Reduction in inspiratory activity in response to sternal vibration.
It has been shown previously that there is a reduction in tidal volume in response to longitudinal sternal vibration at 100 Hz. In the present study it was shown that the effect of such vibration is to reduce tidal volume (VT) and prolong inspiratory time (ti) in such a way that points from vibrated and non-vibrated breaths fall on the same VT:ti curve. This indicates that the normal mechanisms which terminate inspiration are unaffected by vibration. The effect of vibration is simply to reduce the rate at which inspiration proceeds. This was illustrated here when vibration reduced the rate of fall of intrapleural pressure during inspiration, and also reduced the instantaneous ventilation at any level of chemical drive. Electrophysiological recordings made here from phrenic motoneurones support these findings. It is concluded that sensory nerves in the chest wall, which can be excited by vibration, can inhibit inspiration.


Leadership in the managed care era: challenges, conflict, ambivalence.
Mental health organizations are in the midst of massive changes brought about by managed care. This paper explores attitudes and reactions of leaders in mental health organizations to these changes. The leader's own conflicts regarding this approach to mental health care is a major determinant of why some organizations adapt more readily than others. Strategies for leaders that recognize the need to address conflict within the individual and the organization are discussed. The importance of facilitating dynamic interactional processes between leaders and non-leaders in regard to mutual expectations also is emphasized.


Evaluation of a new formulation CLOtest.
The CLOtest and other rapid urease detection kits are widely used in the endoscopic diagnosis of Helicobacter pylori. A new formulation CLOtest has been developed with the goal of obtaining a positive result more rapidly. The aims of this study were to validate the sensitivity and specificity of the new test and compare the time taken for a positive result to be visible in both the new and standard CLOtest. Patients presenting for endoscopy at three Western Australian hospitals were prospectively enrolled. Gastric mucosal biopsies were obtained for the standard and new CLOtest and for histology. Grading of color change was conducted by staff blinded to the type of CLOtest used and conducted according to a standardized color chart. Helicobacter pylori status was defined by the combination of a positive standard CLOtest and histology, against which the new CLOtest was compared. Results were obtained at 1, 3 and 24 h, and at one center, at 10 min intervals for the first hour. Three hundred and thirty-five patients were enrolled. Eighty-eight Helicobacter pylori-positive individuals were identified. At 24 h, the new test correctly identified all 88, with one false-positive result (sensitivity 100%, specificity 99.6%). At 1 h, sensitivity was 93% with a number of early false-positive results reducing specificity to 96%. Compared to the current CLOtest, the new formulation became positive faster at 20 min (P = 0.001, n = 51), but was similar at 1 h (P = 0.06, n = 88) and equivalent at 3 h. The new formulation CLOtest is sensitive and specific, with a trend to give early positive results more quickly, although accuracy at 3 and 24 h is the same.


The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size.
The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07-1.59), 1.07 (95% CI 0.89-1.28), 1.31 (95% CI 1.06-1.62), and 1.81 (95% CI 1.03-3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69-2.14), 1.33 (95% CI 1.02-1.73), and 1.58 (95% CI 1.04-2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46-1.57), 1.34 (95% CI 1.01-1.8), and 1.57 (95% CI 1.03-2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83-4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98-5.54) in those with tumors measuring ≥5 cm. Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.


Outcome after whole brain radiotherapy alone in intracranial leptomeningeal carcinomatosis from solid tumors.
The purpose of the present study was to investigate outcome after whole brain radiotherapy (WBRT) alone as a palliative treatment without concomitant chemotherapy for intracranial leptomeningeal carcinomatosis (LMC). Overall survival and treatment response were retrospectively analyzed in 27 consecutive patients with LMC from breast and lung cancer. All patients had evidence of intracranial manifestations of LMC. Seven potential prognostic factors were evaluated. Median overall survival (OS) for the entire group was 8.1 weeks. OS rates after 6 and 12 months were 26% and 15%, respectively. Improvement of neurological deficits was observed in 3 patients. In 3 of 4 patients with follow-up MRI studies, a decreased size of contrast-enhanced lesions was observed. Prognostic factors for improved OS on univariate analysis were absence of cranial nerve dysfunction, Karnofsky Performance Score (KPS) > 60%, and time interval > 35 months between the initial diagnosis of malignant disease and development of LMC. On multivariate analysis, absence of cranial nerve dysfunction remained the only significant prognosticator for OS (median 3.7 vs. 19.4 weeks, p < 0.001). WBRT alone is an effective palliative treatment for patients unfit/unsuitable for chemotherapy and low performance status suffering from intracranial LMC. However, prognostic factors should be considered in order to identify patients who are likely to benefit from WBRT.


Exopolysaccharide synthesis in Rhizobium leguminosarum bv. trifolii is related to various metabolic pathways.
Rhizobium leguminosarum bv. trifolii synthesizes extracellular polysaccharide (EPS) that is postulated to be a biologically active signalling molecule in clover symbiosis. A group of seven exopolysaccharide-deficient (Exo), non-nitrogen-fixing mutants of R. leguminosarum bv. trifolii strain 24.1 isolated by transposon mutagenesis were complemented to mucoid phenotype by a low-copy plasmid carrying the pssA gene encoding the first glucosyl-IP-transferase. Some of these mutants were not corrected in their symbiotic defect by the pssA gene. Precise localization of Tn5 insertion sites by subcloning and sequencing the adjacent genomic DNA in the Exo mutants identified the disrupted genes and their possible functions. Only one mutant (Rt74) was mutated in pssA gene; others were mutated in diverse genes that were not directly involved in EPS biosynthesis. The suppression of EPS deficiency in these mutants by additional copies of pssA indicated a possible connection between exopolysaccharide biosynthesis and various metabolic pathways.


First Carpometacarpal Joint Motion and Proximal Migration of the First Metacarpal After Tensioning of a Suture Device Suspensionplasty Compared With Trapeziectomy: A Biomechanical Cadaver Study.
The purpose of this cadaveric biomechanical experiment was to evaluate the effects of suture button suspensionplasty of the first carpometacarpal joint on thumb biomechanics and thumb position compared with an intact, arthritic specimen. Six tendons in 8 cadaver hands were loaded to simulate 6 activities of daily living and passively moved through a circumduction motion. Proximal migration of the base of the first metacarpal was measured using optical motion sensors in the intact hand, after trapeziectomy, and following insertion of a suture button suspensionplasty with nominal tightening (approximately 4.5 N) and with firm tightening (approximately 44.5 N). Removal of the trapezium caused a significant increase in the proximal migration of the first metacarpal during a simulated jar grasp, opposition, flexion, extension, and abduction (average, 9.5 mm) compared with its location with the thumb in the intact, neutral position (average, 3.8 mm). Firm tightening of the tightrope caused a near elimination of the proximal migration of the first metacarpal (average, 0.7 mm). In all 6 static loading cases with the trapezium removed, firm tightening caused a significantly smaller migration than in the absence of tightening. This biomechanical cadaver study supports the hypothesis that trapeziectomy results in proximal migration of the first metacarpal. Suture suspensionplasty mitigates against this migration while maintaining normal motion of the first metacarpal compared with the intact state. Firm tightening of the suture does not adversely affect the first metacarpal's mobility and further decreases proximal migration. However, firm tightening may cause impingement between the first and second metacarpals. Suture button suspensionplasty can be used in addition to trapeziectomy in the treatment of basal joint arthritis, and may diminish the need for ligament reconstruction or temporary K-wire insertion.


Genome Sequences of Gordonia Phages GrootJr and NovumRegina.
Two Gordonia bacteriophages, GrootJr and NovumRegina, were discovered, sequenced, and annotated. These phages were isolated from distinct soil and water samples, respectively, on Gordonia terrae 3612. These phages belong to the CR2 subcluster and are similar in genome size and gene content.


Music perception and cerebral asymmetries.
Six experiments investigated the detection of pitch, rhythm and harmony changes in music perception. While RTs did not differentiate between ears for detecting a changed note in either a single line melody or a five note whole tone sequence, the right ear was more accurate. The left ear was faster, and the right more accurate in detecting rhythm changes in a five note sequence. The ears did not differ in detecting harmony changes. Finally, the right ear proved consistently more sensitive (d') in recognizing excerpts from unfamiliar melodies, and except only for female nonmusicians, the left ear was more sensitive for familiar melodies. If the adoption of differintial listening strategies determines the direction of laterality differences such as these, then familiarity also seems important in determining listening strategies.


Dyadic Affective Flexibility and Emotional Inertia in Relation to Youth Psychopathology: An Integrated Model at Two Timescales.
The current review examines characteristics of temporal affective functioning at both the individual and dyadic level. Specifically, the review examines the following three research questions: (1) How are dyadic affective flexibility and emotional inertia operationalized, and are they related to youth psychopathology? (2) How are dyadic affective flexibility and emotional inertia related, and does this relation occur at micro- and meso-timescales? and (3) How do these constructs combine to predict clinical outcomes? Using the Flex3 model of socioemotional flexibility as a frame, the current study proposes that dyadic affective flexibility and emotional inertia are bidirectionally related at micro- and meso-timescales, which yields psychopathological symptoms for youth. Specific future directions for examining individual, dyadic, and cultural characteristics that may influence relations between these constructs and psychopathology are also discussed.


Prostate cancer: post-irradiation incontinence.
The experience of 272 patients with prostate cancer treated between 1976 and 1987 by external irradiation was reviewed to assess causal factors for post-irradiation incontinence and to determine measures to reduce the risk of this complication. No patient had incontinence before definitive irradiation or radical prostatectomy. Post-irradiation incontinence was observed in 19 of 272 patients (7%), including 14 with mild, 2 with moderate and 3 with severe disease. Incontinence after definitive irradiation was not significantly related to tumor stage or tumor control: 8 of 192 patients (4%) had local control and 2 of 33 (6%) had local failure. Incontinence was related to a urological operation performed in 1 of 105 patients (1%) who underwent needle biopsy and 7 of 130 (5.5%) who underwent transurethral prostatectomy before irradiation. Incontinence was more frequent, 2 of 6 patients (33%), and more severe in patients who underwent transurethral prostatectomy after irradiation. Of 31 patients 9 (29%) were incontinent after radical prostatectomy. No additional patient had incontinence after postoperative irradiation. However, 3 patients had a temporary increase in the severity of incontinence. The risk of post-irradiation incontinence may be decreased by more selective use of transurethral prostatectomy. Of 136 patients 26 (20%) underwent transurethral prostatectomy for tissue diagnosis. A needle biopsy would be the procedure of choice. A total of 29 patients with urinary outlet obstruction was treated without transurethral prostatectomy before irradiation. Ten patients with relatively mild urinary outlet obstruction were treated by irradiation alone, while 19 with more severe urinary outlet obstruction had endocrine therapy before irradiation and none of the 29 patients (0%) had post-irradiation incontinence.


Molecular connectivity and antifungal activity. A quantitative structure-activity relationship study of substituted phenols against skin pathogens.
The plot of minimum inhibitory concentration (MIC) vs. 2Xv of twelve phenolic compounds delineates the congeners into three distinct classes: the most potent ortho compounds describe a parabola, para substituted compounds of intermediate potency lie in a line, while the least potent meta derivatives yield a scatter diagram. The same pattern is found for two skin pathogens, Trichophyton rubrum and Epidermophyton floccosum. From non-linear regression analysis 2Xv is found to be excellently correlated with observed MIC values of the most potent ortho compounds against both the test organisms. For both the organisms logP is found to be inferior to 2Xv in the correlation of MIC values. On the basis of regression equations the MIC values of certain ortho substituted phenols are calculated a priori, some of which are corroborated by findings reported in the literature.


Critical thinking: A comparative analysis between nurse managers and registered nurses.
To analyse the levels of critical thinking among nurse managers and registered nurses and to explore the association between these levels and socio-demographic and occupational factors. Critical thinking is an essential skill in advanced clinical nursing. However, few studies to date have explored critical thinking levels in nurse managers or compared them with those recorded in registered nurses. A randomized sample of 44 nurse managers and 295 registered nurses from a tertiary hospital in Barcelona participated in this study. The Nursing Critical Thinking in Clinical Practice Questionnaire was used to measure the level of critical thinking. The data were analysed using multivariate analysis by logistic regression. Levels of critical thinking were higher in nurse managers than in registered nurses. Age, work shift schedule and educational level were associated with a higher level of critical thinking in nurse managers and were predictor factors. This study identified age, work shift schedule and educational level as factors that impact on the acquisition of critical thinking skills among nurse managers. This study provides substantive evidence of the levels of critical thinking among nurse managers. When introducing strategies to enhance these skills, the associated occupational factors should be taken into account.


Patent ductus arteriosus (PDA) and response to late surfactant treatment in premature infants.
To determine the clinical/echocardiography (ECHO) phenotype of patients with hypoxic respiratory failure (HRF) and response to late surfactant, according to patent ductus arteriosus (PDA) status. This retrospective study included infants ≤26+6 weeks gestation who received ≥1 surfactant dose after 6 postnatal days and where PDA status was available by ECHO. Response to surfactant was appraised based on change in respiratory severity score over 48 h. The relationship between PDA status and response to surfactant was evaluated via univariate analysis. We studied late surfactant (n = 71 doses) administration in 35 preterm infants born at a mean weight and GA at birth were 595 g (508, 696) and 23.3 (22.7, 25) weeks, respectively of whom 16 (46%) had a diagnosis of PDA. Positive response to late surfactant treatment was independently associated with absence of PDA [OR 26 (2, 334), p = 0.01] whereas presence of PDA was independently associated with negative response [OR 12 (1.1, 126), p = 0.04]. In neonates ≤26+6 weeks gestation, with HRF, response to surfactant after postnatal day 6 is influenced by PDA status. Future trials should consider PDA status which may enhance diagnostic precision and refine patient selection for late surfactant treatment.


Neighbourhood characteristics and trajectories of health functioning: a multilevel prospective analysis.
Prospective data from over 10 years of follow-up were used to examine neighbourhood deprivation, social fragmentation and trajectories of health. From the third phase (1991-93) of the Whitehall II study of British civil servants, SF-36 health functioning was measured on up to five occasions for 7834 participants living in 2046 census wards. Multilevel linear regression models assessed the Townsend deprivation index and social fragmentation index as predictors of initial health and health trajectories. Independent of individual socioeconomic factors, deprivation was inversely associated with initial SF-36 physical component summary (PCS) score. Social fragmentation was not associated with PCS scores. Deprivation and social fragmentation were inversely associated with initial mental component summary (MCS) score. Neighbourhood characteristics were not associated with trajectories of PCS score or MCS score for the whole set. However, restricted analysis on longer term residents revealed that residents in deprived or socially fragmented neighbourhoods had lowest initial and smallest improvements in MCS score. This longitudinal study provides evidence that residence in a deprived or fragmented neighbourhood is associated with poorer mental health and that longer exposure to such neighbourhood environments has incremental effects. Associations between physical health functioning and neighbourhood characteristics were less clear. Mindful of the importance of individual socioeconomic factors, the findings warrant more detailed examination of materially and socially deprived neighbourhoods and their consequences for health.


Monosynaptic connections between serotonin-containing neurones labelled by 5,6-dihydroxytryptamine-induced pigmentation in the snail Helix pomatia L.
Microelectrophysiological experiments were carried out on in vivo 5,6-dihydroxytryptamine-induced pigment-labelled serotonin-containing neurones of Helix pomatia. Excitatory chemical monosynaptic connections were found between the giant pedal LP3 neurone and several follower cells in the visceral and right parietal ganglia. These neurones have previously been described to be involved in regulation of visceral functions. Monitoring changes in identified monosynaptic connections between pairs of serotonin-containing neurones aids the cellular analysis of behavioural plasticity.


Forensic features and genetic structure of 20 autosomal STR loci in the Han population of Ningde City, Southeastern China.
Short tandem repeat (STR) loci are widely used in forensic medicine and population genetics. To profile 20 autosomal STR loci using the SureID® 21 G Human STR Identification Kit. Samples were obtained from 1412 unrelated Chinese Han individuals from Ningde City, Southeastern China and 20 autosomal STR loci were profiled using the SureID® 21 G Human STR Identification Kit. A total of 261 alleles were observed among 1412 unrelated individuals and the corresponding allelic frequencies ranged from 0.5464 to 0.0004. The combined power of discrimination and exclusion of the 20 autosomal STR loci were 0.99999999999999999922 and 0.999999340285752, respectively. There was no significant deviation from Hardy-Weinberg equilibrium (HWE) and minimal departure from linkage equilibrium (LE) for two pairwise combinations of loci after sequential Bonferroni correction. In the population comparison, phylogenetic analysis was performed between the Han population and other relevant populations on the basis of the shared autosomal STR genotyping. Moreover, the neighbor-joining tree and principal component analysis were analysed based on the Nei's standard genetic distance. The population comparison revealed that the structure of the Ningde Han population was similar to the structure of southern Han populations in China and was significantly different to the other Chinese ethnic groups, such as Kyrgyz, Uzbek, Kazakh, Uyghur, Manchu from Xinjiang and Mongols.


Differences in muscle synergies between healthy subjects and transfemoral amputees during normal transient-state walking speed.
Lower limb amputation is a major public health issue globally, and its prevalence is increasing significantly around the world. Previous studies on lower limb amputees showed analogous complexity implemented by the neurological system which does not depend on the level of amputation. What are the differences in muscle synergies between healthy subjects (HS) and transfemoral amputees (TFA) during self-selected normal transient-state walking speed? thirteen male HS and eleven male TFA participated in this study. Surface electromyography (sEMG) data were collected from HS dominant leg and TFA intact limb. Concatenated non-negative matrix factorization (CNMF) was used to extract muscle synergy components synergy vectors (S) and activation coefficient profiles (C). Correlation between a pair of synergy vectors from HS and TFA was analyzed by means of the coefficient of determination (R2). Statistical parametric mapping (SPM) was used to compare the temporal components of the muscle synergies between groups. the highest correlation was perceived in synergy 2 (S2) and 3 (S3) and the lowest in synergy 1 (S1) and 4 (S4) between HS and TFA. Statistically significant differences were observed in all of the activation coefficients, particularly during the stance phase. Significant lag in the activation coefficient of S2 (due mainly to activated plantarflexors) resulted in a statistically larger portion of the gait cycle (GC) in stance phase in TFA. Understanding the activation patterns of lower limb amputees' muscles that control their intact leg (IL) and prosthetic leg (PL) joints could lead to greater knowledge of neuromuscular compensation strategies in amputees. Studying the low-dimensional muscle synergy patterns in the lower limbs can further this understanding. The findings in this study could contribute to improving gait rehabilitation of lower limb amputees and development of the new generation of prostheses.


Squalene epoxidase (SE) gene related to triterpenoid biosynthesis assists to select elite genotypes in medicinal plant: Cyclocarya paliurus (Batal.) Iljinskaja.
Triterpenoids, known for their anti-inflammatory, anticancer, and hypoglycemic properties, are the major bioactive components in Cyclocarya paliurus (Batal.) Iljinskaja. Selecting elite individuals with high triterpenoids content is the basis of C. paliurus industry for medicinal use. In this study, seasonal variation patterns of total triterpenoids and five triterpene monomers accumulation for three groups with different total triterpenoid contents (TTC; H: 59.74-64.03 mg g-1; M: 47.66-57.08 mg g-1, and L: 35.26-42.22 mg g-1) were surveyed. Seasonal expression dynamics of 6 key genes relevant to triterpenoids biosynthesis, including HMGR, DXR, SQS, SE, LUS, and β-AS, were described by quantitative real-time PCR (qRT-PCR) for three groups. The expression levels of HMGR, SE, LUS, and β-AS genes in group H were higher than in groups M and L. In addition, Pearson correlation analysis showed that they were significantly positively correlated with triterpene accumulation, and the expression level of SE gene not only was significantly correlated with downstream genes, but also exhibited a linear relationship with TTC, especially in September. These results suggest that SE gene could serve as an effective make for screening elite individuals with high TTC from the germplasm of C. paliurus for medicinal use. Further testing on randomly selected individuals in next September proved the feasibility and reliability of SE gene in assisted selection. Also, we successfully cloned the full-length cDNA of SE. Thus, our work provides an efficient way to attain superior genotypes to develop medicinal industry of C. paliurus in practice.


Endomorphin-2 is an endogenous opioid in primary sensory afferent fibers.
Evidence is presented that the recently discovered endogenous mu-selective agonist, endomorphin-2, is localized in primary sensory afferents. Endomorphin-2-like immunoreactivity was found to be colocalized in a subset of substance P- and mu opiate receptor-containing fibers in the superficial laminae of the spinal cord and spinal trigeminal nucleus. Disruption of primary sensory afferents by mechanical (deafferentation by dorsal rhizotomy) or chemical (exposure to the primary afferent neurotoxin, capsaicin) methods virtually abolished endomorphin-2-like immunoreactivity in the dorsal horn. These results indicate that endomorphin-2 is present in primary afferent fibers where it can serve as the endogenous ligand for pre- and postsynaptic mu receptors and as a major modulator of pain perception.


Metastasis prevention with bone-targeted agents: a complex interaction between the microenvironment and tumour biology.
The use of bone-targeted treatments has transformed the clinical care of many patients with metastatic breast cancer. In addition, due to the profound effects of bisphosphonates and denosumab on bone physiology and the bone microenvironment, the potential of bone-targeted agents to modify the process of metastasis has been studied extensively. Many adjuvant trials with bisphosphonates in early breast cancer have been performed. Variable outcomes in terms of disease recurrence have been reported, with any treatment benefits apparently influenced by the age and menopausal status of the patients. Results show that in breast cancer the use of adjuvant bisphosphonates reduce bone metastases and breast-cancer deaths in postmenopausal women. These effects are in addition to the benefits associated with the use of standard adjuvant endocrine, cytotoxic and targeted treatments with prevention of one in six breast-cancer deaths at 10 years. Biomarkers that can predict patient benefit from the use of bone-targeted treatments in the adjuvant setting are being evaluated. Currently, tumour expression of the transcription factor, MAF, seems to be the most promising biomarker; benefits from adjuvant bisphosphonates are seen in the 80% of patients with normal levels of expression irrespective of menopausal status and age, while over expression is associated with a poor prognosis and a higher rate of visceral metastases. Adjuvant bisphosphonates are now part of standard clinical guidelines for postmenopausal women with early breast cancer at intermediate to high risk of recurrence. MAF testing of primary tumours may improve patient selection for treatment.


[Biomechanical considerations on stress and strain of the anchorage of femoral prostheses stems (author's transl)].
The nature of load and stress on implanted femoral prostheses is shown by simplified models. Bending stress is responsible for loosening and fracture of prosthesis stems. Implantation in valgus position diminishes the possibility of failure. Investigations on materials and the strength of form could clear up different influences and shall lead to allbountiful criterions and test-methods.


Association of cytokine gene polymorphisms with the complications of allogeneic haematopoietic stem cell transplantation.
The purpose of our study was to confirm the prevalence of the association between single nucleotide polymorphisms present in genes encoding cytokines and the complications occurring after haematopoietic stem cell transplantation (HSCT). 108 recipients and 81 donors were typed for TNF-α (-308), TGF-β1 (codon 10, 25), IL-10 (-1082, -819, -592), IL-6 (-174) and INF-γ (+874). Our studies have shown a tendency toward association between the occurrence of acute form of graft versus host disease (aGVHD) and IL-6 genotype. Homozygote C/C was less likely to develop aGVHD (p=0,09). Genotype GCC/ATA in IL-10 recipient gene alone had protective effect against the occurrence of aGVHD (p=0,01). Furthermore, GCC/ATA protected the host against developing the disease in the clinically relevant grades (II-IV) (p=0,03). In addition, the recipient's T/T G/G genotype (TGF-β1) predisposed to the development of both acute (p=0,06 - trend) and chronic (p=0,04) GVHD and also severe aGVHD (p=0,004). We also observed a statistically significant association between the genotype of recipient and the risk of infection - the protective function of the G/C IL-6 in the bloodstream infections (p=0,001). Our results suggest that IL-6, IL-10 and TGF-β1 genotypes of recipient are the most associated with the risk of complications after HSCT.


Comparison of mediastinal and non-mediastinal neuroblastoma and ganglioneuroblastoma associated with opsoclonus-myoclonus syndrome: a systematic review and meta-analysis.
Neuroblastoma is the most common malignancy in children younger than seven years of age and is the most frequent extracranial solid tumor that occurs in childhood. While opsoclonus-myoclonus syndrome (OMS), a paraneoplastic neurologic syndrome, affects 2-3% of children with neuroblastoma, and the percentage of mediastinal localization of the tumor is 49%. The objective of this study was to identify and characterize features of the OMS syndrome and treatments of mediastinal and non-mediastinal neuroblastoma associated with OMS. A systematic review of the literature was performed using PubMed, Medline, Web of Science, Embase and Cochrane. The search has no limit on date with the last search done on Dec 31, 2020. There is no publication restrictions or study design filters applied in the search. Fifty-five out of 242 papers were identified and met our study eligibility. There were 77 cases found (28 cases had Mediastinal neuroblastoma, and 49 cases had non-mediastinal neuroblastoma). Data from trials showed that cases with mediastinal neuroblastoma who seemed to have undergone less treatment for OMS [rate ratio (RR) 0.41 (95% CI: 0.22-0.76)] had resulted in decreasing persistent neurologic symptoms [RR 0.31 (95% CI: 0.10-0.96)]. Children who have OMS and mediastinal neuroblastoma may be associated with more favorable clinical and biological characteristics and better outcomes than children who have OMS and non-mediastinal neuroblastoma, and they are more likely to present with a single neurological symptom at first. The OMS in mediastinal neuroblastoma might also be treated effectively through resection of the tumor followed by appropriate radiotherapy and chemotherapy, and no long-term treatments of OMS is indicated.


Loss of interleukin-21 leads to atrophic germinal centers in multicentric Castleman's disease.
Both multicentric Castleman's disease (MCD) and immunoglobulin (Ig)G4-related disease (IgG4-RD) are systemic diseases, presenting with hypergammaglobulinemia and elevated serum levels of IgG4. However, with regard to histopathological findings, MCD shows atrophic germinal centers. On the other hand, expanded germinal centers are detected in IgG4-RD. We extracted germinal centers from specimens of each disorder by microdissection and analyzed the expression of mRNAs by real-time polymerase chain reaction to clarify the mechanisms underlying atrophied germinal centers in MCD. This analysis disclosed loss of interleukin (IL)-21 and B cell lymphoma (Bcl)-6 in the germinal centers of MCD. Loss of IL-21 is considered to be involved in the disappearance of Bcl-6 and leads to atrophied germinal centers in MCD.


The Third Italian Consensus Conference for Malignant Pleural Mesothelioma: State of the art and recommendations.
Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.


Adjuvant probiotic Bifidobacterium animalis subsp. lactis CP-9 improve phototherapeutic treatment outcomes in neonatal jaundice among full-term newborns: A randomized double-blind clinical study.
Probiotics had been used to decreased bilirubin level in neonatal jaundice (NJ) without being further studied mechanism and stratification. The intestinal pathogen Escherichia coli produced β-glucuronidase would increase enterohepatic circulation and elevate serum bilirubin levels (SBLs) which might worsen the disease process of NJ. We hypothesized that some probiotics could decrease bilirubin level through inhibiting the growth of E. coli. It's assumed that adjuvant probiotic intervention might accelerate the phototherapy for NJ and alleviate the severity of the NJ. Besides, it's further study the efficacy of the probiotic intervention in NJ among the full-term and preterm newborns. Firstly, the Bifidobacterium animalis subsp. lactis CP-9 was screened for its anti-E. coli activity. Then, it was orally administered to newborns with NJ in combination with conventional phototherapy (wavelength 425-457 nm) to determine its efficacy. 83 neonatal patients whose serum bilirubinemia was at a concentration of ≥ 15 mg/dL were participated the double-blind randomized trial and conducted in the neonatal ward of China Medical University Children's Hospital (CMUCH, Taichung, Taiwan). The test was conducted in 2 groups: experimental group: phototherapy + B. animalis subsp. lactis CP-9 (n = 43; 5 × 109 CFU/capsule) and control group: phototherapy + placebo (n = 40). The SBL and total phototherapy duration were measured. The experimental group showed improved serum bilirubin decline rate (-0.16 ± 0.02 mg/dL/h; P = .009, 95% CI -0.12 to -0.2), particularly in the first 24 hour of in-hospital care, and reduced total phototherapy duration (44.82 ± 3.23 h; P = .011, 95% CI: 51.3-38.2) compared with the control group. Especially, probiotics had a significant therapeutic effect (serum bilirubin decline rate: -0.18 ± 0.02 mg/dL/h, 95% CI -0.12 to -0.23, P = .014; phototherapy duration: 43.17 ± 22.72 h, 95% CI 51.9-34.3, P = .019) in the low-risk subgroup (full-term newborns). In conclusion, B. animalis subsp. lactis CP-9 synergistically improves treatment outcomes of NJ during in-hospital phototherapy including reduced total phototherapy duration and improved serum bilirubin decline rate, particularly in full-term newborns.


[Diagnostics and therapy of benign bone tumours (author's transl)].
The diagnosis of benign bone tumours must be confirmed histologically; only in rare cases this can be omitted. After having identified the kind of tumour, a specific therapy must be established, covering a wide range, like excochleation as well as amputation. Malignant degeneration and high rates of relapse are possible.


Determination of peripheral color signal density using contrast-enhanced color Doppler ultrasonography in diffuse liver disease.
The study aimed to quantify hepatic vascular changes that accompany the development of chronic liver disease using contrast-enhanced color Doppler ultrasonography and histopathological examination. A series of 62 patients with biopsy-proven chronic liver disease (31 chronic hepatitis, 31 liver cirrhosis) and 8 healthy controls were studied. Altogether, 22 livers (9 chronic hepatitis, 13 liver cirrhosis) obtained at surgery or autopsy were subjected to histopathological examination. Patients with cardiopulmonary disease or intrahepatic tumors were excluded. Intrahepatic color Doppler signals were scanned and counted at the liver surface in a 10 × 30 mm rectangle from liver segment V using color Doppler sonography (SSA 380 A) before and after contrast enhancement with SHU 508A (Levovist). Small arteries 30-1000 µm in diameter were counted on the histopathlogical specimen by microscopy. The number of color Doppler signals increased significantly after contrast enhancement in both patients and controls. The number of color Doppler signals was elevated before and after contrast enhancement when chronic liver disease was present, especially in cases of Child-Pugh grade C liver cirrhosis. Histologically, more arteries 30-125 µm in diameter were present in patients with chronic hepatitis than in those with liver cirrhosis, whereas more arteries ≦ 125 µm in diameter were present in patients with liver cirrhosis than in those with chronic hepatitis. Intrahepatic color Doppler signals are probably derived from peripheral arteries larger than 125 µm in diameter, and the signal density in these arteries increases with progression of the chronic liver disease.


Renal kallikrein mRNA localization by in situ hybridization.
Tissue kallikrein gene expression in rat kidney was examined by in situ hybridization histochemistry. A rat tissue kallikrein cDNA probe, 534 bases in length and complementary to the 3' end of kallikrein mRNA was first used in Northern blot analysis to demonstrate the existence of tissue kallikrein mRNA in rat kidney. Then, kallikrein mRNA's localization in rat kidney sections was studied in situ hybridization histochemistry using the same probe. Positive signals were concentrated in the renal cortex at the vascular pole of the glomeruli and to a lesser degree, the distal tubular cells. Prehybridization with the unlabeled probe can abolish the positive signal; the same result can also be achieved by pretreatment of the tissue section with ribonuclease. By using the same technique, tissue kallikrein mRNA was also localized in granular convoluted tubule and striated duct cells of rat submandibular gland. The results suggest a new site of renal kallikrein synthesis at the vascular pole of the glomerulus. These findings, coupled with the previous studies that tissue kallikrein can participate in activation and releasing of renin, raise a potential physiological role of kallikrein in renin release or prorenin processing at juxtaglomerular cells.


Radiation therapy and simultaneous chemotherapy for recurrent cervical carcinoma.
To evaluate the efficacy and toxicity in patients with recurrence of cervical cancer treated with radiotherapy and simultaneous chemotherapy. Between 1987 and 2001, 24 patients with recurrent cervical carcinoma were treated with concurrent chemoradiotherapy. Nine patients had incomplete tumor resection prior to radiation therapy. Irradiation was delivered to a total dose of 60 Gy, in three patients with central recurrences supplemented by brachytherapy. One patient was treated with brachytherapy alone. Simultaneous chemotherapy was done as a combined therapy of 5-fluorouracil-(5-FU, 600 mg/m(2)/d1-5, 29-33) and cisplatin (20 mg/m(2)/d1-5, 29-33; 16/24 patients) or of 5-FU (1,000 mg/m(2)/d1-5, 29-33) and mitomycin C (10 mg/m(2)/d2, 30; 1/24 patients). Cisplatin alone (25 mg/m(2)/d1-5) and carboplatin alone (800 mg/m(2)/d1-5) were administered in 5/24 patients (21%) and 2/24 patients (8%). The 5-year local recurrence-free survival rate was 37%, disease-free survival 33%, and overall survival 34%. Grade 3 toxicity (NCI-CTC grade 3) occurred mainly as diarrhea (38%), leukopenia (33%), and nausea (21%). Severe toxicity (grade 4) was not seen in any of the patients. Radiation therapy with simultaneous chemotherapy for recurrences of cervical cancer is an effective treatment with acceptable toxicity.


Comparison of Abdominal Computed Tomographic Enhancement and Organ Lesion Depiction Between Weight-Based Scanner Software Contrast Dosing and a Fixed-Dose Protocol in a Tertiary Care Oncologic Center.
This study aimed to evaluate the quality of enhancement and solid-organ lesion depiction using weight-based intravenous (IV) contrast dosing calculated by injector software versus fixed IV contrast dose in oncologic abdominal computed tomographic (CT) examinations. This institutional review board-exempt retrospective cohort study included 134 patients who underwent single-phase abdominal CT before and after implementation of weight-based IV contrast injector software. Patient weight, height, body mass index, and body surface area were determined. Two radiologists qualitatively assessed examinations (4 indicating markedly superior to -4 indicating markedly inferior), and Hounsfield unit measurements were performed. Enhancement (estimated mean, -0.05; 95% confidence interval [CI], -0.19 to 0.09; P = 0.46) and lesion depiction (estimated mean, -0.01; 95% CI, -0.10 to 0.07; P = 0.79) scores did not differ between CT examinations using weight-based IV contrast versus fixed IV contrast dosing when a minimum of 38.5 g of iodine was used. However, the scores using weight-based IV contrast dosing were lower when the injector software calculated and delivered less than 38.5 g of iodine (estimated mean, -0.81; 95% CI, -1.06 to -0.56; P < 0.0001). There were no significant differences in measured Hounsfield units between the CT examinations using weight-based IV contrast dosing versus fixed IV contrast dosing. Oncologic CT image quality was maintained or improved with weight-based IV contrast dosing using injector software when using a minimum amount of 38.5 g of iodine.


A multi-faceted strategy to reduce ventilation-associated mortality in brain-injured patients. The BI-VILI project: a nationwide quality improvement project.
We assessed outcomes in brain-injured patients after implementation of a multi-faceted approach to reduce respiratory complications in intensive care units. Prospective nationwide before-after trial. Consecutive adults with acute brain injury requiring mechanical ventilation for ≥24 h in 20 French intensive care units (ICUs) were included. The management of invasive ventilation in brain-injured patients admitted between 1 July 2013 and 31 October 2013 (4 months) was monitored and analysed. After the baseline period (1 November 2013-31 December 2013), ventilator settings and decision to extubate were selected as targets to hasten weaning from invasive ventilation. During the intervention period, low tidal volume (≤7 ml/kg), moderate positive end-expiratory pressure (PEEP, 6-8 cm H2O) and an early extubation protocol were recommended. The primary endpoint was the number of days free of invasive ventilation at day 90. Comparisons were performed between the two periods and between the compliant and non-compliant groups. A total of 744 patients from 20 ICUs were included (391 pre-intervention; 353 intervention). No difference in the number of invasive ventilation-free days at day 90 was observed between the two periods [71 (0-80) vs. 67 (0-80) days; P = 0.746]. Compliance with the complete set of recommendations increased from 8 (2%) to 52 (15%) patients after the intervention (P < 0.001). At day 90, the number of invasive ventilation-free days was higher in the 60 (8%) patients whose care complied with recommendations than in the 684 (92%) patients whose care deviated from recommendations [77 (66-82) and 71 (0-80) days, respectively; P = 0.03]. The mortality rate was 10% in the compliant group and 26% in the non-compliant group (P = 0.023). Both multivariate analysis [hazard ratio (HR) 1.78, 95% confidence interval (95% CI) 1.41-2.26; P < 0.001] and propensity score-adjusted analysis (HR 2.25, 95% CI 1.56-3.26, P < 0.001) revealed that compliance was an independent factor associated with the reduction in the duration of mechanical ventilation. Adherence to recommendations for low tidal volume, moderate PEEP and early extubation seemed to increase the number of ventilator-free days in brain-injured patients, but inconsistent adoption limited their impact. Trail registration number: NCT01885507.


A window of opportunity: Adverse childhood experiences and time alone with a provider in the United States.
To date, there is limited literature on the relationship between Adverse Childhood Experiences (ACEs) and the quality of health care provider encounters. This is key, as people with a history of ACEs have a greater burden of illness. This study uses data from the 2020-2021 National Survey of Children's Health to examine relationships between ACEs and (1) spending less than ten minutes with a health care provider, and (2) spending time alone with a health care provider. In general, our results suggested most ACEs were associated with higher odds of a provider spending <10 min with a child during their last preventative care visit, while ACEs were inconsistently related to spending time alone with a provider. Each additional ACE was found to be associated with higher odds of both outcomes. This work emphasizes the importance of ACEs screening in a health care setting and may set the groundwork for future research investigating mechanisms within these associations. Given the established link between health care quality and patient-provider trust, and health outcomes, intervention work is needed to develop healthcare practices that may encourage the length and quality of health care provider visits.


How do the macrocyclic lactones kill filarial nematode larvae?
The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms. Recent evidence has shed new light on the likely functions of the ML target, glutamate-gated chloride channels, in filarial nematodes and supports the hypothesis that the rapid clearance of microfilariae that follows treatment involves the host immune system.


2-Amino-anilinium 4-methyl-benzene-sulfonate.
In the extended structure of the title mol-ecular salt, C6H9N2 +·C7H7O3S-, the cations and anions are linked by N-H⋯O hydrogen bonds to generate [010] chains.


Complement-mediated solubilization of rat IgA immune precipitates.
The complement-mediated solubilization (CMS) of immunoprecipitates (IP) consisting of DNP-rat serum albumin (RSA) and rat monoclonal anti-DNP antibodies of the IgA [both polymeric (p-) and monomeric (m-)] or IgG2b (sub)class was studied. In contrast to IgG2b IP, solubilization of IgA IP was only observed in an autologous system, with rat serum as the source of complement. IP prepared using m-IgA were solubilized faster than those prepared using p-IgA. Analysis of both affinity and avidity of the antibodies, indicated that this difference may be due to the lower avidity of the m-IgA antibodies as compared to p-IgA. Analysis of the solubilized IP revealed deposition of C3 and C4 on IgG2b, and only C3 on IgA IP. These results point toward a role of the alternative pathway in the solubilization of IgA IP. Size analysis of the solubilized IgA IP employing sucrose density gradient ultracentrifugation, indicated that these were heterogeneous, with a size generally larger than 19 S.


A 25-bp ancient spliceosomal intron in the TvRab1a gene of Trichomonas vaginalis.
Spliceosomal introns play a key role in eukaryotic genome evolution and protein diversity. A large Rab GTPase family has been identified in a unicellular eukaryote Trichomonas vaginalis. However, the characteristics of introns in Rab genes of T. vaginalis have not been investigated previously. In this study, we identified a 25-bp spliceosomal intron in the T. vaginalis Rab1a (TvRab1a) gene, the smallest intron in T. vaginalis to be characterized to date. This intron contains a canonical splice site at both 5' (GT) and 3' (AG) ends, and a putative branch-point sequence (TCTAAC) that matches the Trichomonad consensus sequence of ACTAAC except for the first nucleotide. The position and phase of the TvRab1a intron are evolutionarily conserved in Rab1 homologous genes across at least five eukaryotic supergroups, including Opisthokonta, Amoebozoa, Excavata, Chromalveolata, and Plantae. These results strongly suggest that the TvRab1a intron is likely to be an ancient spliceosomal intron, and it can therefore be used as a phylogenetic marker to evaluate particular eukaryotic groupings. Identification and characterization of the TvRabla intron may provide an insight into the evolution of the large Rab repertoire in T. vaginalis.


The relationship between prostaglandins and virus replication: endogenous prostaglandin synthesis during infection and the effect of exogenous PGA on virus production in different cell lines and in persistently infected cells.
African Green Monkey Kidney cells were shown to normally synthesize immunoreactive PGE1. Infection of these cells with Sendai virus did not alter rates of PGE1 synthesis, while it stimulated interferon production. PGAs, that we have previously shown to be potent inhibitors of Sendai virus replication in this system, at the same dose (4 micrograms/ml), also strongly inhibited the replication of this virus in HEp-2 cells and in VERO cells, a monkey kidney cell line that does not produce interferon. PGA1 was found to be effective in several cell and virus models, suggesting a broad spectrum of antiviral actions. Finally, we confirmed the observation that PGA1-treatment prevents the establishment of a "carrier state" by Sendai virus, and PGA1-cured cells did not show any sign of persistent infection for periods as long as 110 days after Sendai infection. Attempts to cure already established persistently infected cells were only partially successful.


A complex tissue-specific interplay between the Arabidopsis transcription factors AtMYB68, AtHB23, and AtPHL1 modulates primary and lateral root development and adaptation to salinity.
Adaptation to different soil conditions is a well-regulated process vital for plant life. AtHB23 is a homeodomain-leucine zipper I transcription factor (TF) that was previously revealed as crucial for plant survival under salinity conditions. We wondered whether this TF has partners to perform this essential function. Therefore, TF cDNA library screening, yeast two-hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation assays were complemented with expression analyses and phenotypic characterization of silenced, mutant, overexpression, and crossed plants in normal and salinity conditions. We revealed that AtHB23, AtPHL1, and AtMYB68 interact with each other, modulating root development and the salinity response. The encoding genes are coexpressed in specific root tissues and at specific developmental stages. In normal conditions, amiR68 silenced plants have fewer initiated roots, the opposite phenotype to that shown by amiR23 plants. AtMYB68 and AtPHL1 play opposite roles in lateral root elongation. Under salinity conditions, AtHB23 plays a crucial positive role in cooperating with AtMYB68, whereas AtPHL1 acts oppositely by obstructing the function of the former, impacting the plant's survival ability. Such interplay supports the complex interaction between these TF in primary and lateral roots. The root adaptation capability is associated with the amyloplast state. We identified new molecular players that through a complex relationship determine Arabidopsis root architecture and survival in salinity conditions.


Identification and characterization of novel multiple bacteriocins produced by Lactobacillus sakei D98.
To characterize novel multiple bacteriocins produced by Lactobacillus sakei D98. Lactobacillus sakei D98 isolated from Shubo (rice malt) produced at least three bacteriocins. Using three purification steps, three novel antimicrobial peptides termed sakacin D98a, sakacin D98b and sakacin D98c were purified from the culture supernatant. Amino acid and DNA sequencing analysis revealed that the sakacins D98a, D98b and D98c are novel class IIa-like or class IId bacteriocins. In particular, sakacin D98b has a variant pediocin-box sequence, YANGVXC (with Ala instead of Gly), and a different location for the disulfide bridge (Cys(11) and Cys(18)) from that found in other class IIa bacteriocins. Three novel bacteriocins were identified from Lactobacillus sakei D98. Their antimicrobial spectra and intensities indicate that these sakacins would have different modes of action. In addition, sakacin D98b showed low inhibitory activity against Listeria, probably due to the differences in amino acids and position of the disulfide bridge compared with the other class IIa bacteriocins. Sakacins D98a and D98c are novel bacteriocins belonging to class IId bacteriocins. On the other hand, sakacin D98b, a class IIa-like bacteriocin, has a unique internal structure and activity spectrum.


Two new compounds from Cynanchum amplexicaule.
A new phenolic glycoside, sinapic acid 4-O-beta-d-(6'-sinapoyl)glucopyranoside (1) and a new sucrose ester, 6,6'-di-O-sinapoylsurcose (3), were isolated from the roots of Cynanchum amplexicaule (Sieb. et Zucc.), along with two known compounds, 6-O-[E]-sinapoyl-d-glucopyranoside (2) and sibricose A1 (4). Their structures were elucidated on the basis of both chemical and spectroscopic methods.


Characterising the individual performance responses to mild illness in international swimmers.
To determine individual differences in the impact of illness on the change in performance of swimmers in international competitions. Subjects were members of the Australian swimming team (33 male and 39 female, aged 15-27 years). Swimmers provided a weekly seven day recall of symptoms of illness during final six weeks of preparations for international competition over a three year period. Swimmers were categorised as either ill (one or more episodes of illness) or healthy. The measure of performances was the international point score. Mean changes in points score were calculated for healthy and ill swimmers between a national championship and an international competition ( approximately 16 weeks later). Likelihoods of substantial effects of illness on an individual's true change in performance (beneficial/trivial/harmful) were estimated from means and standard deviations, assuming a smallest substantial change of 6 points. Illness was reported before international performances by 38% of female and 35% of male swimmers. For female swimmers the change in performance was -3.7 (21.5) points (mean (SD)) with illness and -2.6 (19.0) points when healthy; for male swimmers the changes were -1.4 (17.5) points with illness and 5.6 (13.2) points when healthy. The likelihoods that illness had a substantial beneficial/trivial/harmful effect on performance of an individual swimmer were 32%/31%/37% for female and 17%/31%/52% for male participants (90% confidence limits approximately +/-10% to 20%). Although mild illness had only a trivial mean effect on female swimmers and a small harmful mean effect on male swimmers, there were substantial chances of benefit and harm for individuals.


Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study.
Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma. We used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000-31 December 2016) retrospective cohort of reproductive-age (16-45 years, n=83 084) women with asthma. Using Read codes, we defined use, subtypes and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendations of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition. The 17-year follow-up resulted in 456 803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen) and 9% progestogen-only contraceptives. Previous (incidence rate ratio (IRR) 0.94, 95% CI 0.92 to 0.97) and current (IRR 0.96, 95% CI 0.94 to 0.98) use of any, previous (IRR 0.92, 95% CI 0.87 to 0.97) and current use of combined (IRR 0.93, 95% CI 0.91 to 0.96) and longer duration of use (3-4 years: IRR 0.94, 95% CI 0.92 to 0.97; 5+ years: IRR 0.91, 95% CI 0.89 to 0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared with non-use. Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for the influence of hormonal contraceptives on clinical outcomes of asthma in women are required. European Union electronic Register of Post-Authorisation Studies (EUPAS22967).


Growing up with cerebral palsy: contemporary challenges of healthcare transition.
Cerebral palsy is traditionally known as a major cause of chronic disability in childhood. With advances in neonatal care and improved survival, the majority of adolescents with cerebral palsy require ongoing services into adulthood. This paper highlights some of the challenges in their transition from pediatric to adult healthcare and proposes key elements to ensure a smooth transition process.


The role of IL-6, IL-10, TNF-α and PD-1 expression on CD4 T cells in atrial fibrillation.
While not completely understood, the electrical, structural, and communication pathways that play a role in the onset and progression of atrial fibrillation (AF) seem to be connected to the intricate interplay between neurohormones and cellular mediators. Our study's objective was to examine how the expression profiles of the inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF), and programmed death 1 (PD-1) changed in Cluster of Differentiation 4 (CD4) T cells depending on whether atrial fibrillation was paroxysmal or permanent. This analysis would provide new diagnostic markers for the detection and management of atrial fibrillation. In a cross-sectional study, 60 healthy controls, 49 patients with persistent atrial fibrillation, and 50 patients with paroxysmal atrial fibrillation were compared. Serum biomarker levels are found using the ELISA method, which uses enzyme-linked immunosorbent assay. Echocardiography was used to assess heart function. Patients with atrial fibrillation had serum concentrations of IL-6, TNF-a, and IL-10 that were considerably higher than but PD-1 was lower those in the non-AF control group and those in patients with persistent atrial fibrillation. According to the diameter of LA and the serum level of NT-proB-type natriuretic peptide (NT-proBNP) is greater than that of patients with paroxysmal atrial fibrillation than control group. Patients with persistent atrial fibrillation had increased serum levels of low-density lipoprotein cholesterol (LDL-C) compared with those without atrial fibrillation. While PD-1 in patients with paroxysmal atrial fibrillation is closely related to C-reactive protein (CRP), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and very low density lipoprotein cholesterol. In addition, PD-1 in patients with persistent atrial fibrillation is closely related to IL-6, TNF-a, and IL-10. Higher blood concentrations of NT-proBNP, IL-6, IL-10, TNF-, and LDL-C but low level of PD-1 are associated with progression from paroxysmal or chronic AF.


Effect of ginseng total saponin on bovine adrenal tyrosine hydroxylase.
Ginseng total saponin (GTS) can modulate dopaminergic activity at both presynaptic and postsynaptic dopamine receptors (Kim et al., 1998). The present study investigated the effect of GTS on the bovine adrenal tyrosine hydroxylase (TH), which catalyze L/tyrosine to DOP. GTS inhibited the bovine adrenal TH by 42.4, 51.5 and 55.3% at concentrations of 40, 80 and 100 micrograms/ml, respectively. The IC50 value of GTS was 77.5 micrograms/ml. GTS exhibited noncompetitive inhibition with a substrate L-tyrosine. The Ki value was 155 micrograms/ml.


PTEN induces G1 cell cycle arrest and inhibits MMP-9 expression via the regulation of NF-kappaB and AP-1 in vascular smooth muscle cells.
The tumor suppressor PTEN is one of the most commonly inactivated genes in human cancer. PTEN, an inositol phosphatase specific for the products of PI 3-kinase, is known to inhibit PDGF-mediated vascular smooth muscle cell (VSMC) proliferation and migration. However, little is known about the molecular mechanisms by which this tumor suppressor regulates cell growth and migration in VSMC. Here, we show that PTEN expression has the potent inhibitory effect on DNA synthesis of cultured VSMC in the presence of PDGF. The growth suppression of PTEN was mediated by its ability to block cell cycle progression in the G1 phase. Such an arrest correlated with down-regulation of cyclins and CDKs and up-regulation of the CDK inhibitor p21 and p27 expression, whereas up-regulation of p53 by PTEN expression was not observed. Expression of PTEN also led to the inhibition of TNF-alpha-induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, PTEN expression strongly decreased MMP-9 promoter activity in response to TNF-alpha. This inhibition was characterized by down-regulation of MMP-9, which was transcriptionally regulated at NF-kappaB and activation protein-1 (AP-1) sites in the MMP-9 promoter. These findings indicate the efficacy of PTEN in inhibiting cell proliferation, G1-S phase cell cycle progress, and MMP-9 expression through the transcription factors NF-kappaB and AP-1 in VSMC.


Incidence, mechanisms, treatment, and outcomes of donor vessel injury during percutaneous coronary interventions for chronic total occlusion.
Donor vessel injury is a potentially life-threatening complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Our goal was to examine the incidence, mechanisms, treatment, and outcomes of patients with donor vessel injury in a large multicenter CTO PCI registry. We analyzed the baseline clinical and angiographic characteristics, and procedural outcomes of 12,349 CTO PCIs performed between 2012 and 2022 at 44 centers. The incidence of donor vessel injury was 0.35% (n = 43). The baseline clinical characteristics of patients with and without donor vessel injury were similar. Cases complicated by donor vessel injury were more complex with higher Japanese CTO score (2.9 ± 1.1 vs. 2.4 ± 1.3; p = 0.004) and lower procedural success rate (69.8% vs. 85.2%; p = 0.004). The retrograde approach was used more commonly in donor vessel injury cases (68.9% vs. 30.9%; p < 0.001). Most (53.5%) donor vessel injuries were guide catheter-induced, whereas 20.9% were due to donor vessel thrombosis. Of the 43 patients with donor vessel injury, 36 (83.7%) were treated with stenting and seven (16.3%) received a left ventricular assist device. The incidence of major adverse cardiovascular events (MACEs) was significantly higher in cases with donor vessel injury (23.3% vs. 2.0%; p < 0.001). Of the 43 patients with donor vessel injury, five patients (11.6%) experienced acute myocardial infarction and four patients (9.3%) died. Donor vessel injury, occurred in 0.35% of CTO PCIs performed by experienced operators, was mainly due to guide catheter-induced dissection or thrombosis and was associated with lower procedural success and higher MACE.


Domain atrophy creates rare cases of functional partial protein domains.
Protein domains display a range of structural diversity, with numerous additions and deletions of secondary structural elements between related domains. We have observed a small number of cases of surprising large-scale deletions of core elements of structural domains. We propose a new concept called domain atrophy, where protein domains lose a significant number of core structural elements. Here, we implement a new pipeline to systematically identify new cases of domain atrophy across all known protein sequences. The output of this pipeline was carefully checked by hand, which filtered out partial domain instances that were unlikely to represent true domain atrophy due to misannotations or un-annotated sequence fragments. We identify 75 cases of domain atrophy, of which eight cases are found in a three-dimensional protein structure and 67 cases have been inferred based on mapping to a known homologous structure. Domains with structural variations include ancient folds such as the TIM-barrel and Rossmann folds. Most of these domains are observed to show structural loss that does not affect their functional sites. Our analysis has significantly increased the known cases of domain atrophy. We discuss specific instances of domain atrophy and see that there has often been a compensatory mechanism that helps to maintain the stability of the partial domain. Our study indicates that although domain atrophy is an extremely rare phenomenon, protein domains under certain circumstances can tolerate extreme mutations giving rise to partial, but functional, domains.


Scapula fractures.
Scapula fractures are relatively rare fractures which are typically a result of high energy trauma. Associated multisystemic injuries, therefore, occur with a high frequency. The management of scapula fractures has historically been nonoperative, perhaps in part due to the paucity of information regarding outcomes, combined with a relative unfamiliarity with treating these injuries. It is likely, however, that intraarticular fractures, and certain other highly displaced variants, have a better outcome when treated operatively. A well-conceived diagnostic work-up and a properly executed plan of rehabilitation are requisite.


Impact of Use of Smaller Volume, Smaller Vacuum Blood Collection Tubes on Hemolysis in Emergency Department Blood Samples.
Hemolyzed blood samples commonly occur in hospital emergency departments (EDs). Our objective was to determine whether replacing standard large-volume/high-vacuum sample tubes with low-volume/low-vacuum tubes would significantly affect ED hemolysis. This was a prospective intervention of the use of small-volume/vacuum collection tubes. We evaluated all potassium samples in ED patients and associated hemolysis. We used χ2 tests to compare hemolysis incidence prior to and following utilization of small tubes for chemistry collection. There were 35,481 blood samples collected during the study period. Following implementation of small-volume tubes, overall hemolysis decreased from a baseline of 11.8% to 2.9% (P < .001) with corresponding reductions in hemolysis with comment (8.95% vs 1.99%; P < .001) gross hemolysis (2.84% vs 0.90%; P < .007). This work demonstrates that significant improvements in ED hemolysis can be achieved by utilization of small-volume/vacuum sample collection tubes.


The effect of oral zinc loading on the absorption of 65zinc in the rat.
Seven groups of 8 rats each were orally loaded with zinc, the daily dose varying from 1.8 to 58 mg, corresponding to about 3 to 100 times of their estimated daily intake of zinc. To record the absorption of zinc, the rats were given a single dose of 65Zn. The retention of the isotope was measured in a whole animal counter at regular intervals. The dose of 58 mg was obviously toxic, since half of the animals died within 5 days. The net absorption of zinc in the remaining experimental groups was found to vary from about 7% in the group receiving the smallest loading dose to 1.8% in the group receiving the highest dose. From the absorption values, as determined by extrapolation of semilog retention curves, the total amount of absorbed zinc was estimated. It was found to differ from about 170 micrograms to about 530 micrograms zinc daily, increasing three times as the loading dose was increased 16 times. This discrepancy suggests the existence of regulatory mechanisms of the absorption of zinc from the intestine.


Prevention of lung injury during open heart operations for congenital heart defects.
To elucidate free radical-induced lung injury associated with open heart operations for congenital heart defects, we studied 23 such patients. Maximum plasma chemiluminescence level (a marker of peroxylipids) in patients with pulmonary hypertension (n = 8) was higher than in patients with cyanotic disease (n = 8) (1,115.4 +/- 189.9 versus 728.8 +/- 48.3 counts; p < 0.05). There was a significant correlation between the maximum chemiluminescence level and preoperative pulmonary to systemic arterial pressure ratio (r = 0.929; p < 0.05). To investigate the effect of allogeneic leukocytes, we compared pulmonary hypertensive patients without allogeneic leukocyte transfusion during operation (n = 7) with the group with pulmonary hypertension. Both maximum chemiluminescence level during bypass (712.4 +/- 24.9 versus 1,115.4 +/- 189.9 counts; p < 0.05) and percent decrease in pulmonary arterial pressure after bypass (44.7% +/- 6.2% versus 28.2% +/- 4.5%; p < 0.05) were significantly improved, suggesting that depletion of leukocytes decreased the lung injury induced by free radical reaction.


Kinetic study of a complex triangular reaction system in alkaline aqueous-ethanol medium using on-line transmission FTIR spectroscopy and BTEM analysis.
The kinetics of the base-catalyzed reaction of methyl 4-hydroxybenzoate in aqueous-ethanol solvent medium was studied and analyzed via combined on-line transmission FTIR spectroscopy and Band-Target Entropy Minimization (BTEM) technique. This reaction is considered complex since it involves simultaneous hydrolysis and ethanolysis reactions of methyl 4-hydrozybenzoate (MP) to form ethyl 4-hydroxybenzoate (EP) as an intermediate and sodium 4-hydroxybenzoate as a final product. The pure component spectra of the reactive species involved in the reaction were reconstructed using BTEM technique. Their corresponding real concentrations were calculated and subsequently used for analyzing the kinetics of this triangular reaction system. The effects of temperature and solvent mixture compositions were studied. In general, the results show that the rates of both hydrolysis and ethanolysis reactions increase with temperature. Addition of ethanol to the solvent mixture also reduces the rates of the hydrolysis reactions. The effect of solvent mixture on the rate of ethanolysis reaction is more complex and influenced by at least two competing factors, namely the concentration of ethoxide ion in the solution and the stabilization effect on the reactant. The enthalpy and entropy activation parameters, ΔH(‡) and ΔS(‡), of both the hydrolysis and ethanolysis reactions were determined using the Eyring equation and the activation parameters confirm the associative nature in the elementary steps in these reactions. Finally, it is shown that the dominant synthetic pathway in this triangular system changes from direct hydrolysis of methyl 4-hydrozybenzoate to the indirect pathway via ethanolysis and then hydrolysis depending on the solvent mixture composition.


Monolayers of novel Gemini amphiphiles with phthalimide headgroups at the air/water interface: pH and alkyl chain length effects.
A series of novel pH sensitive Gemini amphiphiles of N,N'-dialkyl-N,N'-di(ethyl-phthalimide) ethylenediamines (Di-CnPh, n=6, 8, 10, 12) was synthesized and characterized. It was found that relatively stable spread monolayers of Di-CnPh can be formed at the air/water interface once n≥6, and their stability was improved by increasing the hydrophobic chain length or adding electrolyte. The surface pressure-area (π-A) isotherms of Di-CnPh have been studied in detail by employing the axisymmetric drop shape analysis as penetration Langmuir balance. Furthermore, Brewster angle microscopy (BAM) was employed to confirm the monolayer phase transition from gaseous phase to liquid condensed phase via a liquid expanded phase. Moreover, dilatational rheological measurements of spread Di-CnPh monolayers at the air/water interface were performed, and the influence of the hydrophobic chain length and pH on the dilatational elasticity (ε) and viscosity (η) was also investigated. The results have suggested that the spread Di-CnPh monolayers are spontaneously elastic.


Lymphatic flow in humans as indicated by the clearance of 125I-labeled albumin from the subcutaneous tissue of the leg.
Since the removal of albumin from the extracellular space and its return to the vascular compartment is the essential function of the lymphatic system, the rate at which it is removed from the interstitial tissue may be regarded as a means of estimating lymphatic efficiency. An objective measure of lymphatic function can be obtained by monitoring the rate of clearance following injection of 125I-labeled albumin (RIHSA) from the subcutaneous tissue of a limb. The clearance of 125I-RIHSA from lower limb was monitored in a group of patients with normal limbs, patients with unilateral edema due to deep vein thrombosis, and patients with bilateral edema due to hypoproteinemia. The mean T1/2 in normal legs was 32.7 hr, compared to 23.7 hr in edematous limbs due to deep vein thrombosis and 19.4 in edematous limbs due to hypoproteinemia. There is a clear-cut difference in clearance rate between edematous and nonedematous limbs. This suggests that lymphatic flow is increased in edema due to venous obstruction and hypoproteinemia.


The presentation of depression symptoms in attention-deficit/hyperactivity disorder: comparing child and parent reports.
Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with depression, and outcomes are poor when both are present. Little is known about whether depression symptoms present differently in ADHD compared to the general population, or how reliable young people with ADHD are at reporting these symptoms. This study aimed to describe depression symptoms in a clinical ADHD sample compared to a population sample, and compare self-reports of depression symptoms with parent-reports. Two hundred and forty-nine children with ADHD and their parents completed follow-up questionnaires around 5 years after taking part in a Cardiff University ADHD study. Child depression symptoms were measured using parent- and child-reported Mood and Feelings Questionnaires (MFQ) and compared to a population sample with MFQ data (n = 1460). Within both samples, child- and parent-reported depression symptoms were compared. Although the profile of depression symptoms was similar between young people with ADHD and those in the general population, depression symptoms were much more common in the ADHD sample (parent-rated MFQ score = 24.52 vs. 9.39; child-rated = 21.02 vs. 11.86). The most common symptoms in both samples included irritability, restlessness and concentration difficulties, with core depression symptoms such as feeling miserable/unhappy also prominent. Within the ADHD sample, but not the population sample, children reported depression symptoms less frequently than their parents. Young people with ADHD are at high risk of experiencing symptoms of depression but may under-report the severity of their symptoms. Obtaining parent reports of depression symptoms in this group may be important to avoid missing key indicators of risk.


Reduced self-referential neural response during intergroup competition predicts competitor harm.
Why do interactions become more hostile when social relations shift from "me versus you" to "us versus them"? One possibility is that acting with a group can reduce spontaneous self-referential processing in the moral domain and, in turn, facilitate competitor harm. We tested this hypothesis in an fMRI experiment in which (i) participants performed a competitive task once alone and once with a group; (ii) spontaneous self-referential processing during competition was indexed unobtrusively by activation in an independently localized region of the medial prefrontal cortex (mPFC) associated with self-reference; and (iii) we assessed participants' willingness to harm competitors versus teammates. As predicted, participants who showed reduced mPFC activation in response to descriptions of their own moral behaviors while competing in a group were more willing to harm competitors. These results suggest that intergroup competition (above and beyond inter-personal competition) can reduce self-referential processing of moral information, enabling harmful behaviors towards members of a competitive group.


Interaction of tubulin with phospholipid vesicles. II. Physical changes of the protein.
We have shown that soluble tubulin will bind to small unilamellar vesicles of dipalmitoyl phosphatidylcholine (Klausner, R. D., Kumar, N., Weinstein, J. N., Blumenthal, R., and Flavin, M. (1981) J. Biol. Chem. 256, 5879-5885). This association uniquely occurs at the lipid phase transition. The tubulin, when bound to the vesicles, displays an altered tryptophan fluorescence characterized by a 5-nm blue shift in the emission maximum and a 22% decrease in fluorescence intensity, when compared to soluble tubulin. Tryptophans in vesicle-bound tubulin are less accessible to the aqueous collisional quenchers, acrylamide and iodide, than in soluble tubulin. Circular dichroism studies reveal an increase in alpha-helical content of tubulin as a result of vesicle interaction. Proteolytic digestion by trypsin of vesicle bound tubulin is slower than of soluble tubulin. The beta subunit of tubulin is preferentially protected from trypsin by vesicle interaction. Furthermore, the pattern of tryptic cleavage products is altered by this interaction.


[The spinal periosteal layer and the fibrous sheath of the cervical spinal canal].
At the cervical level, in the foramen, the rachidian nerve is surrounded by two mantles: a dural one and a fibrous one continuing the epidural periosteal sheet of which it is a thickening. We can wonder whether this fibrous sheath is at the origin of some cervical radiculalgias in which one cannot detect any radiological lesion of the skeleton or disk.


Mathematical model of a gene regulatory network reconciles effects of genetic perturbations on hematopoietic stem cell emergence.
Interlinked gene regulatory networks (GRNs) are vital for the spatial and temporal control of gene expression during development. The hematopoietic transcription factors (TFs) Scl, Gata2 and Fli1 form one such densely connected GRN which acts as a master regulator of embryonic hematopoiesis. This triad has been shown to direct the specification of the hemogenic endothelium and emergence of hematopoietic stem cells (HSCs) in response to Notch1 and Bmp4-Smad signaling. Here we employ previously published data to construct a mathematical model of this GRN network and use this model to systematically investigate the network dynamical properties. Our model uses a statistical-thermodynamic framework to describe the combinatorial regulation of gene expression and reconciles, mechanistically, several previously published but unexplained results from different genetic perturbation experiments. In particular, our results demonstrate how the interactions of Runx1, an essential hematopoietic TF, with components of the Bmp4 signaling pathway allow it to affect triad activation and acts as a key regulator of HSC emergence. We also explain why heterozygous deletion of this essential TF, Runx1, speeds up the network dynamics leading to accelerated HSC emergence. Taken together our results demonstrate that the triad, a master-level controller of definitive hematopoiesis, is an irreversible bistable switch whose dynamical properties are modulated by Runx1 and components of the Bmp4 signaling pathway.


The question of canine originsOur Oldest Companions: The Story of the First Dogs Pat Shipman Harvard University Press, 2021. 272 pp.
With few solid leads, a paleoanthropologist explores the emergence of the first dogs.


Intermittent hemodiafiltration as a down-step transition therapy in patients with acute kidney injury admitted to intensive care unit who initially underwent continuous venovenous hemodiafiltration.
Continuous renal replacement therapies (CRRT) are initially employed in patients with acute kidney injury (AKI) in ICU setting. After the period of serious illness, hemodialysis is usually used as a mode of transition from CRRT. Intermittent hemodiafiltration (HDF) is not commonly applied in this scenario. To evaluate the feasibility of using HDF as transition therapy after CVVHDF in critically patients with AKI. An observational and prospective pilot study was conducted in ICU patients with dialysis-requiring AKI. Patients were initially treated with CVVHDF and, after medical improvement, those who still needed renal replacement therapy were switched to HDF treatment. Ten Patients underwent 53 HDF sessions (mean of 5.3 sessions/patient). The main cause of renal dysfunction was sepsis (N = 7; 70%). The APACHE II mean score was 27.6 ± 6.9. During HDF treatment, the urea reduction ratio was 64.5 ± 7.5%, for β-2 microglobulin serum levels the percentage of decrease was 42.0 ± 7.8%, and for Cystatin C was 36.2 ± 6.9%. Five episodes of arterial hypotension occurred (9.4% of sessions). There were 20 episodes of electrolytic disturbance (37.7% of sessions), mainly hypophosphatemia. No pyrogenic or suggestive episode of bacteremia was observed. Hemodiafiltration was safe and efficient to treat critically ill patients with acute kidney injury during the transition phase from continuous to intermittent dialysis modality. Special attention should be paid regarding the occurrence of electrolytic disturbance, mainly hypophosphatemia.


Antibiotics in surgery. An overview.
Antibiotic utilization in the surgical patient has the two unique features of preventive use in high-risk procedures and frequent use in suspected or documented polymicrobial infection. These two features have resulted in the search for agents with broader spectrums. Although numerous antibiotics or combinations of antibiotics can be shown to provide comparable results for both preventive and therapeutic indications, no superior choice has been identified in either area. Indeed, the search for broader spectrums of antibiotics may not further improve the identified results. If this is so, newer areas of exploration in antibiotic therapy in the surgical patient will need to focus on optimizing pharmacologic, toxic, and economic features while preserving comparability in clinical outcome.


BWH emergency radiology--surgical correlation: traumatic spigelian hernia with right colonic injury.
We present a case of a young man who fell off his motorbike 2 days before presentation to the hospital with a complaint of gastrointestinal upset and abdominal pain. Contrast-enhanced CT of the abdomen and pelvis demonstrated a right-sided traumatic spigelian hernia and an ascending colon injury necessitating operative repair of both.


Capillary gas chromatographic-mass spectrometric determination of acid herbicides in soils and sediments.
A capillary gas chromatographic method with selected-ion monitoring (GC-SIM) was applied to eight common herbicides: 2-(4-chloro-o-tolyl-oxy)propionic acid, 3,6-dichloro-2-methoxybenzoic acid, 2-methyl-4-chlorophenoxyacetic acid, 2,3,6-trichlorobenzoic acid, 2,4-dichlorophenoxyacetic acid, 3,5,6-trichloro-2-pyridyloxy-acetic acid, 2,4,5-trichlorophenoxyacetic acid and alpha-(2-methyl-4-chlorophenoxy) butyric acid. The method involves extraction with saturated calcium hydroxide solution, esterification with pentafluorobenzyl bromide, clean-up with a silica gel column and determination by capillary GC-SIM. Recoveries from soil and sediment are over 89% (with the exception of 77% for TBA) with coefficients of variation below 5% (n = 7). The method is suitable for the simultaneous determination of the eight herbicides in environmental samples with high sensitivity and accuracy.


Interactive effects of temperature and copper on photosystem II photochemistry in Chlorella vulgaris.
In natural aquatic ecosystems, temperature conditions may undergo changes depending on the depth of the water column or micro-environmental conditions. In this study, copper effect on the photosynthetic performance of Chlorella vulgaris was investigated at different temperatures by using chlorophyll a fluorescence transients and fluorescence imaging parameters. Copper as a pollutant is known to be an inhibitor of photosystem II (PSII) photochemistry; therefore it was important to know how the change of temperature may alter this effect. PSII photochemistry was investigated when C. vulgaris, affected by different copper concentrations, was exposed to 24, 28 and 31 °C. Increase of temperature induced higher alterating effects to PSII quantum yield, primary photosynthetic electron transport from water splitting system and consequently higher decrease of total photosynthetic performance if compared to copper effect alone. Additional temperature effect to copper inhibition increased energy dissipation via non-photochemical pathway. In this study we indicated that, when C. vulgaris changes temperature conditions, inhibitory effect of copper also undergoes changes. For natural aquatic system we may suppose, when algae are distributed at different depths of water column, that toxicity effect will be dependent to the temperature conditions of the site.


Quantifying human post-mortem movement resultant from decomposition processes.
Post-mortem movement is highly significant in unexplained death investigations, as body position or the position of remains helps to determine cause and manner of death, as well as potentially the circumstances surrounding death. Therefore, understanding post-mortem movement is of forensic relevance in death scene assessments. The aim of this study was to quantify post-mortem movement in anatomical structures of a human donor during decomposition in an Australian environment, an evaluation that has not previously been undertaken. The aim was achieved using time-lapse images of a human donor decomposing in order to capture the post-mortem movement over a 16-month period. Megyesi et al.'s [1] total body score system was used to quantify the decomposition of the donor in each image to determine the decomposition stage. ImageJ software was used to determine the distance from static landmarks to anatomical structures of interest in each image to allow for quantification. Early decomposition progressed rapidly, and advanced decomposition plateaued at 41 post-mortem interval days with a total body score of 24. The results support the conclusion that post-mortem movement does occur in all limbs of the donor. The anatomical structure that produced the most movement was the right styloid process of the radius, moving a total distance of 51.65 cm. A surprising finding of the study was that most post-mortem movement occurs in the advanced decomposition stage, with the lower limbs being the most active. This study supports that post-mortem movement can be quantified using time-lapse imagery, with results supporting movement in all limbs, a process that was active for the entire study period. An interesting finding was that the decomposition plateaued in the advanced stage with the donor remaining in mummification, and not reaching skeletonization after 16 months in situ. These findings are of significant importance to police in death scene assessments and forensic investigations.


Breath hydrogen test after a bean meal demonstrates delayed oro-cecal transit time in children with chronic constipation.
To evaluate oro-cecal transit time in children with chronic constipation. 34 patients with chronic functional constipation age 3 to 13 years and 15 controls without constipation. Oro-cecal transit time was evaluated using the hydrogen breath test after ingestion of lactulose and after a standard meal of cooked beans. Total and segmental colonic transit times were measured with radiopaque markers. Of 34 patients with chronic constipation 61.8% had increased total colonic transit time (>62 hours). Oro-cecal transit time measured with lactulose as substrate was similar (p=0.727) in constipated patients with increased colonic transit time (63.8+/-16.3 minutes), in constipated patients with normal colonic transit time (66.9+/-22.9 minutes), and in controls (65.3+/-15.5 minutes). Using a test meal of beans, the hydrogen breath test showed that oro-cecal transit time of constipated patients with increased total colon transit time was higher (252.4+/-23.2 minutes) than oro-cecal transit time of constipated patients with normal colonic transit time (227.7+/-39.6 minutes) or controls (205.3+/-23.3 minutes) (p<.05). Hydrogen excretion in breath after a bean test meal showed delayed oro-cecal transit time in children with chronic constipation with abnormal total colonic transit time.


Development of global monthly dataset of CMIP6 climate variables for estimating evapotranspiration.
Reliable projection of evapotranspiration (ET) is important for planning sustainable water management for the agriculture field in the context of climate change. A global dataset of monthly climate variables was generated to estimate potential ET (PET) using 14 General Circulation Models (GCMs) for four main shared socioeconomic pathways (SSPs). The generated dataset has a spatial resolution of 0.5° × 0.5° and a period ranging from 1950 to 2100 and can estimate historical and future PET using the Penman-Monteith method. Furthermore, this dataset can be applied to various PET estimation methods based on climate variables. This paper presents that the dataset generated to estimate future PET could reflect the greenhouse gas concentration level of the SSP scenarios in latitude bands. Therefore, this dataset can provide vital information for users to select appropriate GCMs for estimating reasonable PETs and help determine bias correction methods to reduce between observation and model based on the scale of climate variables in each GCM.


Sleep disorders in pregnancy.
Sleep disturbances are common in pregnancy and affect sleep quality. The maternal body is going through constant physical and physiological changes to adapt to the growing fetus. Sleep disorders may manifest at any point during pregnancy; some may result in adverse maternal or fetal outcomes. A strong clinical suspicion is crucial to identify sleep disorders in pregnancy and their management should be evaluated with a multidisciplinary team approach. In this review, we provide an overview of changes in sleep during pregnancy and summarise the key features of common sleep disorders in pregnancy, including practical tips on their management. To provide an overview of common sleep disorders in pregnancy and their management options.To highlight the impact of the physiological changes in pregnancy on sleep.To outline the type of sleep studies available to investigate sleep disorders in pregnancy.


[Developmental dysplasia of the hip in children with a psychomotor disorder. A risk factor for a poor outcome?].
Orthopaedic treatment of developmental dysplasia of the hip (DDH) has a high success rate in cases that are diagnosed early. However, the outcomes of these patients are not really known when they are subsequently diagnosed with some type of cerebral impairment. A retrospective observational study was conducted on cases of DDH with a poor outcome after orthopaedic treatment, being unknown if they had any type of psychomotor disorder. The patients were clinically and radiologically assessed, and afterwards received neurological valuation by the Child Neurology Unit. Of the 325 cases of DDH diagnosed in 293 patients, 10 patients (3%) with 16 hips with DDH were diagnosed of any cerebral impairment. All them were initially treated orthopedically. Clinical and radiologically evolution was succesful only in 4 cases (25%) being necessary any surgical procedure in the remaining 12 cases. After surgical treatment we got an improvement in the Acetabular Index (p=0.005) and Reimers Extrusion Index (p=0.042). Neck-shaft angle and Wiberg CE angle also improved but this difference was not statically significant. Cerebral impairment was diagnosed at 2,5 years of age and the begining of walking was delayed at 2.4 years of age. Cerebral impairment can lead to an unfavourable outcome in the treatment of DDH, with the relative risk of a poor outcome being 7.2 times higher in these patients. An unfavourable outcome with conventional treatment of DDH must make us suspect the presence of some type of neurological disorder, particularly if there is a delay in walking.


Serum carnitine levels in bone marrow transplant recipients.
This study investigated plasma carnitine levels in patients undergoing allogenic bone marrow transplantation. The patients received fat-based TPN (50% fat, 50% CHO; calorie: nitrogen ratio 125:1) for an average of 33 +/- 7.5 days. TPN was started before transplantation and stopped when patients were able to eat. Caloric needs were estimated using the Harris-Benedict equation; 150% of the estimated BEE was given for the first two weeks after transplantation. The amount of TPN was gradually decreased as patients resumed their oral intake. All patients had low-normal serum carnitine levels before transplantation. There was no significant change in total or free serum carnitine levels during the course of TPN. However, in patients who had symptoms of graft vs. host reaction (GVH), the highest carnitine values during GVH (total 72.3 +/- 6.5 and free 61.2 +/- 12.4 mumol/l) were significantly higher (p < 0.001) than the baseline values (total 27.1 +/- 9.3 and free 24.9 +/- 9.6 mumol/l) or the highest non GVH values after transplantation (total 32.0 +/- 10.7 and free 29.0 +/- 10.7 mumol/l, respectively). The serum triglyceride, total cholesterol, and HDL cholesterol remained within normal range. In conclusion, bone marrow transplant patients receiving fat-based TPN have normal circulating levels of carnitine. GVH reaction caused an increase in the carnitine levels, which was probably due to increased tissue catabolism.


Antipsychotic drugs modulate Arc expression in the rat brain.
We found that, in the striatum, acute injections of the first generation antipsychotic (FGA) haloperidol or the second generation antipsychotic (SGA) olanzapine enhanced Arc mRNA levels, however such induction persisted for at least 2 h in haloperidol-treated rats whereas it waned as early as 1 h after olanzapine injection. Conversely, repeated injections led to a persistent decrease of striatal Arc gene expression, regardless of the agent examined. In the frontal cortex, acute injection of both antipsychotics caused a reduction of Arc mRNA levels which persisted for at least 2 h. Following repeated treatment, olanzapine reduced Arc mRNA levels 2 h, but not 24 h, post-treatment whereas haloperidol was ineffective. Of note, the SGA quetiapine regulated the Arc gene expression similarly to olanzapine. Given the particular nature of Arc, our findings show its fine tuning following antipsychotic administration to be highly dependent on the length of the treatment and on the brain region investigated and suggest that antipsychotic drugs affect this marker of neuronal activity differently.