Soil PM10 emission potential under specific mechanical stress and particles characteristics.
Soil can be resuspended in the atmosphere due to wind or mechanical disturbances, such as agricultural activities (sowing, tilling, etc.), producing fine particulate matter (PM). Agriculture is estimated to be the third PM10-emitting sector in Europe, emitting more than the transportation sector. However, very few emission figures are available for the different cropping operations. Moreover, soil Emission Potential (EP) is extremely variable, since is influenced by factors such as humidity, texture, chemical composition, and wind speed. Due to their similarity to tilling emission mechanisms, Soil Resuspension Chambers (SRC) are the most suitable method to estimate the impacts of these factors on soil susceptibility to emit PM10 during cropping operations (Emission Potential, EP). The main objective of this work is to assess the EP of different agricultural soils used for maize cropping in North-Western Italy, studying the influence of soil moisture and physico-chemical characteristics. Therefore, a SRC was developed, based on previous studies, with the goal of being relatively small, easy to operate and low-cost. Using the gathered data, a log-linear multiple regression model was developed to allow soil EP estimation from few physico-chemical parameters (moisture, sand/silt ratio and organic carbon content). The model allows to tailor field Emission Factors (EF) of specific cropping operations to different soil and moisture conditions and was applied to an EF for rotary harrowing, defined in a previous study. The concentration of Potentially Toxic Elements (PTE) in soil-emitted PM10 was determined, founding an enrichment up to 16 times higher than in the original soil, evidencing a possible cause of concern for operator's safety during agricultural activities.


Contralateral circling behavior induced by intranigral microinjections of taurine and GABA in rats.
Circling behavior induced by unilateral microinjections of taurine and gamma-aminobutyric acid (GABA) into the substantia nigra zona reticulata (SNR) was studied in rats. Both taurine (10-100 micrograms/rat) and GABA (30-300 micrograms/rat) induced the contralateral circling behavior in a dose-dependent manner when they were microinjected into the SNR. Neither compound induced ipsilateral circling. An ipsilateral injection of 6-hydroxydopamine (6-OHDA) into the nucleus caudatus putamen (CPU) caused a reduction of the dopamine (DA) content in the injected side and decreased the circling behavior induced by taurine but not GABA. Electrolesion of the ipsilateral nucleus ventromedialis thalami (VM) decreased both taurine- and GABA-induced circling. In contrast, only GABA-induced circling was reduced by the electrolesion of the ipsilateral nucleus parafascicularis thalami (PF). Electrolesion of the ipsilateral nucleus accumbens (ACB) did not modify the circling behavior induced by GABA, but did decrease the circling induced by taurine. Electrolesion of the ipsilateral globus pallidus (GP) or nucleus entopeduncularis (EP) did not attenuate the circling behavior induced by either taurine or GABA. These results suggest that taurine-induced circling behavior may be mediated by the nigrostriatal-nigrothalamic system, and the ACB. In contrast, the nigrothalamic system may play an important role in GABA-induced circling behavior.


NaI/PPh3-Mediated Photochemical Reduction and Amination of Nitroarenes.
A mild transition-metal- and photosensitizer-free photoredox system based on the combination of NaI and PPh3 was found to enable highly selective reduction of nitroarenes. This protocol tolerates a broad range of reducible functional groups such as halogen (Cl, Br, and even I), aldehyde, ketone, carboxyl, and cyano. Moreover, the photoredox catalysis with NaI and stoichiometric PPh3 provides also an alternative entry to Cadogan-type reductive amination when o-nitrobiarenes were used.


Better With Ultrasound: Transesophageal Echocardiography.
Transesophageal echocardiography (TEE) is a safe and minimally invasive tool that can routinely provide high-quality anatomic and hemodynamic information in the severely ill. Despite its potential for frontline acute care clinicians, TEE use has typically been reserved for diagnostic experts in the cardiac-surgical milieu. With the continued evolution of point-of-care ultrasound into increasingly sophisticated domains, TEE has gained steady uptake in many nontraditional environments for both advanced echocardiographic assessment as well as answering more goal directed, fundamental questions. This article introduces the workings of the TEE transducer, presents a systematic approach to a goal-directed hemodynamic assessment, and includes a series of illustrative figures and narrated video presentations to demonstrate the techniques described.


Biogenic link to the recent increase in atmospheric methane over India.
Methane (CH4) is a prominent Greenhouse Gas (GHG) and its global atmospheric concentration has increased significantly since the year 2007. Anthropogenic CH4 emissions are projected to be 9390 million metric tonnes by 2020. Here, we present the long-term changes in atmospheric methane over India and suggest possible alternatives to reduce soil emissions from paddy fields. The increase in atmospheric CH4 concentrations from 2009 to 2020 in India is significant, about 0.0765 ppm/decade. The Indo-Gangetic Plains, Peninsular India and Central India show about 0.075, 0.076 and 0.074 ppm/decade, respectively, in 2009-2020. Seasonal variations in CH4 emissions depend mostly on agricultural activities and meteorology, and contribution during the agricultural intensive period of Kharif-Rabi (i.e., June-December) is substantial in this regard. The primary reason for agricultural soil emissions is the application of chemical fertilizers to improve crop yield. However, for rice farming, soil amendments involving stable forms of carbon can reduce GHG emissions and improve soil carbon status. High crop production in pot culture experiment resulted in lower potential yield-scaled GHG emissions in rice with biochar supplement. The human impact of global warming induced by agricultural activities could be reduced by using biochar as a natural solution.


A second monoclinic polymorph of N-(diethyl-amino-thio-carbon-yl)-N'-phenyl-benzamidine.
The asymmetric unit of the title compound, C(18)H(21)N(3)S, contains five mol-ecules. The equivalent bond distances in the five mol-ecules are in excellent agreement, the r.m.s. fit being within 0.007 Å. The five mol-ecules are linked into a chain consisting of alternating pseudo-enanti-omers by N-H⋯S hydrogen bonds supplemented by weak C-H⋯π inter-actions. The action of a glide plane links the asymmetric unit into an extended chain. A polymorph of the title compound with one mol-ecule in the asymmetric unit was reported by Braun et al. [Cryst. Res. Technol. (1988), 23, 35-39].


Misinterpretation of normal cellular elements in fine-needle aspiration biopsy specimens: observations from the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology.
The College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytopathology is a popular educational program for nongynecologic cytology, with 1018 participating laboratories by the end of 2000. Data generated from this program allow tracking pathologist performance in a wide variety of laboratory practices. To review performance of participating pathologists in making patient diagnoses with fine-needle aspiration biopsy specimens, with particular interest in the false neoplastic diagnoses (both benign and malignant neoplasms) that were submitted for benign aspirates containing only normal cellular components. We reviewed the diagnoses made from 1998 through 2000 by participating pathologists through the use of glass slides containing benign fine-needle aspiration biopsy specimens of the liver, kidney, pancreas, and salivary gland that contained only normal cellular components. The false neoplastic rate for kidney (60%) was the highest, followed by liver (37%), pancreas (10%), and salivary gland (6%). These rates are much higher than what has previously been reported in the literature. This study illustrates that normal cellular elements are a significant pitfall for overinterpretation of fine-needle aspiration biopsy specimens.


Relative contributions of selected multigeneration products to chamber SOA formed from photooxidation of a range (C10-C17) of n-alkanes under high NO x conditions.
A series of chamber experiments was conducted to investigate the composition of secondary organic aerosol (SOA) following oxidation of a range of parent n-alkanes (C10-C17) in the presence of NO x . The relative contribution of selected species representing first, second, and higher generation products to SOA mass was measured using a high-resolution aerosol mass spectrometer. Gas chromatography was also used for a limited set of amenable species. Relative contributions varied substantially across the range of investigated alkanes reflecting slight changes in SOA composition. The contribution of first-generation cyclic hemiacetal is minimal toward the small end of the investigated range and gradually increase with n-alkane size. The relative contribution of second generation and higher nitrate-containing species, in contrast, decrease with an increased alkane size. A similar trend is observed for relative contribution of organonitrates to SOA. Finally, SOA yield and composition are sensitive to water vapor concentrations. This sensitivity is limited to a narrow range (dry to ~15% RH) with little, if any, impact above 15% suggesting that this impact may be negligible under ambient conditions. The impact of water vapor also appears to decrease with increasing alkane carbon number.


An effective intradermal hepatitis B vaccination.
Small dose intradermal (i.d.) inoculation methods of hepatitis B vaccine have been reported to be effective and economical. We determined the best method to obtain high antibody levels within a short period of time and for the long-term maintenance of these levels. A total of 173 female students were randomly allocated to seven groups: six i.d. inoculation groups, to which 6-12 micrograms was administered in three or four divided doses (Groups A-F), and a control group (Group G) which received three 10 micrograms intramuscular (i.m.) inoculations. Serum hepatitis B antibody levels were quantified in weeks 4 and 8, and months 4, 7, and 12. Positivities in all groups were not significantly different at each measurement time. In month 4, geometric mean antibody levels in the three i.d. groups (10-12 micrograms in three divided doses; 79.1-107.0 IU l-1) were significantly higher than in Group G, which had received two of three i.m. injections (17.6 IU l-1; P < 0.01, P < 0.05). In the group which received four 2 micrograms i.d. inoculations, the level was higher than in Group G in month 7, but lower in month 12. It was concluded that three i.d. inoculations, each of 4 micrograms, may be used to obtain high antibody levels within a short period of time. However, it is recommended that a 10 micrograms i.m. injection in month 6 is applied as a booster. Consequently, we could not present an economic and effective low-dose intradermal inoculation method.


One-pot nitro-Mannich/hydroamination cascades for the direct synthesis of 2,5-disubstituted pyrroles using base and gold catalysis.
An efficient, easy to perform, one-pot reaction cascade for the synthesis of 2,5-disubstituted pyrroles from p-toluenesulfonyl protected imines and 4-nitrobut-1-yne under a combination of base and gold(III) catalysis is reported.


Health Professionals' Experiences Supporting People With Type 1 Diabetes Mellitus Who Deliberately Restrict and/or Omit Insulin for Weight, Shape, and/or Appearance: A Meta-synthesis.
It has been reported that health professionals currently lack the required empathy, understanding, and knowledge about the deliberate restriction and/or omission of insulin to influence weight and/or shape, which may impact the quality of care provided. We sought to synthesize existing qualitative research pertaining to health professionals' experiences supporting individuals within this unique population. We conducted a meta-synthesis using a meta-aggregative approach. We searched 5 electronic databases. Eligible articles were qualitative or mixed-methods empirical studies with primary data reporting health professionals' experiences supporting people with type 1 diabetes restricting and/or omitting insulin for weight and/or shape control, written in English, from database inception to March 2022. A final sample of 4 primary studies were included. The analysis indicated that in the absence of standardized screening and diagnostic tools, health professionals found it challenging to decide when behaviour became clinically significant. Health professionals were also challenged by complex perceptions and behaviours relating to their illness management and features of broader health-care systems and organizational factors. Our findings have widespread multidisciplinary implications for health professionals and the broader health-care systems in which they work. We provide evidence-based clinical recommendations and suggestions for vital future research.


Meglitinide (repaglinide) therapy in permanent neonatal diabetes mellitus: two case reports.
Permanent neonatal diabetes mellitus (PNDM) presents with dehydration and hyperglycemia, which usually occurs during the first 12 months of life. Activating mutations of beta-cell adenosine triphosphate-sensitive potassium [KATP] channel subunits that cause opening of the channel are associated with PNDM. Some patients with PNDM respond to administration of a sulfonylurea derivative, which has long action on blood glucose even during hypoglycemia and has an apoptotic effect on beta cells. However, there have been no reports regarding treatment with meglitinide (repaglinide), which has rapid and short duration of action during the rise in blood glucose after meals that is more similar to beta cell function. It has no effects during hypoglycemia, so it does not cause neurological damage, and has no apoptotic effect on beta cells. We report herein the effects of repaglinide administration in the management and clinical outcome of two patients with PNDM during 9 and 10 years of follow-up. Two Iranian infants were brought to our institution with poor general condition, dehydration, lethargy, and poor feeding. They had diabetic ketoacidosis at 52 days and 3.5 months of age, respectively. Their genetic analysis revealed mutations in the KCNJ11 gene encoding KIR6.2, so they both had PNDM. After treatment of diabetic ketoacidosis with insulin, they responded to sulfonylurea (glibenclamide) treatment, but were switched to repaglinide because of blood sugar fluctuations in terms of hyper- and hypoglycemia. Repaglinide was administered with the dosage of 0.04 mg/kg/day divided before every meal. The patients were 10 and 9 years old at the last visit, with normal growth parameters. The values of self-monitored blood glucose were well-controlled, and the hemoglobin A1C (HbA1C) levels ranged from 3.6 to 6.4% during the follow-up period. There was no complication of diabetes, neurological disorder, or adverse effects related to repaglinide. In every neonate or infant < 6 months of age with diabetes mellitus, PNDM should be considered. A trial of oral repaglinide can be performed and substituted for glibenclamide for prevention of hypoglycemia, neurological damage, and apoptosis of beta cells during long-term administration.


Understanding the factors contributing to groundwater salinity in the coastal region of Andhra Pradesh, India.
The present study focused on understanding the factors responsible for groundwater salinity in the coastal region, Prakasam district, Andhra Pradesh, India. Groundwater samples were collected and analysed for pH, EC, TDS, TA, TH, CH, NCH, EA, Ca2+, Mg2+, Na+, K+, HCO3-, Cl-, SO42-, NO3-, and F-. Groundwater quality was assessed using entropy weighted water quality index (EWQI), Chadha and Gibbs diagrams, ionic ratios, chloro-alkaline indices (CA), saturation indices (SI), principal component analysis (PCA), and hierarchical cluster analysis (HCA). TDS vs TH indicated that 86% of groundwater samples fall under brackish-cum-very hard water-quality type, while TA and TH relationship showed that 70% and 30% of groundwater samples fall under non‑carbonate hardness (NCH) and excess alkalinity (EA), respectively. EWQI classified groundwater samples into medium (22%), poor (40%), and exremely poor (38%) water quality types, indicating that most samples are not suitable for drinking purposes. Hydrogeochemical types in Chadha diagram showed saline water (Na+-Cl-) type in 92% of groundwater samples. Ionic ratios indicated that anthropogenic activities resulting from the leaching of surface water pollutants are the main source of groundwater pollution. Base ion exchange was indicated as the main process in CA indices. SI revealed precipitation of the calcite phase and dissolution of the gypsum and halite phases in groundwater. Evaporation appeared in Gibb's diagram as a primary process rather than a geogenic origin. PC1 (Na+, Cl-, SO42-, Mg2+, K+, and NO3-) and PC2 (HCO3- and F-) were considered salinity-process and alkalinity-process, respectively. The main sources of salinity in groundwater are brackish-water aquaculture and salt-making activities with household waste, septic tank spills, irrigation-return-flows, and chemical fertilizers being secondary sources. HCA classified groundwater samples into Group-I (46%), which represents domestic water, agricultural activities, etc., Group-II (30.24%), which shows the influence of both Group-I and Group-II, and Group-III (23.76%), which specifies brackish-water aquaculture and salt-making activities. Consequently, the present study obviously indicated that the groundwater quality of anthropogenic origin has largely overcome the influence of geogenic sources. The EWQI classification spatially delineated the study region into medium, high, and very high vulnerable zones, covering 28.69%, 32.75%, and 38.56%, respectively. Therefore, it is suggested to control the dumping of domestic waste and septic tank leaks, limit irrigation-return-flows and chemical fertilizers, ban brackish water aquaculture and salt production activities, and strictly implement an aquifer recharge management strategy to ensure human health. This study will assist decision-makers in addressing groundwater salinity issues in coastal regions.


Radiomics vs radiologist in bladder and renal cancer. Results from a systematic review.
Radiomics in uro-oncology is a rapidly evolving science proving to be a novel approach for optimizing the analysis of massive data from medical images to provide auxiliary guidance in clinical issues. This scoping review aimed to identify key aspects wherein radiomics can potentially improve the accuracy of diagnosis, staging, and grading of renal and bladder cancer. A literature search was performed in June 2022 using PubMed, Embase, and Cochrane Central Controlled Register of Trials. Studies were included if radiomics were compared with radiological reports only. Twenty-two papers were included, 4 were pertinent to bladder cancer, and 18 to renal cancer. Radiomics outperforms the visual assessment by radiologists in contrast-enhanced computed tomography (CECT) to predict muscle invasion but are equivalent to CT reporting by radiologists in predicting lymph node metastasis. Magnetic resonance imaging (MRI) radiomics outperforms radiological reporting for lymph node metastasis. Radiomics perform better than radiologists reporting the probability of renal cell carcinoma, improving interreader concordance and performance. Radiomics also helps to determine differences in types of renal pathology and between malignant lesions from their benign counterparts. Radiomics can be helpful to establish a model for differentiating low-grade from high-grade clear cell renal cancer with high accuracy just from contrast-enhanced CT scans. Our review shows that radiomic models outperform individual reports by radiologists by their ability to incorporate many more complex radiological features.


On the seclusion of psychiatric patients.
The seclusion of psychiatric patients is viewed by some as a violation of basic human rights, by others as a necessity for the control of violence, and by still others as a therapeutic modality. The purpose of this paper is to synthesize the findings from the limited and descriptive research on this controversial practice. The major conclusions suggested by the findings are: (1) The reason cited for seclusion is more often agitation than violence, raising questions as to its necessity. The lack of relationship between the reason for seclusion and its duration indicates loose and arbitrary criteria and raises the question of bias. (2) The tendency to seclude on admission suggests failure to follow the legal stipulation that less restrictive measures be employed first. (3) Psychotic, involuntary and younger patients are at higher risk for seclusion than other patients. (4) Incidence and duration of seclusion differ widely across institutions indicating unnecessary and excessive use in some units. Differences may be better explained by hospital factors such as location, staff attitudes and treatment philosophy than by patient characteristics. (5) Systematic studies of the effectiveness of seclusion are lacking, as is research on events transpiring during seclusion. (6) Attitudes of patients and staff toward seclusion differ greatly. Patients' attitudes are generally negative, whereas staff members believe seclusion benefits patients and preserves the unit's smooth functioning. Changes in procedures are suggested to reduce the frequency of seclusion, and to make seclusion more rational, effective and humane. Research and clinical implications are discussed.


Healthcare burden and factors of type 2 diabetes mellitus with Schizophrenia.
This study investigated healthcare utilization and expenditure for patients with type 2 diabetes mellitus and schizophrenia and associated factors. Healthcare utilization (outpatient visits and hospitalization) and expenditure (outpatient, inpatient, and total medical expenditure) between 2002 and 2013 of patients with T2DM with schizophrenia (case group) and without (control group) were examined using the Taiwan National Health Insurance Research Database. (1) The average total numbers of outpatient visits and hospital admissions of the case group were 35.14 outpatient visits and 1.09 hospital admissions significantly higher than those of the control group in the whole study period (based on every 3-year period). Nonpsychiatric outpatient visits and nonpsychiatric hospital admissions were significantly more numerous for the case group. (2) The total outpatient expenditure, total inpatient expenditure, and total medical expenditure of the case group were NT$65,000, NT$170,000, and NT$235,000 significantly higher than those of the control group, respectively. Nonpsychiatric outpatient expenditure was significantly lower for the case group, but the inpatient and total nonpsychiatric medical expenditure were similar between groups. (3) Patients who were elder of low income, with complications, and high diabetes mellitus complication severity index had higher total numbers of outpatient visits and hospitalizations and medical expenditure. (4) Women had a higher number of outpatient visits but a lower number of hospitalization and medical expenditure. Lower non-psychiatric outpatient expenditure despite more visits indicated non-psychiatrist may not understand schizophrenia patients and cannot communicate well with them, leading to neglect of medical evaluation and treatment that should be carried out.


The lygaeoid bug family Heterogastridae (Hemiptera: Heteroptera: Lygaeoidea) from Laos and Thailand, with descriptions of three new species.
Laotian and Thai species of the Heterogastridae Stål, 1872 are revised taxonomically. Eight species are recognized, including three new species; Sadoletus laosensis and S. subpellucidus from Laos, and S. melasmus from Thailand. A key to the species in Laos and Thailand is provided.


Is sonication superior to dithiothreitol in diagnosis of periprosthetic joint infections? A meta-analysis.
Even though effective techniques in diagnosis of periprosthetic joint infections (PJIs) have been developed, the optimal modality has yet to be determined. The present meta-analysis aimed to compare the diagnostic accuracy of dithiothreitol (DTT) and sonication against the Musculoskeletal Infection Society criteria in patients undergoing revision joint surgery. We searched the PubMed, Scopus, and Central Cochrane register of controlled trials as well as gray literature until the 9th of November, 2021. We included articles considering the comparative diagnostic accuracy of sonication and DTT in adult patients having revision hip and knee arthroplasty for septic or aseptic reasons. We calculated pooled sensitivity, specificity, and diagnostic accuracy of the above diagnostic techniques against the Musculoskeletal Infection Society (MSIS) criteria and created receiver operating characteristics (ROC) curves to enable comparisons between each other. The quality of included papers was evaluated utilizing QUADAS-2 and QUADAS-C tools. Data from five comparative studies totaling 726 implants were pooled together. The diagnostic accuracy of DTT and sonication were 86.7% (95% CI 82.7 to 90.1) and 83.9% (95% CI 79.7 to 87.5), respectively. Pooled sensitivity and specificity showed no statistically significant differences between DTT and sonication (0.7 [95% CI 0.62 to 0.77] vs 0.72 [95% CI 0.65 to 0.78], p = 0.14; and 0.99 [95% CI 0.97 to 1] vs 0.97 [95% CI 0.93 to 0.99], p = 5.5, respectively). This meta-analysis did not identify any clinically meaningful difference between the diagnostic potential of sonication and the chemical-based biofilm dislodgment methods. This finding remained robust after adjusting for the administration of antibiotics prophylaxis, implementation of the polymerase chain reaction of sonicated fluid, and study quality.


Optimization of macrophage isolation from the Persian sturgeon and the Caspian kutum fish: a comparative study.
The aim of this research was a comparative study on the isolation and culture of head kidney macrophages derived from Acipenser persicous and Rutilus frisii kutum as teleost and chondrostei species of fish. The macrophages were isolated by density gradient sedimentation, followed by adherence to a plastic surface. They exhibited strong phagocytic activity against bacteria. The effect of cell density, incubation time, FBS percentage, pH and temperatures on the cell number and viability were determined and compared. Also, the effect of light/dark regimen on viability, adherence, release of reactive oxygen species (ROS) and nitric oxide (NO) in the macrophages was determined. The results showed that the Caspian kutum macrophages were more sensitive to FBS percentage and cell density whereas the Persian sturgeon macrophages were more sensitive to pH of the cell culture media. The adherence and viability of the macrophages from both fish species firstly increased (P < 0.05) after exposure to a light/dark regimen, but then significantly decreased as did ROS and NO productions. For the first time, this study has determined the optimal conditions for primary culture of macrophages derived from sturgeons, and shows the unique effect of light on the biology of fish immune cells.


Gastrointestinal lesions in parvovirus B19 infection.
A 13-year-old girl with persistent fever, pharyngitis, acute anaemia, peripheral blood and bone marrow positive for parvovirus B19 DNA.Microscopic findings of gastrointestinal biopsy showed diffuse vacuolar alteration of the cytoplasma of duodenal enterocytes and virological analysis demonstrated the presence of parvovirus in lymphocytes of the duodenal wall's epithelial layer.In unexplained gastrointestinal pathologies, the role of parvovirus B19 infection should be investigated.


Approximations, idealizations and 'experiments' at the physics-biology interface.
This paper, which is based on recent empirical research at the University of Leeds, the University of Edinburgh, and the University of Bristol, presents two difficulties which arise when condensed matter physicists interact with molecular biologists: (1) the former use models which appear to be too coarse-grained, approximate and/or idealized to serve a useful scientific purpose to the latter; and (2) the latter have a rather narrower view of what counts as an experiment, particularly when it comes to computer simulations, than the former. It argues that these findings are related; that computer simulations are considered to be undeserving of experimental status, by molecular biologists, precisely because of the idealizations and approximations that they involve. The complexity of biological systems is a key factor. The paper concludes by critically examining whether the new research programme of 'systems biology' offers a genuine alternative to the modelling strategies used by physicists. It argues that it does not.


Limb regeneration: induction in the newborn opossum.
The marsupial Didelphys virginiana (the North American opossumn) is uniquely suited for studies of mammalian limb replacement. By transplanting nervous tissute to the limb, regeneration has been successfully induced in this mammal.


[Bipolar depression. Spectrum of clinical pictures and differentiation from unipolar depression].
Patients with bipolar disorder often present initially with a major depressive episode. The correct diagnosis at the first presentation could help to find an effective medication regimen, to prevent antidepressant-induced rapid cycling and to reduce antidepressant-induced manic episodes, e.g. though combination therapy with a mood stabilizer. Consistent predictors for an underlying bipolar illness are an early age of onset, a highly recurrent illness course with more than five episodes, the presentation of atypical features, psychotic symptoms, the presence of psychiatric comorbidities like anxiety disorders, history of suicide attempts (especially at an early age), positive family anamnesis for bipolar disorder, and a rapid evolvement of the depressive episode. So far there are no pathognomonic markers for bipolar disorder. Therefore we propose to assess the risk of each patient for having bipolar disorder individually. Patients who are at a high risk should at least be informed and should be closely monitored for the development of manic episodes.


Decision regret among women considering planned oocyte cryopreservation: a prospective cohort study.
To (1) prospectively characterize the incidence of decision regret among women considering planned oocyte cryopreservation (planned OC), comparing those who pursued treatment vs those who did not freeze eggs, and (2) to identify baseline predictors for future decision regret. A total of 173 women seen in consultation for planned OC were followed prospectively. Surveys were administered at (1) baseline (< 1 week after initial consultation) and (2) follow-up, 6 months after planned OC among participants who froze eggs or 6 months following consultation in the absence of further communication to pursue treatment. The primary outcome was the incidence of moderate-to-severe decision regret, indicated by a Decision Regret Scale score > 25. We also examined predictors of regret. The incidence of moderate-to-severe regret over the decision to freeze eggs was 9% compared to 51% over the decision not to pursue treatment. Among women who froze eggs, adequacy of information at baseline to decide about treatment (aOR 0.16, 95% CI 0.03, 0.87) and emphasis on future parenthood (aOR 0.80, 95% CI 0.66, 0.99) were associated with reduced odds of regret. Forty-six percent of women who froze eggs regretted not doing so earlier. Among women who did not freeze eggs, the primary reasons were financial and time constraints, correlating with increased odds of decision regret in an exploratory analysis. Among women undergoing planned OC, the incidence of decision regret is low compared to the regret confronting women seen in consultation for planned OC but who do not pursue treatment. Provider counseling is key to offset the regret risk.


Visible absorption spectra of the 4f electron transitions of neodymium, praseodymium, holmium and erbium complexes with fleroxacin and their analytical application.
The absorption spectra of the 4f electron transitions of neodymium, praseodymium, holmium and erbium complexes with fleroxacin in the presence of cetylpyridinium chloride were studied by normal and derivative spectrophotometry. Their molar absorptivity at the maximum absorption bands are about 5.3 (at 571 nm) times greater for neodymium, 2.8 (at 483 nm) times greater for praseodymium, 12.6 (at 448.5 nm) times greater for holmium and 9.7 (at 519 nm) times greater for erbium than those in the absence of complexing agents. The second-derivative spectrum is used both to eliminate the interference from other rare earths and to improve the sensitivity. Beer's law is obeyed from 3.0 - 70 microg ml(-1) for neodymium and holmium, from 6.0 - 70 microg ml(-1) for erbium, and from 12.0 - 70 microg ml(-1) for praseodymium. The relative standard deviations are 1.9% and 1.5% for 7.5 microg ml(-1) of neodymium and holmium, and 2.1% and 1.6% for 15.0 microg ml(-1) of praseodymium and erbium, respectively. Their detection limits (signal-to-noise ratio = 2) are 3.2 microg ml(-1), 1.3 microg ml(-1), (1.1) microg ml(-1) and 2.5 microg ml(-1) for praseodymium, neodymium, holmium and erbium, respectively. A new system for the simultaneous determinations of the praseodymium, neodymium, holmium and erbium in rare earth mixtures with good accuracy and selectivity is proposed.


The ErbB3 binding protein EBP1 regulates ErbB2 protein levels and tamoxifen sensitivity in breast cancer cells.
The ErbB2/3 heterodimer plays a critical role in breast cancer progression and in the development of endocrine resistance. EBP1, an ErbB3 binding protein, inhibits HRG-stimulated breast cancer growth, decreases ErbB2 protein levels and contributes to tamoxifen sensitivity. We report here that ectopic expression of EBP1 in Estrogen Receptor (ER) positive breast cancers that express ErbB2 at both high and low levels decreased ErbB2 protein levels. ErbB2 protein expression was also increased in mammary glands of Ebp1 knock out mice. To define the mechanism of ErbB2 down regulation, we examined the effects of EBP1 on ErbB2 mRNA levels, transcription of the ErbB2 gene and ErbB2 protein stability. We found that ectopic expression of EBP1 decreased steady state levels of endogenous ErbB2 mRNA in all cell lines tested. EBP1 overexpression decreased the activity of an ErbB2 promoter reporter in cells which overxpress ErbB2. However, reporter activity was unchanged or increased in cells which express low endogenous levels of ErbB2. We also found that ectopic expression of EBP1 accelerated ErbB2 protein degradation and enhanced ErbB2 ubiquitination in cells which express both low and high levels of ErbB2. Treatment with proteasome inhibitors prevented this decrease in ErbB2 protein levels. Ablation of EBP1 expression led to tamoxifen resistance that was abrogated by inhibition of ErbB2 activity. These results suggest that EBP1 inhibits expression of ErbB2 protein levels by multiple mechanisms and that EBP1's effects on tamoxifen sensitivity are mediated in part by its ability to modulate ErbB2 levels.


The impact of Purple Heart commendation and PTSD on mortality rates in older veterans.
To determine whether having received a Purple Heart (PH) or having been diagnosed with posttraumatic stress disorder (PTSD) affected mortality in older veterans. We compared mortality rates of older veterans with a PH but without PTSD (PH+/PTSD-) to veterans with a PH and PTSD (PH+/PTSD+), veterans without a PH but with PTSD (PH-/PTSD+), and a comparison group without a PH or PTSD (PH-/PTSD-). Administrative data from the Veterans Integrated Service Network 16 were collected between 10/01/97 and 09/30/99 for veterans who were 65 years or older. Proportional hazards regression was used to compare the survival times for the four groups (n = 10,255) from entry into the study until death or study termination (9/30/2008). The Charleson co-morbidity index was used to control for potential co-morbid illness burden differences between the groups. Older veterans with a PH (PH+/PTSD- and PH+/PTSD+) had significantly lower mortality rates than PH-/PTSD- veterans (hazard ratio [HR] = 0.6, 95% confidence interval [CI] 0.5 to 0.6, P<.0001; and HR = 0.5, 95% CI 0.4 to 0.7, P<.0001). The PH-/PTSD+ group had a higher mortality rate than the PH-/PTSD- group (HR = 1.1, 95% CI 1.0 to 1.2, P<.01). Veterans who had PH citations and survived into their seventh decade had half the mortality rate of veterans without PH citations with or without PTSD. Veterans with PTSD but without a PH had a significantly higher mortality rate compared to (PH-/PTSD-). Veterans who suffer combat injury without developing PTSD may provide a useful study population for determining the factors that confer resilience.


Malignant tumors of the major salivary glands.
A total of 512 patients with major salivary gland tumors were treated at our institution between the years 1960 to 1975. The 147 cases of malignant salivary gland tumors were reviewed according to presenting characteristics and stage, histology, and outcome. Treatment for each type is summarized. The battery of diagnostic aids and prognostic indicators available to the physician are also reviewed. The newer and more controversial procedures of CT scanning, nuclear magnetic resonance scanning, and fine-needle aspiration are discussed in detail. In the past, salivary gland tumors have been classified by histology alone. Current trends employ the TNM staging system in planning treatment and predicting end results. We have found a far better survival rate in patients with various tumor types presenting with stage I or II disease, but point out that patients with high-grade tumors often present with advanced disease. All major salivary gland tumors should be approached according to the principles of cancer surgery. The minimum procedure is thus superficial or total parotidectomy with preservation of the facial nerve. In low-grade malignancies, the diagnostic procedure will have accomplished this definitive treatment. Salivary gland tumors are rare in the pediatric population. Such malignancies often defy radical treatment. Although cure rates in many categories of high-grade tumors are low, the only hope for survival is an initial aggressive surgical approach. Although radiation was used for recurrent disease only during the years of this study, it is currently being used as adjuvant therapy in almost all malignancies except low-grade mucoepidermoid. Recurrences are almost always fatal.


Secrets of the code: do vascular endothelial cells use ion channels to decipher complex flow signals?
The ability of vascular endothelial cells (ECs) to respond to changes in blood flow is essential for both vasoregulation and arterial wall remodelling, while abnormalities in endothelial responsiveness to flow play an important role in the development of atherosclerosis. Endothelial flow responses also have important implications for the field of vascular tissue engineering. In response to changes in fluid dynamic shear stress, ECs exhibit humoral, metabolic, and structural responses. Significantly, ECs respond differently to different types of shear stress. For instance, steady shear stress elicits a profile of responses that differs drastically from oscillatory shear stress. Although our understanding of flow-induced signaling has advanced greatly over the past two decades, how ECs sense shear forces remains to be established. Furthermore, the mechanisms by which ECs discriminate among different flow waveforms are unknown. Activation of flow-sensitive ion channels is one of the most rapid known responses to flow in ECs. In this paper, we argue in favor of an important role for ion channels in shear stress sensing in ECs and propose that these channels may endow ECs with the ability to resolve components of a complex flow signal and hence distinguish among different types of flow.


Incidental findings on staging rectal MRI: clinical significance and outcomes.
Incidental findings (IFs) are commonly seen in staging rectal magnetic resonance imaging (MRI) scans. Their prevalence and clinical significance have not been previously documented. To assess the prevalence, clinical significance, and outcomes of incidental findings in MRI scans performed for the staging of rectal cancer. A retrospective study was performed at a tertiary colorectal imaging institution. Consecutive MRI rectal staging scans with correlative pathology confirmed primary rectal cancer between March 2014 and March 2021 were identified. The respective imaging reports were reviewed for IFs, which were classified as high, moderate, and low, according to their clinical significance. Medical records were reviewed to assess the outcomes of the highly significant IFs. There were 266 eligible patients (97 women; mean age = 64.2 years) during the study period. A total of 120 (45%) patients did not have any IFs. A total of 238 IFs in 146 (55%) patients were found. There were 21 (9%) IFs of high clinical significance, 122 (51%) of moderate clinical significance, and 95 (40%) of low clinical significance. The prostate and uterus had the most IFs of high clinical significance, two of which were subsequently pathology confirmed as prostate adenocarcinomas. IFs were seen in more than half of the staging MRI scans in rectal cancer but less than 10% of these were of high clinical significance. The results of this study highlight the range of potential IFs and can guide future research assessing the potential impact of these IFs on patients and the healthcare system.


Chuanxiongdiolides R4 and R5, phthalide dimers with a complex polycyclic skeleton from the aerial parts of Ligusticum chuanxiong and their vasodilator activity.
Chuanxiongdiolides R4-R6 (1-3), three novel phthalide dimers featuring two classes of unreported monomeric units (ligustilide/senkyunolide A and ligustilide/neocnidilide) with an unprecedented linkage style (3a,7'/7a,7'a), were isolated from the aerial parts of Ligusticum chuanxiong, together with three pairs of enantiomeric phthalide dimers [(-)/(+)-4a/4b, 5a/5b, and 6a/6b]. The bioassays revealed that compounds 1, 3, 4, 5, and 6 showed significant vasodilation effects, and the mechanism may be attributed to Cav1.2 activation blockade. Based on the established compounds library, the structure activity relationship of the phthalides was proposed. Our findings afford possible leads for developing new vasodilator against cardiovascular and cerebrovascular diseases such as hypertension and ischemic stroke.


Integrators of epidermal growth and differentiation: distinct functions for beta 1 and beta 4 integrins.
Mammalian epithelia are critically dependent on interactions with components in the underlying basal lamina for proper morphogenesis and function. Substratum attachment is essential for survival, proliferation, movement, and differentiation; detachment compromises the cell's ability to perform these functions, often resulting in human disease. Interactions with the extracellular matrix are mediated through transmembrane integrin receptors that transmit signals to the cytoskeleton and to signaling molecules within the proliferating cells of the epithelium. In the past year, novel insights have emerged regarding the specific role of integrins in their attachment to extracellular matrix and in their signal transduction pathways within the epidermis.


Experiments inducing prospective polar body nuclei to participate in embryogenesis of the sawfly Athalia rosae (Hymenoptera).
Mature eggs dissected from ovaries of unmated females of Athalia rosae (Hymenoptera: Tenthredinidae), if placed on a filter-paper soaked with distilled water, are activated and develop to haploid males. Occasionally, however, diploid females develop from these artificially activated eggs. Treatment of mature unfertilized eggs dissected from diploid females with ice-cold temperatures immediately before activation and with a high temperature (36° C) upon and immediately after activation resulted in the production of diploid males, diploid females, triploid females and gynandromorphs at high frequency. The same treatment of mature unfertilized eggs dissected from triploid females resulted in the production of only triploid survivors. These results, together with the results on the segregation of a marker mutation, yellow fatbody (yfb), appear to indicate that meiotic divisions were complete in the treated eggs, and that all four nuclei became potentially capable of participating in development with or without automictic fusion.


Noxious and innocuous mechanical cutaneous stimulation increase the sympathetic efferent nerve activity innervating the interscapular brown adipose tissue in anesthetized rats.
Effects of pinching and brushing of the various segmental skin areas (face, ear, neck, forelimb, chest, abdomen, hindlimb) on the activities of the sympathetic efferent nerve innervating the interscapular brown adipose tissue (IBAT) and contributing to its thermogenesis were examined in anesthetized rats. Pinching the face, ear, neck, or forelimb produced significant reflex increases in the efferent nerve activities, whereas pinching the chest, abdomen, or hindlimb did not produce any significant responses. In the case of brushing stimulation, only the stimulation of the ear produced significant increases. These results demonstrated that cutaneous mechanical stimulations at cranial, cervical, and upper thoracic segments were effective in producing reflex increases in the activities of the IBAT sympathetic nerve and that noxious stimulation was more dominant for eliciting the reflex responses.


AMPA/kainate receptors in the ventromedial hypothalamus mediate the effects of glutamate on estrus termination in the rat.
Infusions of glutamate or its selective receptor agonists to the VMH of ovariectomized (OVX) female rats primed with estradiol benzoate (EB) and progesterone (P) inhibit both appetitive and consummatory aspects of sexual behavior whereas selective glutamate receptor antagonists facilitate these measures in females primed with EB alone. Because vaginocervical stimulation (VCS) activates glutamate neurons in the VMH, and induces a faster termination of estros behavior, the present study examined the effects of the AMPA/kainate receptor antagonist DNQX on the induction of estrus termination by manual VCS. Ovx, sexually-experienced rats were primed with EB and P and subsequently received either 1 or 50 distributed VCSs, over the course of an hour, 12 h before a test with sexually vigorous males. Half of the females in each stimulus group received bilateral infusions of 1 μl/side of either DNQX (19.8 mmol/μl) or saline aimed at the VMH immediately prior to VCS or sham stimulation. Saline-infused females given VCS had lower lordosis quotients compared to females given sham stimulation. In contrast, females infused with DNQX prior to VCS displayed more appetitive behaviors and higher lordosis quotients and magnitudes compared to females infused with saline. These data indicate that activation of AMPA/kainate receptors in the VMH by increased glutamate transmission induced by VCS mediates estrus termination.


Clinical pharmacology and drug-drug interactions of lenvatinib in thyroid cancer.
Lenvatinib is a non-selective tyrosine kinase inhibitor (TKI) with high in vitro potency against vascular endothelial growth factor receptors. Although this drug is used to treat several cancer types, it is the most effective TKI used in patients with thyroid cancer. Lenvatinib is well tolerated and the most common adverse drug reactions can be adequately managed by dose adjustment. Particularly, blood pressure and cardiac function monitoring, as well as antihypertensive treatment optimization, may be required in patients treated with lenvatinib. Dose reduction should be taken into account in patients with body weight <60 kg or severe hepatic failure. No significant change in lenvatinib pharmacokinetics has been observed with other patient-related factors and very few data are available on lenvatinib pharmacogenetics. Lenvatinib can be administered orally regardless of food and no clinically relevant drug-drug interactions have been reported.


[Planning combined radiation therapy of rectal cancer taking into account the biological effect of the radiation].
Biologically equivalent doses with various single values, fractionation, irradiated areas, relative biological efficacy, the time of radiation therapy for schedules of intracavitary and gamma-beam radiotherapy were determined for concomitant radiotherapy of rectal cancer patients. A radiation effect implementation factor was introduced making it possible to sum up equivalent dose values in critical points and to obtain equivalent isodose distributions.


High solid fed-batch butanol fermentation with simultaneous product recovery: Part II-process integration.
In these studies, liquid hot water (LHW) pretreated and enzymatically hydrolyzed Sweet Sorghum Bagasse (SSB) hydrolyzates were fermented in a fed-batch reactor. As reported in the preceding paper, the culture was not able to ferment the hydrolyzate I in a batch process due to presence of high level of toxic chemicals, in particular acetic acid released from SSB during the hydrolytic process. To be able to ferment the hydrolyzate I obtained from 250 g L-1 SSB hydrolysis, a fed-batch reactor with in situ butanol recovery was devised. The process was started with the hydrolyzate II and when good cell growth and vigorous fermentation were observed, the hydrolyzate I was slowly fed to the reactor. In this manner the culture was able to ferment all the sugars present in both the hydrolyzates to acetone butanol ethanol (ABE). In a control batch reactor in which ABE was produced from glucose, ABE productivity and yield of 0.42 g L-1 h-1 and 0.36 were obtained, respectively. In the fed-batch reactor fed with SSB hydrolyzates, these productivity and yield values were 0.44 g L-1 h-1 and 0.45, respectively. ABE yield in the integrated system was high due to utilization of acetic acid to convert to ABE. In summary we were able to utilize both the hydrolyzates obtained from LHW pretreated and enzymatically hydrolyzed SSB (250 g L-1 ) and convert them to ABE. Complete fermentation was possible due to simultaneous recovery of ABE by vacuum. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:967-972, 2018.


Substantivity of sunscreens -in vitro evaluation of the transdermal permeation characteristics of some benzophenone derivatives.
Synopsis The in vitro permeation through excised hairless mouse skin of a series of 4-O-(N, N-dimethylaminoalkyl)-benzophenones, non-quaternarized and quaternarized, and of two commercial benzophenone sunscreens, taken as reference compounds, was investigated. The aim of the study was to verify the skin penetration of the highly skin-substantive quaternary ammonium derivatives, in comparison with their parent, non-quaternarized compounds. While the quaternary derivatives proved unable to permeate the skin during the period of observation (45 h), their parent amine hydrochlorides and the reference sunscreens (2-hydroxy-4-methoxy-benzophenone-5-sulphonic acid and 2,2'-dihydroxy-4,4'-dimethoxy-benzophenone 5,5'-sodium disulphonate), showed appreciable transdermal fluxes. These data indicate that the presence of a quaternary ammonium group in a molecule, besides inducing a high affinity for cutaneous keratin, may result in hindered or reduced transdermal (and possibly systemic) absorption. Both features may contribute in improving the safety of a cosmetic sunscreen. Résumé On a analysé la pénétration in vitro au travers de peau excisée de souris sans poils d'une gamme de 4-O-(N, N-dimethylaminoalkyl)benzophenones quaternisés et non quaternisés ainsi que de 2 écrans solaires au benzophénone commercialisés utilisés comme témoins. Cette étude avait pour but de vérifier la pénétration dermique de dérivés d'ammonium quaternaire hautement substantifs sur la peau, par rapport à des composés non quatenaires de la même famille. Tandis que les dérivés quaternaires se sont avérés incapables de pénétrer la peau durant la période d'observation (45 heures), les hydrochlorures d'amine et les écrans solaires témoins (2-hydroxy-4-methoxybenzophenone-5-acide sulfonique et 2,2'-dihydroxy-4,4'-dimethoxy-benzophenone 5,5'-disulphonate de sodium), ont montré des flux transdermiques appréciales. Ces données indiquent que la présence d'un groupe d'ammonium quaternaire dans une molécule, bien que possédant une grande affinité pour la kératine cutanée, peut résulter sur une absorption transcutanée (peut-être même systémique) amoindrie voire annihilée. Chacun de ces facteurs peut contribuer à l'amélioration de la sécurité des écrans solaires cosmétiques.


Effects of pre- and simultaneous treatment with urea on the induction of chromatid aberrations in Vicia faba.
Pre- and simultaneous treatments of Vicia faba root tip meristems with urea and ethyl alcohol, mitomycin C, maleic hydrazide, 3H-thymidine and X-rays, respectively, were found to result in mutagen-specific changes of the spectrum and yield of induced chromatid aberrations.


Synthesis, characterization, antibacterial and emulsifying properties of agar benzoate.
Agar benzoate (AB) with different degrees of substitution (DS) was synthesized by the esterification of agar and benzoic anhydride in aqueous solution. The DS could be regulated by adjusting composition ratio, pH, and temperature. Its chemical structure was determined by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). 13C NMR spectrum of the AB suggested the main substitution occurred at the C-6 in the d-galactopyranose. Cryo-scanning electron microscopy (Cryo-SEM) showed that the aperture of AB was larger than that of agar. The thermal performance of AB decreased slightly, but this did not affect its performance. AB showed the highest relative antibacterial activity against Escherichia coli, S. aureus and Alternaria alternata, reaching 100 % (AB 20 g/L), 100 % (AB 40 g/L) and 19.35 % (7 d incubation), respectively. Moreover, the obtained AB possessed good emulsion stability. These antibacterial AB have broad application prospects in the field of fruit and vegetable preservation.


Discovery of anti-infective adipostatins through bioactivity-guided isolation and heterologous expression of a type III polyketide synthase.
Antibiotic resistance and emerging viral pandemics have posed an urgent need for new anti-infective drugs. By screening our microbial extract library against the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the notorious ESKAPE pathogens, an active fraction was identified and purified, leading to an initial isolation of adipostatins A (1) and B (2). In order to diversify the chemical structures of adipostatins toward enhanced biological activities, a type III polyketide synthase was identified from the native producer, Streptomyces davawensis DSM101723, and was subsequently expressed in an E. coli host, resulting in the isolation of nine additional adipostatins 3-11, including two new analogs (9 and 11). The structures of 1-11 were established by HRMS, NMR, and chemical derivatization, including using a microgram-scale meta-chloroperoxybenzoic acid epoxidation-MS/MS analysis to unambiguously determine the double bond position in the alkyl chain. The present study discovered SARS-CoV-2 main protease inhibitory activity for the class of adipostatins for the first time. Several of the adipostatins isolated also exhibited antimicrobial activity against selected ESKAPE pathogens.


Evaluation of the Role of Ghrelin and Leptin as Biochemical Markers in Female with Polycystic Ovarian Syndrome.
Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is a heterogeneous complex disorder of defined aetiology. Some studies report its association with various endocrine, metabolic and immunological abnormalities. The hunger hormones ghrelin and leptin affect the pathogenesis of PCOS and might lead to the development of Metabolic Syndrome (MS) in obese women. The study aims at evaluating the role of ghrelin and leptin level in females with polycystic ovary syndrome as a biochemical marker for the diagnosis and monitoring progression. The study included one hundred PCOS patients and fifty apparently healthy subjects with regular menstrual cycle, visiting gynecology outpatient clinic of Kalar General Hospital, from the beginning of February 2015 to the end of June 2015. Body Mass Index (BMI) along with serum ghrelin, leptin, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH) and testosterone levels were measured for both groups. Serum leptin was determined using sandwich ELISA, while serum ghrelin was determined using competitive ELISA. Differences between patient and control groups were assessed by using a t-test. Also, one-way Anova was used to test the relationships among different groups. A significant decrease in ghrelin level and an increase in leptin levels in women with PCOS were observed compared to the control group. Also, a significant elevation in serum levels of LH, Testosterone, Prolactin, and a decrease in serum FSH in PCOS patients were observed, when compared to the control group. Additionally, serum ghrelin decreased and serum leptin level increased significantly in women with PCOS compared to controls in all age and BMI groups. A significant decrease in ghrelin and an increase in leptin in PCOS patients were observed than in controls, indicating that they are at high risk for metabolic syndrome development.


Persistence of SARS-CoV-2 in the first trimester placenta leading to transplacental transmission and fetal demise from an asymptomatic mother.
Coronavirus disease 2019 (COVID-19) is caused by infection of the respiratory tract by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which survives in the tissues during the clinical course of infection but there is limited evidence on placental infection and vertical transmission of SARS-CoV-2. The impact of COVID-19 in first trimester pregnancy remains poorly understood. Moreover, how long SARS-CoV-2 can survive in placenta is unknown. Herein, we report a case of a pregnant woman in the first trimester who tested positive for SARS-CoV-2 at 8 weeks of gestation, although her clinical course was asymptomatic. At 13 weeks of gestation, her throat swab tested negative for SARS-CoV-2 but viral RNA was detected in the placenta, and the Spike (S) proteins (S1 and S2) were immunolocalized in cytotrophoblast and syncytiotrophoblast cells of the placental villi. Histologically, the villi were generally avascular with peri-villus fibrin deposition and in some areas the syncytiotrophoblast layer appeared lysed. The decidua also had fibrin deposition with extensive leukocyte infiltration suggestive of inflammation. The SARS-CoV-2 crossed the placental barrier, as the viral RNA was detected in the amniotic fluid and the S proteins were detected in the fetal membrane. Ultrasonography revealed extensively subcutaneous edema with pleural effusion suggestive of hydrops fetalis and the absence of cardiac activity indicated fetal demise. This is the first study to provide concrete evidence of persistent placental infection of SARS-CoV-2 and its congenital transmission is associated with hydrops fetalis and intrauterine fetal demise in early pregnancy.


Persian cats under first opinion veterinary care in the UK: demography, mortality and disorders.
Persian cats are a popular cat breed worldwide, and especially in the US, Europe and Asia. This study aimed to describe the demography, common disorders and mortality in Persians under general practice veterinary care in 2013 in the UK. The study population of 285,547 cats overall included 3235 (1.1%) Persians. Mean adult Persian bodyweight was 3.9 kg (SD 0.9) and median age was 7.0 years (IQR 3.3-11.6). At least one disorder was recorded in 2099 (64.9%) Persians. The most common specific disorders were haircoat disorders (411, 12.7%), periodontal disease (365, 11.3%), overgrown nails (234, 7.2%), and ocular discharge (188, 5.8%). The most common disorder groups were dermatological (578, 17.9%), ophthalmological (496, 15.3%) and dental (397, 12.3%). Median longevity was 13.5 years (IQR 9.9-16.0). The most common grouped causes of death were renal disease (102, 23.4%), neoplasia (37, 8.5%) and mass-associated disorder (35, 8.0%). This is the first study to use general practice data to examine the overall health of Persian cats. With haircoat, ocular and dental disorders being the predominant disorders identified, this study highlights the need for increased owner awareness to manage and prevent the typical health problems associated with this breed's phenotype.


Solution structure of halophilic malate dehydrogenase from small-angle neutron and X-ray scattering and ultracentrifugation.
Data from small-angle X-ray and neutron scattering and ultracentrifugation experiments on solutions of malate dehydrogenase from Halobacterium maris mortui are analysed together to yield a model for the enzyme particle formed by the protein and its interactions with water and salt in the solvent. The halophilic enzyme is stable only in high concentrations of salt and the model has structural features that are absent from non-halophilic malate dehydrogenase. The complementarity of the information derived from the three experimental methods is discussed extensively and quantitatively. It derives from the fact that mass density (ultracentrifugation), electron density (X-rays) and neutron scattering density are independent of each other. Each method gives a different "view" of the same particle, and an analysis of the combined data provided thermodynamic and structural parameters with, apart from the chemical composition of the solutions, only one other assumption: a constant partial specific volume for water equal to 1.00 cm3 g-1. Both the insights gained by this novel approach and its limitations are carefully pointed out. In solvents between 1 M and 5 M-NaCl, the enzyme forms a particle of invariant volume, consisting of a protein dimer (87,000 g mol-1) with which are associated 0.87 g of water and 0.35 g of salt per gram of protein. The partial specific volume of the protein calculated from the combined experimental data is 0.753(+/- 0.030) cm3 g-1, in good agreement with the value calculated from the amino acid composition. The particle has a radius of gyration of 32 A and an equivalent Stokes radius of 43 A. By combining the data from the X-ray and neutron scattering studies, the radii of gyration of the protein moiety alone and of the associated water and salt distribution were calculated. They are 28 A and about 40 A, respectively. The large-angle scattering curves show that the shapes of the particle and of the protein moiety alone are similar. At very low resolution they can be approximated by an ellipsoid of axial ratio 1:1:0.6 (or 1:1:1.5). At higher resolution, it becomes apparent that the particle has a significantly larger interface with solvent than an homogeneous ellipsoid or globular protein. The model has a globular protein core similar to non-halophilic malate dehydrogenase, with about 20% of the protein extending loosely out of the core, forming the large interface with solvent. The main interactions with water and salt take place on this outer part.


Identification of the initial water-site and movement in Gleditsia sinensis seeds and its relation to seed coat structure.
Water uptake is essential for seed germination. However, Gleditsia sinensis seeds have a water-impermeable seed coat, which is beneficial for its adaption to the environment, but prohibits its germination without treatment. This feature may be associated with the structure of the seed coat. Thus, the aim of this research was to identify and describe the initial water uptake site and water movement and to determine the relationship between seed coat structure and water absorption. A water temperature of 80 °C was optimal to break the hardseededness of G. sinensis seeds. Scanning electron microscopy (SEM) images revealed that the seed coat consisted of a palisade layer and light line that can hinder water entry into the seed. Also, a structure of vascular bundles existed in the hilar region. Hot water treatment caused the tightly closed micropyle to open and the cavity beneath it expanded; the layer of palisade cells in the lens was raised. The embryo dye-tracking tests showed that the radicle tip was the initial region to be stained red. After staining for 24 h, the red-stained area on the vascular bundle side of cotyledon was more extensive than that on the other side. Further studies by MRI maps indicated that the micropyle was the initial site for water imbibition. Some water then migrated along the space between the seed coat and the endosperm to the chalazal; simultaneously, the rest of the water reached the embryonic axis and spread into cotyledons. The maps of 20-24 h showed that water was unevenly distributed within the cotyledons in a way that the edge parts were more hydrated than the center. Blocking tests showed that the hilar region was the initial and an important region during seed imbibition. The medial region and chalazal portion were capable of imbibing water when the hilar region was blocked, but water absorption was later and slower than that through the hilar region. MRI technology provides a promising and non-invasive technique to identify the water gap and the path of water movement in the seed. Combined with the results of SEM, the relation between seed coat and its imbibition can be inferred.


Production, characterization, and dietary supplementation effect of rumen-protected fat on ruminal function and blood parameters of sheep.
Rumen-protected fat (RPF) was produced in the 1st experimental stage through melt-emulsification technique using buriti oil (BO) as core, at concentrations of 10% (BO10), 20% (BO20), and 30% (BO30) (w/w), and carnauba wax (CW) as encapsulant material. After obtention and characterization, protected fat microspheres were tested in a 2nd experimental stage on the sheep' diet using six castrated 2-year-old male Santa Ines with initial weight 48.9 ± 5.23 kg, fistulated in rumen and distributed in a double Latin square design with 3 treatments × 3 periods, to evaluate rumen pH, temperature, protozoal count, and blood parameters. There was no difference (P > 0.05) among RPF microspheres for microencapsulation yield. However, microencapsulation efficiency increased (P < 0.05) with BO addition ranging from 36 to 61.3% for BO10 and BO30, respectively. The inclusion of BO10 in the sheep's diet did not affect the ruminal dry matter degradability (DMD) of BO over time (P > 0.05); however, BO20 and BO30 had higher (P < 0.05) DMD values than BO10. No significant differences were observed among RPF for rumen pH and temperature (P > 0.05). There was an increase (P < 0.05) in the protozoal population in the rumen environment due to the microencapsulated BO30 inclusion. There was also increase (P < 0.05) in serum albumin, cholesterol, aspartate aminotransferase (ALT), and gamma-glutamyltransferase (GGT), and a reduction (P < 0.05) in serum triglycerides of the sheep when RPF microspheres increased in the diet. Melt-emulsification proved to be a good technique for microencapsulation of buriti oil into the carnauba wax matrix. RPF from buriti oil protected into carnauba wax is recommended for sheep diet because it increases energy density, without adverse effects on the protozoal populations and blood serum metabolites from the bypass effect in the rumen.


[The ultrastructure of mixed mammary gland tumors in bitches. IV. The incidence of myoepithelial cells in formation of spindle cells (author's transl)].
Spindle cells of myomatous formations of 19 canine mixed mammary tumors were studied by light and electron microscopy. The EM findings indicate that the spindle-shaped tumor cells are mostly of myoepithelial origin. However there were also formations of spindle cells which consisted of fibroblasts or fibrocytes. By light microscopy they are not always clearly distinguishable.


Phage defense origin of animal immunity.
The innate immune system is the first line of defense against microbial pathogens. Many of the features of eukaryotic innate immunity have long been viewed as lineage-specific innovations, evolved to deal with the challenges and peculiarities of multicellular life. However, it has become increasingly apparent that in addition to evolving their own unique antiviral immune strategies, all lifeforms have some shared defense strategies in common. Indeed, critical fixtures of animal innate immunity bear striking resemblance in both structure and function to the multitude of diverse bacteriophage (phage) defense pathways discovered hidden in plain sight within the genomes of bacteria and archaea. This review will highlight many surprising examples of the recently revealed connections between prokaryotic and eukaryotic antiviral immune systems.


[Microflora and immunity in surgical patients. I. Some microfloral indices in the pre- and postoperative periods].
Surgical treatment can lead to the appearance of a purulent staphylococcus infection of endogenous etiology. Endogenous infection originates as a result of the patient's diminished resistance, indicated by an increase in the number of pathogenic staphylococci, the appearance of representatives of the intestinal flora in the oral cavity and on the surface of the skin. No iogenous purulent infection.


Mucosal ulcerogenic action of monochloramine in rat stomachs: effects of polaprezinc and sucralfate.
Effects of a novel zinc compound polaprezinc [N-(3-aminopropionyl)-L-histidinatozinc] and sucralfate on the mucosal ulcerogenic responses induced by monochloramine (NH2Cl) were examined in rat stomachs. Oral administration of NH2Cl (>60 mM) produced severe lesions in unanesthetized rat stomachs, with concomitant increase of lipid peroxidation. These lesions were aggravated by sensory deafferentation but not affected by pretreatment with indomethacin or L-NAME. The mucosal ulcerogenic response to NH2Cl was significantly inhibited by oral pretreatment with either dmPGE2 (10 microg/kg), capsaicin (30 mg/kg), or NOR-3 (3 mg/kg), the NO donor. Gastric lesions induced by NH2Cl were also inhibited by prior oral administration of polaprezinc (3-30 mg/kg) as well as sucralfate (30 and 100 mg/kg). The protective effect of polaprezinc was not affected by any pretreatments such as indomethacin, L-NAME, or sensory deafferentation, while that of sucralfate was significantly mitigated in the presence of either indomethacin or L-NAME. On the other hand, mucosal exposure to NH4OH (60 mM) caused a marked PD reduction in ex vivo stomachs made ischemic by bleeding from the carotid artery, followed by severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischemia were also attenuated by prior application of polaprezinc, while dmPGE2 and sucralfate prevented such lesions without affecting the reduced PD response. These results suggest that: (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa, (2) both polaprezinc and sucralfate protect the stomach against injury caused by NH2Cl, and (3) the mechanisms underlying the protective action of sucralfate may be partly mediated by both endogenous PGs and NO but may be different from those of polaprezinc.


Diaqua-[5,5'-dicarb-oxy-2,2'-(propane-1,3-di-yl)bis-(1H-imidazole-4-carboxyl-ato)]manganese(II).
The complex mol-ecule of the title compound, [Mn(C(13)H(10)N(4)O(8))(H(2)O)(2)] or [Mn(H(4)pbidc)(H(2)O)(2)] (H(6)pbidc = 2,2'-(propane-1,3-di-yl)bis-(1H-imidazole-4,5-dicarb-oxy-lic acid), has 2 symmetry with the twofold rotation axis running through the Mn(2+) cation and the central C atom of the propanediyl unit. The cation is six-coordinated by two N atoms and two O atoms from one H(4)pbidc(2-) anion and two water O atoms in a considerably distorted octa-hedral coordination. In the crystal, adjacent mol-ecules are linked through O-H⋯O and N-H⋯O hydrogen bonds into a three-dimensional network.


Micro and nano Bi2O3 filled epoxy composites: Thermal, mechanical and γ-ray attenuation properties.
Polymer composites have attracted considerable attention as potential light-weight and cost-effective materials for radiation shielding and protection. In view of this, the present work focusses on development of lead-free composites of diglycidyl ether of bisphenol A (DGEBA) epoxy resin with micro (~ 10 μm) and nano (~ 20 nm) bismuth (III) oxide (Bi2O3) fillers, using solution casting technique. Thermal, mechanical and γ-ray attenuation properties of the composites were studied by varying the filler loading. Inclusion of the fillers into epoxy matrix was confirmed both structurally and morphologically by XRD and SEM, respectively. Thermogravimetric analysis (TGA) showed the thermal stability of composites to be as high as 400 °C. The nanocomposites exhibited relatively higher thermal stability than their micro counterparts. Among the composites, 14 wt% nano-Bi2O3/epoxy composites showed highest tensile strength of 326 MPa, which is about 38% higher than 30 wt% micro Bi2O3/epoxy composites. Mass attenuation coefficients (μ/ρ) of the composites were evaluated at γ-ray energies ranging from 0.356 to 1.332 MeV. Nanocomposites showed better γ-ray shielding at all energies (0.356, 0.511, 0.662, 1.173, 1.280 and 1.332 MeV) than micro composites with same filler loading. These studies revealed the significance of nano-sized fillers in enhancing overall performance of the composites.


Validation of the French version of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS).
The Minimal Assessment of Cognitive Function in Multiple sclerosis (MACFIMS) is an internationally recognised battery of neuropsychological tests for patients with multiple sclerosis (MS). To establish regression-based norms for the MACFIMS in French-speaking healthy subjects (HS) and validate its use in persons with multiple sclerosis (PwMS). 136 PwMS, including 43 with relapsing-remitting MS, 46 with secondary progressive MS and 45 with primary progressive MS, as well as 276 HS were enrolled. Regression-based norms and validity were established for the seven tests of the MACIMS: the Symbol Digit Modalities Test (SDMT), the Paced Auditory Serial Addition Test (PASAT), the French learning test (FLT) a French-adapted memory test (or the California Verbal Learning Test (CVLT) at re-testing), the Judgment of Line Orientation Test (JLO), the 'épreuve de classement de cartes de Champagne' (ECCC), a French adaptation of the DKEF-sorting test, the Brief Visuospatial Memory Test (BVMT-R) and the Controlled Oral Word Association Test (COWAT). Regression-based norms of MACFIMS tests were established in the HS population. The MACFIMS battery was able to identify cognitive impairment (CI) (at least two abnormal tests in different domains) in 32.7% of PwMS. The domains with more frequent impairment were (in descending order): learning followed by IPS, delayed memory, verbal fluency and working memory. This study established the regression-based norms for French subjects of the French adaptation of the MACFIMS and its validity in PwMS.


Relationship between malocclusion severity and treatment success rate in Class II nonextraction therapy.
The purpose of this study was to evaluate the treatment success rate of Class II malocclusion without extractions, according to initial severity. Class II subjects (n = 276) were divided into 2 groups according to the severity of the malocclusion. Group 1 comprised 144 patients with bilateral half Class II malocclusion at the initial mean age of 12.27 years. Group 2 comprised 132 patients who initially had bilateral complete Class II malocclusion at the initial mean age of 12.32 years. The patients' initial and final study models were evaluated with Grainger's treatment priority index. Chi-square tests were used to test for differences between the 2 groups for categorical variables. Variables regarding occlusal results were compared with independent t tests. Group 1 had a significantly better final occlusal result, a shorter treatment time, and a higher treatment efficiency index. Based on these results, it was concluded that bilateral half Class II malocclusion has a better treatment success rate than bilateral complete Class II malocclusion when treatment is conducted without extractions.


Change of the litter fall, decomposition, and nutrient release in cork oak forest after anthropogenic disturbances in North West of Tunisia.
In Mediterranean forests, anthropogenic disturbances received little interest in regards to their shrub layer induced enlargement. We studied in the cork oak forest of Beni Métir and in undisturbed and disturbed sites, the relative contribution of the tree (LT, DLT) and shrub (LS, DLS) layers to litter fall, litter decomposition, and nutrients dynamic. Our results showed that disturbance significantly (p < 0.001) reduced (-43%) total litter fall in DS in comparison with S (583 g m-2 year-1); the increased (+ 54%) shrub layer contribution to site litter fall did not counterbalance the decreased input by the tree layer. Leaf litter decomposition was negatively affected (p < 0.001) by disturbance, the remaining mass value being after 2 years, approximately 14 and 33%, respectively, for S and DS. This resulted into a gain of above ground soil organic matter 1.3 higher in DS than it was in S whereas the shrub layer contribution to litter fall increased by 50%. The prevailing driver of decomposition was very probably not related to litter quality but rather site-dependent. Indeed, layers of the same site shared the same remaining mass in spite of significant differences (p < 0.05) in initial content of minerals (N, Ca, and Mn) implicated in biological decomposition. In the disturbed site, the nutrient input by the shrub layer increased by more than double, but its low nutrient quality drastically impaired litter decomposition and mineral return at the site level. In conclusion, this study highlighted the importance of shrub layer which must be taken into account when considering any disturbance assessment and management of Mediterranean forests.


Serological evolution in women with positive antiphospholipid antibodies.
To explore the clinical and serological course of fertile women with positive antiphospholipid (aPL), and the factors and therapeutic implications associated with aPL negativization. Retrospective study including 105 women with a positive aPL serology between 1995 and 2013 attending the obstetric autoimmune pathology clinic of a tertiary facility. Patients were classified into the following 3 groups: patients with primary antiphospholipid syndrome (pAPS, 49), patients with a positive serology for aPL, not meeting clinical criteria (42), and patients with systemic lupus erythematosus and a positive aPL serology (14). They were also classified according to the serological aPL evolution: persistently negative aPL, transiently positive serology, and persistently positive serology according to established criteria. After a mean follow-up of 114.4 ± 37.2 months, 59% of patients had persistently negative antibodies, while 25.7% of patients presented persistently positive aPL serology. Multivariate analysis confirmed that smoking (OR = 4; 95% CI: 1.45-11.08; p = 0.008) was an independent risk factor for positive persistence. Persistent positivity as well as a higher antibody load was associated with higher risk for further pregnancy morbidity. In 29 patients, with persistently negative serology who were asymptomatic, treatment with low-dose aspirin was discontinued. No clinical events related to APS were reported after treatment withdrawal, during the 40.95 months of follow-up. A significant proportion of fertile women with aPL antibodies became negative during follow-up. Tobacco use and the number of positive antibodies are associated with persistently positive serology. Patients with persistently positive aPL serology suffer more obstetric complications. Treatment withdrawal might be safe in selected patients.


Colon cancer stem cells resist antiangiogenesis therapy-induced apoptosis.
Antiangiogenesis is an efficient therapy for eliminating colon cancers, but because of recurrence it remains only palliative. We hypothesized that certain populations of tumor cells resist antiangiogenesis-induced apoptosis and explored the underlying mechanism. We demonstrated that the CD133(+) population of cells in colon cancer is resistant to anti-angiogenesis therapy. Additionally, we identified an anti-apoptotic signaling pathway responsible for this resistance involving PP2A, p38MAPK, MAPKAPK2, and Hsp27. Thus, this pathway may offer a new avenue to develop target therapy for colorectal cancer.


Amelioration of osteogenesis in iPSC-derived mesenchymal stem cells from osteogenesis imperfecta patients by endoplasmic reticulum stress inhibitor.
Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder primarily caused by mutations in COL1A1 or COL1A2, which encode type I collagen. These mutations affect the quantity and/or quality of collagen composition in bones, leading to bone fragility. Currently, there is still a lack of treatment that addresses disease-causing factors due to an insufficient understanding of the pathological mechanisms involved. Induced pluripotent stem cells (iPSCs) were generated from OI patients with glycine substitution mutations in COL1A1 and COL1A2 and developed into mesenchymal stem cells (iPS-MSCs). OI-derived iPS-MSCs underwent in vitro osteogenic induction to study cell growth, osteogenic differentiation capacity, mRNA expression of osteogenic and unfolded protein response (UPR) markers and apoptosis. The effects of 4-phenylbutyric acid (4-PBA) were examined after treatment of OI iPS-MSCs during osteogenesis. OI-derived iPS-MSCs exhibited decreased cell growth and impaired osteogenic differentiation and collagen expression. Expression of UPR genes was increased, which led to an increase in apoptotic cell death. 4-PBA treatment decreased apoptotic cells and reduced expression of UPR genes, including HSPA5, XBP1, ATF4, DDIT3, and ATF6. Osteogenic phenotypes, including RUNX2, SPP1, BGLAP, and IBPS expression, as well as calcium mineralization, were also improved. MSCs differentiated from disease-specific iPSCs have utility as a disease model for identifying disease-specific treatments. In addition, the ER stress-associated UPR could be a pathogenic mechanism associated with OI. Treatment with 4-PBA alleviated OI pathogenesis by attenuating UPR markers and apoptotic cell death.


Legionellosis and biologic therapies.
Biologic therapies are widely used in inflammatory diseases, and they are associated to an increased infection risk, especially to granulomatous and intracellular infections such as Legionella. A review of the literature revealed 105 cases of Legionella pneumonia in patients taking biologic therapies. Sixty-four patients (65.3%) were treated with infliximab, 23 (23.5%) with adalimumab, 5 (5%) with etanercept and 3 (3%) with rituximab. Seventy-one per cent of the patients were treated for rheumatologic diseases and 16% for inflammatory bowel diseases. The majority of the patients received one or more concomitant immunosuppressive drugs, especially steroids (43%). Overall mortality was 19%. Legionella pneumonia might complicate therapy with biologic therapies, especially in patients being treated with infliximab or adalimumab given concomitantly with other immunosuppressive medications during their first 6 months of treatment. Physicians should be aware of this potentially severe association. Early recognition and treatment would likely result in reduced morbidity and mortality.


Age-related reference data of bone microarchitecture, volumetric bone density, and bone strength parameters in a population of healthy Brazilian men: an HR-pQCT study.
In a cross-sectional cohort of 340 healthy Brazilian men aged 20 to 92 years, data on density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop age- and site-specific reference curves. Age-dependent changes differed between the sites and bone compartments (trabecular and cortical). The aim of this study was to establish age-related reference curves for bone densities, microarchitectural properties, and estimated failure load measured by HR-pQCT (distal radius and tibia) in men. Also, to correlate bone stiffness with the other HR-pQCT parameters, areal bone mineral density (BMD) by DXA and trabecular bone score (TBS). Healthy Brazilian men (n = 340) between the ages of 20 and 92 years were recruited. Non-dominant radius and left tibia were scanned using HR-pQCT (Xtreme CT I). Standard and automated segmentation methods were performed, and bone strength estimated by FE analysis. Bone mineral density at lumbar spine, total hip, femoral neck, and TBS were measured using DXA (Hologic, QDR4500). Age-related reference curves were constructed at the distal radius and tibia for volumetric bone density, morphometry, and estimated bone strength parameters. There was a linear relationship with age only for thickness measurements of distal radius (trabecular: R2 0.108, p<0.001; cortical: R2 0.062, p=0.002) and tibia (trabecular: R2 0.109, p<0.001; cortical: R2 0.063, p=0.010), and bone strength at distal radius (R2 0.157, p<0.001). The significant correlations (p <0.05) found by Pearson's correlations (r) between bone stiffness and all other variables measured by HR-pQCT and DXA showed to be stronger at the tibia site than the distal radius. The current study expands the HR-pQCT worldwide database and presents an adequate methodology for the construction of reference data in other populations. Moreover, the correlation of bone strength estimated by FEA with other bone microstructural parameters provided by HR-pQCT helps to determine the contribution of each of these variables to fracture risk prediction in men.


Photoswitching of model ion channels in lipid bilayers.
Membrane proteins can be regulated by alterations in material properties intrinsic to the hosting lipid bilayer. Here, we investigated whether the reversible photoisomerization of bilayer-embedded diacylglycerols (OptoDArG) with two azobenzene-containing acyl chains may trigger such regulatory events. We observed an augmented open probability of the mechanosensitive model channel gramicidin A (gA) upon photoisomerizing OptoDArG's acyl chains from trans to cis: integral planar bilayer conductance brought forth by hundreds of simultaneously conducting gA dimers increased by typically >50% - in good agreement with the observed increase in single-channel lifetime. Further, (i) increments in the electrical capacitance of planar lipid bilayers and protrusion length of aspirated giant unilamellar vesicles into suction pipettes, as well as (ii) changes of small-angle X-ray scattering of multilamellar vesicles indicated that spontaneous curvature, hydrophobic thickness, and bending elasticity decreased upon switching from trans- to cis-OptoDArG. Our bilayer elasticity model for gA supports the causal relationship between changes in gA activity and bilayer material properties upon photoisomerization. Thus, we conclude that photolipids are deployable for converting bilayers of potentially diverse origins into light-gated actuators for mechanosensitive proteins.


Formulation of Research Question and Composing Study Outcomes and Objectives.
Framing an appropriate research question is the most critical and fundamental part of a study. This helps in developing a hypothesis, formulating aims and objectives and methodological execution of the study. Research questions are usually generated by literature backed thorough analysis of the gaps in previous studies and funnelling it to a specific focussed issue. The research question should be framed using the PICO (Population, Intervention/Exposure, Comparator and Outcome) format and should fulfil the FINER (feasible, interesting, novel, ethically sound, and relevant) criteria for practical aspects. Objectives should always be framed in alignment of the research question using SMART (specific, measurable, achievable, realistic and time defined) approach. Outcomes are classified as primary and secondary. It is advisable to have only one primary objective while secondary objectives can be multiple (usually not exceeding five). This paper describes a cascade approach starting from framing the research question and then deciding on the outcomes and study objectives.


Lipoprotein(a) concentration, genetic variants, apo(a) isoform size, and cellular cholesterol efflux in patients with elevated Lp(a) and coronary heart disease submitted or not to lipoprotein apheresis: An Italian case-control multicenter study on Lp(a).
Coronary artery disease (CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking. The objective of this study was to determine relationships between Lp(a) and CLC, the impact of lipoprotein apheresis (LA), and describe the genetic profile of Lp(a). We conducted a multicenter, observational study in Italian patients with hyperLp(a) and premature CAD with (n = 18)/without (n = 16) LA in which blood samples were analyzed for Lp(a) parameter and CLC. Genetic profiling of LPA was conducted in patient receiving LA. Mean macrophage CLC of the pre-LA serum was significantly higher than that of normolipidemic controls (19.7 ± 0.9 μg/mg vs 16.01 ± 0.98 μg/mg of protein, respectively). After LA, serum macrophage CLC was markedly lower relative to preapheresis (16.1 ± 0.8 μg/mg protein; P = .003) and comparable with CLC of the normolipidemic serum. LA did not significantly affect average apo(a) isoform size distribution. No anthropometric or lipid parameters studied were related to serum CLC, but there was a relationship between CLC and the Lp(a) plasma concentration (P = .035). DNA analysis revealed a range of common genetic variants. Two rare, new variants were identified: LPA exon 21, c.3269C>G, p.Pro1090Arg, and rs41259144 p.Arg990Gln, c.2969G>A CONCLUSIONS: LA reduces serum Lp(a) and also reduces macrophage CLC. Novel genetic variants of the LPA gene were identified, and geographic variations were noted. The complexity of these polymorphisms means that genetic assessment is not a predictor of CAD risk in hyperLp(a).


Oxygenated cardioplegia: the metabolic and functional effects of glucose and insulin.
Reports differ as to the efficacy of glucose and insulin as cardioplegic additives. Although deliberate oxygenation of crystalloid cardioplegic solutions improves myocardial protection, little is known about the protection afforded by glucose and insulin in such oxygenated solutions. In the isolated working rat heart, we studied the addition of oxygen, glucose, and insulin, separately and together, to a cardioplegic solution. The solution was equilibrated with O2 or N2, with glucose added as a substrate or sucrose as a nonmetabolizable osmotic control, with or without insulin. Hearts were arrested for 2 hours at 8 degrees C by multidose infusions. Oxygenation decreased lactate production and improved high-energy phosphate and glycogen preservation during arrest, prevented ischemic contracture, and improved functional recovery. The addition of glucose to the oxygenated solution increased the level of adenosine triphosphate at end-arrest from 10.5 +/- 0.5 to 13.9 +/- 0.6 nmol/mg dry weight and glycogen stores from 18.7 +/- 2.5 to 35.7 +/- 5.5 nmol/mg dry weight. The further addition of insulin did not better preserve these metabolites. Improvements in functional recovery due to glucose or insulin in the oxygenated solution attained statistical significance when both additives were included. Glucose increased lactate production significantly only when the solution was nitrogenated. Insulin added to the nitrogenated glucose-containing solution increased adenosine triphosphate and glycogen levels after 1 hour of arrest; and, although insulin did not prevent ischemic contracture from developing during the latter part of arrest with profound depletion of these metabolites, functional recovery was improved. The mechanism of improved functional recovery by insulin is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)


Interaction between neutrophil-derived elastase and reactive oxygen species in cartilage degradation.
The role of proteases and reactive oxygen species (ROS) in polymorphonuclear neutrophil (PMN) induced cartilage degradation in vitro were studied. ONO-5046, a novel synthetic elastase inhibitor, significantly and dose dependently protected cartilage from degradation induced by PMNs stimulated with phorbol myristate acetate (PMA), opsonized zymosan, N-formyl-methionyl-leucyl-phenylalanine plus cytochalasin-B, or A-23187. The degradation by PMA-stimulated PMNs was unaffected by protease inhibitors which lack anti-elastase activity. However, the hydrogen peroxide (H2O2) reducing agent catalase afforded significant protection. Measurement of elastase activity following PMN activation by PMA showed that antioxidants which reduce H2O2 and/or hypochlorous acid decreased elastase activity. Thus, it is suggested that an indirect interaction between ROS and elastase activity may exist in PMN induced cartilage degradation. Furthermore, the possible implication of an endogenous elastase inhibitor(s) is discussed.


Guillain-Barré Syndrome due to COVID-19 Vero Cell Vaccination Associated with Concomitant COVID-19 Infection-induced ARDS and Treated Successfully by Therapeutic Plasma Exchange: A First Case Report from Vietnam.
Post-vaccination adverse reactions have been reported with varying symptoms and severity owing to research and production time pressures during the coronavirus disease 2019 (COVID-19) pandemic. In this article, we report a rare case of Guillain-Barré syndrome (GBS) in a patient with COVID-19 with acute respiratory distress syndrome (ARDS) after receiving Sinopharm's Vero Cell vaccine (China). The patient who was initially negative for COVID-19 was diagnosed with GBS based on paralysis that developed from the lower extremities to the upper extremities, as confirmed by cytoalbuminologic dissociation in the cerebrospinal fluid. The patient's condition worsened with ARDS caused by COVID-19 infection during the hospital stay, and SpO2 decreased to 83% while receiving oxygen through a non-rebreather mask (15 l/min) on day 6. The patient was treated with standard therapy for severe COVID-19, invasive mechanical ventilation, and five cycles of therapeutic plasma exchange (TPE) with 5% albumin replacement on day 11 due to severe progression. The patient was weaned off the ventilator on day 28, discharged on day 42, and was completely healthy after 6 months without any neurological sequelae until now. Our report showed the potential of TPE for GBS treatment in critically ill patients with COVID-19 after COVID-19 vaccination.


Universal to standard precautions in disease prevention: preliminary development of compliance scale for clinical nursing.
The Center for Disease Control and Prevention revised the infection control practice from Universal Precautions to Standard Precautions in 1996. Although the practice of Standard Precautions has been implemented for almost 15 years in clinical settings, recent local research still adopts the Universal Precautions Scale to measure the compliance with the current infection control practice of general frontline nursing staff and students. Despite the scale's sound psychometric properties, that its items may not be sensitive and comprehensive enough to reflect the current compliance of frontline staff to Standard Precautions is questionable. The present study aims to develop a Compliance with Standard Precautions Scale (CSPS) for use by the general frontline nurses and nursing students in clinical settings. The current study employed a recognized instrumentation design. In addition, a preliminary assessment of reliability and validity was described. The CSPS was developed through the modification of the Universal Precautions Scale through five steps: reviewing the infection control guidelines, modifying the items of the Universal Precautions Scale, examining the relevance and adequacy of new items by an expert panel, verifying the linguistic and grammatical issues, and examining the understandability of the items and acceptability of the entire instrument by stakeholders. Internal consistency was examined using Cronbach's alpha statistic. The original 15-item Universal Precautions Scale was revised to the 20-item CSPS, in which 13 items were revised in wording and concept, 2 items were deleted, and 7 items were added. The 20-item new scale obtained the overall content validity index of 0.90, and 100% understandability and acceptability in face validity, and Cronbach's alpha of 0.73. With the explicit justification on each generated item and the satisfactory results of the psychometric testing, the CSPS is a preliminary reliable and valid instrument in measuring the compliance with Standard Precautions of frontline nurses and nursing students in clinical settings.