Men who have sex with men and risk for transfusion-transmissible infections in blood donors in Western countries: A systematic review update.
This systematic review update summarizes evidence concerning transfusion-transmissible infections (TTIs) in male blood donors reporting sex with another man (MSM) or after easing the MSM deferral period. We searched five databases, including studies comparing MSM versus non-MSM donors (Type I), MSM deferral periods (Type II) or infected versus non-infected donors (Type III) in Western countries, and used GRADE to determine evidence certainty. Twenty-five observational studies were included. Four Type I studies suggest that there may be an increased risk for overall TTIs, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and syphilis in MSM donors, but the evidence is very uncertain. There was insufficient evidence of MSM with low-risk sexual behaviour. A Type II study indicates that easing the MSM deferral period to 1 year may have little to no effect on TTI risk. TTI prevalence in blood donors under 5-year, 1-year, 3-month or risk-based deferral in eight other Type II studies was too low to provide clear conclusions on the effect of easing the deferral. Three Type III studies reported that MSM may be a risk factor for HIV. Increased risk of HBV, hepatitis C virus and HTLV-I/II could not be shown. The evidence from Type III studies is very uncertain. There may be an increased risk of HIV in MSM blood donors. Shortening the deferral from permanent to 1 year may have little to no effect on TTI risk. However, there is limited, unclear evidence from observational studies concerning the impact of introducing 3-month or risk-based deferrals.


Small Molecule Inhibition of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4).
In recent years, interleukin-1 receptor-associated kinase 4, IRAK4, has become an attractive target for many medicinal chemistry programmes. Target inhibition is of potential therapeutic value in areas including autoimmune disorders, cancer, inflammatory diseases, and possibly neurodegenerative diseases. Results from high-throughput screening efforts have led, in conjunction with structure-based drug design, to the identification of highly potent and selective small molecule IRAK4 inhibitors from many diverse chemical series. In vitro and in vivo studies with entities from distinct structural classes have helped elucidate the downstream pharmacological responses associated with IRAK4 inhibition as a proof of concept in disease models, leading to the recent initiation of human clinical trials. Within this review, we will highlight the considerable effort by numerous groups dedicated to the development of small molecule IRAK4 inhibitors for the treatment of human disease.


Differential anti-inflammatory and analgesic effects by enantiomers of zaltoprofen in rodents.
In the present study, we investigated the effect of zaltoprofen enantiomers on inflammation and pain and compared their effect with racemic zaltoprofen. S(+)-zaltoprofen potently inhibited the inflammatory response in carrageenan-induced paw edema model, whereas R(-)-zaltoprofen did not. Moreover, the anti-inflammatory effect of S(+)-zaltoprofen was stronger than that of racemic zaltoprofen, suggesting that S(+)-zaltoprofen is an active component of racemic zaltoprofen in terms of anti-inflammatory activity. In contrast, the results of acetic acid-induced writhing model demonstrated that no significant analgesic effect was observed by racemic zaltoprofen and zaltoprofen enantiomers at doses used in carrageenan-induced paw edema model. However, racemic zaltoprofen and zaltoprofen enantiomers all exerted an analgesic effect at higher doses, which is inconsistent with the result of carrageenan-induced paw edema model. Gastric ulcers induced by racemic zaltoprofen and zaltoprofen enantiomers were minimal. Taken together, these results suggest that S(+)-zaltoprofen is a potent and active anti-inflammatory component of racemic zaltoprofen, but both S(+)-zaltoprofen and R(-)-zaltoprofen might seem to contribute to the analgesic effect of racemic zaltoprofen.


Arbuscular mycorrhizal symbiosis increases host plant acceptance and population growth rates of the two-spotted spider mite Tetranychus urticae.
Most terrestrial plants live in symbiosis with arbuscular mycorrhizal (AM) fungi. Studies on the direct interaction between plants and mycorrhizal fungi are numerous whereas studies on the indirect interaction between such fungi and herbivores feeding on aboveground plant parts are scarce. We studied the impact of AM symbiosis on host plant choice and life history of an acarine surface piercing-sucking herbivore, the polyphagous two-spotted spider mite Tetranychus urticae. Experiments were performed on detached leaflets taken from common bean plants (Phaseolus vulgaris) colonized or not colonized by the AM fungus Glomus mosseae. T. urticae females were subjected to choice tests between leaves from mycorrhizal and non-mycorrhizal plants. Juvenile survival and development, adult female survival, oviposition rate and offspring sex ratio were measured in order to estimate the population growth parameters of T. urticae on either substrate. Moreover, we analyzed the macro- and micronutrient concentration of the aboveground plant parts. Adult T. urticae females preferentially resided and oviposited on mycorrhizal versus non-mycorrhizal leaflets. AM symbiosis significantly decreased embryonic development time and increased the overall oviposition rate as well as the proportion of female offspring produced during peak oviposition. Altogether, the improved life history parameters resulted in significant changes in net reproductive rate, intrinsic rate of increase, doubling time and finite rate of increase. Aboveground parts of colonized plants showed higher concentrations of P and K whereas Mn and Zn were both found at lower levels. This is the first study documenting the effect of AM symbiosis on the population growth rates of a herbivore, tracking the changes in life history characteristics throughout the life cycle. We discuss the AM-plant-herbivore interaction in relation to plant quality, herbivore feeding type and site and the evolutionary implications in a multi-trophic context.


Occurrence and patterns of driving behavior for alcoholics in treatment.
The purpose of this study was to investigate the driving behaviors of male alcoholics. Two hundred and fifty-eight male alcoholics receiving treatment for alcoholism completed a self-administered questionnaire about their driving behaviour and official driver records were accessed. On average, the surveyed individuals drank and drove about 8.6 days per month at the legal level of impairment in Canada (i.e., 80 mg%). Evidence showed that about 88.3% of the sample had driven while impaired. The probability of being arrested for impaired driving was estimated to be about one in 1168 impaired driving events. People were divided into three groups according to their number of Driving While Impaired (DWI) arrests in the previous 10 years, as determined by self-reports and official driving records: zero DWI arrests, one DWI arrest, and multiple DWI arrests. Those with multiple DWI arrests drove while impaired more frequently and with more risky styles of driving than people with zero arrests. Those with two or more arrests also reported that they enjoyed driving under a greater variety of situations as compared to those with zero arrests. Multiple offenders had significantly more total collisions than zero time offenders; however, there were no significant differences among the three DWI groups for collisions without alcohol involvement or other types of traffic violations. Results showed that the number of DWI arrests was generally not related to worse driving when sober.


Timing of bariatric surgery for severely obese adolescents: a Markov decision-analysis.
Although controversial, bariatric surgery is increasingly being performed in adolescents. We developed a model to simulate the effect of timing of gastric bypass in obese adolescents on quantity and quality of life. A Markov state-transition model was constructed comparing two treatment strategies: gastric bypass surgery at age 16 versus delayed surgery in adulthood. The model simulated a hypothetical cohort of adolescents with body mass index of 45kg/m(2). Model inputs were derived from current literature. The main outcome measure was quality and quantity of life, measured using quality-adjusted life-years (QALYs). For females, early gastric bypass surgery was favored by 2.02 QALYs compared to delaying surgery until age 35 (48.91 vs. 46.89 QALYs). The benefit was even greater for males, where early surgery was favored by 2.9 QALYs (48.30 vs. 45.40 QALYs). The absolute benefit of surgery at age 16 increased; the later surgery was delayed into adulthood. Sensitivity analyses demonstrated that adult surgery was favored only when the values for adverse events were unrealistically high. In our model, early gastric bypass in obese adolescents improved both quality and quantity of life. These findings are useful for surgeons and pediatricians when counseling adolescents considering weight loss surgery.


Age-related differences in Default Mode Network resting-state functional connectivity but not gray matter volume relate to sacrificial moral decision-making and working memory performance.
Older adults make fewer utilitarian decisions than younger adults during sacrificial moral dilemmas, which are associated with age-related reductions in Default Mode Network resting-state functional connectivity. Decreases on tasks associated with fluid cognitive abilities, such as working memory capacity, are also associated with age-related Default Mode Network changes. Regions within this network demonstrate some of the greatest age-related gray matter atrophy. Age-related changes in structure and function of the Default Mode Network may be associated with poorer working memory capacity and reduced utilitarian moral decision-making. Alternatively, recent theories suggest that age-related changes to Default Mode Network function may be adaptive in the context of tasks that include socioemotional components. As such, reduced within-network resting-state functional connectivity of the Default Mode Network may be associated with differential outcomes in moral decision-making for younger and older adults. In the present study, there were no age-related differences in working memory capacity. Older adults were less likely than younger adults to indicate the utilitarian option when trials involved Instrumental harm. Generally, increased within-network resting-state functional connectivity of the Default Mode Network was associated with better working memory performance in both groups, and reduced bias to endorse the utilitarian option during Incidental dilemmas compared to Instrumental dilemmas in younger adults. Older adults with similar moral decision-making behavior to younger adults demonstrated increased coupling between Default Mode Network and Salience Network regions. These findings suggest that Default Mode Network functional integrity may be differentially associated with age-related changes to working memory capacity and sacrificial moral decision-making.


Preparation and properties of some crystalline symmetrical anhydrides of N alpha-tert.-butyloxycarbonyl-amino acids.
The preparation and properties of 16 crystalline symmetrical anhydrides of N alpha-tert.-butyloxycarbonyl-amino acids is described.


Fibrinogenemia, determined immunonephelometrically, as a possible parameter in the evaluation of peripheral arteriosclerotic arteriopathy.
The concentration of plasma fibrinogen increases with age and is particularly elevated in subjects with vascular changes due to atherosclerosis. Fibrinogen, which is the meeting point of the "cascade" of the coagulation factors and an important regulating factor of plasma viscosity, occupies a key position in atherosclerotic vascular pathology. This indicates the necessity to keep its value within normal limits, to avoid the clinical development of the disease or improve its evolution. Thus, frequent checks of the fibrinogenemia are necessary at various ages even if this means a big organizational burden. However, this checking can be facilitated by using automatic techniques, such as the immunonephelometric method, with which it is possible to carry out a large number of determinations in a short time.


Microstates and power envelope hidden Markov modeling probe bursting brain activity at different timescales.
State modeling of whole-brain electroencephalography (EEG) or magnetoencephalography (MEG) allows to investigate transient, recurring neurodynamical events. Two widely-used techniques are the microstate analysis of EEG signals and hidden Markov modeling (HMM) of MEG power envelopes. Both reportedly lead to similar state lifetimes on the 100 ms timescale, suggesting a common neural basis. To investigate whether microstates and power envelope HMM states describe the same neural dynamics, we used simultaneous MEG/EEG recordings at rest and compared the spatial signature and temporal activation dynamics of microstates and power envelope HMM states obtained separately from EEG and MEG. Results showed that microstates and power envelope HMM states differ both spatially and temporally. Microstates reflect sharp events of neural synchronization, whereas power envelope HMM states disclose network-level activity with 100-200 ms lifetimes. Further, MEG microstates do not correspond to the canonical EEG microstates but are better interpreted as split HMM states. On the other hand, both MEG and EEG HMM states involve the (de)activation of similar functional networks. Microstate analysis and power envelope HMM thus appear sensitive to neural events occurring over different spatial and temporal scales. As such, they represent complementary approaches to explore the fast, sub-second scale bursting electrophysiological dynamics in spontaneous human brain activity.


Comparative effects of RX 781094, mianserin, yohimbine, rauwolscine and prazosin in reversing clonidine inhibition of MIX-stimulated lipolysis in hamster isolated white fat cells.
Different alpha-adrenergic receptor antagonists: RX 781094, yohimbine and rauwolscine (selective alpha 2-adrenergic antagonists); mianserin (tetracyclic anti-depressant, antagonist at alpha 2-presynaptic autoreceptors) and prazosin (selective alpha 1-adrenergic antagonist) were used at concentrations ranging from 10(-7) to 10(-4) M, to reverse clonidine inhibition of MIX-stimulated lipolysis in the hamster fat cell. In this adipose tissue (like human but unlike rat) there co-exist prolipolytic beta-adrenoceptors and antilipolytic alpha-adrenoceptors. Although no effects were observed with prazosin, RX 781094 was ten times more potent than yohimbine or its isomer rauwolscine in reversing clonidine inhibition of the MIX-stimulated lipolysis. Mianserin was an effective blocker only from a concentration of 10(-4) M, consistent with its relative lack of specificity for alpha 2-adrenoceptors cited elsewhere. Overall these results confirm the utility of this model for testing compounds presumed to act at alpha 2-adrenoceptors.


Evaluating work experience in the selection of dietary managers.
Because there is such a low correlation between the work experience inventory and examination scores, the work experience inventory may be measuring another dimension of performance. The use of the work experience inventory in conjunction with application forms and employment tests may provide a better indicator of potential performance than any of those methods alone. This concurrent validity study, however, should be followed by predictive validity studies to determine the effectiveness of the work experience inventory in predicting job success of the dietary manager.


Effect of vagal innervation on the secretory responses of canine gastric pouches exposed to bile.
The changes in the secretory response to a meat meal, after preliminary exposure of vagally innervated and vagally denervated fundic pouches to ox bile at pH 7 and pH 2, have been defined. In the innervated pouches, exposure to bile at both pH levels caused transient inhibition of gastric acid secretion. In both types of pouch, the output of Na+ in the gastric juice was presistently increased due to enhanced exchange diffusion. The changes were more pronounced after exposure to bile at pH 2 than after exposure to bile at pH 7. After exposure to bile, exchange diffusion was more increased in the innervated pouches than in the denervated. The results suggested that the innervated mucosa was more susceptible than was the denervated mucosa to the injurious effects of bile.


Incidence and natural history of pure red cell aplasia in major ABO-mismatched haematopoietic cell transplantation.
Major ABO mismatching is not considered a contraindication to allogeneic haematopoietic stem cell transplantation (HSCT). Modern reduced-intensity conditioning and reduced-toxicity regimens cause much less myeloablation than conventional myeloablative regimens, such as cyclophosphamide with busulfan or total body irradiation, which may affect the incidence of pure red cell aplasia (PRCA). We estimated the incidence and described the natural history of PRCA in patients with major ABO-mismatched donor stem cells. Between 2007 and 2008, 161 (27% of all patients undergoing HSCT) underwent allogeneic HSCT with major ABO-mismatched stem cells and 12 (7·5%) of these patients developed PRCA. Thirty and ninety day T-cell and myeloid cell chimerism and neutrophil and platelet engraftment did not differ between patients who developed PRCA and those who did not. The only risk factor associated with PRCA was the use of a fludarabine/busulfan conditioning regimen. All patients with PRCA needed red cell transfusion for several months after HSCT resulting in significant iron overload. Pure red cell aplasia resolved spontaneously in the majority (seven patients) but only resolved after stopping tacrolimus in three patients. Hence, after major ABO-mismatched HSCT, the incidence of PRCA was 7·5% and it resolved spontaneously or after withdrawal of immunosuppression in the majority of patients.


[Antigenic markers in the hemagglutinins of influenza type A viruses (H1N1) from various periods of circulation].
Hyperimmune rabbit sera were examined by specific adsorption tests for influenza viruses H1N1 isolated in 1942-1952. A comparative immunological analysis revealed the presence of three antigenic determinants in hemagglutinins (HA) of A/Bel/42, A/Weiss/43, A/FM/1/47 and A/FLW/52 viruses. Adsorption of antisera with different drift-variants of H1N1 produced monoreceptor sera to individual antigenic determinants of HA by means of which marker antigens can be identified in HA of viruses isolated in different periods, and one may have an idea of evolutionary variability of influenza virus.


Hantavirus infection-induced thrombocytopenia triggers increased production but associates with impaired aggregation of platelets except for collagen.
We evaluated the mechanisms of thrombocytopenia encountered in hantavirus disease by studying platelet production together with platelet aggregation and deposition to collagen surface. The study group consisted of 31 prospectively recruited, consecutive, hospitalized patients having acute Puumala hantavirus infection. Blood samples were collected acutely and at the control visit and subjected to analysis in Sysmex® XE-5000 to capture mean platelet volume (MPV) and immature platelet fraction (IPF%). Platelet aggregation under low shear rate conditions was assessed with impedance aggregometry Multiplate®, whereas platelet function analyzer (PFA)-100® was applied under blood flow of high shear forces. IPF% was 3.1-fold higher acutely compared with the control (median 7.4%, range 2.0-23.8% vs. median 2.4%, range 1.4%-5.2%, p<0.001) tightly associating with the low platelet count (r=-0.76, p<0.001). Accordingly, acute MPV was high (median 11.4f l, range 9.4-13.1 fl vs. median 10.5 fl, range 9.0-12.0 fl, p=0.003). Acute platelet aggregation in Multiplate® was decreased to all agonists compared with the later control (p<0.05 for all agonists). Aggregation capacity associated with thrombocytopenia (for all agonists r ≥ 0.81, p<0.001), but impaired aggregation occurred also among patients with a nearly normal platelet count. Triggered by collagen, 20% of values were below reference range, while 73% of responses were low with thrombin receptor activating peptide. Significantly, under high shear platelet deposition to collagen surface was normal despite thrombocytopenia. During acute hantavirus disease, platelet aggregation is impaired especially when induced with thrombin. Platelet adhesive mechanisms on collagen are intact despite thrombocytopenia while thrombopoiesis is active.


Patient expectations are better for immunotherapy than traditional chemotherapy for cancer.
The main aim of the study was to explore the expectations and knowledge of advanced-stage cancer patients about immunotherapy. This mixed methods study included 53 cancer patients on immune checkpoint inhibitors (ICIs), 55 cancer patients undergoing chemotherapy (CT), and 53 non-cancer patients. Participants' expectations about ICIs and CT were compared. Additional qualitative data were derived from semi-structured interviews. Among patients who did not receive ICIs, 63 (58%) had never heard of ICIs and 94 (87%) had large gaps in their knowledge of ICIs. Among ICI patients, 33 (62%) simply described ICIs without errors. ICI perception was positive, regardless of whether respondents received or had heard of ICIs, which became particularly evident when compared to CT. ICIs were rated as more promising, and all adverse effects were expected to be significantly lower than those of CT. Knowledge about ICIs was also limited in the interviewed ICI patients. Some patients reported adverse effects of ICIs that were mostly mild and well-tolerated or easily treated. The lack of understanding of ICIs should be improved by activities to increase the knowledge of ICI patients and the general population. In contrast to CT, ICIs invoked fewer negative associations with efficacy and toxicity. Therefore, attention should be paid to risk awareness when educating patients. (Clinical trial registration number: DRKS00011868) Trial Registration: German clinical trials register, www.germanctr.de , number DRKS00011868.


Replacement of maxillary and mandibular molars with single endosseous implant restorations: a retrospective study.
This retrospective report presents findings on 22 patients with 24 implants replacing single molars with implant-supported restorations. Patients with known bruxism habits were not considered for single-molar implant replacement. The patients underwent follow-up for an average of 24 months. The cumulative success rate was 95%, which reflects the loss of one 5 x 6 mm wide implant. Eleven implants were placed in edentulous ridges, and 13 were placed in extraction sockets. Most of the implants were placed in type B and C bone quantity and type 2 and 3 bone quality. All implants were restored on abutments with nonrotating gold cylinders. The occlusion for all restorations was developed to minimize centric contacts and lateral interferences. The frequency of gold retaining-screw loosening was obtained for 21 patients. The gold retaining screws loosened in eight implants between one and three times (38%). No incidence of crown or implant fracture occurred. Within the limits of this study, replacement of single-tooth molars by implant-supported restorations was predictable; however, a high incidence of gold screw loosening was seen.


[The role of Hpi-hydrogen bonds in the stabilization of spiral structures of oligopeptides].
Different possibilities of H-bonds formation for formamide-water complexes and dimers of formamide were studied. Potential energy maps were calculated for di-, tri- and tetrapeptides. The maps provide necessary data to explain the relative stability of different oligopeptide conformers and Ramachandran maps for peptides.


Clinical Impact of the ABO Blood Type in Patients with Rheumatic Diseases: Is there a Link to the ABO and Rhesus?
Several studies have shown associations of ABO and Rh blood groups with various diseases; however, the relationship of ABO and Rh blood groups with rheumatic diseases are scarce. The aim of the present study was to examine whether there is an association between ABO and Rh blood groups and the types of rheumatic diseases. In this multi-centre cross-sectional study, sociodemographic data, type of rheumatic disease, and type ABO and Rh blood groups were examined for patients with different rheumatic diseases. A total of 304 patients; 207 (68.1%) were diagnosed with rheumatoid arthritis, and 40 (13.2%) had systemic lupus erythematosus. The patients were assessed for blood types; 37.8% patients had A type, 27.6% had B type, 19.1% had O type, and 15.4% had AB type. The Rh (+) blood group was more prevalent (89.1%) than Rh (-). Blood group A was more prevalent in patients with rheumatic disease, followed by B, O, and AB respectively, although there was no significant difference in the distribution of ABO groups among rheumatic diseases. Female gender, smoking, and anti-cyclic citrullinated peptide are significantly different between the blood groups within rheumatic diseases. The A and Rh (+) blood groups were more commonly observed in patients with rheumatic diseases. There was lack of association between types of rheumatic diseases and ABO blood groups. The study provides knowledge for the interaction between ABO blood groups and several risk factors related to rheumatic diseases and may serve a guide for future clinical studies.


Role of glutamate and substance P in the amphibian respiratory network during development.
This study tested the hypothesis that glutamatergic ionotropic (AMPA/kainate) receptors and neurokinin receptors (NKR) are important in the regulation of respiratory motor output during development in the bullfrog. The roles of these receptors were studied with in vitro brainstem preparations from pre-metamorphic tadpoles and post-metamorphic frogs. Brainstems were superfused with an artificial cerebrospinal fluid at 20-22 degrees C containing CNQX, a selective non-NMDA antagonist, or with substance P (SP), an agonist of NKR. Blockade of glutamate receptors with CNQX in both groups caused a reduction of lung burst frequency that was reversibly abolished at 5 microM (P<0.01). CNQX, but not SP, application produced a significant increase (P<0.05) in gill and buccal frequency in tadpoles and frogs, respectively. SP caused a significant increase (P<0.05) in lung burst frequency at 5 microM in both groups. These results suggest that glutamatergic activation of AMPA/kainate receptors is necessary for generation of lung burst activity and that SP is an excitatory neurotransmitter for lung burst frequency generation. Both glutamate and SP provide excitatory input for lung burst generation throughout the aquatic to terrestrial developmental transition in bullfrogs.


Characterization of simian virus 40 transcriptional intermediates in infected CV1 cell nuclei.
Simian Virus (SV40) transcriptional intermediates (T.I.) were isolated from infected cell nuclei incubated in vitro in the presence of the four ribonucleoside triphosphates. The nascent mRNA strands in the viral DNA-RNA hybrid molecules were hydrogen bonded to their template by 200-250 nucleotides on the average, as judged from the extent of their RNase resistance and the aspect of T.I. under electron microscope after treatment with 50 per cent formamide. The RNA polymerase involved (RNA polymerase II) synthesized up to full length transcripts at a rate of approximately 150 nucleotides/min. at 25 degrees C. Each SV40 infected cell was found to contain about 200 active T.I. molecules at the peak of late transcription. The DNA in the T.I. molecules was exclusively form I DNA only in cell infected with the tsA30 mutant of SV40 that had been transferred to non-permissive temperature in order to arrest DNA replication, but both form I DNA and molecules behaving as replicative intermediates (R.I.) in wild type infected cells.


Correction: RuCo alloy trifunctional electrocatalysts with ratio-dependent activity for Zn-air batteries and self-powered water splitting.
Correction for 'RuCo alloy trifunctional electrocatalysts with ratio-dependent activity for Zn-air batteries and self-powered water splitting' by Yu Pei et al., Chem. Commun., 2021, 57, 1498-1501, DOI: 10.1039/D0CC07565E.


Neuroendocrine processes in the establishment of pregnancy and pseudopregnancy in rats.
Rats, like mice, hamsters and other small rodents, have a short, incomplete estrous cycle. They lack a spontaneous luteal phase, and the corpora lutea (CL) of the estrous cycle are short-lived and nonfunctional. The activation of the luteal phase in these incompletely cycling females depends on the neuroendocrine reflex provided by the male at the time of mating. In this article we review our research on the cervix-brain-pituitary-ovary interaction at the endocrine, neuroendocrine, neurotransmitter and behavioural levels, dealing with the chain of events initiated by the male and necessary for the establishment of the progestational state.


Multiple ankyloses, facial anomalies, and pulmonary hypoplasia associated with severe antenatal spinal muscular atrophy.
Two unrelated patients with multiple ankyloses, pulmonary hypoplasia, and characteristic facies syndrome had definite evidence of severe spinal muscular atrophy of prenatal onset. In addition, there were specific changes in the adrenal cortex.


Rapid differentiation in a sill-like magma reservoir: a case study from the campi flegrei caldera.
In recent decades, geophysical investigations have detected wide magma reservoirs beneath quiescent calderas. However, the discovery of partially melted horizons inside the crust is not sufficient to put constraints on capability of reservoirs to supply cataclysmic eruptions, which strictly depends on the chemical-physical properties of magmas (composition, viscosity, gas content etc.), and thus on their differentiation histories. In this study, by using geochemical, isotopic and textural records of rocks erupted from the high-risk Campi Flegrei caldera, we show that the alkaline magmas have evolved toward a critical state of explosive behaviour over a time span shorter than the repose time of most volcanic systems and that these magmas have risen rapidly toward the surface. Moreover, similar results on the depth and timescale of magma storage were previously obtained for the neighbouring Somma-Vesuvius volcano. This consistency suggests that there might be a unique long-lived magma pool beneath the whole Neapolitan area.


Labeling of tannic Acid with technetium-99m for diagnosis of stomach ulcer.
Tannic acid is a polyphenolic compound that could be labeled with technetium-99m. To produce about 90% yield of (99m)Tc-tannic acid in acidic media (pH), the conditions required were 150 μg tin chloride, 30 min reaction time, and 200 μg of the substrate. (99m)Tc-tannic was stable for 6 h. Oral biodistribution of (99m)Tc-tannic showed that it concentrated in the stomach ulcer to reach about 50% of the total injected dose at 1 h after orall administration. This concentration of (99m)Tc-tannic in stomach ulcer may be sufficient to radio-image the presence of ulcer in the stomach.


Analysis of immunoglobulin G antibody responses after administration of live and inactivated influenza A vaccine indicates that nasal wash immunoglobulin G is a transudate from serum.
Following intranasal administration of live influenza A virus vaccine or parenteral inoculation of inactivated influenza virus vaccine, immunoglobulin antibody to the influenza virus hemagglutinin was detected in nasal wash specimens from adult volunteers. Several observations supported the suggestion that this immunoglobulin G hemagglutinin nasal wash antibody appeared to be mainly derived from the serum by a process of passive transudation.


Concentration of isoprene in artificial and thylakoid membranes.
Isoprene emission protects plants from a variety of abiotic stresses. It has been hypothesized to do so by partitioning into cellular membranes, particularly the thylakoid membrane. At sufficiently high concentrations, this partitioning may alter the physical properties of membranes. As much as several per cent of carbon taken up in photosynthesis is re-emitted as isoprene but the concentration of isoprene in the thylakoid membrane of rapidly emitting plants has seldom been considered. In this study, the intramembrane concentration of isoprene in phosphatidylcholine liposomes equilibrated to a physiologically relevant gas phase concentration of 20 μL L(-1) isoprene was less than predicted by ab initio calculations based on the octanol-water partitioning coefficient of isoprene while the concentration in thylakoid membranes was more. However, the concentration in both systems was roughly two orders of magnitude lower than previously assumed. High concentrations of isoprene (2000 μL L(-1) gas phase) failed to alter the viscosity of phosphatidylcholine liposomes as measured with perylene, a molecular probe of membrane structure. These results strongly suggest that the physiological concentration of isoprene within the leaves of highly emitting plants is too low to affect the dynamics of thylakoid membrane acyl lipids. It is speculated that isoprene may bind to and modulate the dynamics of thylakoid embedded proteins.


Targeting surface-layer proteins with single-domain antibodies: a potential therapeutic approach against Clostridium difficile-associated disease.
Clostridium difficile is a leading cause of death from gastrointestinal infections in North America. Antibiotic therapy is effective, but the high incidence of relapse and the rise in hypervirulent strains warrant the search for novel treatments. Surface layer proteins (SLPs) cover the entire C. difficile bacterial surface, are composed of high-molecular-weight (HMW) and low-molecular-weight (LMW) subunits, and mediate adherence to host cells. Passive and active immunization against SLPs has enhanced hamster survival, suggesting that antibody-mediated neutralization may be an effective therapeutic strategy. Here, we isolated a panel of SLP-specific single-domain antibodies (VHHs) using an immune llama phage display library and SLPs isolated from C. difficile hypervirulent strain QCD-32g58 (027 ribotype) as a target antigen. Binding studies revealed a number of VHHs that bound QCD-32g58 SLPs with high affinity (K D = 3-6 nM) and targeted epitopes located on the LMW subunit of the SLP. The VHHs demonstrated melting temperatures as high as 75 °C, and a few were resistant to the gastrointestinal protease pepsin at physiologically relevant concentrations. In addition, we demonstrated the binding specificity of the VHHs to the major C. difficile ribotypes by whole cell ELISA, where all VHHs were found to bind 001 and 027 ribotypes, and a subset of antibodies were found to be broadly cross-reactive in binding cells representative of 012, 017, 023, and 078 ribotypes. Finally, we showed that several of the VHHs inhibited C. difficile QCD-32g58 motility in vitro. Targeting SLPs with VHHs may be a viable therapeutic approach against C. difficile-associated disease.


Distribution and further studies on the activity of prostaglandin E in chronic granulomatous inflammation.
Pre-formed granulomata, induced by cannulated, carrageenin-soaked, subdermal sponge implants, were used to further analyse the effects of exogenous PGE and the involvement of endogenous PGE in this model of chronic inflammatory tissue changes in rats. Experiments with 14C-PGE2 indicated that administration of PGE into the sponge creates a kinetic situation likely to imitate, but superimposed upon, the continuous discharge of endogenous PGE in the granuloma. The granuloma-reducing, anti-flammatory effect of PGE can be mimicked by dibutyryl cyclic-AMP, phosphodiesterase inhibitors and indomethacin. Most probably these compounds, in common with PGE, exert their anti-granuloma action through elevation of intracellular cyclic-AMP (in macrophages and/or fibroblasts). The anti-granuloma action is not necessarily associated with a reduction in the endogenous PGE-level and vice versa. The involvement of endogenous PGE in the tissue events of granulomatous inflammation is conjectural as yet.


The Link Between Cannabis Use and Violent Behavior in the Early Phase of Psychosis: The Potential Role of Impulsivity.
Recently, the literature has shown that Cannabis Use (CU) was a risk factor for Violent Behavior (VB) in patients with psychosis, and those in the early phase of psychosis (EPP). These findings are relevant because of the high prevalence of CU in this EPP, and the potential for prevention during this phase of illness. However, there is still a lack of clear explanations, supported by empirical evidence, about what underlies the link between CU and VB against other. This viewpoint reviews the scientific literature on the link between CU and VB, and the involvement of impulsivity in this relationship. This last point will be addressed at clinical and neurobiological levels. Recent studies confirmed that CU is particularly high in the EPP, and is a risk factor for VB in the EPP and schizophrenia. Studies have also shown that impulsivity is a risk factor for VB in psychosis, is associated with CU, and may mediate the link between CU and VB. Research suggests a neurobiological mechanism, as CU affects the structures and function of frontal areas, known to play a role in impulsive behavior. Scientific evidence support the hypothesis of an involvement of impulsivity as a variable that could mediate the link between CU and aggression, particularly, when CU has an early onset. However, this hypothesis should be confirmed with longitudinal studies and by taking into account confounding factors. The studies highlight the relevance of early prevention in the EPP, in addition to interventions focusing on psychotic disorders.


Revisiting the 8th AJCC system for gastric cancer: A review on validations, nomograms, lymph nodes impact, and proposed modifications.
Gastric cancer is the fifth most frequently diagnosed cancer worldwide, behind breast, lung, colorectal, and prostate cancers. In gastric cancer, multimodality treatment shows prospective benefits and also improves survival. Surgery, however, is the mainstay of curative treatment. The staging of gastric cancer patients is critical for harmonization of care. Accurate stages assure that informed clinical decisions are timely made. The American Joint Committee on Cancer (AJCC) staging system is the most widely applied system in to determine the disease's prognosis and survival prediction. The recently adopted 8th AJCC TNM staging system has been revised to enhance its survival predictive power. Subsequent studies have established the validity of the current edition, demonstrating improved stage stratification, discriminatory power, and survival prediction. However, other studies have cast doubt on the superiority of the new edition. Innovations aimed at further improving its prognosis have resulted in developing of novel models. Advances in our understanding of the tumor microenvironment and molecular categorization of cancer have resulted in proposals for their inclusion in TNM staging as potential complementary factors that enhance survival prediction and prognostic assessment ability. The purpose of this study is to conduct a review of the published literature regarding the validity of the 8th AJCC TNM staging system, proposed modifications, and nomograms.


A dorsal nasal advancement flap for off-midline defects.
The repair of nasal tip defects often poses a challenge as many of the commonly used techniques for repair of the distal nose can result in obvious scars, mismatched skin, or distortions of the nasal contour that can compromise the aesthetic outcome. Our aim was to create a novel nasal tip flap and examine outcomes of its use. The dorsal nasal advancement flap was studied in 30 patients. All patients had good to outstanding results and no complications. This new flap, a modified Burow's advancement flap adapted to the nasal tip, provides an alternative to full-thickness skin grafts and transposition, rotation, and pedicle flaps for repair of the distal nose that is easy to execute and has optimal aesthetic results.


Effect of Cell Adhesion Molecule 1 Expression on Intracellular Granule Movement in Pancreatic α Cells.
Although glucagon secreted from pancreatic α cells plays a role in increasing glucose concentrations in serum, the mechanism regulating glucagon secretion from α cells remains unclear. Cell adhesion molecule 1 (CADM1), identified as an adhesion molecule in α cells, has been reported not only to communicate among α cells and between nerve fibers, but also to prevent excessive glucagon secretion from α cells. Here, we investigated the effect of CADM1 expression on the movement of intracellular secretory granules in α cells because the granule transport is an important step in secretion. Spinning disk microscopic analysis showed that granules moved at a mean velocity of 0.236 ± 0.010 μm/s in the mouse α cell line αTC6 that expressed CADM1 endogenously. The mean velocity was significantly decreased in CADM1-knockdown (KD) cells (mean velocity: 0.190 ± 0.016 μm/s). The velocity of granule movement decreased greatly in αTC6 cells treated with the microtubule-depolymerizing reagent nocodazole, but not in αTC6 cells treated with the actin-depolymerizing reagent cytochalasin D. No difference in the mean velocity was observed between αTC6 and CADM1-KD cells treated with nocodazole. These results suggest that intracellular granules in pancreatic α cells move along the microtubule network, and that CADM1 influences their velocity.


Potentiation of the discriminative-stimulus effects of methamphetamine by the histamine H3 receptor antagonist thioperamide in rats.
In order to assess the role of histamine H3 receptors in the discriminative-stimulus effects of methamphetamine, rats were trained to discriminate 1.0 mg/kg methamphetamine, i.p., from saline under a fixed-ratio schedule of food presentation. The histamine H3 receptor antagonist thioperamide (1.0 mg/kg s.c.), which facilitates histamine release, significantly shifted the methamphetamine dose-response curve to the left when tested together with different doses of methamphetamine and markedly extended the time-course of methamphetamine's discriminative-stimulus effects. The histamine H3 receptor agonist R-alpha-methylhistamine (3.0 mg/kg i.p.), which blocks histamine release, did not produce any effects when given alone, but it attenuated the effects of thioperamide on the methamphetamine dose-response curve when both drugs were given together. Thus, methamphetamine's discriminative-stimulus effects are markedly potentiated by the blockade of histamine H3 receptors by thioperamide. This is likely due to thioperamide's actions at histamine H3 autoreceptors on histaminergic neurons to facilitate release of histamine by methamphetamine or at histamine H3 heteroreceptors on other monoaminergic neurons (e.g., dopaminergic, serotonergic or noradrenergic) to facilitate release of other neurotransmitters.


Understanding the dynamic changes of volatile and non-volatile metabolites in black tea during processing by integrated volatolomics and UHPLC-HRMS analysis.
Processing technology has an important effect on the flavor quality of black tea. However, the dynamic changes of volatile and non-volatile metabolites in black tea during processing are poorly understood. In this study, the volatile and non-volatile compounds during black tea processing were comprehensively characterized by integrated volatolomics and UHPLC-Q-Exactive/MS analysis. Volatile and non-volatile metabolites changed continuously throughout the processing process, especially during the withering stage. A total of 178 volatile metabolites and 103 non-volatile metabolites were identified. Among them, 11 volatile components with relative odor activity value greater than 1 (including dimethyl sulfide, 3-methylbutanal, 2-methylbutanal, β-myrcene, β-ocimene, linalool, methyl salicylate, β-cyclocitral, β-citral, citral, and β-ionone) were regarded as key aroma-active components responsible for finished black tea with sweet aroma. This study provides a comprehensive understanding of dynamic evolution trajectory of volatile and non-volatile metabolites during processing, which lays a theoretical foundation for the targeted processing of high-quality black tea.


A Grp on the Hsp90 mechanism.
In a recent issue of Molecular Cell, Dollins et al. (2007) present the crystal structure of Grp94, which highlights the similarity between Grp94 and Hsp90 and provides insight into the resting state of Grp94 and potentially other Hsp90 family members.


In vitro propagation and genetic fidelity study of plant regenerated from inverted hypocotyl explants of eggplant (Solanum melongena L.) cv. Arka Shirish.
Genetic variation due to somaclonal variation in micropropagated plants is a beneficial phenomenon for crop improvement. Genetic integrity of the plants derived through micropropagation becomes crucial if genetic transformation studies have to be carried out. Somaclonal variation in tissue culture is a common phenomenon which makes it mandatory to check for genetic stability of plants. Hypocotyl explants of Solanummelongena L. cv. Arka Shirish inoculated with inverted polarity in MS media supplemented with 0.5 mg L-1 thidiazuron (TDZ) gave maximum number of shoot buds. Elongation of the shoot buds was achieved on MS medium supplemented with 0.5 mg L-1 2, 3, 5-triiodobenzoic acid (TIBA) and 0.1 mg L-1 gibberellic acid (GA3). The elongated shoots were rooted in MS with 1 mg L-1 indole-3-butyric acid (IBA), and the rooted plants were hardened in the greenhouse. Morphological characteristics were similar in both seed-propagated and micropropagated plants. Random amplified polymorphic DNA analysis carried out with 10 primers for genetic stability studies of the regenerated plants generated 96 scorable bands with a total of 1,056 bands for the primers. Comparison of the bands with the mother plant revealed the monomorphic nature and true-to-type clones. The above regeneration protocol will be useful for micropropagation and genetic transformation studies of S.melongena L. cv. Arka Shirish.


Peri-procedural anticoagulation and the incidence of haematoma formation after permanent pacemaker implantation in the elderly.
Haematoma formation is a recognised complication after permanent pacemaker (PPM) implantation. The contribution of peri-procedural anticoagulation to the risk of haematoma formation is unclear. The records of 518 consecutive patients, mean age 76.9±9.8 years, receiving their first PPM (2004-2007) in a single tertiary referral centre were reviewed. Follow-up was complete for 506 patients (97.7%) up to six weeks. Haematomas were diagnosed clinically, and further subdivided according to the need for evacuation. There were 27 instances of haematoma formation in 25 patients (4.9%) with 19 requiring drainage or evacuation. Twenty-one of the 25 patients who developed a haematoma had stopped warfarin and received bridging therapeutic anticoagulation pre- and post-PPM. The incidence of haematoma was significantly greater in those receiving peri-operative therapeutic anticoagulation (26.9% vs 0.9%, p<0.001), but was unaffected by the use of anti-platelet therapy. Most haematomas developed in patients whose heparin was recommenced within 24 hours of implantation. The development of haematoma post-PPM increased median hospital stay significantly (p<0.001). The main indication for anticoagulation in these patients was atrial fibrillation (79.5%) and most of these patients had a low to intermediate risk of peri-procedural thromboembolic events. Peri-operative therapeutic anticoagulation is associated with more than 25-fold increase in haematoma formation post-pacemaker implantation. The risk-benefit ratio of therapeutic anticoagulation should be carefully considered, particularly in patients with a low risk of thromboembolic events.


Identifying cis-acting DNA elements within a control region.
Computational methods can be used to identify DNA sequence motifs that have been conserved through evolution, as well as motifs that correspond to recognition sites for known DNA-binding proteins. These computational methods, when combined with chromatin immunoprecipitation and other basic experiments, can provide preliminary insight into the elements and factors that regulate a gene of interest. When pursuing a more complete understanding of a control region of interest, a comprehensive mutant analysis should generally be performed as a critical step toward more advanced functional studies. This article describes strategies for such a comprehensive analysis. It also summarizes the insights provided by a comprehensive mutant analysis versus a phylogenetic analysis.


Clinical manifestations and growth of patients with urea cycle disorders in Japan.
We have previously examined the clinical manifestations, treatments and prognosis of 177 patients with urea cycle disorders (UCDs) from January 1999 to March 2009 in Japan. In this study, we investigated the incidence of clinical manifestations in different peak blood ammonia level at onset in UCD patients, and examined the growth of OTCD (ornithine transcarbamylase deficiency) patients. The UCD patients who had a high peak blood ammonia level at onset showed significantly high incidence of convulsion and abnormal head computed tomography or magnetic resonance imaging. The patients also showed significantly high incidence of hemodialysis and liver transplantation. Choice of therapeutic agents for long-term treatment is not different between peak blood ammonia levels at the onset, except for the use of special amino-acid formulas. Growth retardation is not affected by high peak blood ammonia level at onset; however, 32% of male and 52% of female OTCD patients over 1 year old were plotted under the 10th percentile, and showed growth failure. The final height of the male and female OTCD patients were 166.2±5.5 and 150.3±7.2 cm, respectively. Although the prognosis of UCDs was improved significantly, it is considered that there are still many difficulties in the UCD patient's life.


Photosensitized inactivation of Acanthamoeba palestinensis in the cystic stage.
To develop alternative approaches for medical and environmental control of pathogenic Acanthamoeba spp. by means of photodynamic treatment with a tetracationic Zn(II)-phthalocyanine (RLP068). Incubation of cyst cultures with RLP068 for 1 h caused an accumulation of readily detectable concentrations of the phthalocyanine, even at doses as low as 0.5 micromol l(-1). RLP068 exhibited no dark toxicity towards cysts up to 5 micromol l(-1) concentration. A decrease of c. 50% in cyst survival in comparison with controls was measured upon incubation of the cysts with 0.5 micromol l(-1) RLP068, followed by exposure to light (600-700 nm) for 20 min at a fluence rate of 50 mW cm(-2) (60 J cm(-2)). After incubation with 3 and 5 micromol l(-1) RLP068 and irradiation, the cysts lost their excystment ability as early as day 5 and up to day 10, and were clearly damaged when observed under an interference contrast microscope. These data indicate the promising use of RLP068 in phototreatment of diseases caused by pathogenic amoebae and in initial disinfection of wastewaters. Rapid and extensive photodamage may be induced in the highly resistant cystic stages by means of 600- to 700-nm light sources.


May an incidental finding on chest CT be a predictor of access in intensive care unit? Role of hepatic steatosis in patients affected by SARS-CoV-2.
Due to the high prevalence of hepatic steatosis (HS), the aim of the study is to verify the frequency of HS incidentally detected in chest computed tomography (CT) imaging in our population affected by SARS-CoV-2 and to investigate its association with the severity of the infection and outcome in terms of hospitalization. We retrospectively analyzed 500 patients with flu syndrome and clinically suspected of having Sars-CoV-2 infection who underwent unenhanced chest CT and have positive RT-PCR tests for Sars-CoV-2 RNA. Two radiologists both with >5 years of thoracic imaging experience, evaluated the images in consensus, without knowing the RT-PCR results. Liver density was measured by a region of interest (ROI), using a liver attenuation value ≤40 Hounsfield units (HU). On 480 patients, 23.1% (111/480) had an incidental findings of HS on chest CT. The steatosis group, included 83 (74.7%) males and 28 (25.3%) females. Patients with HS were more likely to be hospitalized in the intensive care unit (ICU). On univariate analysis, there is a correlation between probability to be intubate (access in the ICU) and HS: patients with HS are twice as likely to be intubated (OR 2.04, CI 95% 1.11-3.73). Chest CT is an important diagnostic tool for COVID-19 and can provide information about the prognosis of the disease. HS can easily be detected on chest CT taken for the diagnosis of the COVID-19 disease, is an important sign for a poor prognosis and possible predictor of admission in ICU.


Wound healing: calcium flashes illuminate early events.
What are the earliest signals produced at a wound edge that mobilise epithelial cells to heal the wound? Live analysis of wound healing in the worm Caenorhabditis elegans shows that calcium may be the key early trigger.


Pretreatment of municipal solid waste incineration fly ash and preparation of solid waste source sulphoaluminate cementitious material.
Municipal solid waste incineration fly ash (MSWI-FA) is a kind of hazardous waste, and it is of great significance to treat it harmlessly and resourcefully. This study proposes the preparation of sulphoaluminate cementitious materials using water-washed MSWI-FA, flue-gas desulfurization gypsum, and aluminum ash. The changes in the composition and morphology of MSWI-FA before and after washing were investigated, and the effects of various washing conditions on the removal rate of chloride salt from MSWI-FA were analyzed. The effect of firing temperature on the mineral content of the sulphoaluminate cementitious material was also investigated. In addition, the strength and heavy metal leaching characteristics of the corresponding materials were tested. The results show that more than 90% of chloride salts were removed by water washing MSWI-FA two times. Using MSWI-FA as the main raw material, the sulphoaluminate cementitious material containing mostly calcium sulphoaluminate and dicalcium silicate could be prepared successfully at 1270 °C; the amount of MSWI-FA in the raw material can be as high as 35% (dry weight). Moreover, the sulphoaluminate cementitious material can effectively solidify heavy metals in the raw materials. The leaching concentrations of eight heavy metal ions, i.e., Cu, Zn, Cd, Pb, Cr, Ni, Ba, and As are far lower than the concentration limits set by national standards.


The effects of toxic and non-toxic serum phenytoin levels on carbohydrate tolerance and insulin levels.
The effect of toxic and non-toxic phenytoin levels on carobhydrate tolerance and insulin levels was studied in 18 patients with epilepsy and 17 control subjects. Toxic levels were defined as a serum level greater than 20 microgram/ml. Toxic levels occurred in 11 patients and nontoxic levels in seven patients. Blood glucose and insulin levels were measured at 30-min intervals for a period of 3 h following the ingestion of 50 g glucose. Blood glucose levels were measured by the ferricyanide method, and serum insulin levels by immunoassay of insulin with insulin antibody precipitate. Serum phenytoin levels were measured by gas liquid chromatography. The insulin profiles were the same for all three groups, but there was a significant delay in reaching peak glucose concentrations in patients with toxic levels of phenytoin. It was therefore confirmed that non-toxic levels of phenytoin do not affect carbohydrate tolerance or insulin levels when phenytoin is used in the routine treatement of epilepsy, and it has also been shown that toxic levels of phenytoin do not affect carbohydrate tolerance when the high levels are detected at an early stage.


Left ventricular hypertrophy caused by a novel nonsense mutation in FHL1.
Emery Dreifuss muscular dystrophy (EDMD) is a hereditary muscular disorder, characterized by contractures, progressive muscular wasting and cardiac involvement. The majority of EDMD patients harbor mutations in the lamin A/C (LMNA) and emerin (STA) genes. Emerging data implicate mutations in FHL1 (four and a half LIM protein 1) gene, located in chromosome Xq26, in EDMD pathogenesis. FHL1 is mainly expressed in striated and cardiac muscle, and plays an important role in sarcomeric protein synthesis, maintenance of cellular integrity, intracellular signaling and genetic transcription pathways. We report the identification of a novel nonsense mutation in FHL1 gene, associated with left ventricular hypertrophy and a family history of stroke and sudden cardiac death. The management implications of this diagnosis are also discussed.


Electrocardiographic recognition of variant angina during permanent pacing.
We present a patient with a permanent ventricular pacemaker who was investigated for episodes of chest pain associated with syncope. Ambulatory electrocardiographic monitoring showed essentially paced rhythm. ST segment elevation of the paced beats was observed during spontaneous chest pain, but the significance of this finding was initially unclear in the context of the abnormal repolarization associated intrinsically with paced rhythm. At angiography, coronary spasm was demonstrated after ergonovine, and this was associated with ST segment elevation during paced rhythm and with chest pain. We conclude that ST segment elevation may indicate myocardial ischemia even when observed in the face of abnormal repolarization associated with paced rhythm.


In situ temperature-compensated ultraviolet spectrophotometry to estimate nitrate and chloride concentrations in estuarine seawater with different salinity and composition.
Various methods have been proposed for in situ measurement of nitrate concentrations from the ultraviolet (UV) absorbance spectrum of seawater with stable salinity and constituents. However, salinity and temperature affect the UV absorption spectrum of seawater. In sea areas with large variability in salinity and water temperature, accurate nitrate ion concentration measurements remain challenging. We performed in situ measurements of nitrate, chloride, and bromide in estuarine seawater with different salinity compositions and applied water temperature compensation. First, the impact of water temperature on the UV absorbance of chloride, bromide, and nitrate was experimentally investigated and represented in a mathematical model. Next, chloride, bromide, and nitrate concentrations were estimated by suppressing the impact of residual components from the UV absorbance spectra of seawater using principal component regression (PCR). Hence, the chloride, bromide, and nitrate concentrations were determined by measuring the UV absorbance spectrum of seawater alone, without measuring water temperature and electrical conductivity. The proposed method was more accurate (±1.39 μM below 100 μM and ±0.90 μM below 20 μM) than the conventional method (±2.35 μM below 100 μM and ±1.88 μM below 20 μM) and PCR without water temperature compensation (±3.67 μM). In a field study, an in situ UV spectrophotometer with water temperature compensation was used to measure depth profiles of nitrate concentrations in estuarine seawater. We successfully measured the depth profiles of low chloride and high nitrate concentrations in the surface layer as well as high chloride and low nitrate concentrations in the lower layer. The proposed method enables in situ measurements of nitrate concentrations in waters with either stable or highly variable salinity and composition. Unlike conventional chemical analysis, our method can describe detailed spatiotemporal variations in nitrate concentrations.


Walking patterns and hip contact forces in patients with hip dysplasia.
Several studies have investigated walking characteristics in hip dysplasia patients, but so far none have described all hip rotational degrees of freedom during the whole gait cycle. This descriptive study reports 3D joint angles and torques, and furthermore extends previous studies with muscle and joint contact forces in 32 hip dysplasia patients and 32 matching controls. 3D motion capture data from walking and standing trials were analysed. Hip, knee, ankle and pelvis angles were calculated with inverse kinematics for both standing and walking trials. Hip, knee and ankle torques were calculated with inverse dynamics, while hip muscle and joint contact forces were calculated with static optimisation for the walking trials. No differences were found between the two groups while standing. While walking, patients showed decreased hip extension, increased ankle pronation and increased hip abduction and external rotation torques. Furthermore, hip muscle forces were generally lower and shifted to more posteriorly situated muscles, while the hip joint contact force was lower and directed more superiorly. During walking, patients showed lower and more superiorly directed hip joint contact force, which might alleviate pain from an antero-superiorly degenerated joint.


Change in serum sodium level predicts clinical manifestations of transurethral resection syndrome: a retrospective review.
Patients undergoing transurethral resection (TUR) of the prostate are at risk of TUR syndrome, generally defined as having cardiovascular and/or neurological manifestations, along with serum sodium concentrations less than or equal to 125 mmol/l. As these symptoms can also occur in patients with serum sodium greater than 125 mmol/l, this study aimed to investigate the relationship between serum sodium concentrations and neurological manifestations of TUR syndrome. Data on patients who underwent TUR of the prostate under local anesthesia over an 8-year period were retrospectively reviewed. Based on their cardiovascular and neurological manifestations, patients were divided into two groups: a symptomatic and an asymptomatic group. Logistic regression analysis was used to detect the risk factors for being symptomatic. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cutoff value of estimated change in serum sodium level that could predict the development of clinical manifestation of TUR syndrome. Of the 229 patients, 60 showed symptoms. Serum sodium level correlated with neurological score (Spearman's correlation coefficient > 0.5). Logistic regression detected that the risk factors for being symptomatic were serum sodium level variables, operation time longer than or equal 90 min, and presence of continuous drainage from the bladder. ROC curve analysis showed that a change in serum sodium level of 7.4 mmol/l was the optimal cutoff value, with a sensitivity of 0.72, a specificity of 0.87, and an area under the curve (AUC) of 0.87. ROC curve analysis also showed that a 7.0% change in serum sodium level was optimal for this parameter, with a sensitivity of 0.70, a specificity of 0.89, and an AUC of 0.87. Changes in serum sodium concentration of > 7 mmol/l and of > 7% could predict the development of cardiovascular and neurological manifestations, which were assumed to be symptoms of TUR syndrome.


Ecotoxicological effects, water quality standards and risk assessment for the anti-diabetic metformin.
Metformin (MET) is among the most consumed pharmaceuticals worldwide. This compound has been frequently detected in fresh surface water. However, ecotoxicological information for MET is still too limited, particularly regarding chronic and behavioral data. This study aimed to help filling these knowledge gaps, by carrying out both acute and chronic studies with four different test organisms from three different trophic levels. We assessed different endpoints, including the swimming behavior of Danio rerio larvae. We also derived both short-term and long-term environmental quality standards (EQS) for the protection of freshwater pelagic biota towards MET adverse effects. A risk quotient (RQ) was calculated for MET in fresh surface water, considering a worst-case scenario. Daphnia similis was by far the most sensitive species evaluated. An EC10 of 4.4 mg L-1 was obtained from the reproduction test with D. similis. A long-term EQS of 88 μg L-1 was derived and a RQ of 0.38 was obtained. An ecological risk is not expected for the chronic exposure of pelagic freshwater species to MET, considering the endpoints and the standard bioassays usually recommended in standard protocols. However, endocrine disruptive effects and potential interactive effects of MET with other co-occurring contaminants cannot be ruled out. To the best of our knowledge, this study presents the first data related with MET effects on population endpoints of D. similis and Hydra attenuata, as well as on the locomotor activity of D. rerio.


Breast macrocysts.
Clinical macrocysts occur in about 7% of adult women. Modern terminology and understanding of benign breast disorders considers microcysts and macrocysts as specific clinical and pathological entities. The terminology and concepts of fibrocystic disease and its many alternative terms have been discarded. Cysts arise as an aberration of normal lobular involution (ANDI) associated with active secretion of apocrine epithelium under hormonal stimulation. They are readily managed in most cases by aspiration alone. Multiple recurrent cysts may constitute a considerable nuisance and justify short-term therapy with danazol. There is increasing evidence that multiple recurrent cysts are associated with a small, but significant increase in breast cancer risk.


X chromosome array-CGH for the identification of novel X-linked mental retardation genes.
Array-CGH technology for the detection of submicroscopic copy number changes in the genome has recently been developed for the identification of novel disease-associated genes. It has been estimated that submicroscopic genomic deletions or duplications will be present in 5-7% of patients with idiopathic mental retardation (MR). Since 30% more males than females are diagnosed with MR, we have developed a full coverage X chromosome array-CGH with a theoretical resolution of 82 kb, for the detection of copy number alterations in patients with suspected X-linked mental retardation (XLMR). First, we have validated the genomic location of X-derived clones through male versus female hybridisations. Next, we validated our array for efficient and reproducible detection of known alterations in XLMR patients. In all cases, we were able to detect the deletions and duplications in males as well as females. Due to the high resolution of our X-array, the boundaries of the genomic aberrations could clearly be identified making genotype-phenotype studies more reliable. Here, we describe the production and validation of a full coverage X-array-CGH, which will allow for fast and easy screening of submicroscopic copy number alterations in XLMR patients with the aim to identify novel MR genes or mechanisms involved in a deranged cognitive development.


Modeling of cadmium(II) removal in a fixed bed column utilizing hydrochar-derived activated carbon obtained from discarded mango peels.
Cadmium is found in many underdeveloped countries' aquatic bodies. Therefore, contaminated water should be treated before consumption; henceforth, efficient and customized point-of-use filtration is foreseeable. Traditionally, carbon-based sorbents have been utilized for such treatments, but alternative sources are also being investigated. Hydrochars made from mango peels using a thermal activation process were employed as an adsorbent instead of activated carbon in this investigation. The prepared material was porous with active surface functionalities, and the interaction of cadmium with the surface was possibly ion-exchange in nature. The performance of a material for a candle water filtering system with a 2.5 cm internal diameter and a 30.48 cm column height was determined using the parameters acquired by the Thomas model. The material was found to be highly efficient at 453.5 L/min/Filter water, whereas 31670.6 L/min/Filter can be treated if the break point and exhaustion point are considered, respectively, as the candle replacement time. These findings indicate that activated hydrochar might be a suitable sorbent for removing cadmium ions from contaminated water.


A new technique for repair of a dislocated sternoclavicular joint using a sternal tension cable system.
An unstable anterior or posterior sternoclavicular joint dislocation can cause severe morbidity with poor shoulder movement and strength. These dislocations need to be repaired, which can be challenging. Many different procedures have been described to obtain a stable joint fixation with varying results. We report a new technique for repairing a sternoclavicular joint dislocation by using a figure-of-eight sternal cable system. This procedure is relatively simple and reproducible to create a stable and functional sternoclavicular joint.


Asymptomatic gastric anisakiasis detected in gastric cancer screening: A case report.
Anisakiasis is a parasitic disease caused by Anisakis simplex and has become an emerging zoonosis as preferences for eating raw or undercooked seafood have become more common. Few case reports of asymptomatic anisakiasis have been published to date. A 79-year-old asymptomatic man underwent esophagogastroduodenoscopy (EGD) for gastric cancer screening. The gastroenterologist diagnosed superficial gastritis without any malignant lesions but found an Anisakis larva while reviewing EGD images. The physician performed a second EGD and removed the larva. The patient reported that he ate the flatfish sashimi for dinner on the day before the first EGD. This case indicates the existence of asymptomatic gastric anisakiasis, indicating that anisakiasis incidence may have previously been underestimated.


Cerebrovascular endothelial cell culture: metabolism and synthesis of 5-hydroxytryptamine.
The presence of 5-hydroxytryptamine was investigated in cultured and propagated cerebrovascular endothelium using immunohistochemistry and high pressure liquid chromatography. These studies demonstrate that the endothelium has the ability to take up and metabolize 5-hydroxytryptamine as well as to synthesize this amine from its precursor L-tryptophan, thus providing evidence for extraneural synthesis of 5-hydroxytryptamine in the central nervous system.


Cyp2d6*3, *4, *5 and *6 polymorphisms and antipsychotic-induced extrapyramidal side-effects in patients receiving antipsychotic therapy.
1. The aim of the present study was to examine the relationship between CYP2D6 polymorphisms and the risk of antipsychotic (AP)-induced extrapyramidal symptoms (EPS) in patients receiving AP treatment. The allele status for CYP2D6*3, CYP2D6*4, CYP2D6*5 and CYP2D6*6 was determined in 267 patients receiving AP therapy. Seventy-nine cases presenting with EPS (Simpson-Angus Scale 3) and 188 controls without EPS (Simpson-Angus > 3) took part in the study. 2. We found a non-significant over-representation of poor metaboliser genotypes among cases, but a significant association between the mutant homozygous genotype for CYP2D6*4 (odds ratio (OR) 4.1, 95% confidence interval (CI) 1.01-16, permutated P value 0.01) and the heterozygous genotype for CYP2D6*6 (OR 5.4, 95% CI 1.13-18, permutated P value 0.003) and the risk of suffering EPS. 3. These results suggest that the CYP2D6 genotype may be a contributory factor in the development of EPS in patients undergoing AP therapy.


Surgical Outcomes of Acute Retinal Necrosis-Related Retinal Detachment in Polymerase Chain Reaction-Positive Patients: A Single-Center Experience.
To evaluate the clinical features, operative techniques, and surgical outcomes of patients who underwent surgery for acute retinal necrosis (ARN)-related retinal detachment (RD). Retrospective, longitudinal, consecutive case series. Patients with polymerase chain reaction-positive ARN presenting from 2011 to 2021 who underwent vitreoretinal surgery for ARN-related RD at our institution. Univariate, multivariate, and survival analyses were used to determine predictors of anatomic and functional outcomes. Single-surgery anatomic success rate, recurrent RD, and visual acuity (VA) at 1 year. Thirty-four eyes of 34 patients (32.4% women, mean age, 45.1 ± 20.4 years) were included for analysis with a median follow-up of 2.5 years (interquartile range [IQR], 0.8-5.5 years). Presenting VA was 1.1 ± 0.8 logarithm of the minimum angle of resolution (LogMAR) (Snellen ∼20/250). The median time from presentation to RD surgery was 1.7 months (IQR, 0.8-4.1 months), and the mean preoperative VA was 1.6 ± 0.8 LogMAR (Snellen ∼20/800). Small-gauge pars plana vitrectomy (PPV) with or without a scleral buckle (SB) was performed for all eyes with an overall single-surgery success rate of 63.6%, with no statistically significant differences in visual/anatomic outcomes between PPV and PPV/SB cases. Silicone oil was used for tamponade in 33 (97.1%) cases and was removed in 10 (30.3%) with good anatomic and final functional outcomes (Snellen ∼20/80). Independent predictors of recurrent RD included the female sex (hazard ratio, 8.38; 95% confidence interval, 2.03-34.68; P < 0.01) and zone 1 retinitis involvement at presentation (hazard ratio, 10.95; 95% confidence interval, 2.12-56.48; P < 0.01). The mean VA at 1 year (VA1year) and at the final follow-up both had a Snellen equivalent of 20/640 (P > 0.05 for both compared with preoperative VA, respectively). Eyes that achieved single-surgery success had VA1year of 20/200 versus hand movements in those with single-surgery failure (P < 0.01). On multivariate linear regression, younger age (P = 0.04) and better presenting VA (P < 0.01) were both associated with better VA1year. Moderate single-surgery anatomic success can be achieved with modern vitreoretinal surgical techniques for ARN-related RD, although visual outcomes remain poor. Further studies investigating interventions for increasing single-surgery success rates, for the inflammatory complications of ARN, and for preventing ARN-related RD are needed.


Regulation of electrogenic anion secretion in normal and cystic fibrosis gallbladder mucosa.
Fluid and ion transport across biliary epithelium contributes to bile flow. Alterations of this function may explain hepatobiliary complications in cystic fibrosis (CF). We investigated electrogenic anion transport across intact non-CF and CF human gallbladder mucosa in Ussing-type chambers. In non-CF tissues, baseline transmural potential difference (PD), short-circuit current (Isc), and resistance (R) were -2.2 +/- 0.3 mV (lumen negative), 40.7 +/- 7.8 microA/cm2, and 66.5 +/- 9.6 Omega. cm2, respectively (n = 14). The addition of forskolin (10(-5) mol/L) to the apical and basolateral baths and that of adenosine 5'-triphosphate (ATP) (10(-4) mol/L) to the apical bath induced significant increases in Isc by 8.0 +/- 1.4 and 10.3 +/- 1.8 microA/cm2, respectively. Depletion of bathing solutions in Cl- and HCO3- significantly reduced baseline Isc and the forskolin- and ATP-induced increases in Isc. Anion secretion was stimulated by extracellular ATP via P2Y2 purinoceptors, as indicated by the effects of different nucleotides on Isc and on 36Cl efflux in cultured gallbladder epithelial cells. This effect was mediated by cytosolic calcium increase and Ca2+/calmodulin-dependent protein kinase II, as ascertained by using inhibitors. In CF preparations, basal PD and Isc were lower than in non-CF, and the response to forskolin was abolished, whereas the response to ATP was enhanced (P <.05 for all). We conclude that electrogenic anion secretion occurs in human gallbladder mucosa under basal state and is stimulated by an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pathway mediated by cystic fibrosis transmembrane conductance regulator (CFTR), and by exogenous ATP via a CFTR-independent pathway that is up-regulated in CF and involves P2Y2 purinoceptors and a calcium-dependent pathway.


Acquired haemophilia in cancer: A systematic and critical literature review.
There is a paucity of data on the clinical presentation and management of cancer patients with acquired haemophilia (AH), we here report a systematic literature review on acquired haemophilia in the context of cancer. Treatment outcomes of AH were defined as complete response (CR), partial response (PR) or no response (NR), based on inhibitor eradication, coagulation factor VIII levels and bleeding control. Reported deaths were either related to cancer or bleeding. Overall, 105 cases were collected and analyzed according to classification of cancer and efficacy of treatments for inhibitor and malignancy. The mean age was 68 years for both males (range 37-86 years) and females (range 43-89 years), 39 patients were female subjects and 66 were males. A solid cancer was diagnosed in 60 subjects, while 45 patients suffered a haematological malignancy. Solid cancers affected mainly males; however, the incidence of solid tumours vs haematological malignancies was not statistically significant (P = .09). Not all patients were treated for their underlying cancer, bleeding and/or inhibitor, in two cases outcome is unavailable. CR was reported in 62.1% (64/103) cases, PR in 9.7% (10/103) cases, NR with or without death was reported in 28.1% (29/103) cases. CR was best achieved when successful and complete elimination of autoantibodies occurred contemporaneously with the successful treatment of the underlying malignancy. In some cases, recurrent autoantibodies were harbingers of relapsed cancer. Type of cancer, inhibitor titer, treatments administered for bleeding control and inhibitor eradication did not significantly affect clinical outcome of analyzed cases.


[The role of PET in lung cancer staging].
The precise staging of lymph-node and distant metastases is pivotal for the choice of surgical procedures and overall therapy planning for patients with lung cancer. FDG-PET/CT plays a central role in the diagnostic algorithm of patients with potentially curable disease. In patients with histologically proven lung cancer, FDG-PET/CT provides a higher diagnostic accuracy in the staging of lymph-node and distant metastases compared to staging with CT alone. Furthermore, as a whole body examination, FDG-PET/CT may replace further additional examinations. Prospective studies have also shown that the number of unnecessary thoracotomies and mediastinoscopies can be reduced by the inclusion of FDG-PET in the preoperative staging.


Concussion and Academic Impairment Among U.S. High School Students.
Sports and physical activities are a frequent cause of traumatic brain injury, primarily concussions, among adolescents. These concussions may adversely affect students' ability to learn and impair academic achievement in educational settings. The 2017 Youth Risk Behavior Survey, conducted among a nationally representative sample of 14,765 U.S. high school students, was analyzed in 2018 to examine associations between self-reported sports- and physical activity-related concussions and symptoms of cognitive impairment (difficulty concentrating, remembering, or making decisions) and self-reported academic grades (mostly A's=4.0, mostly B's=3.0, mostly C's=2.0, mostly D's=1.0, mostly F's=0.0). Adjusted prevalence ratio and the difference in self-reported estimated grade point average were adjusted for sex, race/ethnicity, grade, and athlete status (participation on sports teams) and considered statistically significant if p<0.05. Male students were more likely than female students (17.1% vs 13.0%), and athletes were more likely than nonathletes (21.4% vs 7.6%) to have a self-reported sports- and physical activity-related concussion in the 12 months preceding the survey. Students with a reported sports- and physical activity-related concussion were more likely than students without one to report symptoms of cognitive impairment regardless of whether they were male (adjusted prevalence ratio=1.49), female (adjusted prevalence ratio=1.37), athletes (adjusted prevalence ratio=1.45), or nonathletes (adjusted prevalence ratio=1.42). Self-reported grade point averagedecreased significantly from 3.14 among students who reported no concussions (referent), to 3.04 among students who reported a single concussion, and 2.81 among students who reported ≥2 concussions. School-based programs are needed to monitor students' academic performance and provide educational support and resources to promote academic success following a concussion.


Parvalbumin as a neurochemical marker of the primate optic radiation.
Parvalbumin (PV) is a calcium-binding protein that labels neuronal cell bodies in the magno and parvocellular layers of the primate lateral geniculate nucleus (LGN). Here we demonstrate that PV immunohistochemistry can also be used to trace the optic radiation (OR) of the marmoset monkey (Callithrix jacchus) from its LGN origin to its destinations in the primary visual cortex (V1), thus providing a high-resolution method for identification of the OR with single axon resolution. The emergence of fibers from LGN, their entire course and even the entry points to V1 were clearly defined in coronal, parasagittal, and horizontal sections of marmoset brain. In all cases, the trajectory revealed by PV staining paralleled that defined by high-resolution diffusion tensor imaging (DTI). We found that V1 was the exclusive target for the PV-containing fibers, with abrupt transitions in staining observed in the white matter at the border with area V2, and no evidence of PV-labeled axons feeding into other visual areas. Changes in the pattern of PV staining in the OR were detected following V1 lesions, demonstrating that this method can be used to assess the progress of retrograde degeneration of geniculocortical projections. These results suggest a technically simple approach to advance our understanding of a major white matter structure, which provides a cellular resolution suitable for the detection of microstructural variations during development, health and disease. Understanding the relationship between PV staining and DTI in non-human primates may also offer clues for improving the specificity and sensitivity of OR tractography for clinical purposes.


Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data From the PRESTIGIO Registry.
Currently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population. This was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death. Among 148 PWH followed for a median (interquartile range) of 47 (32-84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85-11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%-13%), and that of ≥1 event or death was 22% (95% CI, 16%-31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07-6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65-1.02). PWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.


Using topical benzocaine before lingual frenotomy did not reduce crying and should be discouraged.
The US Food and Drug Administration has said that oral preparations containing benzocaine should only be used in infants under strict medical supervision, due to the rare, but potentially fatal, risk of methemoglobinemia. This study aimed to determine the analgesic effect of topical application of benzocaine prior to lingual frenotomy in infants with symptomatic tongue-tie. We hypothesised that the duration of crying immediately following frenotomy with topical benzocaine would be shorter than with no benzocaine. This randomised controlled study compared the length of crying after lingual frenotomy in term infants who did, or did not, receive topical application of benzocaine to the lingual frenulum prior to the procedure. We recruited 21 infants to this study. Crying time was less than one minute in all of the subjects. The average length of crying in the benzocaine group (21.6 ± 13.6 sec) was longer than the length of crying in the control group (13.1 ± 4.0 sec), p = 0.103. Contrary to our hypothesis, infants who were treated with topical benzocaine did not benefit from topical analgesia in terms of crying time. The use of benzocaine for analgesia prior to lingual frenotomy in term infants should therefore be discouraged.


Conformational changes of membrane-bound (Na+--K+)-ATPase as revealed by trypsin digestion.
To distinguish ligand-induced structural states of the (Na+--K+)-ATPase, the purified membrane-bound enzyme isolated from rat kidneys was digested with trypsin in the presence of various combinations of Na+, K+, Mg++ and ATP. It was found that first the large and then the small polypeptide chain of the (Na+--K+)-ATPase was degraded, indicating that the lysine and arginine residues of the large chain are more exposed than are those of the small one. The (Na+--K+)-ATPase activity was inactivated in parallel with the degradation of the large polypeptide chain. After the degradation of the large polypeptide chain, about 75% of the (Na+--K+)-ATPase protein remained bound to the membrane, demonstrating that the split protein segments were only partially released. It was found that the combinations of ATP, Mg++, Na+ and K+ present during trypsin digestion influenced the time course and degree of degradation of the (Na+--K+)-ATPase protein. The degradations of the large and the small polypeptide chain were affected in parallel. Thus, certain ATP and ligand combinations influenced neither the degradation of the large nor the degradation of the small polypeptide chain, whereas by other combinations of ATP and ligands the degree of susceptibility of both polypeptide chains to trypsin was equally increased or reduced. In the absence of ATP the time course of trypsin digestion of the (Na+--K+)-ATPase was the same, whether Na+ or K+ was present. With low ATP concentrations (e.g., 0.1 mM), however, binding of Na+ or K+ led to different degradation patterns of the enzyme. If a high concentration of ATP (e.g. 10 mM) was present, Na+ and K+ also influenced the degradation pattern of the (Na+--K+)-ATPase, but differentially compared to that at low ATP concentrations, since the effects of Na+ and K+ were reversed. Furthermore, it was found that the degradation of the small chain was only influenced by certain combinations of ATP, Mg++, Na+ and K+ if the large chain was intact when the ligands were added to the enzyme. The described results demonstrate structural alterations of the (Na+--K+)-ATPase complex which are supposed to include a synchronous protrusion or retraction of both (Na+--K+)-ATPase subunits. The data further suggest that ATP and other ligands primarily alter the structure of the large (Na+--K+)-ATPase subunit. This structural alteration is presumed to lead to a synchronous movement of the small subunit of the enzyme. The structural state of the (Na+--K+)-ATPase is regulated by binding of Na+ or K+ to the enzyme-ATP complex. The effects of Na+ and K+ on the (Na+--K+)-ATPase structure are modulated by the ATP binding to "high affinity" and to "low affinity" ATP binding sites.


Interplay of COVID-19 and cardiovascular diseases in Africa: an observational snapshot.
The COVID-19 pandemic, which started around December 2019 has, at present, resulted in over 450,000 deaths globally, and approximately 1% of these deaths have been reported in Africa. Despite the high prevalence of COVID-19 risk factors, namely: hypertension, diabetes, chronic pulmonary disease, cardiovascular diseases (CVDs) such as rheumatic heart disease, compromised immunity and obesity, low case fatality rates have been recorded in many parts of Africa so far. COVID-19 severity has previously been shown to be worse in patients with CVD and hypertension. We observed the severity of COVID-19 and mortality rates in Africa, and compared outcomes with prevalence of established risk factors (hypertension and CVD). We stratified data as per the United Nations' 5 African subregions. North African countries show a positive association between the risk factors and the mortality rates from COVID-19. However, we observed discordant patterns in the relationship between COVID-19, and either CVD or hypertension, in sub-Saharan African countries. In this paper, we also review the pathogenesis of SARS-CoV-2 infection and how it worsens CVD and postulate that the differences in modulation of the renin-angiotensin-aldosterone system (RAAS) axis which controls angiotensin-converting enzyme (ACE)/ACE2 balance may be an important determinant of COVID-19 outcomes in Africa.


[Dissociation of human serum low density lipoproteins in several immunologically distinct subunits. Isolation and characterization of a B-III subunit].
Low density lipoproteins (d = 1.030-1.055) were partially delipidated with ethyl-ether (LDLe). These LDLe exhibit a spontaneous dissociation several days after delipidation. Four different immunoprecipitation complexes (B-I to B-IV) are observed when using two dimensional immunoelectrophoresis against anti LDLe immunserum. The various subunits of LDLe have different behaviour upon electrophoresis. On disc gel electrophoresis containing urea three bands can be seen; all are phospholipoproteins. The apolipoprotein moiety of LDL and LDLe have the same apparent molecular weight around 550 000. With time several subunits appear in LDLe, the majority of them have a molecular weight around 370 000, 260 000 and 125 000. One of the components from dissociated LDLe containing the immunodeterminant B-III, has been separated by chromatography on heparin-agarose. This LDLe-B-III has the same phospholipid/protein ratio as total LDLe and a protein moiety with an apparent molecular weight of 110 000. This part of apolipoprotein B has no affinity for heparin. Immunocompetition studies by the ELISA technique indicated that sialic acid, one of terminal residues of LDL glycoprotein, is involved in the immunological recognition of LDL and of its derivatives by anti LDL and anti LDLe antisera.


Gene expression profiles in response to Fas stimulation in Trypanosoma cruzi-infected host cells.
To determine the molecular mechanism by which apoptosis is inhibited in Trypanosoma cruzi-infected host cells, we used human cDNA apoptosis chips to compare the gene expression profiles in response with 'death ligands target' (Fas) stimulation in infected and uninfected cells. Of the 164 apoptosis-related genes examined, 20, including those encoding both pro- and anti-apoptotic proteins, were highly up-regulated in the infected group. Genes encoding caspases and apoptosis inhibitors were optimally expressed 10-30 min after induction of apoptosis, whereas genes involved in transcriptional regulation and cell proliferation were up-regulated after 2-24 h. These results suggest that host anti-apoptotic gene(s) may play a crucial role in the inhibition of Fas-mediated apoptosis in T. cruzi-infected cells.


Fetal tissue engineering: chest wall reconstruction.
This study was aimed at applying fetal tissue engineering to chest wall reconstruction. Fetal lambs underwent harvest of elastic and hyaline cartilage specimens. Once expanded in vitro, fetal chondrocytes were seeded onto synthetic scaffolds, which then were placed in a bioreactor. After birth, fetal cartilage constructs (n = 10) were implanted in autologous fashion into the ribs of all lambs (n = 6) along with identical, but acellular scaffolds, as controls (n = 6). Engineered and acellular specimens were harvested for analysis at 4 to 12 weeks postimplantation. Standard histology and matrix-specific staining were performed both before implantation and after harvest on all constructs. Regardless of the source of chondrocytes, all fetal constructs resembled hyaline cartilage, both grossly and histologically, in vitro. In vivo, engineered implants retained hyaline characteristics for up to 10 weeks after implantation but remodeled into fibrocartilage by 12 weeks postoperatively. Mononuclear inflammatory infiltrates surrounding residual PGA/PLLA polymer fibers were noted in all specimens but most prominently in the acellular controls. Engineered fetal cartilage can provide structural replacement for at least up to 10 weeks after autologous, postnatal implantation in the chest wall. Fetal tissue engineering may prove useful for the treatment of severe congenital chest wall defects at birth.


AtREM1, a member of a new family of B3 domain-containing genes, is preferentially expressed in reproductive meristems.
We have isolated and characterized AtREM1, the Arabidopsis ortholog of the cauliflower (Brassica oleracea) BoREM1. AtREM1 belongs to a large gene family of more than 20 members in Arabidopsis. The deduced AtREM1 protein contains several repeats of a B3-related domain, and it could represent a new class of regulatory proteins only found in plants. Expression of AtREM1 is developmentally regulated, being first localized in a few central cells of vegetative apical meristems, and later expanding to the whole inflorescence meristem, as well as primordia and organs of third and fourth floral whorls. This specific expression pattern suggests a role in the organization of reproductive meristems, as well as during flower organ development.


Li-Ion Transfer Mechanism of Gel Polymer Electrolyte with Sole Fluoroethylene Carbonate Solvent.
Although gel polymer electrolytes (GPEs) represent a promising candidate to address the individual limitations of liquid and solid electrolytes, their extensive development is still hindered due to the veiled Li-ion conduction mechanism. Herein, the related mechanism in GPEs is extensively studied by developing an in situ polymerized GPE comprising fluoroethylene carbonate (FEC) solvent and carbonate ester segments (F-GPE). Practically, although with high dielectric constant, FEC fails to effectively transport Li ions when acting as the sole solvent. By sharp contrast, F-GPE demonstrates superior electrochemical performances, and the related Li-ion transfer mechanism is investigated using molecular dynamics simulations and 7 Li/6 Li solid-state nNMR spectroscopy. The polymer segments are extended with the swelling of FEC, then an electron-delocalization interface layer is generated between abundant electron-rich groups of FEC and the polymer ingredients, which works as an electron-rich "Milky Way" and facilitates the rapid transfer of Li ions by lowering the diffusion barrier dramatically, resulting in a high conductivity of 2.47 × 10-4 S cm-1 and a small polarization of about 20 mV for Li//Li symmetric cell after 8000 h. Remarkably, FEC provides high flame-retardancy and makes F-GPE remains stable under ignition and puncture tests.


Effect of diffusion boundary layers on the initial uptake of O2 by red cells. Theory versus experiment.
We have applied theories of mass transfer, in laminar and turbulent flow, to red cells in the stopped-flow apparatus in order to estimate the effect of extracellular diffusion boundary layers on the initial rate of O2 uptake. We compared the theoretical predictions with the results of our previous stopped-flow experiments with suspensions of red cells to which bovine serum albumin (BSA) had been added to decrease O2 solubility and diffusivity (Huxley and Kutchai, 1981). Models of red cells in laminar flow (Friedlander, 1957, 1961; Harriott, 1962) predict a significant retardation of the rate of O2 entry into red cells by diffusion boundary layers. Mixing in the stopped-flow apparatus occurs by convective and turbulent mechanisms in addition to simple molecular diffusion. The more complex theory of mass transfer to particles in turbulent flow (Levich, 1962) shows, because the red cells are highly entrained in the flow, that mixing is not complete on the time scale of initial O2 uptake. The O2 permeability of the diffusion boundary layer, predicted by both laminar and turbulent flow theories, approximates the experimentally obtained value. The theories of mass transfer to particles in laminar flow predict the dependence of the rate of O2 uptake on red cell size observed by other investigators. This suggests that these experimental results may be primarily due to the effect of diffusion boundary layers. Our studies are consistent with the interpretation that red cells in rapid mixing devices may be mixed incompletely with the suspending fluid; thus O2 transfer is limited by molecular diffusion in the immediate vicinity of the erythrocyte. We conclude that the rates of respiratory gas exchange by red cells in flowing systems may be partly limited by diffusion boundary layers.