of specific ligands to the monoamine transporters. Moreover, when tested at the concentrations corresponding to its IC(50) on [(3)H]-DA uptake, HC1 did not induce a significant [(3)H]-DA release, while at a higher concentration (200 ng/ml) it enhanced significantly (by 12%) the synaptosomal DA release. These data suggest that the antidepressant-like effect of H. caprifoliatum on the forced swimming test is due to an increase in monoaminergic transmission, resulting from monoamine uptake inhibition, more potently of dopamine, which may be related to their phloroglucinol contents.


Prostatodynia: clinical and urodynamic characteristics.
Twenty patients with prostatodynia were studied urodynamically with synchronous video-pressure-flow studies and electromyography of the external urethral sphincter. The most striking finding was a significant increase in maximum urethral closure pressure compared to an age and sex-matched control group. Typically, peak and average urinary flow rates were decreased. Another prominent feature was incomplete funneling of the bladder neck during voiding with an accompanying urethral narrowing at the level of the external urethral sphincter. These findings are not consistent with a diagnosis of tension myalgia of the pelvic floor or detrusor-striated sphincter dyssynergia but suggest a primary abnormality involving the pelvic sympathetic nervous system. We believe that more advanced methods than those available currently are needed to elucidate fully the role of the autonomic nervous system, especially its sympathetic component, in the etiology of prostatodynia.


Surrogate for oropharyngeal cancer HPV status in cancer database studies.
The utility of cancer databases for oropharyngeal cancer studies is limited by lack of information on human papillomavirus (HPV) status. The purpose of this study was to develop a surrogate that can be used to adjust for the effect of HPV status on survival. The study cohort included 6419 patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2012, identified in the National Cancer Database (NCDB). The HPV surrogate score was developed using a logistic regression model predicting HPV-positive status. The HPV surrogate score was predictive of HPV status (area under the curve [AUC] 0.73; accuracy of 70.4%). Similar to HPV-positive tumors, HPV surrogate positive tumors were associated with improved overall survival (OS; hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.59-0.91; P = .005), after adjusting for important covariates. The HPV surrogate score is useful for adjusting for the effect of HPV status on survival in studies utilizing cancer databases.


Occult hepatitis B virus infection in pregnant woman and its clinical implication.
The objective of this study was to document the prevalence rate of occult hepatitis B virus (HBV) in healthy pregnant woman and the possibility of transmission to the foetus. This study was performed prospectively with 202 healthy pregnant women. HBV-DNA testing was performed using two specific quantitative tests with two independent sets of sera and cord blood. DNA sequencing analysis was carried out to confirm the specificity of polymerase chain reaction (PCR) product of HBV-DNA testing. Eight of 202 (4%) individuals with the TaqMan PCR assay and 23 of 202 (11.4%) with the COBAS Amplicor HBV Monitor test were HBV-DNA positive. Six (3%) individuals were positive with both methods. Sequencing and genotyping analysis of HBV polymerase gene with sera of the 75th subject resulted in genotype C. HBV-DNA testing with four cord blood samples showed that all were HBV-DNA negative. Occult HBV infection shows a difference in prevalence rate depending on the test method but the existence has been confirmed by sequencing analysis. Our results also suggest that vertical transmission through the cord blood is not so high as to be clinical problems and warrants further investigation.


Beta-lactam antibiotic biosynthetic genes have been conserved in clusters in prokaryotes and eukaryotes.
A cosmid clone containing closely linked beta-lactam antibiotic biosynthetic genes was isolated from a gene library of Flavobacterium sp. SC 12,154. The location within the cluster of the DNA thought to contain the gene for delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), the first step in the beta-lactam antibiotic biosynthetic pathway, was identified by a novel method. This DNA facilitated the isolation, by cross-hybridization, of the corresponding DNA from Streptomyces clavuligerus ATCC 27064, Penicillium chrysogenum Oli13 and Aspergillus nidulans R153. Evidence was obtained which confirmed that the cross-hybridizing sequences contained the ACVS gene. In each case the ACVS gene was found to be closely linked to other beta-lactam biosynthetic genes and constituted part of a gene cluster.


Applying the Sliding Scale Approach to Quantifying Functional Outcomes Up to Two Years After Severe Traumatic Brain Injury.
Outcomes after severe traumatic brain injury (TBI) can be represented by a sliding score that compares actual functional recovery to that predicted by illness severity models. This approach has been applied in clinical trials because of its statistical efficiency and interpretability but has not been used to describe change in functional recovery over time. The objective of this study was to use a sliding scoring system to describe the magnitude of change in Glasgow Outcome Scale Extended (GOSE) score at 6, 12, and 24 months after severe TBI and to compare patients who improved after 6 months to those who did not. This study included consecutive severe TBI patients (Glasgow Coma Scale ≤8; n = 482) from a single center. We grouped patients into four strata based on probability of unfavorable outcome (GOSE = 1-4) using the International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) model, selected a dichotomous GOSE threshold within each stratum, and compared each patient's GOSE to this threshold to calculate a score (GOSE-Sliding Scale [SS]) from -5 to +4 at 6, 12, and 24 months. We compared GOSE-SS at 6 months with GOSE-SS at 12 and 24 months and also compared characteristics of participants who improved after 6 months with characteristics of those who did not using χ2 and t tests. Compared with at 6 months, 40% of patients (n = 74) had improved GOSE-SS at 12 months, and 53% had improved GOSE-SS by 24 months (n = 72). Among those who improved at 12 months, the average magnitude of improvement was 1.7 ± 0.9 and among those who improved at 24 months, the average magnitude of improvement was 1.9 ± 1.0. Those who improved their GOSE-SS score from 6 to 24 months had longer hospital stays (mean-difference = 8.6 days; p = 0.03), longer intensive care unit (ICU) stays (mean-difference = 5.5 days; p = 0.02), and longer ventilator time (mean-difference = 5 days; p = 0.02) than those who worsened. These results support an optimistic long-term outlook for severe TBI patients and emphasize the importance of long-term follow-up in severe TBI survivors.


Protamine-based nanoparticles as new antigen delivery systems.
The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems.


Synthesis of phosphonate and ether analogs of rac-phosphatidyl-L-serine.
The chemical synthesis of four phosphonate-containing phosphatidylserine analogs namely, L-serine (+/-)-[2,3-bis(hexadecyloxy) and 2,3-bis(Palmitoyloxy)-propyl] phosphonates, and L-serine (+/-)-[3,4-bis(hexadecyloxy and 3,4-bis(palmitoyloxy)-butyL]phosphonates is descirbed. (+/-)-2,3-Bis(hexadecyloxy) and 2,3-bis(palmitoyloxy)-prophylphosphonic acids and (+/-)-3,4-bis(hexadecyloxy)butylphosponic acid were prepared by reaction of tris(trimethylsily) phosphite on the corresponding haloalkane. Condensation of the above phosphonic acids or (+/-)-3,4-bis(palmitoyloxy)butylphosphonic acid with N-carboxy-L-serine dibenzyl ester in the presence of trichloroacetonitrile or triisopropylbenzenesulfonyl chloride yielded the protected serine intermediates, which on hydrogenolysis gave the desired L-serine analogs. By a similar route, 1,2-dihexadecyl-rac-glycero-3-phosphoric acid was converted to 1,2-dihexadecyl-rac-glycerophospho-L-serine (L-serine (+/-)-2,3-bis(hexadecyloxy)propyl hydrogen phosphate(ester).


T cell directives for transcriptional regulation in asthma.
Allergic asthma frequently starts in childhood, and environmental factors such as viruses, allergens and occupational exposure can regulate the evolution of the disease. The development of allergen-specific Th2 lymphocytes represents the triggering event for the recruitment and activation of IgE-producing B cells and fibroblasts, followed by the release of soluble factors, thus giving rise to the inflammatory reaction observed in this disease. GATA-3 was identified as a cell lineage-specific factor selectively expressed and activated in the Th2 lineage as a consequence of STAT-6 activation. However, recent literature indicates that blockade of CTLA-4-directed inhibitory signals is sufficient to induce STAT 6-independent Th2 differentiation. A new Th1-restricted transcription factor has been recently identified that transactivates the IFN-gamma gene promoter: T-bet (T-box expressed in T cells). T-bet expression during T cell activation is strongly dependent on IFN-gamma and STAT-1. Mice lacking T-bet have profound defects in the development of the Th1 subset and the production of IFN-gamma, but overproduce Th2 cytokines and, in the absence of immunological challenge, they exhibited airway hyperreactivity to methacholine associated with a peribronchial and perivascular infiltration with eosinophils and lymphocytes. Finally, a small subset of CD4 T cells called T-regulatory (T-reg) cells has been identified. These cells exhibit potent immunosuppressive properties. Although recent reports suggest that the induction of T-reg cells is under the control of the transcription factor Foxp3, the specific signals that preferentially induce development of T-reg cells instead of Th2 cells are still unclear.


Effects of serial administration of kainic acid on the developing brain.
The purpose of this study was to determine whether the repeated administration of kainic acid at 24-hr intervals results in pharmacological kindling. Rather than developing an increased intensity of seizures, this method of serial administration of kainic acid resulted in the development of tolerance to its effects.


Affinity chromatography of sialoglycoproteins, utilising the interaction of serotonin with n-acetylneuraminic acid and its derivatives.
Serotonin, immobilised on Sepharose 4B, has been used to study the affinity chromatography of neuraminic acid and its derivatives. Free N-acetylneuraminic acid and oligosaccharides, polysaccharides, and glycoproteins containing that sugar are specifically bound to the columns. Removal of neuraminic acid from sialoglycoconjugates, or modification of the neuraminic acid residues by periodate oxidation, abolishes their ability to bind to the ligand. The presence of the N-acetyl group, but not the N-glycolyl group, and the integrity of the side chain (C-7-C-9) of the neuraminic acid are essential for binding to serotonin.


A four-directional non-fullerene acceptor based on tetraphenylethylene and diketopyrrolopyrrole functionalities for efficient photovoltaic devices with a high open-circuit voltage of 1.18 V.
Through the conjunction of tetraphenylethylene and diketopyrrolopyrrole functionalities, a novel four-directional non-fullerene electron acceptor (denoted as 4D) was designed, synthesized and characterized. The new chromophore is highly soluble (for instance >30 mg mL(-1) in o-dichlorobenzene), thermally stable, and exhibits energy levels matching those of the conventional and routinely used donor polymer poly(3-hexyl thiophene). A power conversion efficiency of 3.86% was obtained in solution-processable bulk-heterojunction devices with a very high open circuit voltage of 1.18 V.


Prognostic factors affecting disease-free survival in patients with Hodgkin's disease stages IA and IIA treated initially with radiotherapy alone in a single centre during 1973 to 1992.
One hundred forty-nine patients with either stage IA (90 patients) or stage IIA (59 patients) Hodgkin's disease (HD) received radiotherapy alone as their first line treatment. Only stage of the nine factors selected for Cox multivariate analysis was of prognostic significance. Patients with grade 1 nodular sclerosing HD did not have a significantly better disease-free survival than those with grade 2 disease.


Two distinct cinnamoyl-CoA reductases in Selaginella moellendorffii offer insight into the divergence of CCRs in plants.
Two distinct cinnamoyl-coenzyme A reductases (CCRs) from Selaginella moellendorffii were evaluated, and of these, SmCCR2-1, which has both distinct sequence motifs and catalytic properties, was clustered into a new CCR subgroup. Cinnamoyl-coenzyme A reductases (CCRs) have been reported in many land plants to have critical functions in monolignol biosynthesis. In this study, we performed a genome-wide screen and obtained two distinct SmCCRs from S. moellendorffii. Phylogenetic analysis indicated that SmCCR2 (both SmCCR2-1 and 2-2) and SmCCR3 together with PpaCCR belong to a distinct subgroup of genuine CCRs with variations in the NAD(P)H-binding motif. Enzymatic assays showed detectable activity by both SmCCR1 and SmCCR2-1 toward four hydroxycinnamoyl-CoA esters. SmCCR1, which clustered with reported CCRs from angiosperms and gymnosperms, exhibited specificity toward feruloyl-CoA, while SmCCR2-1 showed a preference for sinapoyl-CoA. Interestingly, the reaction temperature profiles for SmCCR1 and SmCCR2-1 are complementary. Homology models and molecular simulations suggest that the variations in NADPH-binding motifs, especially R(X)6K instead of R(X)5K, affect the NADP+ conformation. Notably, the signature motif NWYCY was replaced with NGYCL in SmCCR1 and with EWYCL in SmCCR2-1, while the signature residues H202 and R253, reported in a previous study, were conserved in SmCCR1 and SmCCR2-1 but varied in SmCCR-like genes. It is likely that NWYCY is not a reliable signature for CCRs in plants. The detectable activity of site-direct mutant S123T of SmCCR1 suggested that S123 which consists of catalytic triad is changeable. Possible evolution process for the emergence of two subgroups of genuine CCRs was also revealed. Altogether, these findings revise our understanding of CCRs with regard to divergence and active sites.


When believing is seeing: the effect of scripts on eyewitness memory.
Two studies examined the conditions under which event schema or scripts produce gap-filling errors in eyewitness accounts of a robbery. In Study 1, scripts for the robbery of a convenience store were identified. Results revealed high agreement among the 120 participants concerning the sequence of actions for such a robbery. Based on the information obtained in Study 1, participants in Study 2 (N = 144) viewed one of two sequences of slides depicting a robbery of a convenience store by a lone robber. In one sequence, three central script actions were omitted and in the other, three peripheral script actions were omitted. In addition, rate of exposure was varied (2 vs. 8 sec) as was the length of the retention interval (5 min vs. 1 week). As predicted, there was a higher rate of false recognition for central as opposed to peripheral actions, and this tendency was exaggerated for the longer retention interval. The theoretical and practical implications of the findings are discussed.


Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): is a clinical benefit still achievable?
There are few clinical data on the sequential use of aromatase inhibitors (AI). This paper focuses on the relevance of clinical benefit CB (CR + PR + SD > or = 6 months) in postmenopausal metastatic breast cancer (MBC) patients treated with the steroidal aromatase inhibitor (SAI) formestane (FOR). who had already received non-steroidal aromatase inhibitor (nSAI): letrozole (LTZ) or anastrozole (ANZ). Twenty postmenopausal women with MBC were analysed in this retrospective two-centre study with the sequence nSAI-FOR. When receiving ANZ, 1 of 11 achieved a complete response and 9 of 11 a stable disease > or = 6 months, and receiving LTZ 1 of 9 achieved a partial response and 4 of 9 a stable disease > or = 6 months. The analysis of the entire population treated with FOR showed an overall CB of 55% (11 of 20) with a median duration of 15 months and median time to progression (TTP) of 6 months. Formestane 250 mg once bi-weekly seems to be an attractive alternative third-line hormonal therapy for the treatment of patients with MBC, previously treated with nSAI.


Pyrene-labeled gangliosides: micelle formation in aqueous solution, lateral diffusion, and thermotropic behavior in phosphatidylcholine bilayers.
By use of the excimer technique, the formation in aqueous solution of pyrene-labeled ganglioside micelles and their lateral diffusion and distribution in phosphatidylcholine membranes were investigated. For these studies 12-(1-pyrenyl)dodecanoic acid was covalently attached to the ceramide part of lysogangliosides GM1, GM2, GM3, GD1a, and GD1b. The 12-(1-pyrenyl)dodecanoic acid substitute of phosphatidylcholine was used for comparison. All pyrene-labeled gangliosides were present in aqueous solution in a predominantly micellar form down to 2 X 10(-8) M, which is the technical limit of this method. The tendency to aggregate is highest for PyGD1a and PyGD1b. In fluid dipalmitoylphosphatidylcholine bilayers the excimer-to-monomer fluorescence intensity ratio of pyrene-labeled gangliosides PyGM1, PyGM2, PyGM3, PyGD1a, and PyGD1b increases linearly with ganglioside concentration. The calculated diffusion coefficients for gangliosides are comparable to 1.6 X 10(-7) cm2/s, which is the diffusion coefficient of pyrene-labeled phosphatidylcholine [Galla, H.-J., & Hartmann, W. (1980) Chem. Phys. Lipids 27, 199-219]. In comparison to phosphatidylcholine, the diffusion of monosialogangliosides is slightly increased, with that diffusion of disialogangliosides being slightly decreased. Ca2+ ions up to 200 mM do not affect ganglioside diffusion significantly. The shape of the lipid phase transition curves obtained by the excimer technique yields information on the lateral distribution of the tested probe molecules. Pyrene-labeled phosphatidylcholine was taken as reference for a system with complete miscibility but nonideal mixing. 1-Acyl-2-[10-(1-pyrenyl)decanoyl]-sn-glycero-3-phosphocholine (PyPC) is known to be randomly distributed in the gel and in the fluid-crystalline lipid phase of dipalmitoylphosphatidylcholine bilayer membranes. It distributes preferentially into the fluid phase in the phase-transition region. In comparison, PyPC in dimyristoylphosphatidylcholine membranes is an example of a system with nearly ideal mixing [Hresko, R. C., Sugar, J. P., Barenholz, Y., & Thompson, T. E. (1986) Biochemistry 25, 3813-3828]. Phase-transition curves of pyrene-labeled gangliosides exemplify a nearly ideal mixing system with PyGD1a or PyGD1b producing best effects. The monosialogangliosides, however, exhibit less ideality of mixing, the deviation from an ideal mixing behavior increasing with decreasing number of both neutral sugar residues and sialic acid groups. Addition of Ca2+ triggers a tightening of the phosphatidylcholine bilayer and thus induces a change in the lateral distribution of the gangliosides at the phase transition.(ABSTRACT TRUNCATED AT 400 WORDS)


Clinical characteristics of odontogenic sinusitis with periapical lesions.
Although the symptoms and radiographic signs may mimic rhinogenic sinusitis, odontogenic sinusitis (OS) with periapical lesions (PALs) is fundamentally an endodontic infection. It is considered to be one of the main causes of OS, especially when presented unilaterally. Despite this routine dental examination is not performed and periapical infection frequently remains undiagnosed by otolaryngologists and radiologists. This prospective observational study covered a group of 61 patients with symptomatic OS with PAL. Assessment of quality of life was done using the 22-item Sino-Nasal Outcome Test-22 (SNOT-22) and Oral Health-Impact Profile-14 (OHIP-14). Temporal and etiological relationship between the dental cause and sinonasal complication was established among the otolaryngologist and dental specialist based on the clinical symptoms, nasal endoscopy described according to the modified Lund-MacKay scale, computed tomography (CT) scans measured and scored in compliance with Lund- Kennedy, Zinreich and Estrela scales. Out of 61 patients, 28 (46%) were women and 33 (54%) men. Group median age 49.1 years, ranged from 22.8 to 78.9 years. Total OHIP-14 score was 12.7 ± 11.3, with the highest value obtained in domains describing physical pain (mean 2.9 ± 2.4, median 3) in which the highest score was obtained in item 3 - painful aching in mouth and/or teeth - scored ≥2 by 52.5% of participants. Concerning dental symptoms 11.5% of patients were asymptomatic. Total SNOT-22 score was 40.7 ± 21.1, with the highest value in domains describing nasal symptoms. 23% of patients reported mild, 44.3% moderate and 32.7% severe symptoms. In the endoscopic evaluation 86.8% of cases presented discharge, 73.8% mucosal edema. In 11.5% of cases the polypoid tissues was observed in nasal cavities. The first molar tooth was the most frequently affected with an incidence of 42.6%, followed by the second molar (27.9%). In 33 (48.5%) of cases the inflammatory process caused the discontinuity of the sinus floor, which in 51.5% coexisted with total maxillary sinus opacification. 10 teeth (14.7%) had the periapical lesions with a diameter exceeding 8 mm. In case of the multi-rooted teeth, PALs were usually encountered at more than one root (57.4%). Maxillary and ethmoid sinus were affected in 54% of cases and additional frontal sinus involvement in 32.8%. In 69.6% patients, ostiomeatal complex was obstructed. Persistent sinonasal symptoms such as rhinorrhea, post-nasal drip and nose congestion along with dental pain may suggest endodontic nature of OS, especially after previous root-canal treatment. The bigger the PAL is in diameter and the closer to the maxillary sinus, the greater effect on its mucosal involvement and obstruction of ostiomeatal complex is observed. PALs around molar or premolar tooth apexes with coexistence of unilateral sinus opacifications should be noticed and mentioned by radiologists and evaluated by dental specialists in order to refer the patient to further treatment.


Phosphatidylinositol 4, 5 bisphosphate and the actin cytoskeleton.
Dynamic changes in PM PIP(2) have been implicated in the regulation of many processes that are dependent on actin polymerization and remodeling. PIP(2) is synthesized primarily by the type I phosphatidylinositol 4 phosphate 5 kinases (PIP5Ks), and there are three major isoforms, called a, b and g. There is emerging evidence that these PIP5Ks have unique as well as overlapping functions. This review will focus on the isoform-specific roles of individual PIP5K as they relate to the regulation of the actin cytoskeleton. We will review recent advances that establish PIP(2) as a critical regulator of actin polymerization and cytoskeleton/membrane linkages, and show how binding of cytoskeletal proteins to membrane PIP(2) might alter lateral or transverse movement of lipids to affect raft formation or lipid asymmetry. The mechanisms for specifying localized increase in PIP(2) to regulate dynamic actin remodeling will also be discussed.


Characterization and regulation of HMG-CoA reductase during a cycle of juvenile hormone synthesis.
The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase was characterized in cockroach corpora allata which produce insect juvenile hormone III (methyl-(10R)10,11-epoxy-3,7,11-tri-methyl-2E,6E-dodecadienoate ). HMG-CoA reductase is a microsomal enzyme dependent on NADPH and dithiothreitol (or glutathione) for activity. The enzyme selectively reduced (3S)-HMG-CoA to (3R)-mevalonate with an apparent KM of 7.6 microM. Mevinolin was a competitive inhibitor of HMG-CoA reductase with a KI of 2.4 nM. No evidence for a modulation of enzyme activity by phosphorylation was obtained. Levels of HMG-CoA reductase were not altered after incubation of the corpora allata with either mevinolin (to decrease isoprenoid flux) or with mevalonate or farnesol (to increase isoprenoid flux). Split pairs of corpora allata were used to compare JH III synthetic activity with HMG-CoA reductase activity during the cycle of JH III synthesis that controls vitellogenesis and oocyte growth in adult females. Both activities changed over 10-fold and peaked on day 5 after emergence/mating, but JH III synthesis did not parallel HMG-CoA reductase activity precisely thereafter. The half-life of HMG-CoA reductase measured in the presence of cycloheximide was significantly different between low and high activity glands and was not related to the half-life of JH III synthesis. The results suggest that HMG-CoA reductase should not be considered 'the rate-limiting enzyme' in juvenile hormone synthesis by Diploptera punctata corpora allata.


Glutathione and lipid peroxidation in the aging rat.
1. Tissue extracts were prepared from liver, kidney, heart, brain, lung and spleen of male Sprague-Dawley rats of different ages (1-36 months); each of the extracts was analyzed for reduced glutathione (GSH) and lipid peroxides. 2. At all ages the GSH content in the liver was 3-10 times higher than that in other tissues. 3. In the old (36 months) rat the GSH content of all the tissues studied were lower (35-60%) than that in 2.5 month old rat. 4. The lipid peroxides levels increased by age in all tissues studied. 5. These findings indicate that general characteristics of aging tissue may include a decrease in GSH content and increase in lipid peroxides showing a decrease in reducing potential in senescence.


The influence of a brittle Cr interlayer on the deformation behavior of thin Cu films on flexible substrates: Experiment and model.
Thin metal films deposited on polymer substrates are used in flexible electronic devices such as flexible displays or printed memories. They are often fabricated as complicated multilayer structures. Understanding the mechanical behavior of the interface between the metal film and the substrate as well as the process of crack formation under global tension is important for producing reliable devices. In the present work, the deformation behavior of copper films (50-200 nm thick), bonded to polyimide directly or via a 10 nm chromium interlayer, is investigated by experimental analysis and computational simulations. The influence of the various copper film thicknesses and the usage of a brittle interlayer on the crack density as well as on the stress magnitude in the copper after saturation of the cracking process are studied with in situ tensile tests in a synchrotron and under an atomic force microscope. From the computational point of view, the evolution of the crack pattern is modeled as a stochastic process via finite element based cohesive zone simulations. Both, experiments and simulations show that the chromium interlayer dominates the deformation behavior. The interlayer forms cracks that induce a stress concentration in the overlying copper film. This behavior is more pronounced in the 50 nm than in the 200 nm copper films.


Analysis of 61 SNPs from the CAD specific genomic loci reveals unique set of SNPs as significant markers in the Southern Indian population of Hyderabad.
The present study is a part of the major project on coronary artery disease (CAD) carried out at Indian Statistical Institute, Hyderabad to investigate the pattern of association of SNPs selected from the CAD specific genomic loci. The study is expected to portray the genetic susceptibility profile of CAD specifically in the Southern Indian population of Hyderabad. The study was conducted in a cohort of 830 subjects comprising 350 CAD cases and 480 controls from Hyderabad. A prioritized set of 61 SNPs selected from the NHGRI GWAS catalogue were genotyped using FluidigmNanofluidic SNP Genotyping System and appropriate statistical analyses were used in interpreting the results. After data pruning, out of 45 SNPs qualified for the association analysis, four SNPs were found to be highly significantly associated with increased risk for CAD even after Bonferroni correction for multiple testing (p < 0.001). These results were also replicated in the random subsets of the pooled cohort (70, 50 and 30%) suggesting internal consistency. The ROC analysis of the risk scores of the significant SNPs suggested highly significant area under curve (AUC = 0.749; p < 0.0001) implying predictive utility of these risk variants. The rs10455872 of LP(A) gene in particular showed profound risk for CAD (OR 35.9; CI 16.7-77.2) in this regional Indian population. The other significant SNP associations observed with respect to the pooled CAD cohort and in different anatomical and phenotypic severity categories reflected on the role of genetic heterogeneity in the clinical heterogeneity of CAD. The SNP rs7582720 of WDR12 gene, albeit not individually associated with CAD, was found to be conferring significant risk through epistatic interaction with two SNPs (rs6589566, rs1263163 in ZPR1, APOA5-APOA4 genes) of the 11q23.3 region.


Toll-like receptor 4 activation in Barrett's esophagus results in a strong increase in COX-2 expression.
Barrett's esophagus (BE) is known to progress to esophageal adenocarcinoma in a setting of chronic inflammation. Toll-like receptor (TLR) 4 has been linked to inflammation-associated carcinogenesis. We aimed to determine the expression and functional activity of TLR4 in the esophagus and whether TLR4 activation in BE could promote carcinogenesis by inducing COX-2 expression. TLR4 expression in esophageal adenocarcinoma, BE, duodenum, reflux esophagitis and normal squamous esophagus biopsies was assessed using real-time PCR and validated by in situ hybridization and immunohistochemistry. Ex vivo cultures of BE, duodenum and normal squamous esophagus biopsies and a BE cell line (BAR-T) were stimulated with the TLR4 agonist lipopolysaccharide (LPS). To evaluate the effect of TLR4 activation, NF-κB activation, IL8 secretion and expression and COX-2 expression were determined. TLR4 expression was significantly increased in esophageal adenocarcinoma, BE, duodenum and reflux esophagitis compared to normal squamous esophagus. LPS stimulation resulted in NF-κB activation and a dose-dependent increase of IL8 secretion and mRNA expression. The induction of IL8 was more evident in BE compared to normal squamous esophagus. Upon LPS stimulation, COX-2 expression increased significantly in ex vivo cultured BE biopsies, which was observed in both epithelium and lamina propria cells. However, no effect was found in duodenum and normal squamous esophagus biopsies. TLR4 activation in BE results in a strong increase in COX-2 and may contribute to malignant transformation.


Genetic Analysis of LigA, LipL32, Loa22, and OmpL1 Antigens from Leptospira spp. Sejroe Serogroup: How Close We Are To a Vaccine Against Bovine Leptospirosis?
Bovine leptospirosis has as main causative agents Leptospira spp. from Sejroe serogroup. Vaccination is a crucial step to control this infection. The use of conserved proteins among Leptospira spp. is of great importance for a protective immune response. The aim of the present study is to genetically analyze antigens of Leptospira spp. from Sejroe serogroup strains isolated from cattle for a preliminary evaluation of vaccine candidates. Genes associated with antigenicity-LigA, LipL32, Loa22, and OmpL1-were analyzed through bioinformatic and immunoinformatic tools. Despite high diversity observed in strains, on an amino acid level, highly conserved regions were observed (> 90%), particularly in LipL32 gene. Moreover, highly conserved amino acid regions (> 30 aa) were observed in all genes, regardless of species, geographical origin or biological source of isolation. Superposed structures of protein fragments including all the predicted MHC-II and B-Cell epitopes were demonstrated. Results presented herein are preliminary, but a fundamental step towards the development of an efficient vaccine against bovine leptospirosis, a silent but enormously concerning disease.


French recommendations for the management of non-infectious chronic uveitis.
This French National Diagnostic and Care Protocol (NDPC) includes both pediatric and adult patients with non-infectious chronic uveitis (NICU) or non-infectious recurrent uveitis (NIRU). NICU is defined as uveitis that persists for at least 3 months or with frequent relapses occurring less than 3 months after cessation of treatment. NIRU is repeated episodes of uveitis separated by periods of inactivity of at least 3 months in the absence of treatment. Some of these NICU and NIRU are isolated. Others are associated with diseases that may affect various organs, such as uveitis associated with certain types of juvenile idiopathic arthritis, adult spondyloarthropathies or systemic diseases in children and adults such as Behçet's disease, granulomatoses or multiple sclerosis. The differential diagnoses of pseudo-uveitis, sometimes related to neoplasia, and uveitis of infectious origin are discussed, as well as the different forms of uveitis according to their main anatomical location (anterior, intermediate, posterior or panuveitis). We also describe the symptoms, known physiopathological mechanisms, useful complementary ophthalmological and extra-ophthalmological examinations, therapeutic management, monitoring and useful information on the risks associated with the disease or treatment. Finally, this protocol presents more general information on the care pathway, the professionals involved, patient associations, adaptations in the school or professional environment and other measures that may be implemented to manage the repercussions of these chronic diseases. Because local or systemic corticosteroids are usually necessary, these treatments and the risks associated with their prolonged use are the subject of particular attention and specific recommendations. The same information is provided for systemic immunomodulatory treatments, immunosuppressive drugs, sometimes including anti-TNFα antibodies or other biotherapies. Certain particularly important recommendations for patient management are highlighted in summary tables.


The effect of dexmedetomidine on neuroprotection in pediatric cardiac surgery patients: study protocol for a prospective randomized controlled trial.
Infants undergoing cardiac surgery under cardiopulmonary bypass are vulnerable to postoperative neurodevelopmental delays. Dexmedetomidine has been shown to have protective effects on the heart, kidneys, and brain in animals and adults undergoing cardiac surgery with cardiopulmonary bypass. We hypothesized that dexmedetomidine would have a neuroprotective effect on infants undergoing cardiopulmonary bypass and planned a prospective randomized controlled trial with postoperative neurodevelopment measurements. This is a single-center, prospective, double-blinded, randomized controlled trial with 1:1 allocation. A cohort of 160 infants undergoing cardiac surgery with cardiopulmonary bypass will be enrolled. After induction, dexmedetomidine will be infused with a loading dose of 1 μg/kg and a maintenance dose of 0.5 μg/kg/h or the same amount of normal saline will be administered. Upon initiation of cardiopulmonary bypass, an additional dose of dexmedetomidine (0.01 μg/cardiopulmonary priming volume) will be mixed with the cardiopulmonary bypass circuit. The primary outcome will be the proportion of infants who score lower than 85 in any of the cognitive, language, or motor Bayley scales of infant development-III tests 1 year after the surgery. Other feasible outcome measures will include differences in plasma glial fibrillary acidic protein, troponin I, interleukin-6, urinary neutrophil gelatinase-associated lipocalin, and perioperative major adverse events. The results of the Bayley scales of infant development-III test from the study group and the control group will be compared using a chi-squared test under intention-to-treat analysis. A generalized estimating equation will be used to analyze repeated measurements over time. This study will enable us to assess whether the use of dexmedetomidine can alter the early neurodevelopmental outcome in infants undergoing cardiac surgery with cardiopulmonary bypass and also estimate effects of dexmedetomidine on other organs. ClinicalTrials.gov NCT04484922. Registered on 24 July 2020.


Linear shear rheology of aging β-casein films adsorbing at the air/water interface.
In this work, the viscoelasticity of fragile β-casein films has been followed using different macro- and microrheological techniques. The modulus of the complex surface viscosity |η∗| varies with time, allowing for the monitoring of the protein adsorption and annealing. β-casein adsorption creates a soft glassy gel at the interface that experiences an aging process. Macrorheological experiments with multiple probe sizes in addition to microrheological experiments demonstrated the consistency of the surface rheological properties over a broad range of viscosities. Surface pressure measurements were performed to complement the characterization of the processes.


Ibrutinib and novel BTK inhibitors in clinical development.
Small molecule inhibitors targeting dysregulated pathways (RAS/RAF/MEK, PI3K/AKT/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer patients. Recently Bruton's tyrosine kinase (BTK), a crucial terminal kinase enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an attractive target for therapeutic intervention in human malignancies and autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in early clinical trials and has progressed into phase III trials. However, additional research is necessary to identify the optimal dosing schedule, as well as patients most likely to benefit from BTK inhibition. This review summarizes preclinical and clinical development of ibrutinib and other novel BTK inhibitors (GDC-0834, CGI-560, CGI-1746, HM-71224, CC-292, and ONO-4059, CNX-774, LFM-A13) in the treatment of B-cell malignancies and autoimmune disorders.


Direct effect of chronic hypoxia in suppressing large conductance Ca(2+)-activated K(+) channel activity in ovine uterine arteries via increasing oxidative stress.
Chronic hypoxia has a direct effect in down-regulating the BKCa channel β1 subunit and inhibiting the BKCa channel activity in uterine arteries of pregnant sheep. Oxidative stress plays a causal role in hypoxia-mediated suppression of BKCa channel function. The steroid hormone-induced effect on BKCa channels is a target of hypoxia-mediated oxidative stress. Inhibition of oxidative stress ameliorates the adverse effect of hypoxia both ex vivo and in vivo in pregnant sheep exposed to long-term high-altitude hypoxia. Our findings provide novel evidence of a causative role of oxidative stress in hypoxia-mediated inhibition of the BKCa channel activity in uterine arteries and new insights in understanding and alleviating pregnancy complications associated with gestational hypoxia such as pre-eclampsia and fetal growth restriction. Uterine arteries of pregnant sheep acclimatized to long-term high-altitude hypoxia were associated with a decrease in large-conductance Ca(2+)-activated K(+) (BKCa) channel activity. The present study tested the hypothesis that prolonged hypoxia has a direct effect in suppressing BKCa channel activity by increasing oxidative stress. Uterine arteries were isolated from non-pregnant and near-term (∼142 days) pregnant sheep, and were treated ex vivo with 21.0 or 10.5% O2 for 48 h. The hypoxia treatment significantly increased the production of reactive oxygen species in uterine arteries, which was blocked by N-acetylcysteine. In uterine arteries of pregnant sheep, hypoxia significantly inhibited BKCa channel current density, decreased NS1619-induced relaxations and increased pressure-dependent tone, which were annulled by N-acetylcysteine. In accordance, hypoxia resulted in down-regulation of BKCa channel β1 subunit, which was restored in the presence of N-acetylcysteine. In addition, the N-acetylcysteine treatment significantly increased BKCa channel β1 subunit abundance and BKCa channel current density in uterine arteries from pregnant sheep exposed to high-altitude hypoxia (3801 m, PaO2: 60 mmHg) for 110 days. In uterine arteries of non-pregnant animals, hypoxia inhibited steroid hormone-induced up-regulation of BKCa channel current density and NS1619-mediated relaxations, which were reversed by N-acetylcysteine. Furthermore, the synthetic superoxide dismutase and catalase mimetic EUK-134 also ablated the effects of hypoxia on BKCa channel currents in uterine arteries. The results demonstrate a direct effect of hypoxia in inhibiting the BKCa channel activity in uterine arteries via increased oxidative stress.


Clinical application and refinement of the microdissected thin groin flap transfer operation.
A microdissected thin groin flap is a uniform thin flap with a long vascular pedicle prepared by microdissection of the deep branch of the superficial circumflex femoral system (SCIS). However, the safe dimensions of the flap are not known, and anatomical variations of the SCIS sometimes impede elevation of the flap based on the deep branch. Therefore, modifications of the operation and accumulation of empirical knowledge are required for safe preparation of the flap. Thirty cases of various types of tissue defects were reconstructed using microdissected thin groin flaps. Among these, large flaps exceeding 20 cm on the long axis were investigated to estimate the maximum dimensions of the flap. Additionally, new operative procedures were developed to overcome anatomical variations of the SCIS and to assist preparation of a thin flap. One flap was lost due to a venous thrombosis. A small distal area of three large flaps became necrotic. The perforators from the deep branches were absent in five cases, and three of these flaps were successfully elevated based on the superficial branch using the new method. The clinically deduced safe dimensions of the flap ranged from 5 x 2 cm to 25 x 12 cm. The microdissected thin groin flap was found to be useful for coverage of various types and sizes of skin defects. Through improved operative procedures, a large and extremely thin flap can be prepared safely even if the perforator from the SCIS is absent.


65 zinc absorption in patients with insulin-dependent diabetes mellitus assessed by whole-body counting technique.
The gastrointestinal absorption of zinc was measured in patients with insulin-dependent diabetes mellitus. The concentration of zinc in serum was similar to healthy individuals. However the urinary excretion rate of zinc relative to the creatinine excretion, was approximately doubled (p less than 0.001) in the diabetics. The absorption of 65Zn tended to be lower in diabetics, but did not reach the level of statistical significance (retention percent 30.6 versus 42.6 (p greater than 0.10). A hypothesis of intracellular zinc depletion with time in insulin-dependent diabetics is proposed.


The effect of calcitonin treatment on plasma nitric oxide levels in post-menopausal osteoporotic patients.
Several recent studies have revealed a wide role for nitric oxide (NO) in bone metabolism. Low doses of NO cause bone resorption, but higher doses of NO inhibit bone resorbing activity. Cytokines are potent stimulators of NO production. NO is a very short-lived molecules. It exists for only 6-10 s only before it is converted by oxygen and water into the end-products nitrates and nitrites. Osteoporosis is a metabolic bone disease, characterized by a decreased amount of bone and increased susceptibility to fracture. NO may be involved as a mediator of bone disease such as post-menopausal osteoporosis. Calcitonin is a peptide hormone that inhibits bone resorption. The function of calcitonin in some cells is often unclear. In this study 30 post-menopausal osteoporotic women of ages ranging between 55 and 59 years without systemic diseases and free of any drug therapy were included. Twenty of them, randomly chosen, were treated with calcium (500 mg day(-1))+calcitonin (nasal spray 100 U day(-1)) and the other 10 women (control group) were treated with calcium only. This treatment was applied for 6 months and NO values were measured in each of the two groups before and after treatment. Our findings demonstrate that NO regulates osteoclastic bone resorption activity in association with calcitonin.


Facile Synthesis of cis-Dichloro-(1,4,7-Triazacyclononane) Platinum(II) and its Screening Against Human Ovarian Cancer (SK-OV-3) and Leukemia (K-562) Cell Lines.
A simple method for the preparation of cis-dichloro(1,4,7-triazacyclononane)platinum(II), cis-Pt(tacn)Cl(2) is presented, together with the results of screening the compound against the K-562 (leukemia) and SK-OV-3 (ovarian) human cancer cell lines. While the compound shows no activity against K-562 cells, there is evidence for some cytotoxicity against SK-OV-3. The compound is much less effective than cisplatin, and its limited solubility restricts the useable concentration range.


Molecular karyotyping and gene expression analysis in childhood cancer patients.
The genetic etiology of sporadic childhood cancer cases remains unclear. We recruited a cohort of 20 patients who survived a childhood malignancy and then developed a second primary cancer (2N), and 20 carefully matched patients who survived a childhood cancer without developing a second malignancy (1N). Twenty matched cancer-free (0N) and additional 1000 (0N) GHS participants served as controls. Aiming to identify new candidate loci for cancer predisposition, we compared the genome-wide DNA copy number variations (CNV) with the RNA-expression data obtained after in vitro irradiation of primary fibroblasts. In 2N patients, we detected a total of 142 genes affected by CNV. A total of 53 genes of these were not altered in controls. Six genes (POLR3F, SEC23B, ZNF133, C16orf45, RRN3, and NTAN1) that we found to be overexpressed after irradiation were also duplicated in the genome of the 2N patients. For the 1N collective, 185 genes were affected by CNV and 38 of these genes were not altered in controls. Five genes (ZCWPW2, SYNCRIP, DHX30, DHRS4L2, and THSD1) were located in duplicated genomic regions and exhibited altered RNA expression after irradiation. One gene (ABCC6) was partially duplicated in one 1N and one 2N patient. Analysis of methylation levels of THSD1 and GSTT2 genes which were detected in duplicated regions and are frequently aberrantly methylated in cancer showed no changes in patient's fibroblasts. In summary, we describe rare and radiation-sensitive genes affected by CNV in childhood sporadic cancer cases, which may have an impact on cancer development. KEY MESSAGES: • Rare CNV's may have an impact on cancer development in sporadic, non-familial, non-syndromic childhood cancer cases. • In our cohort, each patient displayed a unique pattern of cancer-related gene CNVs, and only few cases shared similar CNV. • Genes that are transcriptionally regulated after radiation can be located in CNVs in cancer patients and controls. • THSD1 and GSTT2 methylation is not altered by CNV.


When Autonomous Systems Meet Accuracy and Transferability through AI: A Survey.
With widespread applications of artificial intelligence (AI), the capabilities of the perception, understanding, decision-making, and control for autonomous systems have improved significantly in recent years. When autonomous systems consider the performance of accuracy and transferability, several AI methods, such as adversarial learning, reinforcement learning (RL), and meta-learning, show their powerful performance. Here, we review the learning-based approaches in autonomous systems from the perspectives of accuracy and transferability. Accuracy means that a well-trained model shows good results during the testing phase, in which the testing set shares a same task or a data distribution with the training set. Transferability means that when a well-trained model is transferred to other testing domains, the accuracy is still good. Firstly, we introduce some basic concepts of transfer learning and then present some preliminaries of adversarial learning, RL, and meta-learning. Secondly, we focus on reviewing the accuracy or transferability or both of these approaches to show the advantages of adversarial learning, such as generative adversarial networks, in typical computer vision tasks in autonomous systems, including image style transfer, image super-resolution, image deblurring/dehazing/rain removal, semantic segmentation, depth estimation, pedestrian detection, and person re-identification. We furthermore review the performance of RL and meta-learning from the aspects of accuracy or transferability or both of them in autonomous systems, involving pedestrian tracking, robot navigation, and robotic manipulation. Finally, we discuss several challenges and future topics for the use of adversarial learning, RL, and meta-learning in autonomous systems.


Incidence of epithelial dysplasia after partial gastric resection.
Because of the higher risk of cancer in the gastric stump, an increased incidence of pre-cancerous conditions should be exspected also in the resected stomach. Therefore, a combined endoscopic and bioptic study was performed in order to investigate the incidence of dysplasias in the gastric stump after resection for benign conditions. Among 101 patients with gastric resection, 2 cases were excluded from this study because of preceeding gastric cancer and one because of cancer of the gastric stump. In 43 of the remaining 98 patients, a Billroth-I-resection (gastroduodenostomy) had been carried out. In the remaining 55 patients with a Billroth-II-resection (gastroenterostomy) 9 had an additional enteroanastomosis of Braun whereas in the residual 46 patients this enteroanastomosis was lacking. This distinction was made because of a facultative or obligatory bile reflux. The average age of the B-I-group was 68 years, of the B-II-group with enteroanastomosis 69 years, and the B-II-group without enteroanastomosis 62 years. A non-operated group matched for age served as control group. Biopsy particles from the anastomotic region were gained by endoscopy and cut in step sections. The classification of dysplasias (degree I-III) followed the criteria given by Nagayo as modified by Grundmann. Inflammatory reactive changes were separated from these. A few changes could not be classified definitely and were listed as unclassified dysplasia. While dysplastic changes of low degree were quite numerous in every group, the dysplasias of higher degree were only found in a small number of cases. In the 46 cases with B-II-resection without Braun's enteroanastomosis, there were 5 dysplasia II and 3 dysplasia II. In the 9 cases with B-II-resection and with Braun's enteroanastomosis, there was 1 dysplasia I and no dysplasia III. In the 43 patient with B-I-resection only 2 dysplasia II and no dysplasia III were found. In the control group of 98 patients matched for age there were only 5 cases with dysplasia I and 1 case with dysplasia III. Patients with higher degrees of dysplasia showed a higher age and a longer interval after operation. There was also a correlation between higher degrees of dysplasia and severe atrophic changes in the mucosa. Correlating the degree of dysplasia with the reason for gastric resection, most of the dysplastic changes occurred in patients resected for gastric ulcer, whereas cases resected for duodenal ulcer showed only 2 dysplasias I. The discussion refers to the few data about dysplasia of the gastric stump available from the literature. Atrophic and increased regenerative changes obviously play a role in the pathogenesis of these dysplastic changes. As a causative factor the role of bile reflux is discussed. A further diagnostic and therapeutic regimen for the different forms of dysplasia is proposed.


Analysis of the Incidence of Macrosomia in Japan by Parental Nationalities at 5-year Intervals From 1995 to 2020.
We investigated trends in the incidence rate of macrosomia and its association with parental nationalities using Vital Statistics data in Japan. We used singleton birth data every 5 years from 1995 to 2020. The incidence rate of macrosomia was calculated according to specific attributes (maternal age, infant's sex, parental nationalities, parity, and household occupation) over time (years). In addition, a log-binomial model was used to investigate the relationship between the incidence of macrosomia and the attributes. This study compared Korea, China, the Philippines, Brazil, and other countries with Japan in terms of parental nationalities. "Other countries" indicates countries except for Japan, Korea, China, the Philippines, and Brazil. The study included 6 180 787 births. The rate of macrosomia in Japan decreased from 1.43% in 1995 to 0.88% in 2020, and the decrease was observed across all parental nationalities. The rates for Japanese parents were the lowest values among parental nationalities during the timespan investigated. Multivariate regression analysis showed that mothers from Korea, China, the Philippines, Brazil, and other countries had a significantly higher risk of macrosomia than those from Japan (risk ratio, 1.91, 2.82, 1.59, 1.74, and 1.64, respectively). Furthermore, fathers from China, the Philippines, Brazil, and other countries had a significantly higher risk of macrosomia than those from Japan (risk ratio, 1.66, 1.38, 1.88, and 3.02, respectively). The rate of macrosomia decreased from 1995 to 2020 in Japan for parents of all nationalities, and the risk of macrosomia incidence was associated with parental nationality.