Infection of Aotus azarae boliviensis monkeys with different strains of Plasmodium vivax.
Sixty-seven splenectomized Aotus azarae boliviensis were infected with strains of Plasmodium vivax from Southeast Asia (2), New Guinea (2), North Korea (1), and Central America (3). Maximum parasitemias varied among the different strains, with the mean maximum parasitemia for the primary infection period being 16,200 per mm3. Animals previously infected with Plasmodium falciparum and Plasmodium malariae produced maximum parasitemias of 30,200 and 11,900 per mm3, respectively. Gametocytes infective to Anopheles freeborni mosquitoes were produced with 7 of the 8 strains examined.


Prodrug of proline analogue reduces hypoxic pulmonary hypertension in rats.
A polymeric prodrug of the proline analogue cis-4-hydroxy-l-proline (CHOP), poly(ethylene glycol)-lysine-CHOP or CHOP-PEG, prevents hypoxic pulmonary hypertension in rats by inhibiting collagen accumulation. A more potent prodrug was synthesized by increasing the loading of CHOP on the carrier from 14 to 100%. Pulmonary antihypertensive efficacy and pharmacokinetics are described in the rat hypoxia model. The antihypertensive effect of CHOP-PEG in rats exposed to 10% O2 for 7d showed approximately 2 x 10(2)-fold greater potency than monomeric CHOP. Routes of administration were compared to determine the lowest dose of CHOP-PEG that reduced right ventricular pressure approximately 50% vs. untreated hypoxic controls at 7d. Total doses required were: continuous s.c. via an osmotic minipump, 0.8 mg; single s.c., 10mg; single i.v., 40 mg; and single intratracheal 90 mg. Efficacy for at least 7d postdosing in pre-established pulmonary hypertension was shown. Using an ELISA-based assay, biphasic i.v. and stable s.c. pharmacokinetic profiles were observed 72 h after single injections and 7d after continuous s.c. infusion. Thus, this CHOP-PEG formulation prevents and reverses chronic hypoxic pulmonary hypertension in rats, is most effective when given by continuous s.c. infusion, and has favorable pharmacokinetic properties. Potent inhibitors of fibrosis appear to be promising agents in treating pulmonary hypertension and possibly other fibrosing diseases.


Partial deletions of the autoregulatory C-terminal domain of Artemis and their effect on its nuclease activity.
Artemis is a 692 aa nuclease that is essential for opening hairpins during vertebrate V(D)J recombination. Artemis is also important in the DNA repair of double-strand breaks via the nonhomologous DNA end joining (NHEJ) pathway. Therefore, absence of Artemis has been shown to result not only in the blockage of lymphocyte development in vertebrates, but also sensitivity of organisms and cells to double-strand break-inducing events that arise in the course of normal metabolism. Nonhomologous DNA end joining (NHEJ) is the major pathway for the repair of double-strand DNA breaks in most vertebrate cells during most of the cell cycle, including in resting cells. Artemis is the primary nuclease for resection of damaged DNA at double-strand breaks. Artemis alone is inactive as an endonuclease, though it has 5'-exonuclease activity. The endonuclease activity requires physical interaction with DNA-PKcs and subsequent activation steps. Truncation of the C-terminal half of Artemis permits Artemis to be active, even without DNA-PKcs. Here we create a systematic set of deletions from the Artemis C-terminus to determine the minimal extent of C-terminal deletion for Artemis to function in a DNA-PKcs-independent manner. We discuss these data in the context of recent structural studies. The results will be useful in future studies to determine the full range of functions of the C-terminal region of Artemis in the regulation of its endonuclease activity.


Evaluation of Biosurfactant Production by Bacillus Species Using Glucose and Xylose as Carbon Sources.
Lignocellulosic material is one of the raw materials that can be used to reduce the cost of biosurfactant production because it is cheap, abundantly available, and contains cellulose and hemicellulose which can be hydrolyzed to glucose and xylose as carbon sources. This study aimed to evaluate biosurfactant production by Bacillus species using glucose and xylose as carbon sources, which are the most abundant sugar monomers from the hydrolysis of lignocellulosic materials. In this study, biosurfactants were produced by six bacterial isolates belonging to the Bacillus genus. The six bacterial isolates were identified molecularly through 16S rRNA sequencing. The results showed that the six bacterial isolates were identified as B. subtilis ITBCC46, B. subtilis ITBCC40, B. subtilis ITBCC31, B. siamensis ITBCC36, B. xiamenensis ITBCC43, and B. subtilis ITBCC30. All Bacillus species used in this study could be grown on glucose or xylose media. Biosurfactants produced by B. subtilis ITBCC46, B. subtilis ITBCC40, B. subtilis ITBCC31, and B. siamensis ITBCC36 could reduce surface tension below 40 mN/m (32.70 to 39.15 mN/m). All biosurfactants produced by these Bacillus species had more than 50% emulsification stability. These characteristics indicated that the biosurfactants had the desired quality.


Sensory reinforcement of head turning with nonambulatory, profoundly mentally retarded persons.
Two experiments examined the reinforcing value of response contingent sensory events consisting of combinations of visual, auditory, and vibratory stimulation. Ten nonambulatory, profoundly mentally retarded individuals participated in these studies. Four different stimulus combinations were required to achieve operant conditioning of head turning responses in 6 participants. These sensory reinforcers included 5-s simultaneous presentations of picture, music, and vibration (N = 2), picture and music (N = 2), picture and vibration (N = 1), and picture alone (N = 1). These results indicate that systematically varying a multimodal sensory event is a fruitful procedure for identifying positive reinforcers for nonambulatory, profoundly mentally retarded persons.


Effect of ethanol extract of black soybean coat on physicochemical properties and biological activities of chitosan packaging film.
Chitosan (CS) with an ethanol extract of black soybean coat (EBSC) was prepared, and its physicochemical properties and antioxidant and antibacterial activities were tested. The results showed that EBSC significantly increased the thickness and UV-Vis light barrier ability of the CS-based films, while the swelling degree, water vapor permeability, and tensile strength decreased. The CS-EBSC films had smooth surfaces, compact cross-sections, and no cracks, and they had higher crystallinity than the CS film. Fourier transform-infrared spectroscopy indicated that there were noncovalent bonds (hydrogen bonds) between EBSC and CS. Furthermore, the CS-EBSC III film presented a stronger ABTS radical scavenging ability (66.58%) and could effectively inhibit Bacillus subtilis, Escherichia coli, and Staphylococcus aureus. The lipid oxidation test proved that CS-EBSC films significantly reduced the peroxide value of lard. The results above indicate that CS-EBSC films could be used as an active packaging material to improve the shelf life of food.


Temporal Changes in Racial and Ethnic Disparities in the Utilization of Left Atrial Appendage Occlusion in the United States.
Racial and ethnic disparities in the access to left atrial appendage occlusion (LAAO) have been previously described. However, it remains unclear if there have been any changes in these disparities over the years and if the disparities include other racial and ethnic groups not previously studied. We aimed to determine the temporal evolution of the racial and ethnic disparities in the utilization of LAAO from 2016 to 2019. We conducted a retrospective cohort study using the National Inpatient Sample from 2016 to 2019. International Classification of Diseases, 10th edition codes were used to identify all adult admissions with atrial fibrillation (AF) and those who underwent LAAO. The sample was divided into Asian American and Pacific Islander, Black, Hispanic, White, and other races/ethnicities. Our primary outcome was the utilization of LAAO in patients admitted with a diagnosis of AF. The Cochran-Armitage test was conducted to evaluate the yearly trend in LAAO utilization stratified by race/ethnicity. Multivariable regression analysis was conducted to assess the association of race/ethnicity with multiple end points. A total of 59,415 patients underwent LAAO. The highest yearly increase in LAAO utilization was seen in White patients (trend: 0.16%, p <0.001). Furthermore, compared with White patients, the yearly increase in LAAO utilization was lower in all other racial/ethnic groups. Black patients had the lowest odds of who underwent LAAO (odds ratio = 0.45, 95% confidence interval 0.40 to 0.50, p <0.001). In conclusion, significant gaps exist in the utilization of LAAO between racial and ethnic groups, and they appear to continue worsening from 2016 to 2019.


Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta.
Protein kinase C (PKC), which comprises 11 closely related isoforms, has been implicated in a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis and tumour development. Among the PKC isotypes, PKC-delta is unique in that its overexpression results in inhibition of cell growth. Here we show that mice that lack PKC-delta exhibit expansion of the B-lymphocyte population with the formation of numerous germinal centres in the absence of stimulation. The rate of proliferation in response to stimulation was greater for B cells from PKC-delta-deficient mice than for those from wild-type mice. Adoptive transfer experiments suggested that the hyperproliferation phenotype is B-cell autonomous. Production of interleukin-6 was markedly increased in B cells of PKC-delta-null mice as a result of an increase in the DNA-binding activity of NF-IL6. Furthermore, the PKC-delta-deficient mice contain circulating autoreactive antibodies and display immune-complex-type glomerulonephritis, as well as lymphocyte infiltration in many organs. These results suggest that PKC-delta has an indispensable function in negative regulation of B-cell proliferation, and is particularly important for the establishment of B-cell tolerance.


Synergic effects of kallikrein-kinin and prostaglandins on renin release on infusion of isolated hog kidney with aldosterone.
The effects of infusion of a large amount of aldosterone into the renal artery of isolated perfused hog kidney on the release of renin, prostaglandins (PG) and kinin and the excretion of urinary kallikrein were investigated. Infusion of aldosterone at a rate of 100 ng/min (100 to 800 ng/ml of perfusate) resulted in significant releases of renin, PG (PGE2 , 6-0-PGF1 alpha), and kinin and increase in urinary kallikrein. Infusion of aldosterone and an inhibitor of kallikrein, aprotinin, decreased the releases of renin, PG and kinin and infusion of aldosterone with indomethacin decreased the release of PG but increased that of kinin and urinary kallikrein without significant change in renin releases. These findings suggest that the release of renin by aldosterone may result from synergic effects of renal PG and the kallikrein -kinin system.


Simultaneous analysis of single-photon timing data for the one-step determination of activation energies, frequency factors and quenching rate constants. Application to tryptophan photophysics.
A general global analysis of single-photon timing data is presented in which each fluorescence decay curve can be described by a different decay law. The model parameters can be held in common within one curve and/or between related curves. Any or all parameters can be kept fixed, or they may be variable to seek optimum values. This general analysis allows the determination of activation energies, frequency factors and quenching rate constants in one step. The construction of the global mapping table which relates parameters in one experiment to those in another is explained in detail. The use and performance of this general simultaneous analysis are examined using tryptophan fluorescence decays at pH 6.0 obtained at various emission wavelengths as a function of temperature and added solute quencher. The results show that tryptophan at pH 6.0 decays as a biexponential with decay times which are independent of the analysis wavelength. The decay component with the short lifetime has a deactivation rate constant of 1.4 x 10(9) s-1 independent of temperature. The decay component with the long lifetime has an activation energy of 28 kJ/mol and a frequency factor of 3 x 10(13) s-1; its temperature-independent decay rate constant equals 1 x 10(8) s-1. Recursion formulas for a computer program to estimate activation energies, frequency factors, and decay rate constants are provided.


Causes of neonatal deaths in a pediatric hospital neonatal unit. An autopsy study of a ten-year period.
A study is presented of 1020 consecutive autopsies on newborn infants who died during the first 28 days of life at the Children's Hospital, University of Helsinki, during 1969-1978. The infants were grouped into four categories according to their weight at birth and into early (0-7 days) and late (8-28 days) neonatal groups according to their age at death. 77.5% of the cases fell into the early neonatal group. The most common causes of death were hyaline membrane disease (HMD) and cerebral haemorrhage (CH), which together accounted for 41.9% of all the deaths. Congenital anomaly was the second most common group of causes, comprising 35.3% of the cases. A gradual fall in the total number of deaths was conspicuous during the ten-year period. There was a statistically significant decrease in the number of deaths from HMD and CH in the weight categories 1001-1500 g and 1501-2500 g. The fall is considered to reflect improvement in both obstetrics and neonatal medicine.


Liposome reconstitution of a minimal protein-mediated membrane fusion machine.
Biological membrane fusion is dependent on protein catalysts to mediate localized restructuring of lipid bilayers. A central theme in current models of protein-mediated membrane fusion involves the sequential refolding of complex homomeric or heteromeric protein fusion machines. The structural features of a new family of fusion-associated small transmembrane (FAST) proteins appear incompatible with existing models of membrane fusion protein function. While the FAST proteins function to induce efficient cell-cell fusion when expressed in transfected cells, it was unclear whether they function on their own to mediate membrane fusion or are dependent on cellular protein cofactors. Using proteoliposomes containing the purified p14 FAST protein of reptilian reovirus, we now show via liposome-cell and liposome-liposome fusion assays that p14 is both necessary and sufficient for membrane fusion. Stoichiometric and kinetic analyses suggest that the relative efficiency of p14-mediated membrane fusion rivals that of the more complex cellular and viral fusion proteins, making the FAST proteins the simplest known membrane fusion machines.


Effect of TNF-α -308G/A (rs1800629) Promoter Polymorphism on the Serum Level of TNF-α Among Iraqi Patients with Generalized Vitiligo.
Vitiligo is a chronic acquired pigmentary disorder of the skin; it results from immunological distruction of functioning melanocytes. The cytokine TNF-α plays a central role in the initiation of melanocyte apoptosis in vitiligo. Single nucleotide polymorphism (SNP) in the promoter region of the gene coding for serum TNF-α may affect its production. The aim of this study is to assess serum TNF-α as a risk factor for generalized vitiligo among Iraqi patients and to rule out that polymorphism at the -308 position affects serum TNF-α. This case-control study was conducted at Sulaymaniyah Dermatology Teaching Center (SDTC), Iraq. Serum concentration of TNF-α was measured using enzyme linked immunosorbent assay (ELISA) technique in 80 patients with generalized vitiligo and 40 clinically healthy controls. The amplification refractory mutation system polymerase chain reaction (ARMS-PCR) technique was used for detection of TNF-308G/A gene polymorphism. TNF-α level correlated with TNF-308G/A gene polymorphism. Serum concentration and TNF -308G/A gene polymorphism have been analyzed in correlation with demographic features and clinical characteristics of patients with generalized vitiligo. Statistically significant elevation of serum TNF-α seen in patients compared to a control group (p-value 0.01). Significantly higher TNF-α level (p-value 0.01) found among patients with active generalized vitiligo. Elevated serum levels of TNF-α were significantly associated with both TNFA1 (TNF-308G) allele (p-value 0.04) and TNFA2 (TNF-308A) allele (p-value 0.03). TNF-α -308GA polymorphism was not affected by demographic features and clinical characteristics of patients with generalized vitiligo. TNF-α in the serum is a risk factor for generalized vitiligo among Iraqi patients. Patients with active vitiligo have a higher serum TNF-α level. No difference was found between serum level of TNF-α with TNF-α polymorphism at position -308 (TNF -308). This involves substituting G allele for the A allele.


Cognitive load decreases cooperation and moral punishment in a Prisoner's Dilemma game with punishment option.
The present study serves to test whether cooperation and moral punishment are affected by cognitive load. Dual-process theories postulate that moral behavior is intuitive which leads to the prediction that cooperation and moral punishment should remain unaffected or may even increase when cognitive load is induced by a secondary task. However, it has also been proposed that cognitive control and deliberation are necessary to choose an economically costly but morally justified option. A third perspective implies that the effects of cognitive load may depend on the specific processes involved in social dilemmas. In the present study, participants played a simultaneous Prisoner's Dilemma game with a punishment option. First, both players decided to cooperate or defect. Then they had the opportunity to punish the partners. In the cognitive-load group, cognitive load was induced by a continuous tone classification task while the no-load group had no distractor task. Under cognitive load, cooperation and moral punishment decreased in comparison to the no-load condition. By contrast, hypocritical and antisocial punishment were not influenced by the dual-task manipulation. Increased cognitive load was associated with a bias to punish the partners irrespective of the outcome of the Prisoner's Dilemma game, suggesting that punishment was applied less purposefully in the cognitive-load condition. The present findings are thus in line with the idea that the availability of cognitive resources does not always have a suppressive effect on moral behaviors, but can have facilitating effects on cooperation and moral punishment.


Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence.
Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions.


Serum-stimulated cell growth causes oscillations in casein kinase II activity.
We have tested the effects of serum-stimulated growth of quiescent WI38 human lung fibroblasts on cellular casein kinase II (CK-II) activity. Using the casein kinase II synthetic substrate RRREEETEEE we find a transient 6-fold elevation in CK-II activity in cell homogenates within 30 min following serum stimulation. Additional cycles of CK-II activation and inactivation are seen at 12 and 24 h after stimulation. The oscillations in CK-II activity are largely independent of de novo protein synthesis, and, thus, are likely to reflect cycles of post-translational activation and inhibition of the cellular kinase pool. In contrast to the activity profile of CK-II, we find that cyclic AMP-dependent protein kinase is rapidly inhibited upon serum-stimulation of WI38 cells. These results demonstrate that CK-II activity is subject to unique cellular regulation during proliferation and are consistent with the postulate that CK-II plays an important role in cell growth.


Moderate Electric Field Treatment Enhances Enzymatic Hydrolysis of Cellulose at Below-Optimal Temperatures.
Saccharification of cellulosic biomass for the fermentation of transportation fuels faces several challenges. Cellulose is highly stable, and even with enzymatic assistance, decomposition of cellulose is slow. Additionally, the enzymes are expensive and sensitive to thermal and mechanical inactivation. In this work, we studied the effects of moderate electric field (MEF, in the range from 1 to 1000 V per cm) treatments on the effectiveness of enzymatic saccharification. MEF treatments were applied to determine their effects on enzyme activity. We considered the effects of field strength, frequency, application regime and temperature. It was found that the enzyme responded to alterations in the frequency of the waveform, with 50 to 60 Hz maximizing the effects of the field, although the effects of field strength and application regime were more significant. It was found that the electric field could have a positive, negative, or negligible effect depending on the field strength. Most notably, when MEF treatments were applied over a range of temperatures, it was found that MEF treatment significantly improved enzyme activity at lower temperatures, leading to the observation that MEF treatment imitates a temperature increase. Calculations simulating the electrophoretic motion of the enzymes verified that the magnitude of motion associated with the MEF treatments was qualitatively similar to the change in molecular motion associated with temperature increases.


Genetic variability analysis of partially salt tolerant local and inbred rice (Oryza sativa L.) through molecular markers.
Random Amplified Polymorphic DNA (RAPD) analysis was performed to assess the genetic variability in sixteen selected germplasms of rice, Oryza sativa L. using eight decamer RAPD primers. The data obtained from this investigation reveals a high level of polymorphism between cultivars. The primers produced a total of 255 bands of which all 255 bands were polymorphic indicating 100% polymorphism. The size of the amplified bands ranged from 220 bp to 2290 bp. The number of polymorphic fragments ranged from 24 to 49 with an average of 32 polymorphic fragments for each primer. The primer OPX04 produced the maximum number (49) of polymorphic bands while the OPB04 and OPB17 produced the minimum number (24) of polymorphic bands. The polymorphic information content (PIC) values ranged from 0.6616 to 0.8845 with an average of 0.832. The highest PIC value (0.8845) was obtained for primer OPL03. The RAPD data was analyzed to determine the pair-wise genetic similarity coefficients which ranged from 0.00 to 0.83. The BRRIdhan 23 and the BRRIdhan 41 varieties were the closest genotypes with the highest similarity index of 83%. This was followed by 77% similarity between a pair of cultivars Kalamona and Horkuch. On the other hand, 100% dissimilarity was seen between BRRIdhan 53, BRRIdhan 50, BRRIdhan 10, BRRIdhan 70, BRRIdhan 54, BRRIdhan 40, BRRIdhan 23, BRRIdhan 47, BRRIdhan 41 and Dadsail respectively and between BRRIdhan 53 and Horkuch; indicating a high level of variability between paired genotypes. Cluster analysis was performed using Unweighted Paired Group of Arithmetic Means (UPGMA). The UPGMA dendrogram resolved the selected rice cultivars into four clusters.


Fear and the brain: where have we been, and where are we going?
In recent years, there has been an explosion of interest in the neural basis of emotion. Much of this enthusiasm has been triggered by studies of the amygdala and its contribution to fear. This work has shown that the amygdala detects and organizes responses to natural dangers (like predators) and learns about novel threats and the stimuli that predict their occurrence. The latter process has been studied extensively using a procedure called classical fear conditioning. This article surveys the progress that has been made in understanding the neural basis of fear and its implications for anxiety disorders, as well as the gaps in our knowledge.


Central obesity is important but not essential component of the metabolic syndrome for predicting diabetes mellitus in a hypertensive family-based cohort. Results from the Stanford Asia-pacific program for hypertension and insulin resistance (SAPPHIRe) Taiwan follow-up study.
Metabolic abnormalities have a cumulative effect on development of diabetes, but only central obesity has been defined as the essential criterion of metabolic syndrome (MetS) by the International Diabetes Federation. We hypothesized that central obesity contributes to a higher risk of new-onset diabetes than other metabolic abnormalities in the hypertensive families. Non-diabetic Chinese were enrolled and MetS components were assessed to establish baseline data in a hypertensive family-based cohort study. Based on medical records and glucose tolerance test (OGTT), the cumulative incidence of diabetes was analyzed in this five-year study by Cox regression models. Contribution of central obesity to development of new-onset diabetes was assessed in subjects with the same number of positive MetS components. Among the total of 595 subjects who completed the assessment, 125 (21.0%) developed diabetes. Incidence of diabetes increased in direct proportion to the number of positive MetS components (P ≪ 0.001). Although subjects with central obesity had a higher incidence of diabetes than those without (55.7 vs. 30.0 events/1000 person-years, P ≪ 0.001), the difference became non-significant after adjusting of the number of positive MetS components (hazard ratio = 0.72, 95%CI: 0.45-1.13). Furthermore, in all participants with three positive MetS components, there was no difference in the incidence of diabetes between subjects with and without central obesity (hazard ratio = 1.04, 95%CI: 0.50-2.16). In Chinese hypertensive families, the incidence of diabetes in subjects without central obesity was similar to that in subjects with central obesity when they also had the same number of positive MetS components. We suggest that central obesity is very important, but not the essential component of the metabolic syndrome for predicting of new-onset diabetes. ( NCT00260910, ClinicalTrials.gov).


Skills integration in a simulated and interprofessional environment: an innovative undergraduate applied health curriculum.
The objective of our study was to propose an innovative applied health undergraduate curriculum model that uses simulation and interprofessional education to facilitate students' integration of both technical and "humanistic" core skills. The model incorporates assessment of student readiness for clinical education and readiness for professional practice in a collaborative, team-based, patient-centred environment. Improving the education of health care professionals is a critical contributor to ultimately improving patient care and outcomes. A review of the current models in health sciences education reveals a scarcity of clinical placements, concerns over students' preparedness for clinical education, and profession-specific delivery of health care education which fundamentally lacks collaboration and communication amongst professions. These educational shortcomings ultimately impact the delivery and efficacy of health care. Construct validation of clinical readiness will continue through primary research at The Michener Institute for Applied Health Sciences. As the new educational model is implemented, its impact will be assessed and documented using specific outcomes measurements. Appropriate modifications to the model will be made to ensure improvement and further applicability to an undergraduate medical curriculum.


[Importance of Bdellovibrio in regulating microbial cenoses and self-purification processes in domestic sewage].
The bacterial parasite Bdellovibrio was directly proved to be involved in the regulation of microbial cenoses and in the self-purification of domestic waste waters. The incidence of heterotrophs, Gram-negative bacteria, E. coli and Bdellovibrio was followed up in dynamics in the microecological system of waste waters for ten days. In control experiments, bdellovibrions were removed using pteridine as a vibriostatic agent. In the absence of bdellovibrions, the cell number of the studied microorganisms did not increase after reaching a stationary level. In the control, the total incidence of heterotrophs decreased 1355 times, that of Gram-negative bacteria fell down 527 times, and that of E. coli cells dropped 3419 times due to the interaction between the host bacteria and Bdellovibrio. The variations in the number of interacting cells were characteristic of a two-component parasite-host system.


Meta-analysis of prophylactic abdominal drainage in pancreatic surgery.
Intra-abdominal drains are frequently used after pancreatic surgery whereas their benefit in other gastrointestinal operations has been questioned. The objective of this meta-analysis was to compare abdominal drainage with no drainage after pancreatic surgery. PubMed, the Cochrane Library and Web of Science electronic databases were searched systematically to identify RCTs comparing abdominal drainage with no drainage after pancreatic surgery. Two independent reviewers critically appraised the studies and extracted data. Meta-analyses were performed using a random-effects model. Odds ratios (ORs) were calculated to aggregate dichotomous outcomes, and weighted mean differences for continuous outcomes. Summary effect measures were presented together with their 95 per cent confidence intervals. Some 711 patients from three RCTs were included. The 30-day mortality rate was 2·0 per cent in the drain group versus 3·4 per cent after no drainage (OR 0·68, 95 per cent c.i. 0·26 to 1·79; P = 0·43). The morbidity rate was 65·6 per cent in the drain group and 62·0 per cent in the no-drain group (OR 1·17, 0·86 to 1·60; P = 0·31). Clinically relevant pancreatic fistulas were seen in 11·5 per cent of patients in the drain group and 9·5 per cent in the no-drain group. Reinterventions, intra-abdominal abscesses and duration of hospital stay also showed no significant difference between the two groups. Pancreatic resection with, or without abdominal drainage results in similar rates of mortality, morbidity and reintervention.


Morphometric study of lymphangiogenesis in different lesions of psoriasis vulgaris with correlation to disease activity.
In the last decades, attention to the role of lymphangiogenesis in psoriasis has been paid. Our study was conducted to evaluate podoplanin-stained lymphatic vessels and the level of lymphangiogenesis in papular psoriatic lesions and psoriatic plaques and ascertain if podoplanin provides any additional prognostic information. Number of lymphatic vessels and total lymphatic vessel area were morphometrically analyzed in podoplanin-stained sections, using anti-D2-40, together with the immunohistochemical study of epidermal Ki-67 in psoriasis vulgaris (n = 20) (papules = 7 and plaques = 13) and control skin specimens (n = 20). The number of lymphatic vessels and total lymphatic vessel area were higher in psoriasis cases compared with normal skin (p = 0.01, p = 0.01 respectively). In psoriatic plaques, the number of lymphatic vessels, total lymphatic vessel area, and epidermal Ki-67 immunoreactivity were higher than in papular lesions (p = 0.002, p = 0.008, and p = 0.01, respectively). Psoriasis vulgaris is found to be a lymphangiogenesis-dependent disease, and the lymphatic vascular network is in remodeling and expanding process. Podoplanin may be implicated in the pathogenesis of psoriasis and could be used as a prognostic biomarker for disease severity and progression.


Complete Genome Sequence of a Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Variant with a New Insertion in Glycoprotein 5, Isolated from a Stillborn Fetus.
Here, we report the complete genome sequence of strain GD-2011, a highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) that was isolated from a stillborn fetus. The GD-2011 strain is characterized by a discontinuous 30-amino acid deletion in the nonstructural protein 2. In addition, GD-2011 had a 1-amino acid insertion in glycoprotein 5, which does not exist in any other HP-PRRSV strains.


Associations of flow disruptions with patient, staff, and process outcomes: a prospective observational study of robotic-assisted radical prostatectomies.
Technological advancements in the operating room (OR) have sparked new challenges for surgical workflow, OR professionals, and patient safety. Disruptive events are frequent across all surgical specialties, but little is known about their effects on patient outcomes and the influence of systemic factors. The aim was to explore the associations of intraoperative flow disruptions (FDs) with patient outcomes, staff workload, and surgery duration. Prospective, single-center, and multi-source study comprising direct and standardized OR observations of urologic surgical procedures, clinical patient outcomes, and staff- and patient-reported outcome data (PROMs; 3-month follow-up). All data were recorded between 01/2020 and 10/2021. FDs were assessed using standardized procedure observations. Linear and logistic regression analyses including multiple system factors were used to explore the effects of FDs on surgical outcomes. 61 robotic-assisted radical prostatectomy procedures were captured (with 61 patients and 243 staff reports). High rates of FDs were observed; however, our analyses did not show significant relationships with patient complication rates. Equipment- and patient-related FDs were associated with increased staff workload. No association was found between higher rates of FDs and procedure duration. FDs were not related to inferior patient outcomes. Our findings may inform future OR investigations that scrutinize the complex interplay of human, team, process, and technological components that mitigate the effects of FDs during surgery.


Prognostic role of glomerular electron microscopy lesions in IgA nephropathy: "the devil is in the details".
Transmission electron microscopy enables examination of ultrastructural glomerular changes; while this tool has already been applied in IgA nephropathy (IgAN), limited information exists on the prognostic value in this disease. We aimed to systematically investigate ultrastructural lesions and assess their role in predicting the evolution of IgA nephropathy to end-stage kidney disease. A single-center retrospective study was performed on 107 consecutive IgAN patients (median age 42 years, 67% male, estimated glomerular filtration rate 46 mL/min, proteinuria 1.0 g/g) between 2010 and 2015, who were followed-up until end-stage kidney disease, death, or end of study (January 2021). A pathologist evaluated the Mesangial hypercellularity (M), Endocapillary hypercellularity (E), Segmental glomerulosclerosis (S), and Tubular atrophy/interstitial fibrosis-Crescents (C) (MEST-C) score and transmission electron microscopy lesions according to a comprehensive protocol that encompassed all glomerular structures. Patients were followed up for a median of 7.1 years; 32 (43%) reached end-stage kidney disease. Patients who reached kidney failure had higher comorbidity score, more frequent arterial hypertension, lower estimated glomerular filtration rate, and higher MEST-C score. In terms of transmission electron microscopy lesions, patients who progressed to end-stage kidney disease had more frequent podocyte activation, effacement, and presence of microvilli; more frequent signs of endothelial cell activation and fenestration; higher mesangial cell proliferation. In the univariate Cox proportional hazard regression, higher MEST-C score and lesions detected by transmission electron microscopy in podocytes, endothelial cells, and mesangial cell proliferation were associated with shorter kidney survival time. In the multivariate Cox proportional hazard regression, only higher MEST-C score, presence of podocytes with microvilli, and mesangial cell proliferation were associated with end-stage kidney disease. This study shows that, besides the MEST-C score, the presence of podocytes with microvilli and mesangial cell proliferation are associated with poor kidney survival in IgAN patients, highlighting the prognostic value of lesions detected by transmission electron microscopy.


Impacts of autochthonous dissolved organic matter on the accumulation of methylmercury by phytoplankton and zooplankton in a eutrophic coastal ecosystem.
The bioaccumulation of methylmercury (MeHg) within the pelagic food webs is a crucial determinant of the MeHg concentration in the organisms at higher trophic levels. Dissolved organic matter (DOM) is recognized for its influence on mercury (Hg) cycling in the aquatic environment because of its role in providing metabolic substrate for heterotrophic organism and serving as a strong ligand for MeHg. However, the impact of DOM on MeHg bioaccumulation in pelagic food chains remain controversial. Here, we explored MeHg bioaccumulation within a pelagic food web in China, in the eutrophic Bohai Sea and adjacent seas, covering a range of DOM concentrations and compositions. Our findings show that elevated concentrations of dissolved organic carbon (DOC) and phytoplankton biomass may contribute to a reduction in MeHg uptake by phytoplankton. Moreover, we observe that a higher level of autochthonous DOM in the water may result in more significant MeHg biomagnification in zooplankton. This can be explained by alterations in the structure of pelagic food webs and/or an increase in the direct consumption of DOM and particulate organic matter (POM) containing MeHg. Our study offers direct field monitoring evidence of dual roles played by DOM in regulating MeHg transfers from water to phytoplankton and zooplankton in coastal pelagic food webs. A thorough understanding of the intricate interactions is essential for a more comprehensive evaluation of ecological risks associated with MeHg exposure in coastal ecosystems.


Microvessel damage by B. jararacussu snake venom: pathogenesis and influence on muscle regeneration.
The loss of muscle mass consequent to poor muscle regeneration is a common sequela following the injection of Bothrops jararacussu snake venom. Since an intact microvasculature plays a central role in the success of muscle regeneration, the poor muscle regeneration seen after envenomation could be explained by damage to the local microvasculature. In this work, we investigated the pathogenesis of microvessel damage caused by B. jararacussu venom and its correlation with poor muscle regeneration. The right soleus muscle of adult mice was injected with 80 microg of venom and the mice were killed from 2 min to 3 months later. Similarly, the soleus muscle of other mice was injected with 80 microg of bothrosptoxin-I (BthTX-I), a non-vasculotoxic myotoxin. Tissue samples were prepared for analysis by electron (venom only) and light (venom and BthTX-I) microscopy. The extent of revascularization was assessed using light microscopy by examining recanalization of thrombi and calculating the individual capillary-to-fiber-ratio, the number of capillaries around a fiber and the capillary/muscle cell ratio. Microvessel damage by venom started within 5 min and, after 6 h, there was total degeneration of the capillaries with failure of the local microcirculation. The time-course of the ultrastructural lesions suggested that endothelial cells were probably damaged by a direct action of B. jararacussu venom on these cells. The revascularization of muscle damaged by venom, but not by BthTX-I, occurred later and was very poor. These results indicate a central role for vascular lesions in muscle regeneration after damage by B. jararacussu venom.


Instructor-led vs. peer-led debriefing in preoperative care simulation using standardized patients.
Debriefing involves the active participation of learners to identify and close gaps in knowledge and skills. Varied debriefing methods are used in simulation, but no empirical studies have examined the effectiveness of peer-led debriefing in simulation using standardized patients. The purpose of this study was to compare the effects of two debriefing methods (instructor-led vs. peer-led) on nursing skills, knowledge, self-confidence, and quality of debriefing among undergraduate nursing students in South Korea. A nonequivalent control group pretest-posttest design was used. Fifty-seven third-year nursing students were randomly assigned to instructor-led (n = 26) or peer-led (n = 31) debriefing groups after a simulation of preoperative care. Structured questions and areas for discussion guided debriefing in both groups. Self-administered questionnaires were used to collect data on students' knowledge and self-confidence in providing preoperative care. Faculty evaluated students' nursing skills during pre- and post-simulation practice. Students evaluated the quality of the debriefings. Nursing skills for preoperative care (p < .001) and the quality of debriefing (p < .001) were statistically higher in the instructor-led group compared to the peer-led group. There were no statistically significant differences in knowledge (p = .445) and self-confidence (p = .686). Knowledge and self-confidence from pre-test to posttest were improved in both groups. The instructor-led debriefing showed improved nursing skills and higher quality debriefing. However, peer-led debriefing led by a non-trained peer also rendered positive results. Thus, peer-led debriefing may be considered a useful strategy for improving nursing students' self-confidence.


Oral administration of a dominant T-cell determinant peptide inhibits allergen-specific TH1 and TH2 cell responses in Cry j 2-primed mice.
Oral immunotherapy with a peptide for allergic immune responses is theoretically a promising therapy but has not been established yet. To evaluate immune suppressive efficacy of oral administration of an immunodominant peptide, we investigated changes in T-cell proliferation, TH1 - and TH2 -cytokine production, and TH1 - and TH2 -mediated antibody production in mice after oral administration of a peptide. Peptide p246-259, containing a dominant T-cell determinant of Cry j 2, which is the major allergen in Japanese cedar pollen, was used in this study. Groups of mice received p246-259 or PBS alone before or after they were primed intranasally with Cry j 2 and cholera toxin. In another experiment mice were primed intraperitoneally with Cry j 2 and alum. Proliferative response and cytokine production by nasal-associated lymph node cells against Cry j 2 were investigated. Amounts of systemic anti-Cry j 2 IgE and IgG antibodies were also measured. Oral administration of the peptide to mice before, or even after, the sensitization induced oral tolerance in T-cell responses against the allergen; the tolerance was associated with decreased production of TH1 (IFN-gamma and IL-2) and TH2 (IL-4) cytokines. Allergen-specific TH1 -mediated (IgG2a and IgG2b) and TH2 -mediated (IgG1 and IgE) antibody responses were also inhibited. Oral administration of a dominant T-cell determinant peptide induces immunologic tolerance in both TH1 and TH2 cell responses against the whole protein allergen. Our study is the first, to our knowledge, to demonstrate the potential for peptide-based oral immunotherapy in order to treat allergic immune responses.


JNK modulates the effect of caspases and NF-kappaB in the TNF-alpha-induced down-regulation of Na+/K+ATPase in HepG2 cells.
An inhibition of the Na(+)/K(+)ATPase was previously shown to accompany and potentiate apoptosis in different experimental models. Since TNF-alpha is known to be a pro and anti-apoptotic cytokine, this work was undertaken to study the effect of TNF-alpha on the Na(+)/K(+)ATPase in HepG2 cells and to determine the signaling pathway involved. Cells were incubated for 1 h with TNF-alpha in presence and absence of PDTC, SP600125 and FK009, respective inhibitors of NF-KB, c-JNK, and caspases. The activity of the pump was assayed by measuring the ouabain-inhibitable release of inorganic phosphate, and changes in its expression were monitored by western blot analysis. TNF-alpha decreased significantly the activity and protein expression of the Na(+)/K(+)ATPase. NF-kappaB and caspases were found to be the main effectors of the cytokine, mediating respectively down-regulation and up-regulation of the pump. Their activity was however modulated at 1 h by c-JNK, which stimulated the caspases and inhibited NF-kappaB, resulting in a net inhibition of the ATPase, and probably favoring the apoptotic pathway.


The concept of the "perisinusoidal functional unit" of the liver--importance to pathological processes.
Non-hepatocytes account for 30 per cent of cells in the liver, with sinusoid-coating endothelial and Kupffer cells being the most common types. In addition, there are some scattered pit cells in the wall. Ito cells (perisinusoidal cells, lipocytes) are located in the Disse space. In this paper a review is given of structural and functional changes of cells in response to pathological conditions with reference to the importance of such changes due to diseases of the liver and the organism in large. Cooperation and interaction among non-hepatocytes, the vascular pole of hepatocytes, and Disse space as the site of reaction are summarised under the concept of the "Perisinusoidal Functional Unit", and the concept is explained in greater detail by examples (lipoprotein catabolism, processes of phagocytosis, vitamin A storage, virus infections, accumulation of pathological substances, fibrosis, and capillarization).


Stress and displacement between maxillary protraction with miniplates placed at the infrazygomatic crest and the lateral nasal wall: a 3-dimensional finite element analysis.
The purpose of this study was to compare the pattern and amount of stress and displacement between maxillary protraction with miniplates placed at the infrazygomatic crest and the lateral nasal wall. Three-dimensional finite element models for the skull and the curvilinear type of miniplate were constructed. After a protraction force (500 g/side) was applied to the distal end of the miniplate with a forward and 30° downward vector to the maxillary occlusal plane, stress distributions in the circummaxillary sutures and displacements of the surface landmarks were analyzed. There was a difference in the maximum stress distribution area according to the site of the miniplate: infrazygomatic crest and middle part of the maxilla in the infrazygomatic crest and paranasal area adjacent to the pyriform aperture in the lateral nasal wall. Stress values of the frontonasal, frontomaxillary, zygomaticomaxillary, and pterygomaxillary sutures were greater in the infrazygomatic crest than in the lateral nasal wall. The site of the miniplate produced differences in the major displacement areas: infrazygomatic crest, maxillary dentition, anterior maxilla, and upper part of the maxillary tuberosity in the infrazygomatic crest and the lateral nasal wall, maxillary dentition, anterior maxilla, and lower part of the maxillary tuberosity in the lateral nasal wall. The lateral nasal wall exhibited forward, downward, and outward displacements of ANS, Point A, and prosthion. However, the infrazygomatic crest showed forward and upward displacements of ANS, Point A, and prosthion, and outward displacement of the zygomatic process of the maxilla and the maxillary process of the zygomatic bone. The site of miniplate placement should be considered to obtain proper stress and displacement values in different areas with maxillary hypoplasia.


[Bone transplants in prosthetic knee surgery].
The authors refer on their experience using bone grafting of tibial defects in total knee arthroplasty. The advantages, the technique, the casuistry and the results of this method are illustrated.


Targeting cancer with small-molecular-weight kinase inhibitors.
Protein and lipid kinases fulfill essential roles in many signaling pathways that regulate normal cell functions. Deregulation of these kinase activities lead to a variety of pathologies ranging from cancer to inflammatory diseases, diabetes, infectious diseases, cardiovascular disorders, cell growth and survival. 518 protein kinases and about 20 lipid-modifying kinases are encoded by the human genome, and a much larger proportion of additional kinases are present in parasite, bacterial, fungal, and viral genomes that are susceptible to exploitation as drug targets. Since many human diseases result from overactivation of protein and lipid kinases due to mutations and/or overexpression, this enzyme class represents an important target for the pharmaceutical industry. Approximately one third of all protein targets under investigation in the pharmaceutical industry are protein or lipid kinases.The kinase inhibitors that have been launched, thus far, are mainly in oncology indications and are directed against a handful of protein and lipid kinases. With one exception, all of these registered kinase inhibitors are directed toward the ATP-site and display different selectivities, potencies, and pharmacokinetic properties. At present, about 150 kinase-targeted drugs are in clinical development and many more in various stages of preclinical development. Kinase inhibitor drugs that are in clinical trials target all stages of signal transduction from the receptor protein tyrosine kinases that initiate intracellular signaling, through second-messenger-dependent lipid and protein kinases, and protein kinases that regulate the cell cycle.This review provides an insight into protein and lipid kinase drug discovery with respect to achievements, binding modes of inhibitors, and novel avenues for the generation of second-generation kinase inhibitors to treat cancers.


Clinical and health costs impact of progress in diagnosis and treatment in venous thromboembolic disease: evolution in 15 years.
The therapeutic and diagnostic approach in deep vein thrombosis (DVT) has changed enormously in the last two decades with the introduction of ultrasound, low-molecular-weight heparin (LMWH), and premature motion. The aim of this study is to evaluate these changes and analyze their clinical and economic aspects. We registered all inpatients with a diagnosis of DVT during 1994 (n=110) and 2009 (n=75) and their sociodemographic and clinical features in a descriptive observational design. We performed a comparison of diagnostic techniques, length of stay, inpatient complications, and costs thus derived for both series, based on 2009 prices, so that we could get comparable results. Ninety-one percent of inpatients in 1994 were diagnosed by venography, whereas, in 2009, the diagnosis was based on clinical features, D-dimer, and ultrasound in 100% of patients. Inpatient treatment went from 7% LMWH in 1994 to 96% in 2009, and as outpatient from 82% acenocumarol to 90.6% LMWH. Complications decreased by 13.3%. Length of stay was 2.7 higher in 1994. Globally, the cost per patient decreased by 63.39%, based primarily on reduced length of stay. The current diagnostic and therapeutic approach in DVT allows for effective treatment, fewer complications, and a drastic reduction in inpatient costs.


Age-related changes in penile erections and circulating testosterone in middle-aged male rats.
The relationship between aging changes in pituitary-testicular function and the penile erection reflex was examined in middle-aged male rats. Significant decline in circulating LH and testosterone is first apparent in male rats during middle-age (13-15 mos). In Experiment 1, middle-aged (13-15 mos) and young (3-4 mos) rats were tested for erections responses. The erections were measured in animals held supine and mechanically stimulated by retraction of the penile shealth. Middle-aged rats had substantially fewer erections than young animals. In Experiment 2, groups of middle-aged and young animals were castrated and provided equivalent levels of circulating testosterone (T) through the use of Silastic capsules. The levels were measured directly by radioimmunoassay of plasma T. In animals with supraphysiological T levels, erection frequency was low, but there was no significant difference between middle-aged and young animals. The results suggest that middle-aged rats do not have irreversible deficiencies in the somatic and neural mechanisms regulating erection nor are they significantly less responsive to androgen stimulation. The decline in circulating testosterone with age may therefore be a primary factor in the reduction of penile erections in middle-aged rats.


Elements of the health culture of Polish society.
The purpose of this article is to characterize Polish society from the point of view of health culture. The article is based on research conducted in 1978 on the representative national sample. In that research we sought to trace the dependence of styles of being sick, methods of treatment, and the entire related sphere of behavior on the following factors: socio-demographic characteristics of patients, with special attention to their position in social structure; availability of medical care service--in reality and perceived subjectively; estimation of the state of health of patients; confidence in medicine as a social institution, system of knowledge and in health care service; medical knowledge of patients; availability of other sources of help, alternative to official medicine.


Quantum Ratcheted Photophysics in Energy Transport.
In this paper, we explore the scope of vibrations as quantum ratchets that serve as nonthermal routes to achieving population transport in systems where excitation transport between molecules is otherwise energetically unfavorable. In addition to their role as channels of transport, we investigate the effect of resonance of the vibrations, which are described by Huang-Rhys mixing, with excitonic energy gaps, which leads to strongly mixed vibronic excitons. Finally, we explore the interplay of resonance and Huang-Rhys mixing with electronic coupling between the molecules, in the presence of a dissipative bath, in optimizing transport in such systems. We find that while resonance is desirable, a moderate electronic coupling has a stronger positive effect in contrast to a large electronic coupling, which results in delocalized excitations across molecules and hampers unidirectional transport. We also report a special resonance regime that is able to circumvent the transport problems arising from large electronic couplings.


Immunogenicity of the Lyme disease antigen OspA, particleized by cobalt porphyrin-phospholipid liposomes.
Outer surface protein A (OspA) is a Borrelia lipoprotein and an established Lyme disease vaccine target. Admixing non-lipidated, recombinant B. burgdorferi OspA with liposomes containing cobalt porphyrin-phospholipid (CoPoP) resulted in rapid, particulate surface display of the conformationally intact antigen. Particleization was serum-stable and led to enhanced antigen uptake in murine macrophages in vitro. Mouse immunization using CoPoP liposomes that also contained a synthetic monophosphoryl lipid A (PHAD) elicited a Th1-biased OspA antibody response with higher IgG production compared to other vaccine adjuvants. Antibodies were reactive with intact B. burgdorferi spirochetes and Borrelia lysates, and induced complement-mediated borreliacidal activity in vitro. One year after initial immunization, mice maintained high levels of circulating borreliacidal antibodies capable of blocking B. burgdorferi transmission from infected ticks to human blood in a feeding chamber.


Short-term effect of delayed-onset muscle soreness on trunk proprioception during force reproduction tasks in a healthy adult population: a crossover study.
The aim of this study was to evaluate the effects of lumbar muscle delayed-onset muscle soreness (DOMS) on the ability of the trunk muscles to reproduce different levels of force. Twenty healthy adults (10 males and 10 females) were recruited for this study. Force reproduction in trunk extension and flexion was assessed at 50 and 75% of participants' maximal isometric voluntary contraction in flexion and extension before and after a lumbar muscle DOMS protocol. Trunk proprioception was evaluated and compared between these conditions using different variables such as constant errors (CE), absolute errors (AE), variable errors (VE) and time to peak force (TPF). For each variable, repeated measure ANOVAs were conducted. AE were higher when participants had to reach the target post-DOMS protocol in extension compared to flexion and in the presence of higher demand of force (p = 0.02). For VE, results showed that participants were more variable in extension than in flexion when the required force was higher (p = 0.04). CE variable was higher when participants had to reach the force target in extension compared to flexion under the effect of DOMS (p = 0.02). Results also showed that participants took less time to reach the force target post-DOMS protocol in extension (0.62 ± 0.20 s) and in flexion (0.53 ± 0.19 s) than pre-DOMS protocol in extension (0.55 ± 0.15) and in flexion (0.50 ± 0.20) (p < 0.001). Lumbar muscle DOMS affects trunk proprioception during force reproduction tasks especially in trunk extension and at higher force.


Interpretation of analytical toxicology results in life and at postmortem.
Interpretation of analytical toxicology results from live patients is sometimes difficult. Possible factors may be related to: (i) the nature of the poison(s) present; (ii) sample collection, transport and storage; (iii) the analytical methodology used; (iv) the circumstances of exposure; (v) mechanical factors such as trauma or inhalation of stomach contents; and (vi) pharmacological factors such as tolerance or synergy. In some circumstances, detection of a drug or other poison may suffice to prove exposure. At the other extreme, the interpretation of individual measurements may be simplified by regulation. Examples here include whole blood alcohol (ethanol) in regard to driving a motor vehicle and blood lead assays performed to assess occupational exposure. With pharmaceuticals, the plasma or serum concentrations of drugs and metabolites attained during treatment often provide a basis for the interpretation of quantitative measurements. With illicit drugs, comparative information from casework may be all that is available. Postmortem toxicology is an especially complex area since changes in the composition of fluids such as blood depending on the site of collection from the body and the time elapsed since death, amongst other factors, may influence the result obtained. This review presents information to assist in the interpretation of analytical results, especially regarding postmortem toxicology. Collection and analysis of not only peripheral blood, but also other fluids/tissues is usually important in postmortem work. Alcohol, for example, can be either lost from, or produced in, blood especially if there has been significant trauma, hence measurements in urine or vitreous humour are needed to confirm the reliability of a blood result. Measurement of metabolites may also be valuable in individual cases.


Hippocampal electrophysiological changes during the elicited metabolic syndrome in Wistar rats.
The Metabolic Syndrome (MS) is a set of alterations that increase the risk of developing type 2 diabetes mellitus (DM2). There is evidence that obesity and the development of metabolic syndrome lead to alterations in cognitive processes. In this work it was proposed to determine if generating the metabolic syndrome produces changes in the electric unitary spontaneous activity in the hippocampus as a possible sustain of the learning alterations. In Wistar rat with a hypercaloric diet, metabolic syndrome was provoked, and this was confirmed with the determination of body and metabolic parameters as a measure of intraperitoneal fat, glucose, triglycerides, and cholesterol. Electrophysiological records were made in the hippocampus and it was determined that rats treated with a hypercaloric diet show a significant decrease in such activity. Thus, it is shown that rats that were caused metabolic syndrome, alter their hippocampal electrophysiological activity.


Safety of tongue base procedures for sleep apnoea in adults: A systematic review and metanalysis from the YO-IFOS study group.
Tongue base and hypopharynx are the major sites of obstruction in OSA patients with failed palatal surgery. In recent years, several minimally invasive procedures have been developed to address tongue base obstruction. However, the research focus has consistently been on the effectiveness of surgery in reducing obstructive sleep apnoea rather than on postoperative complications. In this systematic review and metanalysis we aim to review the complication rate of minimally invasive base of tongue procedures for OSAS in adults. PubMed (Medline), the Cochrane Library, EMBASE, Scopus, SciELO and Trip Database. Data sources were checked by three authors of the YO-IFOS sleep apnoea study group. Three authors extracted the data. Main outcome was expressed as the complication rate and 95% confidence interval for each surgical technique. 20 studies (542 patients) met the inclusion criteria. The mean complication rate is 12.79%; 4.65% for minor complications, 6.42% if they are moderate, and 1.77% if severe. The most reported complication overall is infection, in 1.95% of cases, followed by transient swallowing disorder, occurring in 1.30% of the total sample. The heterogeneity amongst the included studies prevents us from obtaining solid conclusions. The available evidence suggests that minimally invasive base of tongue procedures may present a wide spectrum of complication rates, ranging from 4.4% in tongue base radiofrequency to up to 42.42% in tongue base ablation.


Synthesis of bimannich base with thiazole and its corrosion inhibition effect on H2S and CO2 at high temperature.
A bimannich-based TZBM containing a thiazole ring was obtained by synthesis of mannich bases. TZBM featured a stable structure at 260 °C, and corrosion inhibition effect on carbon steel in a gas-liquid environment with Cl- + H2S + CO2 at 180 °C. By analyzing the weight loss of steel exposed to different TZBM concentrations, the coverages of the inhibitor adsorbed on the surfaces were determined, and the results conformed to Langmuir isotherm model. Furthermore, the negative Gibbs free energy indicated that the adsorption was a spontaneous process.


Dear deer? Maybe for now. People's perception on red deer (Cervus elaphus) populations in Portugal.
The human dimension of wildlife is a subject of increasing interest, especially considering the potential impact of people's perceptions on decision-making concerning wildlife management and thus on species' distribution and abundance. This is particularly important for species that inhabit human-dominated landscapes, where conflicts are likely to arise. These conflicts typically emerge between different human collectives when their interests collide and thus an assessment of their perceptions is valuable. Throughout Europe, ungulates have expanded, and Portugal is no exception. The expansion of red deer (Cervus elaphus) comes with benefits (e.g. hunting opportunities), but also with costs (e.g. vehicle collision or damage to crops), that can shape people's perceptions of these populations. To assess perceptions of red deer populations in continental Portugal, we developed a questionnaire survey with three interest groups: general public, farmers and hunters (total n = 1532). Our results show that perceptions about red deer were generally positive with a high acknowledgement of deer benefits, which we link to a broad level of sympathy towards this species. In addition, farmers showed a higher concern with crop damage caused by deer than non-farmers. Nonetheless, a general lack of knowledge regarding wildlife was present, particularly among younger people, who are potentially more apart and disconnected from nature. Now is the time to implement preventive and mitigation measures - e.g. fencing, reduction of population density - which can be a small contribution to address this problem. The focus should be put on people's acceptance of the required strategies to manage deer populations (which can also include unpopular practices, such as hunting). For that, an evaluation of people's attitudes towards deer populations and awareness of associated problems is essential. People's opinions, as well as the success of monitoring and management strategies, should be evaluated through multi-disciplinary teams, that include natural and social scientists, to ensure their success.


Immature teratoma of the ovary.
Four cases of immature teratoma of the ovary are presented and the recent literature is reviewed. The majority of these tumors were confined to one ovary at the time of diagnosis, and more than 75% occurred in women under 25 years of age. The two most important prognostic parameters were stage of disease and histologic grade. Optimal survival occurred when surgical tumor debulking was followed by combination chemotherapy. The addition of hysterectomy with contralateral adnexectomy did not improve the survival of patients with disease confined to one ovary. Similarly, postoperative radiation therapy was not shown to be beneficial in patients with this disease. Analysis of presently available data suggests that patients with teratocarcinoma of the ovary should be treated with tumor excision followed by at least 12 courses of chemotherapy with vincristine, actinomycin D, and cyclophosphamide. alpha-Fetoprotein may be useful as a biochemical marker of disease status in selected patients.


Structure-activity studies of C- and N-terminal fragments of cholecystokinin 26-33 in guinea pig isolated tissues.
In vitro structure-activity studies with cholecystokinin (CCK)/gastrin-related peptides, including C- and N-terminal fragments of CCK 26-33, were undertaken in guinea pig gallbladder and ileum. The general order of potency in both smooth muscle preparations is CCK 26-33 greater than CCK 1-33 greater than 27-33 much much greater than nonsulfated (NS) CCK 26-33 greater than pentagastrin greater than CCK 30-33. None of the CCK fragments exhibit antagonistic properties such as in guinea pig, rat and mouse pancreatic acinar cells and hog duodenum. These observations suggest the existence of CCK receptor sub-types in peripheral tissues.


Evaluation of the quality of life of patients with chronic rhinosinusitis by means of the SNOT-22 questionnaire.
SNOT-22 is a questionnaire used to assess the quality of life of patients with chronic rhinosinusitis (CRS). It is broadly utilized to assess the surgical treatment of patients with CRS. In Brazil there are no studies utilizing the SNOT-22 in non-surgical patients. To use the SNOT-22 questionnaire to assess the quality of life of individuals with chronic rhinosinusitis without previous surgery and with indication for clinical treatment. Prospective and analytical cohort and cross-sectional controlled clinical trial. We had 2 groups, one made up of patients with CRS and another one with adult individuals without the sinonasal disease, consecutively seen in an otorhinolaryngology clinic in Salvador, Bahia, between August of 2011 and June of 2012. They all filled out the Consent Form, a registration form and the SNOT-22. 176 patients, 78 with CRS and 98 without the disease, the groups matched as far as gender, medication and respiratory allergies were concerned. Age was 40.7 + 13.5 years in the study group and 37.8 + 12.9 in controls (p = 0.26). The SNOT-22 median value in the study group was 53, compared to 8 in the control group (p = 0.001). Chronic rhinosinusitis reduces the quality of life of patients, according to the SNOT-22 questionnaire.


Analysis of Biomechanical Response After Corneal Crosslinking with Different Fluence Levels in Porcine Corneas.
To evaluate corneal stiffening of porcine corneas induced by corneal crosslinking (CXL) with constant irradiance as a function of total fluence. Ninety corneas from freshly enucleated porcine eyes were divided into five groups of 18 eyes. Groups 1-4 underwent epi-off CXL using a dextran-based riboflavin solution and an irradiance of 18 mW/cm2, group 5 served as the control group. Groups 1 to 4 were treated with a total fluence of 20, 15, 10.8, and 5.4 J/cm2, respectively. Thereafter, biomechanical measurements were performed on 5 mm wide and 6 mm long strips using an uniaxial material tester. Pachymetry measurements were performed on each cornea. At 10% strain, the stress was 76, 56, 52, and 31% higher in groups 1-4, respectively compared to the control group. The Young's modulus was 2.85 MPa for group 1, 2.53 MPa for group 2, 2.46 MPa for group 3, 2.12 MPa for group 4, and 1.62 MPa for the control group. The difference between groups 1 to 4 and the control group 5 were statistically significant (p = <0.001; p = <0.001; p = <0.001; p = 0.021). In addition, group 1 showed significantly more stiffening than group 4 (p = <0.001), no other significant differences were found. Pachymetry measurements revealed no statistically significant differences among the five groups. Additional mechanical stiffening can be achieved by increasing the fluence of the CXL. There was no threshold detected up to 20 J/cm2. A higher fluence could compensate the weaker effect of accelerated or epi-on CXL procedures.


Proteomic scale high-sensitivity analyses of GPI membrane anchors.
Glycosylphosphatidylinositol (GPI) anchored proteins are ubiquitous in eukaryotic cells. Earlier analysis methods required large amounts of purified protein to elucidate the structure of the GPI. This paper describes methods for analyzing GPIs on a 'proteomic' scale. Partially purified proteins may be run on sodium dodecyl sulphate polyacrylamide gel electrophoresis and then blotted onto a polyvinylidene difluoride (PVDF) membrane. Following identification of the protein the piece of PVDF may be subjected to various chemical treatments, which are specific for GPI structures. The first method uses gas chromatography-mass spectrometry and it enables the presence of a GPI anchor to be confirmed. The second method depends on the cleavage of phosphate bonds and permits the carbohydrate structure to be elucidated by electrospray or matrix assisted laser desorption ionization-time of flight mass spectrometry. The final method described uses deamination of the glucosamine residue to release the lipid moiety for analysis by mass spectrometry.


Macroeconomic dataset for comparative studies on coastal and inland regions in innovation space of Russia.
This article presents regional-level data that can be used for comparative territorial studies on innovation dynamics. The dataset covers a series of 50 indicators grouped into a matrix of 5 elements of regional innovation system (human resources - HR, infrastructure, research & development sector - R&D, innovative milieu, framework conditions) and 5 components of innovation security (economic, scientific and technological - S&T, social, political, geo-ecological). This complex set of interrelated data enables to grasp the catalyst and inhibitor factors that have a significant impact on the sustainable development of a particular regional innovation system. The innovation security approach used enables to consider the locus of innovation processes, account for the relationship between individual components of regional innovation systems and acknowledge for the unique properties of the regions. The database includes statistics for a total set of 85 regions of the Russian Federation over a period of 2015 and 2016. Spatial differentiation is made on to coastal and inland regions. This enables to identify the development patterns as influenced by the global trend of coastalization.


Corrigendum: Risk Factors for Delirium Are Different in the Very Old: A Comparative One-Year Prospective Cohort Study of 5,831 Patients.
[This corrects the article DOI: 10.3389/fpsyt.2021.655087.].


Family history and body mass index predict perceived risks of diabetes and heart attack among community-dwelling Caucasian, Filipino, Korean, and Latino Americans--DiLH Survey.
The purpose of the study was to explore the perceived risk for diabetes and heart attack and associated health status of Caucasian, Filipino, Korean, and Latino Americans without diabetes. A cross-sectional survey was conducted with 904 urban adults (mean age 44.3±16.1 years; 64.3% female) in English, Spanish or Korean between August and December 2013. Perceived risk for developing diabetes was indicated by 46.5% (n=421), and 14.3% (n=129) perceived themselves to be at risk for having a heart attack in their lifetime. Significant predictors of pessimistic diabetes risk perceptions: Filipino (adjusted odds ratio [AOR]=1.7; 95% CI: 1.04-2.86) and Korean (AOR=2.4; 1.33-4.48) ethnicity, family history of diabetes (AOR=1.4; 1.00-1.84), female gender (AOR=1.4; 1.04-1.96), high cholesterol (AOR= 1.6; 1.09-2.37) and higher body mass index (BMI) (AOR=1.1; 1.08-1.15). Predictors of pessimistic heart attack risk perceptions were family history of an early heart attack (AOR=2.9; 1.69-5.02), high blood pressure (AOR=2.4; 1.45-3.84), and higher BMI (AOR=1.1; 1.04-1.12) after controlling for socio-demographic factors. Older age, physical inactivity, smoking, and low HDL levels were not associated with risk perceptions. Multiple risk factors were predictive of greater perceived diabetes risk, whereas, only family history of heart attack, high blood pressure and increases in BMI significantly contributed to perceived risk of heart attack among ethnically diverse at risk middle-aged adults. It is important that healthcare providers address the discordance between an individual's risk perceptions and the presence of actual risk factors.


Escherichia coli emphysematous endophthalmitis and pyelonephritis. Case report and review of the literature.
Emphysematous escherichia coli endophthalmitis occurred in a 72-year-old patient as a complication of E. coli septicemia secondary to emphysematous pyelonephritis and endocarditis. This is the first reported case of endogenous emphysematous endophthalmitis secondary to E. coli septicemia.


Characterizing the spatial distribution of ambient ultrafine particles in Toronto, Canada: A land use regression model.
Exposure models are needed to evaluate the chronic health effects of ambient ultrafine particles (<0.1 μm) (UFPs). We developed a land use regression model for ambient UFPs in Toronto, Canada using mobile monitoring data collected during summer/winter 2010-2011. In total, 405 road segments were included in the analysis. The final model explained 67% of the spatial variation in mean UFPs and included terms for the logarithm of distances to highways, major roads, the central business district, Pearson airport, and bus routes as well as variables for the number of on-street trees, parks, open space, and the length of bus routes within a 100 m buffer. There was no systematic difference between measured and predicted values when the model was evaluated in an external dataset, although the R(2) value decreased (R(2) = 50%). This model will be used to evaluate the chronic health effects of UFPs using population-based cohorts in the Toronto area.


Spatial inequalities of COVID-19 mortality rate in relation to socioeconomic and environmental factors across England.
In this study, we aimed to examine spatial inequalities of COVID-19 mortality rate in relation to spatial inequalities of socioeconomic and environmental factors across England. Specifically, we first explored spatial patterns of COVID-19 mortality rate in comparison to non-COVID-19 mortality rate. Subsequently, we established models to investigate contributions of socioeconomic and environmental factors to spatial variations of COVID-19 mortality rate across England (N = 317). Two newly developed specifications of spatial regression models were established successfully to estimate COVID-19 mortality rate (R2 = 0.49 and R2 = 0.793). The level of spatial inequalities of COVID-19 mortality is higher than that of non-COVID-19 mortality in England. Although global spatial association of COVID-19 mortality and non-COVID-19 mortality is positive, local spatial association of COVID-19 mortality and non-COVID-19 mortality is negative in some areas. Expectedly, hospital accessibility is negatively related to COVID-19 mortality rate. Percent of Asians, percent of Blacks, and unemployment rate are positively related to COVID-19 mortality rate. More importantly, relative humidity is negatively related to COVID-19 mortality rate. Moreover, among the spatial models estimated, the 'random effects specification of eigenvector spatial filtering model' outperforms the 'matrix exponential spatial specification of spatial autoregressive model'.


A preliminary study on expression and significance of pre-S1 protein in liver tissue of patients with HBV infection.
Rabbit antiserum to Pre-S1 protein was used to establish peroxidase-antiperoxidase (PAP) and avidin-biotin-peroxidase complex (ABC) immunohistochemical techniques for detection of Pre-S1 protein in paraffin-embedded liver tissue. Pre-S1 protein could be expressed in hepatocyte cytoplasm and on membrane in some cases with chronic viral hepatitis, cirrhosis and hepatocellular carcinoma (HCC), and its expression was intimately associated with HBsAg, HBcAg in liver and HBV DNA in serum, indicating that pre-S1 protein may represent the essential component of hepatitis B virus (HBV) and also serve as one of the markers of HBV infection. The incidence of Pre-S1 protein was slightly lower in nontumorous liver of HCC than in other cases and Pre-S1 protein could not be detected in tumorous tissue of HCC suggesting that expression of pre-S1 protein may be suppressed in HCC cases.


Preparation of fragments of carcinoembryonic antigen and identification of a major subset of antigenic determinants.
The detailed immunochemistry of a limited molecular domain of carcinoembryonic antigen (CEA) was examined, by using new methods to prepare and purify immunoreactive fragments. Fragments of CEA were prepared by digestion of the reduced and alkylated glycoprotein with protease V8, chymotrypsin or trypsin, or by chemical cleavage at cysteine residues with 2-nitro-5-thiocyanobenzoic acid. The products were fractionated by high performance liquid chromatography (HPLC) on a reversed phase support, and the most immunoreactive fragment was recovered from each of the four mixtures. The Mr of these purified fragments ranged from 30,000-35,000, the amino acid compositions were similar, and all contained carbohydrate. The four independently derived fragments gave similar inhibitions of CEA binding to anti-CEA antisera; maximum values were 15-55% depending on the antiserum employed. Competitive assays with pairs of fragments in different combinations showed that the four contained essentially the same subset of antigenic determinants. The fragments were quite resistant to further enzymatic digestion, but comparison of the HPLC profiles of mild acid hydrolysates of two of the fragments showed substantial similarity. These results suggest that the CEA molecule includes a region of about 30,000 mol. wt that is contained between consecutive cysteine residues, is relatively resistant to a number of residue-specific proteases, and constitutes a significant subset of antigenic determinants. Assays to identify cleavage products with different antigenic specificities were negative, suggesting that other determinants were destroyed or that the corresponding antibody populations were too small to detect.


[Influence of packed red cell transfusions on blood selenium concentration in pediatric hemato-oncology].
In humans approx. 10% of the total body selenium (Se) content is present in the blood being evenly distributed among plasma and red cells. The important role of Se in antioxidative biological pathways is proven. Many parents of children with malignancies ask for supplementation with Se as part of complementary therapy during or after the oncological treatment. However, toxic Se concentrations may easily be reached in children. In order to analyse whether Se is also supplied by red cell transfusions (RCT), we determined Se concentration in whole blood prior and after packed RCT in pediatric patients with hemato-oncological diseases. EDTA-blood was collected from 17 patients (median age: 4 years, range: 1 month - 17 years) with aplastic anemia, acute leukemia and solid tumours prior and after RCT (n=60). Patients received a median of 2 transfusions (range: 1-14). Samples were also collected from the transfusion blood bags and Se concentration was determined quantitatively by atomic absorption spectrometry. 95% of the specimen collected from the transfusion bags exhibited selenium concentrations within the normal adult range. Mean Se concentration in the patients' blood prior to RCT was 66.2 microg/l (range: 38.0-166.4 microg/l) and increased to 70.7 microg/l (range: 14.1-105.1 microg/l) thereafter (statistically not significant). Applying age dependant reference values Se concentrations were below the lower limit in 45% of the samples prior to RCT and only in 26% after RCT. The reason for this increase was the fact that Se concentrations were often just marginally below the age-dependant lower limit prior to RCT and in the lower normal range thereafter. 43% of the patients with hemato-oncological diseases in this study exhibited no Se deficiency at any time point. In the remaining 57% of the patients a transient or persistent Se deficiency was detected with blood levels partially far below the lower threshold of the age adjusted normal range. The Se deficiency was corrected in four out of eight patients by RCT. As Se levels may fluctuate in individual pts a supplementation should only be initiated if based on regular monitoring of the Se concentration.


A novel hydrogen sulfide prodrug, SG1002, promotes hydrogen sulfide and nitric oxide bioavailability in heart failure patients.
Recent studies demonstrate robust molecular cross talk and signaling between hydrogen sulfide (H2 S) and nitric oxide (NO). Heart failure (HF) patients are deficient in both H2 S and NO, two molecules that are critical for cardiovascular homeostasis. A phase I clinical trial of a novel H2 S prodrug (SG1002) was designed to assess safety and changes in H2 S and NO bioavailability in healthy and HF subjects. Healthy subjects (n = 7) and heart failure patients (n = 8) received oral SG1002 treatment in escalating dosages of 200, 400, and 800 mg twice daily for 7 days for each dose. Safety and tolerability were assessed by physical examination, vital signs, and ECG analysis. Plasma samples were collected during a 24-h period each week for H2 S and NO analysis. BNP and glutathione levels were analyzed as markers of cardiac health and redox status. Administration of SG1002 resulted in increased H2 S levels in healthy subjects. We also observed increased H2 S levels in HF subjects following 400 mg SG1002. Nitrite, a metabolite of NO, was increased in both healthy and HF patients receiving 400 mg and 800 mg SG1002. HF subjects treated with SG1002 displayed stable drug levels over the course of the trial. SG1002 was safe and well tolerated at all doses in both healthy and HF subjects. These data suggest that SG1002 increases blood H2 S levels and circulating NO bioavailability. The finding that SG1002 attenuates increases in BNP in HF patients suggests that this novel agent warrants further study in a larger clinical study.


Gestational 1-nitropyrene exposure causes fetal growth restriction through disturbing placental vascularity and proliferation.
1-Nitropyrene (1-NP) is a widely distributed pollutant in the environment and is best known for its mutagenicity and carcinogenicity. In this study, we evaluated the effects of 1-NP exposure in different gestational stages on the pregnant outcomes. Pregnant mice were administered with 1-NP by gavage daily in early (GD1-GD6), middle (GD7-GD12) or late pregnancy (GD13-GD17), respectively. We found that gestational 1-NP exposure had no effect on implantation sites per litter, preterm delivery and fetal death. Interestingly, mice exposed to 1-NP in late pregnancy showed a significant reduction in fetal weight and crown-rump length. Correspondingly, placental weight and diameter were markedly reduced in dams exposed to 1-NP in late pregnancy. Additional experiment showed maternal 1-NP exposure in late pregnancy reduced blood sinusoid area of placental labyrinthine region in a dose-dependent manner. Although gestational 1-NP exposure had little effect on placental cell apoptosis, as determined by the TUNEL assay, the rate of Ki67-positive cell, a marker of cell proliferation, was reduced in placental labyrinthine region of mice exposed to 1-NP in late pregnancy. These findings provide evidence that gestational 1-NP exposure induces fetal growth restriction in a stage-dependent manner. Placenta is a toxic target in the process of 1-NP-induced fetal growth restriction.


Technique-associated outcomes in horses following large colon resection.
To compare survival and complications in horses undergoing large colon resection with either sutured end-to-end or stapled functional end-to-end anastomoses. Retrospective cohort study. Twenty-six client-owned horses with gastrointestinal disease. Retrospective data were retrieved from the medical records of 26 horses undergoing colectomy, including 14 horses with sutured end-to-end and 12 horses with stapled functional end-to-end anastomoses, between 2003 and 2016. Records were evaluated for signalment, medical and surgical treatments, and survival to hospital discharge. Long-term follow-up was obtained through owner contact. Continuous variables were compared with Mann-Whitney tests. Fisher's exact testing was used to compare survival to hospital discharge. Survival time was compared by constructing Kaplan-Meier survival curves and performing log-rank curve comparison testing. Mean age of horses undergoing colectomy was 13 years. Reason for colectomy was prophylaxis (12) or salvage (14). Mean surgical time was 169 minutes. Mean hospitalization time was 9 days, which did not differ with anastomosis type (P = .62). Nine of 12 horses undergoing stapled functional end-to-end anastomosis and 12 of 14 horses undergoing sutured end-to-end anastomosis survived to hospital discharge (P = .63). Survival time did not differ with anastomosis technique (P = .35). Short- and long-term survival outcomes are not different between sutured end-to-end or stapled functional end-to-end anastomoses in horses undergoing colectomy.


Medical interventions for chronic rhinosinusitis in cystic fibrosis.
Chronic rhinosinusitis frequently occurs in people with cystic fibrosis. Several medical interventions are available for treating chronic rhinosinusitis in people with cystic fibrosis; for example, different concentrations of nasal saline irrigations, topical or oral corticosteroids, antibiotics - including nebulized antibiotics - dornase alfa and modulators of the cystic fibrosis transmembrane conductance regulator (CFTR) (such as lumacaftor, ivacaftor or tezacaftor). However, the efficacy of these interventions is unclear. This is an update of a previously published review. The objective of this review is to compare the effects of different medical interventions in people diagnosed with cystic fibrosis and chronic rhinosinusitis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search of trials register: 09 September 2021. We also searched ongoing trials databases, other medical databases and the reference lists of relevant articles and reviews. Date of latest additional searches: 22 November 2021. Randomized and quasi-randomized trials of different medical interventions compared to each other or to no intervention or to placebo. Two review authors independently assessed trials identified for potential inclusion in the review. We planned to conduct data collection and analysis in accordance with Cochrane methods and to independently rate the quality of the evidence for each outcome using the GRADE guidelines. We identified no trials that met the pre-defined inclusion criteria. The most recent searches identified 44 new references, none of which were eligible for inclusion in the current version of this review; 12 studies are listed as excluded and one as ongoing. We identified no eligible trials assessing the medical interventions in people with cystic fibrosis and chronic rhinosinusitis. High-quality trials are needed which should assess the efficacy of different treatment options detailed above for managing chronic rhinosinusitis, preventing pulmonary exacerbations and improving quality of life in people with cystic fibrosis.


Unravelling the molecular interactions between the SARS-CoV-2 RBD spike protein and various specific monoclonal antibodies.
Vaccination against SARS-CoV-2 just started in most of the countries. However, the development of specific vaccines against SARS-CoV-2 is not the only approach to control the virus and monoclonal antibodies (mAbs) start to merit special attention as a therapeutic option to treat COVID-19 disease. Here, the main conformations and interactions between the receptor-binding domain (RBD) of spike glycoprotein of SARS-CoV-2 (S protein) with two mAbs (CR3022 and S309) and the ACE2 cell receptor are studied as the main representatives of three different epitopes on the RBD of S protein. The combined approach of 1 μs accelerated molecular dynamics (aMD) and ab-initio hybrid molecular dynamics is used to identify the most predominant interactions under physiological conditions. Results allow to determine the main receptor-binding mapping, hydrogen bonding network and salt bridges in the most populated antigen-antibody interface conformations. The deep knowledge on the protein-protein interactions involving mAbs and ACE2 receptor with the spike glycoprotein of SARS-CoV-2 increases background knowledge to speed up the development of new vaccines and therapeutic drugs.


Differential toxicity of a phenolic glycoside from quaking aspen to Papilio glaucus butterfly subspecies, hybrids and backcrosses.
Papilio glaucus subspecies, hybrids and backcrosses exhibit greatly different abilities to use quaking aspen (Populus tremuloides) and other members of the Salicaceae as host plants. This study was conducted to test the hypotheses that phenolic glycosides account for the differences in larval performance, and that differential performance is correlated with differential larval esterase activities. To test the hypotheses we conducted first instar survival trials and fourth (penultimate) instar feeding trials with tremulacin, a phenolic glycoside. We also conducted assays of β-glucosidase, esterase, and glutathione transferase activities, using midgut enzyme preparations from fifth instars. First instar survival on the tremulacin treated diet generally improved with a higher proportion of Papilio glaucus canadensis genes in the genotype, although survival in one backcross treatment was surprisingly low. Penultimate instars of P.g. glaucus and P.g. australis fed tremulacin treated black cherry leaves experienced a severe reduction in growth rate relative to larvae fed control leaves. This seriously suppressed growth was partially due to reduced consumption rates and reduced conversion efficiencies, however, approximate digestibility was not affected. In contrast, P. g. canadensis and hybrids showed no differences in growth rates between tremulacin treated and control leaves. Reciprocal backcrosses of hybrids with P. g. glaucus resulted in slightly suppressed growth on treated versus control leaves. The results suggest that after a certain threshold, increased proportions of P. g. glaucus genes resulted in poorer growth performance with tremulacin in the diet. Soluble esterase activities generally increased with the proportion of Papilio glaucus canadensis genes in the genotype, and paralleled overall trends in larval survival and feeding performance. We conclude that phenolic glycosides such as tremulacin are responsible for differential performance of Papilio glaucus subspecies, hybrids and backcrosses fed plants in the Salicaceae, and that detoxification of phenolic glycosides by midgut esterase explains why some Papilio glaucus genotypes can effectively utilize these plants.


Association between sex and mortality in adults with in-hospital and out-of-hospital cardiac arrest: A systematic review and meta-analysis.
Conflicting data exists regarding the association between sex and mortality in adults with in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA). We therefore conducted a meta-analysis to investigate the association between sex and mortality in adults with IHCA and OHCA. We systematically searched MEDLINE and Cochrane databases to identify studies reporting sex-specific mortality in adults following IHCA or OHCA from inception to April 2020. Data were pooled using random-effects models. The primary outcome of interest was in-hospital (or 30-day) all-cause mortality. We included 21 observational studies with a total of 1,029,978 adult patients - 622,085 men and 407,893 women. Seven studies included patients only with IHCA and 14 studies included patients only with OHCA. Female sex was associated with significantly higher mortality following OHCA [odds ratio (OR) 1.56, 95% confidence interval (CI) 1.32-1.84, p < 0.001) and a trend toward higher mortality following IHCA (OR 1.10, 95%CI 1.00-1.20, p = 0.052). In adults with cardiac arrest, female sex was associated with significantly higher mortality following OHCA and a trend toward higher mortality following IHCA.


Effect of gaze direction on neck muscle activity during cervical rotation.
Control of the neck muscles is coordinated with the sensory organs of vision, hearing and balance. For instance, activity of splenius capitis (SC) is modified with gaze shift. This interaction between eye movement and neck muscle activity is likely to influence the control of neck movement. The aim of this study was to investigate the effect of eye position on neck muscle activity during cervical rotation. In eleven subjects we recorded electromyographic activity (EMG) of muscles that rotate the neck to the right [right obliquus capitis inferior (OI), multifides (MF), and SC, and left sternocleidomastoid (SCM)] with intramuscular or surface electrodes. In sitting, subjects rotated the neck in each direction to specific points in range that were held statically with gaze either fixed to a guide (at three different positions) that moved with the head to maintain a constant intra-orbit eye position or to a panel in front of the subject. Although right SC and left SCM EMG increased with rotation to the right, contrary to anatomical texts, OI EMG increased with both directions and MF EMG did not change from the activity recorded at rest. During neck rotation SCM and MF EMG was less when the eyes were maintained with a constant intra-orbit position that was opposite to the direction of rotation compared to trials in which the eyes were maintained in the same direction as the head movement. The inter-relationship between eye position and neck muscle activity may affect the control of neck posture and movement.


Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury.
Spinal cord injury (SCI) leads to severe sensory and motor dysfunction below the lesion. However, the cellular dynamic responses and heterogeneity across different regions below the lesion remain to be elusive. Here, we used single-cell transcriptomics to investigate the region-related cellular responses in female rhesus monkeys with complete thoracic SCI from acute to chronic phases. We found that distal lumbar tissue cells were severely impacted, leading to degenerative microenvironments characterized by disease-associated microglia and oligodendrocytes activation alongside increased inhibitory interneurons proportion following SCI. By implanting scaffold into the injury sites, we could improve the injury microenvironment through glial cells and fibroblast regulation while remodeling spared lumbar tissues via reduced inhibitory neurons proportion and improved phagocytosis and myelination. Our findings offer crucial pathological insights into the spared distal tissues and proximal tissues after SCI, emphasizing the importance of scaffold-based treatment approaches targeting heterogeneous microenvironments.


Computed tomography of internal jugular vein thrombosis.
Thrombosis of the internal jugular vein was diagnosed by computed tomography in two cases. On contrast computed tomography, the thrombosed vein appeared as an enlarged vein containing a low density lumen surrounded by a sharply defined wall. This entity should be looked for whenever a patient is examined by computed tomography for acute cervical swelling or inflammatory ear disease.