Transcriptional regulation of a contractile gene by mechanical forces applied through integrins in osteoblasts.
We examined mechanotranscriptional regulation of the contractile gene, alpha-smooth muscle actin (SMA), in osteoblastic cells. Tensile forces were applied through collagen-coated magnetite beads to ROS17/2.8 cells. These cells were desmin-, vimentin+ and expressed low levels of SMA. After force application (480 piconewton/cell), SMA protein and mRNA were increased but beta-actin was unchanged. Beads coated with bovine serum albumin or poly-L-lysine produced no change of SMA. In cells transiently transfected with plasmids containing the SMA promoter fused to beta-galactosidase or green fluorescent protein coding sequences, SMA promoter activity was increased by approximately 60% after 4 h of force, whereas control (Rous sarcoma virus) promoter activity was unaffected. Transfections with beta-galactosidase or green fluorescent protein reporter constructs showed that force-loaded cells exhibited higher beta-galactosidase activity than cells without force. Cytochalasin D and latrunculin B inhibited force-induced increases of SMA promoter activity. Deletion analyses showed that SMA promoter activity was increased approximately 70% after force with a minimal construct containing 155 bp upstream of the translation start site. The force effect on the SMA promoter was abrogated in cells transfected with CArG-B box mutants. Gel mobility shift analyses of nuclear extracts showed strong binding to the CArG-B motif after force. We conclude that the CArG-B box is a force-responsive element in the SMA promoter.


The plurennial life cycles of the European Tettigoniidae (Insecta: Orthoptera) : 2. The effect of photoperiod on the induction of an initial diapause.
In eggs of European Tettigoniidae species, an initial diapause can occur just after blastoderm formation and a final diapause close to the end of embryonic development. The effect of photoperiod experienced maternally on the induction of the initial diapause was studied, using 13 species from Central and Southeastern Europe. In Conocephalus dorsalis and Platycleis albopunctata there was no initial diapause induced by photoperod, while, in Tettigonia-and Saga-species and in Metrioptera saussuriana it occurred independently of day length. In Metrioptera roeseli, M. bicolor, Leptophyes punctatissima, Eupholidoptera smyrnensis, and Decticus verrucivorus, oviposition at short day induced an initial diapause, while after oviposition at long day, the eggs developed directly until final diapause. On the other hand, in up to 1/4 of the eggs of Pholidoptera griseoaptera an initial diapause was induced by long day length. Populations of D. verrucivorus from different latitudes differed with respect to the critical day length. For E. smyrnensis and M. roeseli, a photoperiodic response curve was calculated.In the Rhodian population of E. smyrnensis, the dormancy sequence of initial and final embryonic diapause can be used for aestivation and hibernation within an annual life cycle, while enabling hibernation in successive years for the Central European species. The population of D. verrucivorus near Aachen has an "obligatory" plurennial life cycle, since the critical day length for development without initial diapause is above the range of day length occurring in the field.


[Study on inhibitory effects of Taxus chinensis var. mairei aqueous extract on the proliferation of tumor cells].
To study the inhibitory effects of Taxus chinensis var. mairei Aqueous Extract (TAE) on SGC-7901 and MCF-7 cells, and to explore its mechanisms. The inhibitory effects of TAT and Paclitaxel on the proliferation of SGC-7901 and MCF-7 cells were tested by MTT method. Their effects on the morphology of SGC-7901 and MCF-7 cells were observed by microscope. Its effects on the cell apoptosis were detected by flow cytometry. The TAE had inhibitory effects on the proliferation of tumor cells, and its mechanisms were correlated to inducing the apoptosis of tumor cells. TAE had inhibitory effects on the proliferation of tumor cells.


Improvement of freeze-fracture autoradiography for localization of soluble substances in tissue samples.
Freeze-fracture autoradiography is accepted as an adequate technique for localization studies of soluble substances at the electron microscopical level. The method, however, involves many critical preparation steps, among them a protective carbon coating of the developed nuclear emulsion adhering to the replica. We demonstrate here that this additional carbon coating may be omitted. This simplification leads to a significant improvement of the sample yield as compared with the previously described procedures.


The role of obstructive apnea in sudden infant death syndrome and apparent life threatening event.
In sudden infant death syndrome (SIDS) apnea is the terminal event; whether or not an obstructive apnea is the primary event is unknown. Collapse of the pliable pharyngeal airway during life would not be detected after death and is therefore hard to prove. The distinctive distribution of petechiae at necropsy can be explained by negative intrathoracic pressure before death suggesting upper airway obstruction. Obstructive sleep apneas have been documented in subsequent SIDS victims: however, polysomnography is not predictive for individual infants. It is unknown how many ALTE (apparent life threatening event) infants would have died of SIDS without intervention. About 4-10% of these events are caused by upper airway obstruction. There have been well documented cases of ALTE infants who in time developed the symptoms of obstructive sleep apnea syndrome (OSAS). Obstructive apnea certainly causes some cases of ALTE; whether it also causes a subgroup of SIDS is unknown.


The lost productivity cost of absenteeism due to COVID-19 in health care workers in Iran: a case study in the hospitals of Mashhad University of Medical Sciences.
Human resources management plays an important role in social development and economic growth. Absence from work due to health problems can make obstacles to the growth of economy. This study conducted aimed to estimate the absenteeism costs of COVID-19 among the personnel of hospitals affiliated to Mashhad University of Medical Sciences in Mashhad, Iran. This cross-sectional study was conducted between February 19, 2020, and September 21, 2020. The absenteeism costs were calculated using the human capital approach. Finally, we applied the linear regression to assess the impact of variables on the lost productivity of absenteeism due to COVID-19 among the personnel of hospitals affiliated to Mashhad University of Medical Sciences. The results of this study showed that 1958 personnel had COVID-19. The total of absenteeism days in our study were 32,209 days, with an average of 16.44 absenteeism days. Total costs due to absenteeism were estimated to be nearly $1.3 million, with an average of $671.4 per patient. The results of regression model showed that gender (male), age (> 50 years), employment Type (non-permanent) and monthly income had a positive relationship with the absenteeism cost. Also, there are a negative significant relationship between absenteeism cost with job (physicians) and work experience. Absenteeism costs of COVID-19 in the hospitals of Mashhad University of Medical Sciences represent a significant economic burden. The findings of our study emphasize the emergency strategies to prevent and control COVID-19 among the healthcare workers. It can decrease the economic impacts of COVID-19 and improve human resources management during the COVID-19 pandemic.


Social and physical anhedonia in relation to cerebral laterality and electrodermal habituation in unmedicated psychotic patients.
The neglect of psychophysiological investigation of social anhedonia, in contrast to physical anhedonia, was addressed by examining relations between electrodermal orienting responses and their lateral asymmetry in unmedicated schizophrenic, bipolar/schizoaffective, and unipolar depressive patients and normal control subjects. In support of relations between social withdrawal and right-hemispheric reactivity, social anhedonia was associated with a predominance of right-hemispheric influences in schizophrenic and bipolar/schizoaffective patients but not in depressive patients. Anhedonia in all but the depressive group was also related to responsiveness, particularly when fast habituators were pooled with nonresponders and compared with moderate and slow habituators. Anhedonia was higher in the more responsive group. This was particularly true of physical anhedonia. The results support associations between both types of anhedonia--social and physical--and psychophysiology, and they also suggest that anhedonia is not a unitary concept.


Preoperative Vision and Surgeon Volume as Predictors of Visual Outcomes after Cataract Surgery.
To evaluate the relationship between preoperative vision and surgeon volume with visual outcomes after cataract surgery. Retrospective cohort study. Patients aged ≥18 years old enrolled in the Kaiser Permanente Southern California Health Plan who underwent cataract surgery by nontrainee surgeons. Patients who underwent cataract surgery between January 1, 2013 and December 31, 2015, were included. A multivariate analysis using Generalized Additive Mixed Models was performed to determine the relationship between surgeon volume and postoperative visual acuity after controlling for patient age, preoperative visual acuity, history of diabetes, and history of diabetic retinopathy. Modeling was done for the relationship between preoperative vision and visual outcomes while controlling for surgeon volume, patient age, history of diabetes, and history of diabetic retinopathy. Absolute letter change and percentage of patients to achieve ≥5 Early Treatment Diabetic Retinopathy Study (ETDRS) letter gain postoperatively. There were 103 920 cataract surgeries performed by 136 surgeons included in this analysis. Patients whose surgeons performed <91.0 surgeries/year (95% confidence interval [CI], 61.1-139; P < 0.05) gained fewer letters postoperatively than the overall average, whereas those whose surgeons performed >91 but <227 surgeries/year (95% CI, 169-∞; P < 0.05) gained more letters than average. Although statistically significant, the difference between the lowest and highest performing surgeons was approximately 1.25 letters. Surgeons who performed <110 surgeries/year (95% CI, 81.7-149; P < 0.05) had fewer patients who gained ≥5 letters. Surgeons who performed >110 but <293 surgeries/year (95% CI, 232-∞; P < 0.05) were approximately 15% more likely to have patients who gained ≥5 letters. Patients with preoperative vision <74.7 letters (95% CI, 74.7-74.8; P < 0.05) and <75.8 letters (95% CI, 75.8-75.9; P < 0.05) gained more letters and were more likely to gain ≥5 letters postoperatively, respectively. Patients whose vision is approximately 20/32 or worse are more likely to have significant visual gains after cataract surgery. Although statistically significant differences exist in postoperative vision based on surgeon volume, these do not appear to be clinically meaningful. Overall, visual outcomes are functionally comparable across a wide range of surgeon volumes.


Rapid eye movement sleep contributes to the formation of new axonal varicosities in mouse cerebellar parallel fibers after motor training.
Synaptic structural plasticity is essential for the development, learning and memory. It is well established that sleep plays important roles in synaptic plasticity after motor learning. In cerebellar cortex, parallel fibers of granule cells make excitatory synapses to the dendrites of Purkinje cells. However, the synaptic structural dynamics between parallel and Purkinje cells after motor training and the function of sleep in cerebellar synaptic plasticity remain unclear. Here, we used two-photon microscopy to examine presynaptic axonal structural dynamics at parallel fiber-Purkinje cell synapses and investigated the effect of REM sleep in synaptic plasticity of mouse cerebellar cortex following motor training. We found that motor training induces higher formation of new axonal varicosities in cerebellar parallel fibers. Our results also indicate that calcium activities of granule cells significantly increase during REM sleep, and REM sleep deprivation prevents motor training-induced formation of axonal varicosities in parallel fibers, suggesting that higher calcium activity of granule cells was crucial for promoting newly formed axonal varicosities after motor training. Together, these findings reveal the effect of motor training on parallel fiber presynaptic structural modification and the important role of REM sleep in synaptic plasticity in cerebellar cortex.


KDM4B histone demethylase and G9a regulate expression of vascular adhesion proteins in cerebral microvessels.
Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression. Inhibition of G9a and EZH2, histone methyltransferases responsible for methylation at H3K9 and H3K27, respectively as well as G9a overexpression demonstrated the involvement of G9a in TNF-α-induced ICAM1 expression and leukocyte adhesion and transmigration. A specific role for KDM4B, a histone demethylase targeting H3K9me2, in TNF-α-induced ICAM1 upregulation was validated with siRNA. Moreover, treating mice with a KDM4 inhibitor ML324 blocked TNF-α-mediated neutrophil adhesion. Similarly, TNF-α-induced VCAM1 expression was suppressed by G9a overexpression and KDM4B knockdown. Collectively, we demonstrated that modification of H3K9me2 by G9a and KDM4B regulates expression of vascular adhesion molecules, and that depletion of these proteins or KDM4B reduces inflammation-induced leukocyte extravasation. Thus, blocking ICAM1 or KDM4B could offer a novel therapeutic opportunity treating brain diseases.


Temporal association between childhood psychopathology and substance use disorders: findings from a sample of adults with opioid or alcohol dependency.
Adults with substance use disorders (SUD; alcohol or drug abuse or dependence) were evaluated to determine if childhood-onset psychopathology preceded the onset of SUD. Using structured psychiatric interviews, we assessed 47 clinically referred adults with SUD (27 with opioid dependence and 20 with alcohol dependence), with attention to childhood-onset psychopathology. A sequence of psychopathology and SUD was reconstructed using mean diagnosis onset data. Sixty-two percent of the 47 SUD adults (mean age 39.3+/-6.6 years) had early-onset SUD (defined as < or = 18 years) and 38% had late-onset SUD (> or = 19 years at onset). Psychopathology preceded the onset of SUD in 56% of adults. Attention deficit/hyperactivity disorder, multiple anxiety, and disruptive disorders typically preceded the onset of SUD; in contrast, mood disorders (specifically depressive and bipolar disorders) followed the onset of SUD. The majority of clinically referred adults with SUD had psychopathology that began in childhood, frequently preceding the onset of their SUD. These findings further highlight the importance of targeting antecedent disorders for preventive and early intervention programs aimed at reducing the risk for SUD.


DNA breaks and chromosome pulverization from errors in mitosis.
The involvement of whole-chromosome aneuploidy in tumorigenesis is the subject of debate, in large part because of the lack of insight into underlying mechanisms. Here we identify a mechanism by which errors in mitotic chromosome segregation generate DNA breaks via the formation of structures called micronuclei. Whole-chromosome-containing micronuclei form when mitotic errors produce lagging chromosomes. We tracked the fate of newly generated micronuclei and found that they undergo defective and asynchronous DNA replication, resulting in DNA damage and often extensive fragmentation of the chromosome in the micronucleus. Micronuclei can persist in cells over several generations but the chromosome in the micronucleus can also be distributed to daughter nuclei. Thus, chromosome segregation errors potentially lead to mutations and chromosome rearrangements that can integrate into the genome. Pulverization of chromosomes in micronuclei may also be one explanation for 'chromothripsis' in cancer and developmental disorders, where isolated chromosomes or chromosome arms undergo massive local DNA breakage and rearrangement.


New Insight into the Role of the Calvin Cycle: Reutilization of CO2 Emitted through Sugar Degradation.
Ralstonia eutropha is a facultative chemolithoautotrophic bacterium that uses the Calvin-Benson-Bassham (CBB) cycle for CO2 fixation. This study showed that R. eutropha strain H16G incorporated (13)CO2, emitted by the oxidative decarboxylation of [1-(13)C1]-glucose, into key metabolites of the CBB cycle and finally into poly(3-hydroxybutyrate) [P(3HB)] with up to 5.6% (13)C abundance. The carbon yield of P(3HB) produced from glucose by the strain H16G was 1.2 times higher than that by the CBB cycle-inactivated mutants, in agreement with the possible fixation of CO2 estimated from the balance of energy and reducing equivalents through sugar degradation integrated with the CBB cycle. The results proved that the 'gratuitously' functional CBB cycle in R. eutropha under aerobic heterotrophic conditions participated in the reutilization of CO2 emitted during sugar degradation, leading to an advantage expressed as increased carbon yield of the storage compound. This is a new insight into the role of the CBB cycle, and may be applicable for more efficient utilization of biomass resources.


Scientific basis for medicinal use of Citrullus lanatus (Thunb.) in diarrhea and asthma: In vitro, in vivo and in silico studies.
Citrullus lanatus (Thunb.) is a member of the Cucurbitaceae family, commonly farmed as an edible vegetable around the globe. It has been used in traditional therapies in addition to nutritional advantages. Traditional herbal practitioners employ C. lanatus seeds to treat gastrointestinal, respiratory, and urinary diseases in Pakistan and India. However, more investigation is needed to understand the effect of C. lanatus seeds on treating gastrointestinal, respiratory, and urinary disorders. This research aimed to use network pharmacology and molecular docking to understand multi-target mechanisms of C. lanatus seeds against asthma and diarrhea and to validate its effects using biological tests to investigate antispasmodic and bronchodilator capabilities. The ground seeds of C. lanatus were extracted in hexane, dichloromethane, ethanol, and aqueous for sequential extracts. The bioactive components in sequential extracts of C. lanatus seeds were identified using LC ESI-MS/MS, and specific compounds were quantified using HPLC. The quantified bioactive compounds of C. lanatus were subjected to in silico studies for network pharmacology and molecular docking to elucidate their role in antispasmodic and bronchodilator properties. The sequential extracts were tested on isolated rabbit tissue, i.e., jejunum, trachea, and urinary bladder. The antiperistalsis, antidiarrheal and antisecretory studies were also performed in animal models. In silico studies indicate that bioactive chemicals from sequential extracts of C. lanatus seeds interfere with asthma and diarrhea-associated pathogenic genes. Those are members of calcium mediate signaling, cholinergic synapse, regulation of cytosolic calcium concentration, smooth muscle contraction, and inflammatory responses. It was also found that rutin, quercitrin, stearic acid, umbelliferone, and kaempferol were stronger binding to voltage-gated calcium channels and muscarinic M3 receptor, thus exerting calcium channel blocker activity and cholinergic receptor stimulant response. On isolated jejunum, trachea, and urinary preparations, sequential extracts of C. lanatus seeds elicited the spasmolytic response and showed the relaxation of spastic contractions of K+ (80 mM) and carbachol (1 µM). Furthermore, it induced a non-parallel rightward shift in calcium concentration-response curves with suppression. In animal models, C. lanatus seed extracts exhibited partially or completely antiperistalsis, antidiarrheal, and antisecretory effects. Thus, Citrullus lanatus had therapeutic benefits by modulating the contractile response through calcium-mediated signaling target proteins, hence exerting bronchodilator and antidiarrheal properties. The current study provides evidence for further mechanistic studies and the development of C. lanatus seeds as a potential therapeutic intervention for patients with gastrointestinal, respiratory, and urinary disorders.


Blood pressure reductions: correcting for regression to the mean.
Reductions in high blood pressure (BP) from participating in screening and treatment programs are often assessed by comparing BP measurements before and after participation. The interpretation of such changes in measured blood pressure is confounded by the tendency of high pressures to decline as a result of a statistical artifact--regression to the mean. The problem arises whenever baseline measurements are used both for selection of participants and for comparisons with pressures obtained later. We developed a statistical model which predicts the average decline due to regression for participants in a screening or treatment program. This regression effect must be subtracted from the observed reduction in BP (the difference between baseline and later measurements) to obtain the average net reduction in BP from the program. The regression effect is estimated as the product of two factors. The first factor is the proportion of the variance in the baseline (preprogram) measurement due to measurement error and the short-term variation (e.g., 0.24 for two replications averaged). The second factor is the difference between the mean baseline pressure of full participants and that of the underlying population of potential participants. The model was first illustrated with successive BP measurements from community screening programs, where the "program" was only remeasurement. The mean observed decline in diastolic BP between screens for 145 persons with elevated baseline BP was 7 mm Hg. After adjustment for regression to the mean, the net decline between screens was estimated to be 2 mm Hg. This decline is apparently due to the pressor effect, or stress of screening, and agrees with findings from other studies. Next the model was applied to the treatment phase of the Hypertension Detection and Follow-up Program. Overall, net reductions predicted by the model agree with those from independent measurements to within 0.1 mm Hg. The findings indicate the one can compute net reductions in BP from before-and-after comparisons in screening and treatment programs with reasonable accuracy, and these net reductions are generally much smaller than the crude BP declines.


Predictors of in-hospital mortality in elderly patients with bacteraemia admitted to an Internal Medicine ward.
Infectious diseases are a common cause of increased morbidity and mortality in elderly patients. Bacteraemia in the elderly is a difficult diagnosis and a therapeutic challenge due to age-related vicissitudes and to their comorbidities. The main purpose of the study was to assess independent risk factors for in-hospital mortality among the elderly with bacteraemia admitted to an Internal Medicine Ward. Overall, a cohort of 135 patients, 65 years of age and older, with bacteraemia were retrospectively studied. Data related to demographic information, comorbidities, clinical parameters on admission, source and type of infection, microorganism isolated in the blood culture, laboratory data and empirical antibiotic treatment was recorded from each patient. Multivariate logistic regression was performed to identify independent predictors of all-cause in-hospital mortality. Of these 135 patients, 45.9% were women. The most common infections in this group of patients were urinary tract infections (46.7%). The main microorganisms isolated in the blood cultures were Escherichia coli (14.9%), Methicillin-resistant Staphylococcus aureus (MRSA) (12.0%), non-MRSA (11.4%), Klebsiella pneumoniae (9.1%) and Enterococcus faecalis (8.0%). The in-hospital mortality was 22.2%. Independent prognostic factors associated with in-hospital mortality were age ≥ 85 years, chronic renal disease, bacteraemia of unknown focus and cognitive impairment at admission (OR, 2.812 [95% CI, 1.039-7.611; p = 0.042]; OR, 6.179 [95% CI, 1.840-20.748; p = 0.003]; OR, 8.673 [95% CI, 1.557-48.311; p = 0.014] and OR, 3.621 [95% CI, 1.226-10.695; p = 0.020], respectively). By multivariate analysis appropriate antibiotic therapy was not associated with lower odds of mortality. Bacteraemia in the elderly has a high mortality rate. There are no set of signs or clinical features that can predict bacteraemia in the elderly. However, older age (≥ 85 years), chronic renal disease, bacteraemia of unknown focus and severe cognitive impairment adversely affects the outcome of elderly patients with bacteraemia admitted to an Internal Medicine ward.


Impact of endoscopic and histological evaluations of two different types of mesh plug for a groin hernia model.
The biological responses to mesh in vivo have been evaluated in some papers, but the in vivo condition of mesh and plugs have not been sufficiently evaluated. This study evaluated the endoscopic observations and histological assessments of mesh plugs using swine models. An artificial abdominal hernia was established in the porcine abdomen, and repaired using three different sizes of two types of plug, Proloop (ATRIUM Medical Corporation, Hudson, NH, USA) or Perfix (BARD Medical Division, Covington, GA, USA). The in vivo conditions of each plug were periodically observed using a laparoscope. Moreover, a histological evaluation of the plugs was performed 3 months after implantation. The laparoscopic observation revealed that inversion of the plugs occurred in 10 out of 18 cases repaired with Perfix, while no case repaired with Proloop inverted. The large and medium sizes of Perfix plugs were inclined by an average of more than 30°. In addition, the triangular shape of Perfix plugs was broken and the vertical/horizontal ratio was enlarged during the observation period, while Proloop plugs shrank both vertically and horizontally. The inflammatory cell count was significantly lower within the Proloop plugs than within Perfix plugs. Proloop plugs are apparently superior because they are stable even 3 months after implantation.


Cross-modal utilization of information: recognition memory for environmental stimuli.
In a study of cross-modal recognition memory for vision and audition photographs were matched for meaningful content with naturalistic sounds. Fifteen subjects inspected pictures and were tested with sounds and for 15 other the procedure was reversed. The two cross-modal groups were further divided into subgroups of 5 to test at one of three delays: immediate, 2 days, or 7 days. Accuracies for recognition of vision-audition for the respective retention intervals were 88.0%, 81.8%, and 75.4% and for audition-vision 87.9%, 85.1%, and 76.7%. Delay interval significantly affected cross-modal recognition. There was no interaction. Vision-audition recognition accuracy did not differ from audition-vision. The cross-modal recognition for both was high. Neither differed from a comparable intra-modal recognition memory for naturalistic sounds (Lawrence, 1974).


Positively regulated glycerol/G3P-dependent Bacillus subtilis gene expression system based on anti-termination.
Plasmid pLALA was constructed for glycerol or glycerol-3-phosphate inducible plasmid-borne gene expression in Bacillus subtilis and closely related Gram-positive bacteria. Gene expression using pLALA is based on anti-termination of transcription and involves the B. subtilis GlpP protein that in the presence of glycerol-3-phosphate acts as an anti-terminator protein by binding to the 5'-untranslated region of glpD mRNA. Properties and the usefulness of the system, denoted LALA, were validated by inducible production in B. subtilis strains of two water-soluble proteins (beta-galactosidase and a protein phospho-tyrosine phosphatase), and one integral membrane protein (heme A synthase). Advantages with LALA is that it is based on positive control, does not involve a DNA-binding protein, and that glycerol, a cheap and stable compound, can be used as inducer of gene expression.


The estimated incidence of depressive disorder and its determinants in the Finnish ODIN sample.
In contrast to the huge number of prevalence studies, there are relatively few incidence studies of depressive disorders. Furthermore, estimates of incidence vary remarkably between existing studies. The aim of this paper is to add knowledge about the incidence and determinants of depressive disorder, based on the Finnish sub-sample of the European Outcomes of Depression International Network study. The random population sample in the Finnish sub-study consisted of 2,999 subjects, aged 18-64, selected from one urban and one rural area. In the baseline survey, potential cases of depressive disorder were identified using the Beck Depression Inventory. SCAN-2 interview was used to assign caseness against ICD-10 criteria. Findings from the 1-year follow-up survey with those who responded in the baseline survey (N=1,939), using the same case-finding instruments, were used to estimate the incidence rate of depressive disorder. The estimated annual incidence rate for all depressive disorders, including both first-time and recurrent episodes, was 28.5 per 1,000; for first-time episodes it was 20.5 per 1,000. Significant predictors for experiencing a depressive episode were: suffering from self-perceived long-term illness or handicap, experiencing little or no concern from friends, low sense of coherence, low self-confidence, uncertainty about one's future and reporting two or more threatening life events during the preceding 6 months. About 3% of the working-age population experience an episode of depressive disorder each year. Due to recall problems, the estimate of first-time incidence may be too high.


Quantum-enabled temporal and spectral mode conversion of microwave signals.
Electromagnetic waves are ideal candidates for transmitting information in a quantum network as they can be routed rapidly and efficiently between locations using optical fibres or microwave cables. Yet linking quantum-enabled devices with cables has proved difficult because most cavity or circuit quantum electrodynamics systems used in quantum information processing can only absorb and emit signals with a specific frequency and temporal envelope. Here we show that the temporal and spectral content of microwave-frequency electromagnetic signals can be arbitrarily manipulated with a flexible aluminium drumhead embedded in a microwave circuit. The aluminium drumhead simultaneously forms a mechanical oscillator and a tunable capacitor. This device offers a way to build quantum microwave networks using separate and otherwise mismatched components. Furthermore, it will enable the preparation of non-classical states of motion by capturing non-classical microwave signals prepared by the most coherent circuit quantum electrodynamics systems.


Clostridium difficile PSI polysaccharide: synthesis of pentasaccharide repeating block, conjugation to exotoxin B subunit, and detection of natural anti-PSI IgG antibodies in horse serum.
Clostridium difficile is the most common cause of antimicrobial-associated diarrhea in humans and may cause death. Previously, we discovered that C. difficile expresses three polysaccharides, named PSI, PSII, and PSIII. It has now been established that PSII is a conserved antigen abundantly present on the cell-surface and biofilm of C. difficile. In contrast, the expression of PSI and PSIII appears to be stochastic processes. In this work, the total chemical synthesis of the PSI pentasaccharide repeating unit carrying a linker at the reducing end, α-l-Rhap-(1→3)-β-d-Glcp-(1→4)-[α-l-Rhap-(1→3)]-α-d-Glcp-(1→2)-α-d-Glcp-(1→O(CH2)5NH2, was achieved by a linear synthesis strategy from four monosaccharide building blocks. The synthesized PSI pentasaccharide was conjugated to a subunit of C. difficile exotoxin B yielding a potential dual C. difficile vaccine. More significantly, sera from healthy horses were shown to contain natural anti-PSI IgG antibodies that detected both the synthetic non-phosphorylated PSI repeat and the native PSI polysaccharide, with a slightly higher recognition of the native PSI polysaccharide.


Single-step bulk purification of synthetic tetrapeptide tuftsin by high performance liquid chromatography.
A protocol on reversed phase high performance liquid chromatogrpahy (RP-HPLC) using water-acetonitrile gradients under lesser stringent conditions, has been devised to obtain highly purified tuftsin in bulk amount. The protocol was also tested for two different preparations of tuftsin to yield identical quality of peptide.


Rhesus macaque TRIM5 alleles have divergent antiretroviral specificities.
TRIM5alpha is a potent barrier to cross-species retroviral transmission, and TRIM5alphas from different species have divergent antiretroviral specificities. Multiple TRIM5 alleles circulate within rhesus macaque populations. Here we show that they too have different antiretroviral specificities, highlighting how TRIM5 genotypes contribute to protection in an individual or a population.


Robotic-assisted Thoracoscopic Transdiaphragmatic Adrenalectomy (RATTA) for Metastatic Renal Cell Carcinoma.
Robotic-assisted thoracoscopic transdiaphragmatic adrenalectomy (RATTA) represents a novel surgical approach for the management of adrenal pathology in patients with a history of extensive transperitoneal or retroperitoneal procedures. Here we report the first described case of RATTA in a 56-year-old woman with metastatic renal cell carcinoma to the left adrenal gland and right lung. With the assistance of cardiothoracic surgery, this patient underwent robotic-assisted thoracoscopic pulmonary wedge resection and RATTA. In brief, after completion of the pulmonary wedge resection by thoracic surgery the diaphragm was incised starting at the left crus and extending laterally through the diaphragmatic muscle, exposing the retroperitoneal space and fat. The adrenal gland with mass was identified, dissected from surrounding structures, and extracted. The diaphragm was then closed using Ethibond suture with polytetrafluoroethylene felt pledgets. A 22-Fr chest tube was placed in the thoracic cavity. Operative and postoperative courses were uncomplicated. The patient was discharged on postoperative day 4. Pathology confirmed metastatic clear cell renal cell carcinoma in both the left adrenal and the right lung nodules with negative surgical margins. The case described here highlights the surgical technique and ideal patient population in which RATTA serves as a feasible and safe alternative to conventional laparoscopic approaches in the treatment of adrenal pathologies.


Social phobia and alcoholism: a complex relationship.
The relationship between social phobia and alcoholism is complex. Alcohol problems typically develop secondary to social phobia, with patients reporting that they find alcohol helpful in coping with the symptoms of anxiety. However, excessive alcohol consumption may actually precipitate anxiety symptoms, and thus a vicious circle of anxiety and alcoholism is established. The clinician must consider the possibility of comorbidity in patients presenting with either alcoholism or social phobia. Only when both components of the condition are adequately assessed and treated can the cycle of social phobia and alcohol abuse be broken.


A denoising method based on cyclegan with attention mechanisms for improving the hidden distress features of pavement.
Ground Penetrating Radar (GPR) is one of the most used devices for road structural damages detection. However, due to the different roadbed conditions and various disturbances in the nearby environment during detection, there are great difficulties in interpreting detection images, which also hinders automatic detection based on deep learning. In this work, we design a GPR image denoising method based on Cyclegan. We select the most suitable generator and add different attention mechanisms. After denoising the natural GPR road detection image, using the Yolo (You Only Look Once) to test the accuracy of the original image and the denoised image after adding different attention mechanisms. The detection accuracy is improved by 30%. The results of the detection network and the evaluation of the denoised images by GPR image interpreters indicate that the method has the following advantages: lower requirements for training data sets, a wide range of data sources, low cost, good denoising effect, and automatic detection of GPR images. It is of great help to the automatic detection of GPR images.


The ABCs of personalized incremental dialysis start, Le Mans style.
Thrice weekly hemodialysis (HD) is considered the standard of care for patients with end-stage chronic kidney disease (CKD) on extracorporeal renal replacement therapy. However, recent evidence has shown that up to one third of patients start dialysis with a residual kidney function that could allow a reduced frequency/dialysis dose. Interest towards HD schedules other than thrice weekly and the lessons learned from peritoneal dialysis, in addition to growing attention to patients' quality of life, have promoted renewed attention towards incremental HD (iHD). iHD comprises once and twice weekly schedules, makes it possible to soften the "dialysis shock" at the inception of therapy and is patient-friendly. Moreover, it might contribute to preserving residual kidney function longer. Nevertheless, iHD is performed differently in different settings and no guidelines exist on this subject. Taking advantage of the experience accrued with regard to the treatment of advanced CKD both in the outpatient clinic and in the dialysis unit in Le Mans, where two thirds of incident HD patients start in an incremental way, we aimed to present the practical aspects of iHD and discuss its advantages and drawbacks.


Platelet factor-4 (CXCL4/PF-4): an angiostatic chemokine for cancer therapy.
Platelet factor-4 (CXCL4/PF-4) is the first chemokine identified to have several biological functions. Notably, CXCL4/PF-4 inhibits endothelial cell proliferation and migration, leading to suppression of angiogenesis. Since angiogenesis is essential for the growth of most primary tumors and their subsequent metastases, it is a target for cancer therapy; due to its multiple functions, CXCL4/PF-4 is a potential clinical anti-tumor agent. This report reviews the mechanisms of CXCL4/PF-4 angiostatic activity, including interference with angiogenic growth factors bFGF-2 and VEGF165, activation of CXCR3B, interactions with integrins, interference with cell cycle, interactions with factors such as VEGF121 and CXCL8/IL-8, and derived molecules of CXCL4/PF-4 with angiostatic and anti-tumoral activities in different models in vivo or in vitro.


Autoreactive memory Th17 cells are principally derived from T-bet+RORγt+ Th17/1 effectors.
Effector Th17 cells, including IFN-γ-IL-17+ (eTh17) and IFN-γ+IL-17+ (eTh17/1) subsets, play critical pathogenic functions in the induction of autoimmunity. As acute inflammation subsides, a small proportion of the effectors survive and convert to memory Th17 cells (mTh17), which sustain chronic inflammation in autoimmune diseases. Herein, we investigated the differential contributions of eTh17 versus eTh17/1 to the memory pool using an experimental model of ocular autoimmune disease. Our results show that adoptive transfer of Tbx21-/- CD4+ T cells or conditional deletion of Tbx21 in Th17 cells leads to diminished eTh17/1 in acute phase and functionally compromised mTh17 in chronic phase. Further, adoptive transfer of disease-specific eTh17/1, but not eTh17, leads to generation of mTh17 and sustained ocular inflammation. Collectively, our data demonstrate that T-bet-dependent eTh17/1 cells generated during the acute inflammation are the principal effector precursors of pathogenic mTh17 cells that sustain the chronicity of autoimmune inflammation.


A new potent and selective non-peptide gastrin antagonist and brain cholecystokinin receptor (CCK-B) ligand: L-365,260.
L-365,260 (3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-N'-(3-methylphenyl)urea), interacted in a stereoselective and competitive manner with guinea pig stomach gastrin and brain cholecystokinin (CCK) receptors. The affinity of L-365,260 for both gastrin (Ki = 1.9 nM) and brain CCK-B (Ki = 2.0 nM) receptors was greater than 2 orders of magnitude higher than its affinity for peripheral pancreatic CCK-A receptors or various other receptors. L-365,260 exhibited a similar high affinity for brain CCK-B receptors of rats, mice and man. A somewhat lower affinity for gastrin and brain CCK-B (IC50 = 20-40 nM) receptors was observed in dog tissues. In vivo, oral administration of L-365,260 antagonized gastrin-stimulated acid secretion in mice (ED50 = 0.03 mg/kg), rats (ED50 = 0.9 mg/kg) and guinea pigs (ED50 = 5.1 mg/kg). L-365,260 did not affect basal acid secretion and did not antagonize histamine- or carbachol-stimulated acid secretion in mice. L-365,260 represents a potentially powerful new tool for investigating gastrin and brain CCK-B receptors, and possibly their role in physiology and disease.


Neonatal mononuclear cell metabolism: further evidence for diminished monocyte function in the neonate.
The metabolic capacity of neonatal monocytes was compared to the metabolic capacity of adult monocytes by two entirely different methods: the selective diminution of monocyte contamination of whole mononuclear cells and the isolation of relatively purified populations of monocytes. Monocyte removal from whole mononuclear cells produced a diminution in the pyruvate kinase (PK) activity (from 28.6 +/- 1.1 to 15.6 +/- 1.2 nmoles/min/10(7) cells) and an increase in adenosine triphosphate (ATP) content (from 7.9 +/- 1.0 to 9.5 +/- 0.8 nmoles/10(7) cells) in adult cells. No change in PK activity (from 13.5 +/- 1.3 to 14.0 +/- 1.3) was observed in cord cells, but the ATP content of cord cells was higher after monocytes depletion (from 4.7 +/- 0.5 to 6.2 +- 0.7). The suggestion of metabolic vulnerability was confirmed by metabolic analysis of isolated adult and cord monocytes. The PK activity of adult monocytes was greater than that of cord monocytes (57 +/- 9 and 25 +/- 0.3, respectively) and the ATP content of adult monocytes (5.7 +/- 0.2) was greater than that of cord monocytes (2.3 +/- 0.1). The data confirm prior observations of diminished energy metabolism in neonatal mononucler cells and suggest that the metabolic perturbations may, in part, correlate with functional immaturity of the neonatal monocyte.


The potential of dental-protective chewing gum in oral health interventions.
The authors provide an overview of chewing gum as a delivery vehicle for dental-protective agents, highlighting xylitol and its potential application in caries-prevention programs for children. The authors reviewed selected clinical investigations and previous reviews associated with chewing gum containing substances such as calcium, bicarbonate, carbamide, chlorhexidine, fluoride and xylitol and their effects on reducing caries. They searched the MEDLINE database by using the key words "dental caries," "oral health," "calcium," "bicarbonate," "carbamide," "chlorhexidine," "fluoride" and "xylitol." Chewing gum is being used as a delivery vehicle for substances such as calcium, bicarbonate, carbamide, chlorhexidine, fluoride and xylitol to improve oral health and reduce caries. These substances exhibit properties that are protective of the oral environment and mediate common oral diseases. The debate for advocating xylitol use in caries prevention is advancing; however, chewing gum use by young schoolchildren in the United States is hindered by choking hazard concerns and lack of specific xylitol dosing recommendations. The use of chewing gum containing dental-protective substances, particularly xylitol, in caries-prevention programs can reduce the tooth decay epidemic. Chewing gum use by children in the school setting should be reconsidered.


Pulmonary function and respiratory symptoms in workers exposed to respirable silica dust: A historical cohort study.
The adverse health effects of silica are still a major concern in some industries. The purpose of this study was to evaluate pulmonary function in a group of sub-radiological silicotic workers after 11 years of silica dust exposure. The study sample consisted of 381 exposed and 254 non-exposed workers. The history of pulmonary function parameters was obtained from workers' medical records. The data were collected through interviews with employees and completing questionnaires on demographic variables, detailed occupational and medical history, and respiratory symptoms. Workers' exposure to silica dust was also determined. The mean frequency of workers' exposure to silica dust was 6.3 times greater than its exposure limit. All pulmonary function parameters were significantly lower in the silica-exposed workers, and the difference between the two groups was still statistically significant after adjusting the potential confounding variables. FEV1 showed the greatest reduction, and FVC and FEV1 showed a significant decreasing trend. Also the prevalence of respiratory symptoms was significantly higher in smokers than in nonsmokers among silica-exposed workers. Even in the absence of radiographic evidence of silicosis, exposure to high levels of silica dust is associated with reductions in pulmonary function. In the absence of radiological evidence of silicosis, progressive deterioration of FEV1 over time most likely indicates sub-radiological silicosis. The effects were associated with the severity and duration of exposure. Exposure to sub-TLV levels of silica dust may not affect pulmonary function. Smoking appears to have a synergistic effect in relatively high silica exposures.


A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben.
A discriminant function based on topological descriptors was derived from a training set composed by anticonvulsants of clinical use or in clinical phase of development and compounds with other therapeutic uses. This model was internally and externally validated and applied in the virtual screening of chemical compounds from the Merck Index 13th. Methylparaben (Nipagin), a preservative widely used in food, cosmetics and pharmaceutics, was signaled as active by the discriminant function and tested in mice in the Maximal Electroshock (MES) test (i.p. administration), according to the NIH Program for Anticonvulsant Drug Development. Based on the results of Methylparaben, Propylparaben (Nipasol), another preservative usually used in association with the former, was also tested. Both methyl and propylparaben were found active in mice at doses of 30, 100, and 300 mg/kg. The discovery of the anticonvulsant activities in the MES test of methylparaben and propylparaben might be useful for the development of new anticonvulsant medications, specially considering the well-known toxicological profile of these drugs.


Phenomenology and diagnostic stability of paediatric bipolar disorder in a Spanish sample.
Paediatric bipolar disorder (BD) has gained validity, and substantial research in the last 20 years has dissipated the controversy surrounding it. However, data on the prevalence, prodromes, phenomenology, and longitudinal stability of paediatric BD are still required. We reviewed the medical records of all patients (n = 72) with DSM-IV BD evaluated over a 15-year period. We assessed the most frequently present symptoms prior to and at the time of diagnosis, the diagnostic stability of the disorder and its subtypes (I, II and NOS). Patients [75% boys, median age (interquartile range, IQR) at diagnosis 12.6 (9.6-15.7) years] underwent follow up for a median period of 3.86 (1.8-5.9) years. There was a median delay from symptom onset to diagnosis of 2.3 (1.2-4.8) years. At the time of diagnosis, 37.5% had BD-I, 8.3% BD-II, and 54.2% BD-NOS. At follow-up, 62.5% had BD-I, 8.3% had BD-II, and 23.6% had BD-NOS, whereas 4.2% no longer met the DSM-IV criteria for BD. Our sample size limited the BD subtype analyses. Some of information was collected retrospectively. 95.8% of our sample retained a BD diagnosis after a median follow-up period of 3.86 years. BD-I patients maintained their diagnosis and subtype of BD. Half of all patients with baseline BD-NOS maintained their BD subtype, but most of the other half showed conversion to BP-I at follow up. Only 4.2% of the sample (all with BD-NOS at baseline) did not meet criteria for BD at follow up, and these patients were stable.


MIR155 Regulation of Ubiquilin1 and Ubiquilin2: Implications in Cellular Protection and Tumorigenesis.
Ubiquilin (UBQLN) proteins are adaptors thought to link ubiquitinated proteins to the proteasome. However, our lab has recently reported a previously unappreciated role for loss of UBQLN in lung cancer progression. In fact, UBQLN genes are lost in over 50% of lung cancer samples examined. However, a reason for the loss of UBQLN has not been proposed, nor has a selective pressure that could lead to deletion of UBQLN been reported. Diesel Exhaust Particles (DEP) are a major concern in the large cities of developing nations and DEP exposed populations are at an increased risk of developing a number of illnesses, including lung cancer. A connection between DEP and UBQLN has never been examined. In the present study, we determined the effect of DEP on lung cell lines and were interested to determine if UBQLN proteins could potentially play a protective role following treatment with DEP. Interestingly, we found that DEP treated cells have increased expression of UBQLN proteins. In fact, over-expression of UBQLN was capable of protecting cells from DEP toxicity. To investigate the mechanism by which DEP leads to increased UBQLN protein levels, we identified and interrogated microRNAs that were predicted to regulate UBQLN mRNA. We found that DEP decreases the oncogenic microRNA, MIR155. Further, we showed that MIR155 regulates the mRNA of UBQLN1 and UBQLN2 in cells, such that increased MIR155 expression increased cell invasion, migration, wound formation and clonogenicity in UBQLN-loss dependent manner. This is the first report of an environmental carcinogen regulating expression of UBQLN proteins. We show that exposure of cells to DEP causes an increase in UBQLN levels and that MIR155 regulates mRNA of UBQLN. Thus, we propose that DEP-induced repression of MIR155 leads to increased UBQLN levels, which in turn may be a selective pressure on lung cells to lose UBQLN1.


Attitudes of Polish physicians, nurses and pharmacists towards the ethical and legal aspects of the conscience clause.
While healthcare professionals' right to invoke the conscience clause has been recognised as a fundamental human right, it continues to provoke a heated debate in Polish society. Although public discourse is filled with ethical and legal considerations on the conscience clause, much less is known about the attitudes of healthcare professionals regarding that matter. The aim of this study was therefore to describe the attitudes of Polish physicians, nurses and pharmacists towards the ethical and legal aspects of the conscience clause. We analysed a group of three hundred healthcare professionals: physicians, nurses and pharmacists in Poznan, Poland, using a standard questionnaire comprising of 29 questions about various ethical and legal aspects of the conscience clause and participants' personal experiences with the conscience clause. The study was conducted between January and March 2020. This research shows that although most Polish healthcare workers support the right to invoke the conscience clause they differ significantly in their opinions on to whom and to what medical procedures the conscience clause should apply to. It also demonstrated that while the conscience clause is rarely invoked in Poland, most healthcare professionals declare that the current legal regulations in that sphere are unclear and inaccurate. While there is an urgent need to raise the awareness regarding the conscience clause among medical students and healthcare professionals and educate them about such issues, it is even more important to improve the legal system in regard to the CC so that it protects both HCPs' right to the CC and safeguards patients' rights to medical services.


Characterization of novel fucosyl- and tyvelosyl-containing glycoconjugates from Trichinella spiralis muscle stage larvae.
The monosaccharide composition of an affinity-purified family of antigenically-related Trichinella spiralis larval glycoproteins was determined by gas chromatography/mass spectrometry. This group of 6 major glycoproteins, designated TSL-1, originates in the muscle stage (L1) larval stichosome. They are present on the L1 surface and in excretory/secretory products of L1 larvae, are stage-specific, and are highly immunodominant. The glycosyl composition of the TSL-1 antigens was remarkable in 2 respects: (1) fucose accounted for 36 molar percent of the glycosyl residues; and (2) a 3,6-dideoxyhexose was identified, which accounted for at least 24 molar percent of the glycosyl residues. Previously, 3,6-dideoxyhexoses have been found only in certain Gram-negative bacterial lipopolysaccharides and in ascaroside alcohols (ascarylose) of Ascaris eggs. The 3,6-dideoxyhexose found in the TSL-1 antigens also was found in ES. This Trichinella sugar has been chemically identified as a 3,6-dideoxyarabinohexose, the same as found in Ascaris eggs. However, the absolute configuration of the TSL-1 sugar is D-(tyvelose), not L-(ascarylose) as is found in Ascaris eggs. Methylation analysis indicated that the TSL-1 3,6-dideoxy-D-arabinohexose was present entirely as non-reducing terminal residues. Approximately 83% of the fucose was also present as non-reducing terminal residues, with the remaining fucose found as 3,4-linked branched residues.


On the cooperative formation of non-hydrogen-bonded water at molecular hydrophobic interfaces.
The unique structural, dynamical and chemical properties of air/water and oil/water interfaces are thought to play a key role in various biological, geological and environmental processes. For example, non-hydrogen-bonded ('dangling') OH groups--which create surface defects in water's hydrogen bonding network and are experimentally detected at both macroscopic (air/water or oil/water) and microscopic (dissolved hydrophobic molecule) interfaces--are thought to catalyse some chemical reactions. However, how the size, curvature or charge of the exposed hydrophobic surface influences water's propensity to form dangling OH defects has not yet been established quantitatively. Here we use Raman multivariate curve resolution to probe spectroscopically the hydrophobic hydration shell and, using a statistical multisite analysis, we show that such interfacial dangling OH structures are entropically stabilized and their formation is cooperative (the probability that a non-hydrogen-bonded OH group will form depends nonlinearly on the hydrophobic surface area). We thus expose an important difference between the chemical properties of molecular and macroscopic oil/water interfaces.


The diagnostic utility of trichorhinophalangeal syndrome type 1 immunohistochemistry for metastatic breast carcinoma in effusion cytology specimens.
Trichorhinophalangeal syndrome type 1 (TRPS1) is a novel immunohistochemical marker with excellent performance in distinguishing breast carcinoma from other cancers in surgical specimens. The aim of this study was to evaluate the diagnostic utility of TRPS1 compared with GATA3 for metastatic breast carcinoma in effusion cytology specimens. In total, 91 cell blocks of malignant effusion specimens, including 47 metastatic breast carcinomas (nine triple-negative breast carcinomas [TNBCs] and 38 non-TNBCs) and 44 nonmammary malignancies, were selected for TRPS1 and GATA3 immunohistochemistry. Modified H scores ≥ 200 were considered positive staining. The positive rate of TRPS1 was similar between TNBC and non-TNBC (77.8% vs 73.3%, p = .802), whereas the positive rate of GATA3 was lower in TNBC than in non-TNBC (66.7% vs 89.5%, p = .087). The positive rate of TRPS1 was significantly higher in breast carcinoma than in urothelial carcinoma (74.5% vs 0%, p < .001), whereas the positive rate of GATA3 showed no difference between these two (85.1% vs 85.7%, p = .956). Notably, diffuse and strong aberrant expression of TRPS1 was observed in one lung adenocarcinoma and one serous adenocarcinoma in this series. The overall sensitivity, specificity, positive predictive value, and negative predictive value of TRPS1 immunohistochemistry for breast carcinoma were 74.5%, 95.5%, 94.6%, and 77.8%, respectively. TRPS1 is a sensitive and specific marker for metastatic breast cancer in serous effusion cell-block specimens. It shows superior sensitivity and specificity compared with GATA3, especially in the TNBC setting and for excluding urothelial carcinoma.


Cyclodextrin-based nanogels for pharmaceutical and biomedical applications.
Hydrophilic nanogels combine the advantages of hydrogels with certain advantages that are inherent in their nanoscale size. Similar to macrogels, nanogels can contain and protect drugs and regulate their release by incorporating high-affinity functional groups, stimuli-responsive conformations and biodegradable bonds into the polymer network. Similar to nanoparticles, nanogels can easily be administered in liquid form for parenteral drug delivery. The nanoscale size of nanogels gives them a high specific surface area that is available for further bioconjugation of active targeting agents. Biodistribution and drug release can be modulated through size adjustments. The incorporation of hydrophilic cyclodextrin (CD) moieties into the polymeric network of the nanogels provides them with a drug loading and release mechanism that is based on the formation of inclusion complexes without decreasing the hydrophilicity of the network. The covalent attachment of CD molecules to the chemically crosslinked networks may enable the CDs to display fully their ability to form complexes, while simultaneously preventing drug release upon media dilution. The preparation, characterization and advantages for pharmaceutical and biomedical applications of CD-based nanogels are reviewed in this article.


A study on the toxigenesis by Clostridium botulinum in nitrate and nitrite-reduced dry fermented sausages.
Nitrite has been traditionally used to control Clostridium botulinum in cured meat products. However, in the case of dry fermented sausages, environmental factors such as pH, aw and the competitive microbiota may exert a more relevant role than nitrite in the inhibition of the growth and toxin production by C. botulinum. In this challenge test study, two varieties of Mediterranean dry sausages (salchichón and fuet) were inoculated with spores of C. botulinum Group I (proteolytic) and C. botulinum Group II (nonproteolytic). Sausages were prepared with 150 mg/kg of NaNO3 and 150 mg/kg of NaNO2 (maximum ingoing amounts allowed by the European Union regulation), with a 25% and 50% reduction, and without nitrate/nitrite. The initial pH in both products was 5.6, and decreased to values below 5.0 in salchichón and to 5.2 in fuet. Lactic acid bacteria counts reached 8-9 log cfu/g after fermentation. The aw decreased from initial values of 0.96 to about 0.88-0.90 at the end of ripening. Botulinum neurotoxin was not detected in any of the sausages, including those manufactured without nitrate and nitrite. Despite the environmental conditions were within the range for germination and growth of C. botulinum Group I during the first 8 days of the ripening process in fuet and 10-12 days in salchichón, acidity, aw and incubation temperature combined to inhibit the production of toxin, independently of the concentration of curing agents. Although decreasing or even removing nitrate/nitrite from the formula did not compromise safety regarding C. botulinum in the conditions tested in this study, their antimicrobial role should not be underestimated in the case that other hurdles could fail or other ripening conditions were used, and also considering the effect of nitrite on other pathogens.


Detection of β-globin Gene Mutations Among β-thalassaemia Carriers and Patients in Malaysia: Application of Multiplex Amplification Refractory Mutation System-Polymerase Chain Reaction.
β-thalassaemia is one of the most common single-gene disorders worldwide. Each ethnic population has its own common mutations, accounting for the majority of cases, with a small number of mutations for the rarer alleles. Due to the heterogeneity of β-thalassaemia and the multi-ethnicity of Malaysians, molecular diagnostics may be expensive and time consuming. A simple polymerase chain reaction (PCR) approach involving a multiplex amplification refractory mutation system (MARMS) and one amplification refractory mutation system (ARMS), consisting of 20 β-globin gene mutations, were designed and employed to investigate β-thalassaemia patients and carriers. Out of 169 carriers tested with the MARMS, Cd 41/42 (-TTCT), Cd 26 (A-G) HbE, IVS 1-1 (G-T), and IVS 1-5 (G-C) were the most common mutations, accounting for 78.1%. Among the Malays, Cd 26 (A-G) HbE, Cd 41/42 (-TTCT), IVS 1-1 (G-T), and IVS 1-5 (G-C) were the most common mutations, accounting for 81.4%, whereas Cd 41/42 (-TTCT) and IVS 2-654 (C-T) were most common among the Chinese (79.1%). We propose the use of this cheap, easy to interpret, and simple system for the molecular diagnostics of β-thalassaemia among Malaysians at the Institute for Medical Research (IMR).


Attenuation of morphine tolerance by intrathecal gabapentin is associated with suppression of morphine-evoked excitatory amino acid release in the rat spinal cord.
This study was designed to investigate the effect of acute and chronic intrathecal (i.t.) injection of gabapentin (GBP) on the antinociceptive effect of morphine and tolerance development using a tail-flick latency test. Levels of excitatory amino acids (EAA) in i.t. CSF dialysates were also measured by high performance liquid chromatography. Male Wistar rats were implanted with either one or two i.t. catheters for drug injection or pump infusion and with a microdialysis probe for CSF dialysate collection. The effect of acute GBP (10 microg i.t.) injection on the morphine dose response was examined in both naïve rats and rats made tolerant by continuous infusion of morphine (15 microg/h i.t.) for 5 days. At such a low dose (10 microg i.t.), GBP did not enhance morphine's antinociception in naïve rats. In morphine-tolerant rats, however, acute GBP (10 microg i.t.) injection potentiated morphine's antinociception and yielded a 14.6-fold shift in morphine's dose-response curve. When GBP (10 microg/h i.t.) was co-infused with morphine (15 microg/h i.t.) to examine its effect on the development of morphine tolerance, GBP attenuated the development of morphine tolerance. The effect of GBP and morphine on CSF glutamate and aspartate levels was examined in naïve rats, and the effect of morphine challenge on CSF glutamate and aspartate levels was examined in rats previously infused for 5 days with morphine alone or morphine plus GBP. Acute injection of GBP (10 microg i.t.), morphine (50 microg i.t.), or GBP (10 microg i.t.) followed by morphine (50 microg i.t.) 30 min later had no significant effect on CSF EAA concentration in naïve rats; however, in tolerant rats, morphine challenge (50 microg i.t.) increased aspartate and glutamate levels to 221 +/- 22% and 296 +/- 43%, respectively, of those before morphine challenge, and this phenomenon was inhibited by GBP co-infusion. Our results show that GBP, at a dose without enhanced effect on morphine's antinociception in naïve rats, not only potentiates morphine's antinociceptive effect in morphine-tolerant rats but also attenuates the development of morphine tolerance. The mechanism of the effect of GBP on morphine tolerance might be via suppression of the EAA concentration in spinal CSF dialysate.


Performance of UK wastewater treatment works with respect to trace contaminants.
This study examined the performance of 16 wastewater treatment works to provide an overview of trace substance removal in relation to meeting the objectives of the Water Framework Directive (WFD). Collection and analysis of over 2400 samples including sewage influent, process samples at different stages in the treatment process and final effluent has provided data on the performance of current wastewater treatment processes and made it possible to evaluate the need for improved effluent quality. Results for 55 substances, including metals, industrial chemicals and pharmaceuticals are reported. Data for sanitary parameters are also provided. A wide range of removal efficiencies was observed. Removal was not clearly related to the generic process type, indicating that other operational factors tend to be important. Nonetheless, removals for many substances of current concern were high. Despite this, current proposals for stringent water quality standards mean that further improvements in effluent quality are likely to be required.


Impact of COVID-19 in gynaecological oncology care: a systematic rapid review.
Synthesis of available evidence on clinical practice in gynaecological oncology during the COVID-19 pandemic is highly warranted, as women with cancer are at increased risk due to their systemic immunosuppressed state and changes in their care are inevitable. Rapid review of available data is a quick way of providing useful information and insight into the way medical practice has been affected by the COVID pandemic. We conducted a systematic rapid review, based on a literature search of MEDLINE/PubMed, Embase, and Cochrane CENTRAL. We considered all studies on gynaecological oncology care during the COVID-19 pandemic using relevant keywords and MeSH terms. Selection criteria were English language, studies with more than five cases and publication in peer-review journal. Nine retrospective studies, one systematic review and five questionnaire surveys were included. Quality of the studies has been assessed. Development of higher quality evidence is warranted. Mortality of COVID-19 infection is higher in patients with gynaecological cancer than in non-cancer patients. Reported delays in diagnosis and management of cancer and changes in treatments, may affect the natural history of cancer and increase patients' anxiety and fear of disease progression while causing concerns to healthcare professionals affecting their clinical practice. The number of new diagnoses has declined. Prioritization is important, face-to-face interactions should be limited, and appropriate protective measures are essential. Cancer surgery, chemotherapy, and radiotherapy should continue as high priority practices. The COVID-19 pandemic has affected clinical practice significantly. Adaptations in clinical practice may improve mortality and complication rates.


TRIB3‒GSK-3β interaction promotes lung fibrosis and serves as a potential therapeutic target.
Pulmonary fibrosis (PF) is a chronic, progressive, fatal interstitial lung disease with limited available therapeutic strategies. We recently reported that the protein kinase glycogen synthase kinase-3β (GSK-3β) interacts with and inactivates the ubiquitin-editing enzyme A20 to suppress the degradation of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPβ) in alveolar macrophages (AMs), resulting in a profibrotic phenotype of AMs and promoting the development of PF. Here, we showed that chronic lung injury upregulated the stress response protein tribbles homolog 3 (TRIB3), which interacted with GSK-3β and stabilized GSK-3β from ubiquitination and degradation. Elevated GSK-3β expression phosphorylated A20 to inhibit its ubiquitin-editing activity, causing the accumulation of C/EBPβ and the production of several profibrotic factors in AMs and promoting PF development. Activated C/EBPβ, in turn, increased the transcription of TRIB3 and GSK-3β, thereby establishing a positive feedback loop in AMs. The knockdown of TRIB3 expression or the pharmacologic disruption of the TRIB3‒GSK-3β interaction was an effective PF treatment. Our study reveals an intact profibrotic axis of TRIB3‒GSK-3β‒A20‒C/EBPβ in AMs, which represents a target that may provide a promising treatment strategy for PF.


Aggressive disseminated Rhizomucor pusillus infection in a Ph-like acute lymphoblastic leukemia patient: Early detection by cell-free DNA next-generation sequencing.
Disseminated Rhizomucor pusillus infection is a very rare but fatal complication in immunocompromised patients, because of aggressive clinical process with delayed diagnosis by routine laboratory tests. Recently, cell-free DNA next-generation sequencing (cfDNA NGS) has been used for the timely detection of infectious pathogens including mucormycosis. Herein, we described an 18-year-old male with Philadelphia-like acute lymphoblastic leukemia who received a timely diagnosis of R. pusillus infection by cell-free DNA next-generation sequencing, and confirmed by silver staining and qPCR on biopsy tissue. To the best of our knowledge, this was the first case of disseminated R. pusillus infection detected by cfDNA NGS and confirmed by histology in an adult leukemia patient. In addition, this case was supposed to be the most extensive R. pusillus infection diagnosed, involving the lung, skin, liver, kidney, spleen and brain, and the only one case who survived the infection had a favorable outcome through treatment with liposome amphotericin B sequential posaconazole. This case suggested that cfDNA NGS could be used to successfully detect rare pathogen infections, and this was especially important for R. pusillus because timely diagnosis and effective treatment could improve the prognosis of this kind of patient.


Bone-marrow mononuclear cells reduce neurodegeneration in hippocampal CA1 layer after transient global ischemia in rats.
Global cerebral ischemia (GCI) results in death of the pyramidal neurons in the CA1 layer of the hippocampus. In this study we used the four-vessel occlusion (4VO) model of GCI to investigate a potential neuroprotective role of bone-marrow mononuclear cells (BMMCs) transplantation. BMMCs (3×10(7)) were injected through the carotid artery, 1 or 3 days after ischemia (DAI), and the number of cells undergoing degeneration was investigated in brains at 7 DAI. A significant decrease in the number of dying cells was observed in the treated group, compared to animals treated with saline. Biodistribution of the injected cells (1 or 3 DAI) was investigated by (99m)Technetium labeling of the BMMCs and subsequent image analysis 2h after transplantation. In addition, the presence of CellTrace(™)-labeled BMMCs was investigated in tissue sections of the hippocampal area of these transplanted animals. BMMCs treatment significantly reduced the number of FJ-C positive cells in the hippocampal CA1 layer at 7 DAI. We also observed a decrease in the number of activated microglia/macrophage (ED1-positive cells) in the BMMCs-treated group compared with the untreated group. Our data show that BMMCs are able to modulate the microglial response and reduce neurodegeneration in the CA1 layer.


Alpha-Ketoglutarate dietary supplementation to improve health in humans.
Alpha-ketoglutarate (AKG) is an intermediate in the Krebs cycle involved in various metabolic and cellular pathways. As an antioxidant, AKG interferes in nitrogen and ammonia balance, and affects epigenetic and immune regulation. These pleiotropic functions of AKG suggest it may also extend human healthspan. Recent studies in worms and mice support this concept. A few studies published in the 1980s and 1990s in humans suggested the potential benefits of AKG in muscle growth, wound healing, and in promoting faster recovery after surgery. So far there are no recently published studies demonstrating the role of AKG in treating aging and age-related diseases; hence, further clinical studies are required to better understand the role of AKG in humans. This review will discuss the regulatory role of AKG in aging, as well as its potential therapeutic use in humans to treat age-related diseases.


Task analysis complements neuroimaging: an example from working memory research.
When functional neuroimaging researchers draw conclusions about the sensory, cognitive, or motor processes that are associated with changes in brain activity, they are making assumptions about the component processes involved in performing a complex behavioral task. We demonstrate the danger in making such assumptions using, as an example, the n-back task, which has been widely used in neuroimaging studies of working memory. Neuroimaging researchers have assumed that the letter n-back task only engages processes involved in the short-term maintenance and manipulation of verbal information. We report three behavioral experiments demonstrating that the letter n-back task additionally recruits spatial processes. A fourth experiment suggested that the location n-back task may recruit verbal processes in addition to spatial processes. These results call into question conclusions that have been drawn about the neural basis of working memory. More broadly, our results demonstrate that task analysis is a vital partner of neuroimaging in the cognitive neuroscience enterprise.


Ca2(+)-dependence of arachidonic acid redistribution among phospholipids of cultured mouse keratinocytes.
Mouse keratinocytes cultured in a medium containing less than 0.1 mM Ca2+ (low Ca2+) incorporated [1-14C]arachidonic acid (AA) into phospholipids by kinetics including; (i) a rapid labelling of phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer) and both acid-stable and alkenylacyl forms of phosphatidylcholine (PtdCho); and (ii) a slow but long-lasting radiolabel incorporation into both acid-stable and alkenylacyl forms of phosphatidylethanolamine (PtdEtn), partly associated with a net radioactivity loss from acid stable-PtdCho. Under low Ca2+ conditions no radioactivity transfer apparently occurred between PtdIns and other phospholipid classes. When cells were prelabelled for 24 h with [1-14C]AA and reincubated in label-free medium containing 1.2 mM Ca2+ (normal Ca2+), an early and extensive loss of radioactivity from PtdIns was observed, reasonably in connection with Ca2+ stimulation of phosphoinositide turnover. Cell shift to normal Ca2+ did not result in an increased synthesis of labelled eicosanoids, but was consistent with an increase of radioactivity incorporation into diacylglycerol (DAG) and with a complex pattern of [1-14C]AA redistribution, eventually leading to a marked radioactivity incorporation into acid stable-PtdEtn (but not into alkenylacyl-PtdEtn) and to a labelling decrease of acid stable-PtdCho. The possible mechanisms driving AA recycling after cell shift to normal Ca2+ are discussed.


Adequacy of Mediastinal Lymph Node Sampling in Patients With Lung Cancer Undergoing Lung Resection.
Intraoperative mediastinal lymph node sampling (MLNS) is a crucial component of lung cancer surgery. Whilst several sampling strategies have been clearly defined in guidelines from international organizations, reports of adherence to these guidelines are lacking. We aimed to assess our center's adherence to guidelines and determine whether adequacy of sampling is associated with survival. A single-center retrospective review of consecutive patients undergoing lung resection for primary lung cancer between January 2013 and December 2018 was undertaken. Sampling adequacy was assessed against standards outlined in the International Association for the Study of Lung Cancer 2009 guidelines. Multivariable logistic and Cox proportional hazards regression analyses were used to assess the impact of specific variables on adequacy and of specific variables on overall survival, respectively. A total of 2380 patients were included in the study. Overall adequacy was 72.1% (n= 1717). Adherence improved from 44.8% in 2013 to 85.0% in 2018 (P< 0.001). Undergoing a right-sided resection increased the odds of adequate MLNS on multivariable logistic regression (odds ratio 1.666, 95% confidence interval [CI]: 1.385-2.003, P< 0.001). Inadequate MLNS was not significantly associated with reduced overall survival on log rank analysis (P= 0.340) or after adjustment with multivariable Cox proportional hazards (hazard ratio 0.839, 95% CI 0.643-1.093). Adherence to standards improved significantly over time and was significantly higher for right-sided resections. We found no evidence of an association between adequate MLNS and overall survival in this cohort. A pressing need remains for the introduction of national guidelines defining acceptable performance.


Spontaneous Topological States and Their Mutual Transformations in a Rare-Earth Ferrimagnet.
Nontrivial chiral spin textures with nanometric sizes and novel characteristics (e.g., magnetic skyrmions) are promising for encoding information bits in future energy-efficient and high-density spintronic devices. Because of antiferromagnetic exchange coupling, skyrmions in ferrimagnetic materials exhibit many advantages in terms of size and efficient manipulation, which allow them to overcome the limitations of ferromagnetic skyrmions. Despite recent progress, ferrimagnetic skyrmions have been observed only in few films in the presence of external fields, while those in ferrimagnetic bulks remain elusive. This study reports on spontaneously generated zero-field ground-state magnetic skyrmions and their subsequent transformation into traditional magnetic bubbles via intermediate states of (bi-)target bubbles during a magnetic anisotropy change in the rare-earth ferrimagnetic crystal DyFe11 Ti. Spontaneous reversible topological transformation driven by a temperature-induced spin reorientation transition is directly distinguished using Lorentz transmission electron microscopy. The spontaneous generation of magnetic skyrmions and successive topological transformations in ferrimagnetic DyFe11 Ti are expected to advance the design of topological spin textures with versatile properties and potential applications in rare-earth magnets.


A time-saving method for performing a clinical remount procedure with complete dentures.
Occlusal disharmony is one cause of uncomfortable dentures. Remounting complete dentures to eliminate occlusal discrepancies at the time of delivery has several advantages. This time-saving method for clinically remounting complete dentures is easy and quick and helps preserve denture supporting tissues.


pKa values of peptides in aqueous and aqueous-organic media. Prediction of chromatographic and electrophoretic behaviour.
In the present work, models describing the effect of the pH on the chromatographic and electrophoretic behaviour for polyprotic peptides were compared. The proposed models can be simultaneously used for determination of dissociation constants and selection of the optimum pH for the separation of peptides, in water and acetonitrile-water mixtures widely used in liquid chromatography and in capillary electrophoresis. The models use the pH value measured in the acetonitrile-water mixture instead of the pH value in water and take into account the effect of the activity coefficients. They permit the determination of the acidity constants in the aqueous and hydro-organic mobile phase from chromatographic retention and electrophoretic migration measurements, respectively. The values obtained by both proposed techniques agree with the potentiometric values previously determined. The suitability of the proposed models for predicting chromatographic and electrophoretic behaviour of compounds studied from a limited number of experimental data was also compared. The separation between solutes by both techniques in a complex mixture can be easily predicted, making simple and rapid pH selection to achieve optimum separation.


Urine cytology after flexible cystoscopy.
To correlate urine cytology findings before and after flexible cystoscopy. A total of 153 patients undergoing surveillance for bladder tumour provided voided urine for cytology before and immediately after flexible cystoscopy. Of the 153 patients, 116 had negative urine cytology before and after (96%) a visibly normal cystoscopy and 37 had positive urine cytology before and after cystoscopy that showed recurrent tumour. Urine cytology immediately after flexible cystoscopy correlates well with results of urine cytology before cystoscopy.


Primary leiomyosarcoma of the femur.
Leiomyosarcoma usually arises in the uterus, gastrointestinal tract, retroperitoneum, or soft tissue. Primary leiomyosarcoma of bone is rare. We encountered two patients with primary leiomyosarcoma of the femur; one was a 24-year-old woman and the other, a 41-year-old woman. Bone destruction observed on plain radiographs was minimal in both patients. Magnetic resonance imaging (MRI) showed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, with these areas being much larger than the findings to be expected from the plain radiographs. Histological examination revealed spindle-cell sarcoma, with an interlacing pattern, acidophilic cytoplasm and blunt-ended or "cigar-shaped" nuclei, in both patients. In both patients, immunohistochemical examination showed positive staining for vimentin, desmin, and alpha-smooth muscle actin. Extensive examination of the gastrointestinal tract and uterus revealed no primary lesion. Therefore, the leiomyosarcoma in the femur was considered to be primary rather than metastatic. Histological examination, including immunohistochemistry, and the exclusion of an extraskeletal primary lesion, is necessary in diagnosing primary leiomyosarcoma of bone.


Structural abnormalities in paediatric moyamoya disease revealed by clinical magnetic resonance imaging, regionally distributed relative signal intensities and volumes.
Moyamoya disease (MMD) is a rare, progressive cerebrovascular disorder, with an unknown aetiology and pathogenesis. It is characterized by steno-occlusive changes at the terminal portion of the internal carotid artery (ICA), which is accompanied by variable development of the basal collaterals called moyamoya vessels. In this study, we investigate the potential for structural T1 magnetic resonance imaging (MRI) to help characterize MMD clinically, with the help of regionally distributed relative signal intensities (RRSIs) and volumes (RRVs). These RRSIs and RRVs provide the ability to characterize aspects of regional brain development and represent an extension to existing automated biomarker extraction technologies. This study included 269 MRI examinations from MMD patients and 993 MRI examinations from neurotypical controls, with regional biomarkers compared between groups with the area under the receiver operating characteristic curve (AUC). Results demonstrate abnormal presentation of RRSIs and RRVs in the insula (15- to 20-year old cohort, left AUC: 0.74, right AUC: 0.71) and the lateral orbitofrontal region (5- to 10-year old cohort, left AUC: 0.67; 15-20 year cohort, left AUC: 0.62, right AUC: 0.65). Results indicate that RRSIs and RRVs may help in characterizing brain development, assist in the assessment of the presentation of the brains of children with MMD and help overcome standardization challenges in multiprotocol clinical MRI. Further investigation of the potential for RRSIs and RRVs in clinical imaging is warranted and supported through the release of open-source software.


[The effect of mercasolyl on immunologic indicators in patients with diffuse toxic goiter].
A study of system of cellular and humoral immunity, unspecific defense in 187 patients with diffuse toxic goiter before and after treatment with mercasolyl revealed that despite the clinical effect, the agent did not essentially influence the content and functional activity of T-lymphocytes. The effect was more favourable on the content of immunoglobulins, titer of antithyroid antibodies. This was observed in mild and average severe course of the disease. It is suggested that mercasolyl effects lymphocytes synthesizing autoantibodies to the thyroid gland.


Identification of new C27 and C24 bile acids in the bile of Alligator mississippiensis.
Biliary bile acids of Alligator mississippiensis were analyzed by gas-liquid chromatography-mass spectrometry after fractionation by silica gel column chromatography. It was shown that the alligator bile contained 12 C27 bile acids and 8 C24 bile acids. In addition to the C27 bile acids, such as 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-cholestanoic acid, 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid, 3 alpha,12 alpha-dihydroxy-5 beta-cholestanoic acid, 7 alpha,12 alpha-dihydroxy-3-oxo-5 beta-cholestanoic acid, and 3 alpha,12 alpha-dihydroxy-7-oxo-5 beta-cholestanoic acid, identified previously in the bile of A. mississippiensis, 3 alpha,7 beta-dihydroxy-5 beta-cholestanoic acid, 3 alpha,7 beta,12 alpha-trihydroxy-5 beta-cholestanoic acid, 7 beta,12 alpha-dihydroxy-3-oxo-5 beta-cholestanoic acid, 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestanoic acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholestanoic acid, and 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholestanoic acid were newly identified. And in addition to the C24 bile acids, such as chenodeoxycholic acid, ursodeoxycholic acid, cholic acid, and allocholic acid, identified previously, deoxycholic acid, 3 alpha,7 alpha-dihydroxy-5 beta-chol-22-enoic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-chol-22-enoic acid, and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-chol-22-enoic acid were newly identified.


Noise-Dependent Fish Distribution in Kelp Beds.
The marine marbled rockfish Sebastiscus marmoratus is dependent on kelp beds and rocks for survival and reproduction. We found that sound production and hearing sensitivity in S. marmoratus are closely matched in the frequency domain. We also found that the juvenile rockfish prefers the habitat of the larger macroalgae Sargassum horueri rather than the habitat containing the smaller algae Ulva pertusa where the adult rockfish prefers to live. Our underwater noise recording data from these two habitats indicate that their spectra of the background noise have different values. The results suggest that the acoustic cues may be critical for pelagic larvae when selecting the preferential habitat in which to settle.


Renal cyst evolution in childhood: a contemporary observational study.
Children with renal cysts often undergo ultrasound (US) monitoring to identify malignant transformation or polycystic kidney disease (PKD). However, the utility of ongoing surveillance is uncertain. The objective of this study was to assess the natural history of simple or minimally complex cysts and the proportion of progression to autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), or malignancy. The institutional review board approved retrospective chart review at one institution between 2004 and 2014. Eligible patients had ≤3 simple or minimally complex cyst(s) discovered on US without an initial diagnosis of multicystic dysplastic kidney, genitourinary malignancy, ADPKD, or ARPKD. Patient demographics and cyst details were recorded at identification and follow-up visits. Logistic regression was used to examine univariate association between diagnosis of ADPKD/ARPKD and each recorded variable. Eighty-seven eligible patients were identified. Twenty-two patients were identified antenatally or in the first year of life; the remaining 65 were identified at >1 year of age, median 7.6 years (interquartile range [IQR]: 4.2, 10.6). Most (60/87, 69%) had a solitary cyst at initial US. The median length of follow-up was 4.1 years (IQR: 1.9, 6.8) with median 3 follow-up US (IQR: 2, 5). Eleven patients (12.6%) were diagnosed with ADPKD. One patient (1.2%) was diagnosed with ARPKD. A median 2 follow-up US (IQR: 1, 4) procedures were performed over a median of 2.2 years (IQR: 1.0, 3.9) to obtain diagnoses of ADPKD or ARPKD. No patients developed malignancy. This study's results reveal that children identified to have a small number of simple or minimally complex renal cysts on initial US are unlikely to require additional treatment for these cysts as transformation to PKD or malignant condition is rare. Supporting this are results from literature that although simple cysts in childhood may evolve over time, most do not require any surgical or invasive treatment in the long term. Limitations include retrospective design and single institution. Autosomal dominant polycystic kidney disease/autosomal recessive polycystic kidney disease diagnosis occurs early in follow-up evaluation in children with simple or minimally complex cysts. Malignant transformation did not occur in any patients in this study. This study examines the natural history of renal cysts in childhood. Following up simple renal cysts routinely beyond 2-3 years after initial detection may not be optimal due to the use of limited medical resources.


Iowa record-linkage study: death rates in psychiatric patients.
The Iowa record-linkage study was developed to investigate death rates in psychiatric patients, and involved computer matching of death certificates with a roster of patients. A list of all patients admitted to our hospital from 1972 through 1981 was obtained and after removing duplicate entries the list was pared to 5412 names. The record included multiple identifiers (e.g., name, gender, date-of-birth, hospital number). This information was then linked by computer with all Iowa death certificates for the same period; a total of 331 deaths were identified. Patients were assigned to a single psychiatric diagnostic category based on a computer program that reviewed each patient's clinical diagnoses and picked the one with the highest priority in a hierarchy we had created. Age and sex adjusted mortality tables were constructed, allowing us to compute expected numbers of deaths. Relative risk for premature death was greatest among women, and those under 20 years. Risk was associated with all psychiatric diagnoses and was significantly higher among patients of either gender with an organic mental disorder or schizophrenia; women with acute schizophrenia, depressive neuroses, alcoholism, drug abuse, and psychophysiological disorders; and men with neuroses. Death from natural causes, especially from heart disease, was significantly excessive among women, while death from accidents and suicides was excessive for both men and women. The overall SMR was 1.65 (P < 0.001). Most importantly, we found that the greatest excess of mortality occurred within the first 2 years following hospital discharge. Thus, we were able to demonstrate that risk of mortality in general, and of suicide specifically, differed according to age, gender, diagnosis, and portion of the follow-up. We have subsequently used this method to investigate specific risk factors associated with mortality in mood disorders, schizophrenia, and antisocial personality disorder. Findings from these studies are reported.


Reduced fibrinolytic potential in patients with arterial occlusive disease (AOD) in comparison with normal subjects.
When combining angioplasty and local lysis with urokinase (UK) in treatment of peripheral arterial occlusions we have observed marked differences in the individual patient's response irrespective of the age of the thrombus. The extensive arteriosclerotic changes revealed by angiography in some of these patients suggest a reduced fibrinolytic potential depending on the underlying disease. In the standard in vitro test system we measured the UK-dependent thrombolysis in blood samples from 10 normal controls at UK concentrations of 150, 200, and 300 IU/ml of whole blood. In comparison we determined the whole blood thrombolysis time (WBTT) of 10 patients with AOD using UK concentrations of 150, 200, and 300 IU/ml of whole blood. The mean WBTT values for normal controls obtained at UK concentrations of 150 IU/ml, 200 IU/ml, and 300 IU/ml, respectively, amounted to 9.5, 5.5, and 3.5 minutes, respectively, while in patients mean values of 20.7, 8.1, and 5.5 minutes, respectively, were found. Studies on plasma samples had shown that the lysis time could be shortened in a dose-dependent manner by addition of lys-plasminogen (LYS-PLASMINOGEN Steam Treated) and to some extent also glu-plasminogen. Since lys-plasminogen gave clearly superior results we tried to improve the lytic potential in terms of a shortening of the WBTT by adding different doses of lys-plasminogen (0.14-0.56 CU/ml whole blood) to each patient sample. Although the individual response varied, the addition of lys-plasminogen to the patient samples resulted in a clear dose-dependent improvement of pathologically prolonged lysis times.(ABSTRACT TRUNCATED AT 250 WORDS)


pH effects in plasmin-catalysed hydrolysis of alpha-N-benzoyl-L-arginine compounds.
The steady-state kinetics of plasmin (EC 18.104.22.168) catalysed reactions with some alpha-N-benzoyl-L-arginine compounds is investigated in the pH range 5.8--9.0. The results are interpreted in terms of a three-step mechanism, which involves enzyme-substrate complex formation, followed by acylation and deacylation of the enzyme. Alpha-N-Benzoyl-L-arginine methyl ester and ethyl ester show the same pH behaviour. The kinetic parameter kc/Km is influenced by two groups with pK values of 6.5 and 8.4, respectively. kc is affected only by the group with pK equal to 6.5 and Km only by the group with pK equal to 8.4. It is suggested that the group with pK equal to 6.5 is the 1-chloro-3-tosyl-amido-7-amino-2-heptanone-sensitive histidine residue in the active site and that the group with pK equal to 8.4 is perhaps the alpha-amino group of the N-terminus in analogy to trypsin and chymotrypsin. alpha-N-Benzoyl-L-arginine amide is not hydrolysed by plasmin, but proves to be a competitive inhibitor, Ki = 12.8 +/- 1.8 mM, pH = 7.8. Also the product alpha-N-benzoyl-L-arginine is a competitive inhibitor, Ki = 26 +/- 3.1 mM, pH = 7.8. Estimates of individual rate constants are compared with similar trypsin data.


Heat-induced changes in the rat parotid gland.
Gland size, amylase activity, total proteins and DNA concentrations were measured in parotid gland during chronic heat exposure (34 degrees C). Subcellular fractionation was performed. Exposure to heat resulted in a decrease in gland size and in DNA concentration; amylase activity/100 mg tissue and amylase specific activity to protein concentration ratio increased. Subcellular fractions, except plasma membrane, decreased significantly. Thus, chronic heat exposure slows down the production of gland constituent proteins, whereas acinar function, e.g. the production and storage of exportable proteins, is not disturbed. The reduced gland size is apparently due to hypoplasia.


Incidence and long-term outcome of postradiotherapy moyamoya syndrome in pediatric patients with primary brain tumors: a single institute experience in Taiwan.
We aimed to investigate the incidence and long-term outcome of moyamoya syndrome in pediatric patients with primary brain tumors after receiving cranial radiotherapy (RT) in a single institute in Taiwan. The complete medical records, medical images, and RT notes of 391 pediatric patients with primary brain tumors treated with cranial RT between January 1975 and December 2005 in Taipei Veterans General Hospital (TVGH), Taiwan, were entered into an electronic registry and reviewed. Eight (2%) cases of post-RT moyamoya syndrome were identified in the sample of 391 patients. The median latency was 3 years post-RT. Among the eight patients, three had craniopharyngioma, two had optic glioma, two had medulloblastoma, and one had a suprasellar astrocytoma. The prescribed physical doses of RT were in the range of 40-54 Gy. The incidence was highest in those with optic glioma (0.039/person-year), followed by craniopharyngioma (0.013/person-year), astrocytoma (0.003/person-year), and medulloblastoma (0.002/person-year). No patients died of vasculopathy. No difference in crude incidence was found between our results and those of other series. The incidence of moyamoya syndrome was diagnosis dependent, with the highest incidence among patients with optic glioma. No regional difference in incidence was found. Long-term, stable neurological function may be achieved following timely surgical intervention.


Is there still a role for a diet very low in protein, with or without supplements, in the management of patients with end-stage renal failure?
Historically, studies in humans have not shown conclusively that low-protein diets ameloriate the progression of renal disease. However, recent trials have demonstrated that, in patients with advanced renal insufficiency, low-protein diets may slow the loss of renal function and defer the onset of end-stage renal disease.