Persistence of pneumolysin in the cerebrospinal fluid of patients with pneumococcal meningitis is associated with mortality.
Poor prognosis in Pneumococcal meningitis may be associated with high pneumolysin levels in cerebrospinal fluid (CSF). In patient samples we showed that pneumolysin levels in CSF remained high after 48 hours in nonsurvivors of meningitis compared with survivors. Selective antipneumolysin treatment may present a novel therapeutic option.


Homicide among young Black men in Toronto: an unrecognized public health crisis?
This commentary addresses the high homicide rates among young Black men in Toronto, Ontario. It posits that homicide among this population is an unrecognized major public health crisis that should be a priority for the field. The author suggests that the dramatic rate of Black homicides in Toronto is a consequence of income inequality, poverty, poor quality of life, mental health risks, and sustained racism. The commentary calls upon public health scientists to prioritize research about violence and homicide among young Black men in Toronto. It suggests that current and future policy making would be better served by their enquiries into the nature and causes of the persisting dilemma.


Magnetism and opaque mineralogy of basalts from the Mid-Atlantic Ridge at 45 degrees N.
The volcanic layer may be only 200 m thick at 45 degrees N and oxidation of titanomagnetite may be responsible for the decrease in amplitude of the magnetic anomalies away from the ridge axis.


Potential impact of the 4CMenB vaccine on oropharyngeal carriage of Neisseria meningitidis.
The analysis of the potential impact of the meningococcal vaccines in asymptomatic carriers has become one of the key aspects in the evaluation of new vaccines and of their impact on disease control. An important step in this direction is provided by the analysis of the sequence variability and surface-exposure of the 4CMenB (Bexsero®) vaccine antigens, as well as the cross-reactivity of vaccine induced antibodies, in isolates from healthy carriers. The Spanish Reference Laboratory, in collaboration with the University Hospital Marqués de Valdecilla in Santander (Spain), carried out a meningococcal carrier survey between May 2010 and April 2012 (population aged 4 to 19 years). The present study was done on 60 meningococcal carrier strains representative of the overall strain panel obtained and compared to invasive strains isolated in Spain in the same time. We found quantifiable levels of fHbp and NHBA expression and immunologic cross-reactivity in 10% and 75% of analyzed carrier strains, respectively, so the potential impact of the 4CMenB vaccine on Spanish asymptomatic carrier strains is expected to be mediated by the NHBA antigen.


The vectorcardiogram in subjects with sex chromosome aneuploidy.
Vectorcardiographic variables have been studied in patients with sex chromosome abnormalities and compared with normal controls. Several of these variables were found to be correlated with the number of sex chromosomes in the karyotype, some being related to the number of X chromosomes, some to the number of Y chromosomes, and others to both. The variables concerned included time intervals and vector magnitudes in both the QRS and ST-T wave complexes. The heart rate itself proved dependent on both the X and the Y chromosome complements. The correlations could not be explained by age, height, or weight differences between the seven different karyotype groups studied. The dependences of variables other than the heart rate remained after correction for between-group heart rate differences. The findings are discussed.


BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, is caused by mutations in genes involved in the transforming growth factor beta (TGF-β) signaling pathway (ENG, ACVRL1, and SMAD4). Yet, approximately 15% of individuals with clinical features of HHT do not have mutations in these genes, suggesting that there are undiscovered mutations in other genes for HHT and possibly vascular disorders with overlapping phenotypes. The genetic etiology for 191 unrelated individuals clinically suspected to have HHT was investigated with the use of exome and Sanger sequencing; these individuals had no mutations in ENG, ACVRL1, and SMAD4. Mutations in BMP9 (also known as GDF2) were identified in three unrelated probands. These three individuals had epistaxis and dermal lesions that were described as telangiectases but whose location and appearance resembled lesions described in some individuals with RASA1-related disorders (capillary malformation-arteriovenous malformation syndrome). Analyses of the variant proteins suggested that mutations negatively affect protein processing and/or function, and a bmp9-deficient zebrafish model demonstrated that BMP9 is involved in angiogenesis. These data confirm a genetic cause of a vascular-anomaly syndrome that has phenotypic overlap with HHT.


Mechanisms regulating skin immunity and inflammation.
Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.


The Decline of Elective Colectomy Following Diverticulitis: A Population-Based Analysis.
The indications for interval elective colectomy following diverticulitis are unclear; evidence lends increasing support for nonoperative management. This study aims to evaluate the temporal trends in the use of elective colectomy following diverticulitis. This is a population-based retrospective cohort study using administrative discharge data. This study was conducted in Ontario, Canada. Patients who had had an episode of diverticulitis managed nonoperatively and were eligible for elective colectomy, from 2002 to 2012, were selected. Changes in the proportion of patients who undergo elective colectomy following an episode of diverticulitis treated nonoperatively were evaluated. Cochran-Armitage was used to test for trends; adjusted analysis was performed by using multivariable logistic regression with generalized estimating equations. A total of 14,124 patients were admitted with an episode of diverticulitis and treated nonoperatively, making them eligible for interval elective colectomy. Median follow-up was 3.9 years (maximum, 10; interquartile range, 1.7-6.4). Overall, 1342 (9.5%) patients underwent elective colectomy; 33% of these colectomies were performed laparoscopically, and 7.5% patients received an ostomy. In-hospital mortality was 0.2%. The majority (76%) of elective operations were performed within 1 year of discharge (median, 160 days; interquartile range, 88-346). The proportion of patients undergoing elective colectomy within 1 year of discharge declined from 9.6% of patients in 2002 to 3.9% by 2011 (p < 0.001). The decline was most pronounced in patients <50 years of age (from 17% to 5%), and those with complicated disease (from 28% to 8%) (all p < 0.001). In multivariable regression, younger age, lower medical comorbidity, complicated disease, and early readmission were associated with elective colectomy. After adjusting for changes in patient characteristics, the odds of elective surgery decreased by 0.93 per annum (adjusted OR; 95% CI, 0.90-0.95). Administrative health databases contain limited clinical detail; the rationale for elective surgery was not available. Consistent with evolving practice guidelines, there has been a decrease in the use of elective colectomy following an episode of diverticulitis.


A new gene in E. coli RNA synthesis.
A novel spontaneous temperature sensitive mutant of Escherichia coli, which stops synthesizing stable RNA and some proteins immediately upon temperature shift from 30 degrees C to 42 degrees C, is described. Stable RNA species are not preferentially degraded in the mutant at the nonpermissive temperature. The guanine polyphosphate compounds, ppGpp (MS1) and pppGpp (MS2), are not produced at 42 degrees C. The mutant strain does not grow at 42 degrees C in either broth or defined minimal medium supplemented with any of a variety of carbon sources. The temperature sensitive mutation in this strain maps between dap A, E and pts I and defines a new locus affecting RNA synthesis in E. coli.


Lovastatin in glomerulonephritis patients with hyperlipidaemia and heavy proteinuria.
Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, was given to 14 patients with unremittent nephrotic syndrome (heavy proteinuria with hyperlipidaemia) for 6 months. Treatment was started at an initial dose of 20 mg/day, increasing to a maximum of 80 mg/day. Treatment was well tolerated except in two patients: one developed rhabdomyolysis and one severe hypertriglyceridaemia requiring an additional antihyperlipidaemic agent. Lovastatin was effective in reducing serum cholesterol, LDL-C and apolipoprotein B in the remaining 12 patients. Cholesterol was reduced by 31% from 8.24 +/- 0.49 mmol/l (mean +/- SEM) to 5.7 +/- 0.18 mmol/l after 6 months (P less than 0.001). LDL-C was normalized to 3.26 +/- 0.21 mmol/l from a pretreatment value of 5.76 +/- 0.48 mmol/l (P less than 0.001), a decrease of 43%. Serum apolipoprotein B was also normalized to 1.11 +/- 0.09 g/l from a basal level of 1.51 +/- 0.10 g/l (P less than 0.05). Triglyceride, HDL-C and apolipoprotein A1 concentrations were unchanged. Proteinuria as well as renal albumin clearance were unchanged. GFR by plasma radioisotope Cr-EDTA clearance for the whole group was unaltered by treatment. However, among those with relatively good pretreatment renal function (GFR greater than 70 ml/min per 1.73 m2), GFR increased at the end of 6 months' treatment (118.2 +/- 15 ml/min per 1.73 m2 versus 77.6 +/- 8.4 ml/min per 1.73 m2 in wash-out phase).(ABSTRACT TRUNCATED AT 250 WORDS)


Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer.
Much attention has been paid to preoperative treatment as a new strategy especially for borderline resectable pancreatic cancer (BRPC). The purpose of this study was to define the optimal indication of neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer. We analyzed consecutive 184 patients who had undergone pancreatic resection in Nara Medical University Hospital. Resectability status was classified by NCCN guidelines. Full-dose gemcitabine with concurrent radiation was used as NACRT. We evaluated 85 patients treated with NACRT in comparison with 99 patients without NACRT as control. The regimen of NACRT was well tolerated and feasible. The perioperative outcomes were almost comparable. The postoperative complications were significantly less frequent in NACRT group than non-NACRT group. The pathological effects on both resectable and borderline tumors were favorable in NACRT group compared to non-NACRT group. The overall survival of resectable pancreatic cancer was significantly better than that of BRPC regardless of whether the patients were treated with or without NACRT. The prognosis of the patients with NACRT in resectable tumors was significantly better than without, while there was no significant difference in BRPC. Furthermore, multivariate analysis of various factors in the patients with NACRT identified resectability status and completion of adjuvant chemotherapy as independent prognostic factors. NACRT did not improve the prognosis of the patients with BRPC, although it induced substantial pathological antitumor effect. In contrast, the prognosis of resectable pancreatic cancer treated with NACRT was favorable. Therefore, resectable pancreatic cancer may be good indication for multimodal treatment including NACRT.


Production, faecal egg counts and worm burdens of ewe lambs which grazed six contrasting forages.
Lambs were grazed on monospecific swards of one of six forages, some containing condensed tannins (CT); sulla (Hedysarum coronarium), Lotus corniculatus and L. pedunculatus and some without CT (lucerne (Medicago sativa), plantain (Plantago lanceolata) and a ryegrass/white clover pasture (Lolium perenne/Trifolium repens)) to evaluate effects of forage type on gastrointestinal nematode burdens, faecal egg count as well as liveweight gain (LWG), wool growth and dag formation over a 42-day period. A new allotment of feed was provided at seven-day intervals, and feed was available ad libitum. Total worm burdens in a pre-treatment slaughter group were ca. 22000 of which ca. 5000 were in the abomasum. Within each forage type, 10 of the 25 lambs (NP) were given an anthelmintic drench at 14-day intervals and the remaining 15 lambs (P) were not drenched. Daily gains of the NP lambs were double that of P lambs which grazed either L. corniculatus, lucerne or pasture, but parasitism had a lesser effect on performance of lambs which grazed sulla and L. pedunculatus. Plantain was not palatable and all lambs performed poorly. Highest daily gains in P lambs were for those which grazed sulla (175 g/day) and L. pedunculatus (160 g/day) with total worm burdens of 13100 and 23000 for the respective treatment groups. The other forages resulted in lower daily LWG in P lambs, and performance was not related to either worm burdens or worm species. This experiment has shown that, when sulla is fed, there is a reduction in worm burdens and faecal egg count (FEC), but with Maku lotus which also contains CT, the good level of performance was achieved despite in high worm burdens and FEC. The mechanisms by which these forages enable high levels of productivity in the face of a parasitism appear to differ, but both could be incorporated into forage feeding systems to reduce dependence on anthelmintic drenches.


Blood mitochondrial enzymatic assay as a predictor of long-term outcome in severe traumatic brain injury.
Recent studies have observed the central role of mitochondrial dysfunction in severe traumatic brain injury (sTBI). One hundred and seven sTBI patients (18-65years old, presenting within 8hours of injury) were randomised for a placebo controlled phase II trial of progesterone with or without hypothermia. We serially analysed blood mitochondrial enzymes (Complex I [C1], Complex IV [C4] and pyruvate dehydrogenase complex [PDH]) using a dipstick assay at admission and 7days later for 37 patients, irrespective of assigned group. Favorable Glasgow Outcome Scale (GOS) at 1year was associated with admission C1 levels above 0.19μg, admission C4 levels above 0.19μg and day 7 C1 levels above 0.17μg, all per 25μl of blood. Unfavorable GOS at 1year was associated with admission serum PDH levels above 0.23μg/25μl of blood. Survivors at 1year had significantly higher admission serum C1 levels above 0.19μg/25μl and day 7 C1 levels above 0.17μg/25μl. To our knowledge this is the first clinical trial associating blood mitochondrial enzymes with long-term outcome in sTBI. Serial monitoring and optimisation of blood C1, C4 and PDH levels could aid in prognostication and potentially guide in using mitochondrial targeted therapies. Blood mitochondrial enzymatic assay might suggest global reduction-oxidation status.


Attentional control in learning to discriminate bars and gratings.
Transfer effects of learning a spatial-frequency and a bar-width discrimination task on the performance in three other discrimination tasks (relative bar position, local width, and global-size discrimination) have been investigated. In the spatial-frequency discrimination learning task, subjects were trained with grating stimuli which varied in spatial frequency, relative bar position, and grating patch size, but only spatial frequency was relevant for discrimination. The bar-width discrimination learners had to judge the width of single grating bars appearing at random positions distributed around a display center. During the course of 10 consecutive days, all subjects showed a significant reduction of discrimination thresholds. Regarding learning transfer, we find that practicing the spatial-frequency discrimination task yields quite strong improvement of bar-width discrimination and, vice versa, learning bar-width discrimination also leads to strong improvement of spatial-frequency discrimination performance, indicating involvement of coding pathways which are shared by both tasks. On the other hand, there is no performance improvement when subjects do different tasks (grating patch size and relative bar position discrimination) with the same stimulus material as the learning stimuli. The finding of task-driven selective learning for only one local stimulus attribute among other local and global attributes shows that feature-based attentional preselection of basic stimulus attributes is involved in learning. Moreover, differential learning effects for two different local stimulus features indicate that, governed by top-down control, different neural pathways starting from the same low-level code base may be formed in the course of discrimination training.


Studies on lectins. XXXIX. S-Glycosyl polyacrylamide gels for affinity chromatography of lectins.
Hydrophilic water-insoluble gels suitable for affinity chromatography of lectins have been prepared by copolymerization of acrylamide, N,N'-methylene bisacrylamide and alkenyl 1-thioglycosides. Water-soluble copolymers of analogous type have been obtained by omitting the cross-linking agent, N,N'-methylene bisacrylamide. In affinity chromatography of the Ricinus communis lectin it could be shown that the capacity for the lectin of the water insoluble copolymers was more than four times higher in copolymers having the S-beta-D-galactosyl ligand attached through a methylene bridge than in derivatives with a nonamethylene spacer. None of the insoluble S-beta-D-glycosyl copolymers prepared could be shown usable as affinity adsorbent for glycosidases though the corresponding soluble copolymers inhibited the activity of the enzymes.


Studies on PEG-modified SLNs loading vinorelbine bitartrate (I): preparation and evaluation in vitro.
In this study, the conjugate of PEG2000-stearic acid (PEG2000-SA) was used to prepare PEGylated solid lipid nanoparticles loading vinorelbine bitartrate (VB-pSLNs) by cold homogenization technique. The particle size and zeta potential of resulted VB-pSLNs ranged 180-250nm and 0-10mV, which were determined using a Zetasizer, respectively. Although the drug entrapment efficiency (EE) slightly decreased after the PEG modification of VB-SLNs, above 60 % EE could be reached. The drug release tests in vitro indicated the faster drug release from VB-pSLNs than that from VB-SLNs without PEG modification. To investigate the cellular uptake of VB-pSLNs, the chemical conjugate of octadecylamine-fluorescein isothiocynate (FITC-ODA) was synthesized, and was used as a fluorescence marker to incorporate into nanoparticles. The results from cellular uptake indicated that the phagocytosis of VB-pSLNs by RAW264.7 cells was inhibited effectively by the PEG modification of SLNs, while the uptake by cancer cells (MCF-7 and A549) could be improved significantly. The assay of anticancer activity in vitro demonstrated that the anticancer activity of VB was significantly enhanced by the encapsulation of SLNs and pSLNs due to the increased cellular internalization of drug. The results suggested that SLNs and pSLNs could be excellent carrier candidates to entrap VB for tumor chemotherapeutics.


Terahertz vibration-rotation-tunneling spectroscopy of the water tetramer-d8: combined analysis of vibrational bands at 4.1 and 2.0 THz.
We report the measurement of terahertz vibration-rotation-tunneling spectra of (D(2)O)(4) in the spectral region near 4.13 THz. The characterization of this perpendicular band extends a previously reported study [J. Chem. Phys. 111, 7801 (1999)]. We observed 239 new transitions, each being split into a doublet of constant (approximately 192 MHz) spacing. These are included in a combined fit with the 113 previously measured transitions of the 2.03 THz parallel band using an effective Hamiltonian similar to that used in the global fit of the water trimer. The detailed understanding of the water tetramer evolving from this work underlies our efforts to quantify the contribution of many-body forces to the hydrogen bonding interactions in condensed phase water.


Shift of visual field advantage by learning experience of foreign words.
Effects of Hebrew words learning on visual field advantage were examined with Japanese subjects. Subjects who showed no visual field advantage to Hebrew words in the first testing were assigned randomly into four experimental groups; learn pronunciation only, learn meaning only, learn both pronunciation and meaning, and learn nothing. After then, subjects were re-tested for Hebrew words discrimination. A right visual field advantage appeared in both pronunciation only and pronunciation plus meaning groups. These results suggest that mastery of pronunciation seems to be a crucial factor in producing a shift of visual field advantage.


Pandemic Puppies: Man's Best Friend or Public Health Problem? A Multidatabase Study.
The public health implications of the COVID-19 pandemic reach beyond those of the disease itself. Various centers have anecdotally reported increases in the incidence of dog bite injuries which predominate in pediatric populations. The reasons for this increase are likely multifactorial and include an increase in canine adoptions, remote learning, and psychosocial stressors induced by lockdowns. We hypothesized that there was a significant increase in the proportion of dog bite injuries at our institution and within a nationally representative cohort. We queried our electronic health record and the National Electronic Injury Surveillance System (NEISS) for all records pertaining to dog bites between 2015 and 2020, and the annual incidence was calculated. Poisson regression was then used to estimate whether there was a significant difference in the adjusted risk ratio for each year. The institutional and national cohorts revealed relative increases in the incidence of dog bite injury of 243 and 147.9 per 100,000 over the study period, respectively. Both cohorts observed significant increases of 44% and 25% in the annual incidence relative to 2019, respectively. Poisson regression revealed a significantly elevated adjusted relative risk in the institutional cohort for 2020 (2.664, CI: 2.076-3.419, P < 0.001). The national cohort also revealed an increase (1.129, CI: 1.091-1.169, P < 0.001). A nationwide increase in the incidence of dog bite injuries among children was observed during COVID-19 in 2020. These findings suggest that dog bites remain a public health problem that must be addressed by public health agencies.


Evaluation of baroreceptor reflex function in the chronic mild stress rodent model of depression.
There is a bidirectional relationship between mood disorders (e.g., depression) and altered cardiovascular regulation (e.g., heart disease); however, the precise causal and/or common mechanisms underlying this association are unclear. In previous studies, we have noted indications of altered sympathetic drive to the heart in rats that exhibit anhedonia, an operational sign of depression induced by subjecting the animals to a series of mild and unpredictable stressors (chronic mild stress (CMS) rodent model of depression). The purpose of the present study was to more fully characterize baroreceptor reflex function in rats with experimentally induced depression. Male, Sprague-Dawley rats were exposed to either 4 weeks of mild, unpredictable stressors (CMS group) or standard housing conditions (control group). Depression-like behavior, resting hemodynamic and cardiac parameters, and baroreceptor reflex function were investigated in all animals after the CMS period. CMS produced anhedonia, evidenced by reduced sucrose intake and sucrose preference, as well as elevated resting heart rate (HR), slightly elevated blood pressure, and reduced HR variability. These animals also exhibited significantly attenuated sympathoexcitatory responses to hypotension, and an elevation of basal sympathetic nerve activity. These findings suggest that CMS is associated with altered sympathoexcitatory responses after baroreceptor unloading and provide further insights into potential common mechanisms underlying the association of depression and altered cardiovascular control.


Mastic (Pistacia lentiscus) gum and oral health: a state-of-the-art review of the literature.
The aim of this state-of-the-art review is to provide a comprehensive overview of the various therapeutic effects of Mastic (Pistacia lentiscus) gum on oral health. The search of the literature was conducted across thirteen databases for relevant publications published through May 2022 in English, Arabic, or Greek using a combination of keywords and phrases. Out of 246 papers, the search procedure identified 14 papers for inclusion. Mastic gum displayed antibacterial and antimicrobial properties and inhibited plaque accumulation, constituting a beneficial adjuvant in caries prevention. In the treatment and prevention of periodontal diseases, Pistacia lentiscus essential oil provided effective antibacterial activity against a variety of periodontal bacteria as well as anti-inflammatory properties. For oral cancer, several clinical trials revealed interesting results against cell proliferation, induction of apoptosis, and regulation of intracellular signaling pathways. This indicates the potential of Mastic gum to serve as a preventive and therapeutic agent for oral mucosa inflammation and oral cancer. No notable toxic or side effects were reported in the clinical trials reviewed. This review highlights the various beneficial effects of Mastic gum in the prevention and potential treatment of oral diseases. Further research targeting Pistacia lentiscus products is required in order to validate and utilize these products to prevent and to treat oral health diseases.


Precocious puberty in a seven-year-old boy due to human chorionic gonadotropin producing pineal tumor detected by nuclear magnetic resonance computed tomographic scanning.
We report a 7-year-old boy who developed incomplete sexual precocity due to a human chorionic gonadotropin (HCG)-producing tumor in the pineal region. The patient presented enlarged testes (3 x 2 x 2 cm) bilaterally, enlarged penis, pubic hair development of Tanner Stage III, advanced bone age and growth spurt. Initial hormonal studies showed an adult male level of testosterone (13 ng/ml) and a high level of HCG as well as HCG-beta subunit. A high basal level of LH, probably due to immuno-cross-reactivity with HCG, and low basal level of FSH, probably suppressed by testosterone, did not respond to LH-RH infusion. Search for the site of HCG production failed at the initial workup, but calcification without definite signs of tumor in the pineal region was found by conventional brain CT scan. Because of subsequent progression of clinical and laboratory findings of sexual precocity, nuclear magnetic resonance computed tomographic (NMR-CT) scan was performed, which confirmed the presence of a pineal tumor three months later. The patient was treated with 4,500 rad. of radiation therapy, and responded dramatically to this regimen. He has been followed for more than two years without any signs of recurrence. We have reported here a very rare case of incomplete sexual precocity due to an HCG-producing intracranial tumor in the pineal region. An NMR-CT scan is a very useful tool for the diagnosis of some types of pineal tumor, such as germinoma, which are highly radiosensitive.


Platelet-rich fibrin increases proliferation and differentiation of human dental pulp cells.
Platelet-rich fibrin (PRF) by Choukroun's technique is derived from an autogenous preparation of concentrated platelets without any manipulation. When delicately pressed between 2 gauzes, the PRF clot becomes a strong membrane with high potential in clinical application. However, the effect of PRF on dental pulp cells (DPCs) remains to be elucidated. This study was to determine the biological effects of PRF on DPCs. PRF samples were obtained from 6 healthy volunteers. Human DPCs were derived from healthy individuals undergoing extraction for third molars. Cell proliferation resulting from PRF was evaluated by colorimetric assay. Western blot was used to evaluate the expression of osteoprotegerin (OPG). Alkaline phosphatase (ALP) activity was examined by substrate assay. PRF did not interfere with cell viability of DPCs (P > .05). DPCs were observed to attach at the edges of PRF by phase-contrast microscopy. PRF was found to increase DPC proliferation during 5-day incubation period (P < .05). PRF was found to increase OPG expression in a time-dependent manner (P < .05). ALP activity was also significantly up-regulated by PRF (P < .05). PRF was demonstrated to stimulate cell proliferation and differentiation of DPCs by up-regulating OPG and ALP expression. These findings might serve as a basis for preclinical studies that address the role of PRF in reparative dentin formation.


Global incidence, mortality, and burden of esophageal cancer, and its correlation with SDI, metabolic risks, fasting plasma glucose, LDL cholesterol, and body mass index: An ecological study.
Esophageal cancer (EC) is one of the most common gastrointestinal malignancies. The geographical variation shows the influence of genetic factors, ethnicity, and distribution of various risk factors. Accurate knowledge of EC epidemiology at the global level will help to develop management strategies. Therefore, the present study was conducted to investigate the global and regional disease burden of EC, including the incidence, mortality, and burden of this cancer in 2019. Incidence, mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) associated with EC in 204 countries in different classifications were extracted from the global burden of disease study. After collecting information on metabolic risks, fasting plasma glucose (FPG), low-density lipoprotein (LDL) cholesterol, and body mass index (body mass index), the relationship between age-standardized incidence rate (ASIR), mortality rate, and DALYs with these variables was determined. In 2019, 534,563 new cases of EC were reported worldwide. The highest ASIR is related to regions with medium sociodemographic index (SDI), and high middle income according to the World Bank, the Asian continent, and the western Pacific region. In 2019, a total of 498,067 deaths from EC were recorded. The highest mortality rate due to ASR is in countries with medium SDI and countries with upper middle income of the World Bank. In 2019, 1,166,017 DALYs were reported due to EC. The ASIR, ASDR, and DALYS ASR of EC showed a significant negative linear correlation with SDI, metabolic risks, high FPG, high LDL cholesterol, and high BMI (p < 0.05). The results of this study showed significant gender and geographic variation in the incidence, mortality, and burden of EC. It is recommended to design and implement preventive approaches based on known risk factors and improve quality and access to efficient and appropriate treatments.


Effect of implant size and shape on implant success rates: a literature review.
Understanding and using biomechanical theories that effect endosseous implant design may improve the performance of implants in varying load conditions and allow the clinician to better apply this information with potentially improved success rates. The following article presents information from English peer-reviewed journals identified by a Medline search covering the years from 1974 through 2004, and attempts to integrate information available in the dental literature and address current controversies and issues in selecting diameter, length, and shapes of dental implants.


Who provides gynecologic care?
To determine who provides gynecologic care for women who see internists, we interviewed 474 women who had return appointments at an academic primary care internal medicine center (PCC). Interview data indicated that 241 patients (51 percent) received gynecologic care in the PCC, 145 patients (31 percent) received gynecologic care from a non-PCC source, 48 patients (10 percent) did not receive needed care, and 40 patients (8 percent) did not require gynecologic care. Among the 145 patients who received gynecologic care from a non-PCC source, 121 (83 percent) received routine services that were readily available in the PCC. After completion of the interview, 28 (23 percent) of these 121 patients indicated that they did not plan to return to their non-PCC gynecologic provider. An economic analysis revealed that the savings to the patients and their insurers that could be realized by providing gynecologic care in the PCC for patients who were willing to switch from a non-PCC source would nearly offset the cost of providing routine gynecologic care to those patients who are in need of such care but are not now receiving it. Because internists are being trained to provide most routine gynecologic services, they often should be able to save their patients the cost and inconvenience of an extra visit to another physician.


Health research participants are not receiving research results: a collaborative solution is needed.
Health research participants want the results of the studies in which they participate but do not typically receive them. Researchers generally express support for sharing results with participants but, in practice, may be unprepared or unwilling to do so. Many funders call for increased dissemination of research results beyond academic and clinical audiences, but few funders sponsor research to improve result sharing with participants. Although the solution appears straightforward (e.g., funders could incentivize researchers to share results with participants), there are critical gaps in knowledge that suggest the need for a more deliberate approach. For example, what ethical or practical concerns discourage researchers from returning results to participants? What exactly do participants plan to do with the results that they would like to receive? What are the best channels of communication for sharing results with particular participant populations? To address these knowledge gaps, we argue for a collaborative process to develop a research agenda related to result sharing with participants. With support and encouragement by funders, such research should evaluate the effects of different types of results (and results from different types of studies) on participants' behaviors, attitudes, and emotions; it should also examine the researchers' ethical, financial, logistical, methodological, and skill-related concerns and constraints related to sharing results with participants. Over time, collaborative research between researchers and participants can yield an evolving set of evidence-based guidelines for ethical, effective result sharing with participants.


Relation between plasma antioxidant vitamin levels, adiposity and cardio-metabolic profile in adolescents: Effects of a multidisciplinary obesity programme.
In vivo and in vitro evidence suggests that antioxidant vitamins and carotenoids may be key factors in the treatment and prevention of obesity and obesity-associated disorders. Hence, the objective of the present study was to determine the relationship between plasma lipid-soluble antioxidant vitamin and carotenoid levels and adiposity and cardio-metabolic risk markers in overweight and obese adolescents participating in a multidisciplinary weight loss programme. A therapeutic programme was conducted with 103 adolescents aged 12-17 years old and diagnosed with overweight or obesity. Plasma concentrations of α-tocopherol, retinol, β-carotene and lycopene, anthropometric indicators of general and central adiposity, blood pressure and biochemical parameters were analysed at baseline and at 2 and 6 months of treatment. Lipid-corrected retinol (P < 0.05), β-carotene (P = 0.001) and α-tocopherol (P < 0.001) plasma levels increased significantly, whereas lipid-corrected lycopene levels remained unaltered during the treatment. Anthropometric indicators of adiposity (P < 0.001), blood pressure (P < 0.01) and biochemical parameters (P < 0.05) decreased significantly, whereas fat free mass increased significantly (P < 0.001). These clinical and biochemical improvements were related to changes in plasma lipid-corrected antioxidant vitamin and carotenoid levels. The adolescents who experienced the greatest weight loss also showed the largest decrease in anthropometric indicators of adiposity and biochemical parameters and the highest increase in fat free mass. Weight loss in these adolescents was related to an increase in plasma levels of lipid-corrected α-tocopherol (P = 0.001), β-carotene (P = 0.034) and lycopene (P = 0.019). Plasma lipid-soluble antioxidant vitamin and carotenoid levels are associated with reduced adiposity, greater weight loss and an improved cardio-metabolic profile in overweight and obese adolescents.


[Construction and identification of small interfering RNA expression plasmid targeting Sox9 and the function to cell growth and apoptosis of human chondrosarcoma cells HTB94].
To construct small interfering (siRNA) Sox9 expression plasmid and transfer it into human chondrosarcoma cells HTB-94, and to check the mRNA and protein expression of Sox9 and cell growth and apoptosis of HTB-94 human chondrosarcoma cells. siRNA(Sox9) expression plasmid was designed and synthesized. And it was transferred into HTB-94 human chondrosarcoma cells. Then the expression of the mRNA and protein of Sox9, cell growth and apoptosis in transferred HTB-94 human chondrosarcoma cells were checked. The recombinant plasmid was confirmed by enzyme digestion analysis and DNA sequencing. The expression of the mRNA and protein expression of Sox9 in transferred HTB-94 were significantly reduced. The cell growth of HTB-94 was inhibited, and the apoptosis of HTB-94 was remarkably increased. siRNA (Sox9) expression plasmid could be transferred into HTB-94 human chondrosarcoma cells. And it can reduce the mRNA and protein expression of the HTB-94, inhibit the cell growth and cause the apoptosis of the tumor cells.


Novel computational and experimental approaches for investigating the thermodynamics of metabolic networks.
Thermodynamic analysis of metabolic networks has emerged as a useful new tool for pathway design and metabolic engineering. Understanding the relationship between the thermodynamic driving force of biochemical reactions and metabolic flux has generated new insights regarding the design principles of microbial carbon metabolism. This review summarizes the various lessons that can be obtained from the thermodynamic analysis of metabolic pathways, illustrates concepts of computational thermodynamic tools, and highlights recent applications of thermodynamic analysis to pathway design in industrially relevant microbes.


Synthesis of 1-D-6-O-[2-(N-hydroxyaminocarbonyl)amino-2-deoxy-alpha-D-glucopyranosyl]-myo-inositol 1-(n-octadecyl phosphate): a potential metalloenzyme inhibitor of glycosylphosphatidylinositol biosynthesis.
1-D-6-O-[2-(N-hydroxyaminocarbonyl)amino-2-deoxy-alpha-D-glucopyranosyl]-myo-inositol 1-(n-octadecyl phosphate) was prepared to probe the reaction mechanism of the putative zinc-dependent metalloenzyme 2-acetamido-2-deoxy-alpha-D-glucopyranosyl-(1-->6)-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol biosynthesis.


Prevalence and distribution of ossification of the ligamenta flava in a 16th-18th century skeletal population sample from Poland.
This study aimed to determine the prevalence of the ossification of the ligamenta flava (OLF) among skeletal remains from Poland. 124 skeletons aged 25 years and older were analyzed. The presence and size of OLF were observed macroscopically. OLF was recorded at the cranial and caudal attachment sites of each vertebra. The following factors were analyzed: age at death, sex, and presence of other spondyloarthropathies. The crude prevalence of OLF in the analyzed series was 68.55 %. OLF was located most frequently in the lower thoracic spine. A statistically significant relationship was observed between the presence of OLF and age at death. OLF coincided with degenerative spondyloarthropathies of the thoracolumbar spine. The results of this study indicate that OLF was not a rare condition in past populations of European ancestry. Analysis of OLF prevalence in skeletal materials can contribute to reconstruction of the conditions and lifestyles of past people. This study shed new light on the prevalence of OLF and provides information on the variability of OLF in past European populations. The evaluation of the prevalence of OLF represents an important contribution to the field of paleopathology in understanding disease changes in prehistoric and historic human populations. The analyzed material came from unknown populations without demographic data. Sex and age at death were assessed using standard anthropological methods. It is important to understand the influence of sociocultural factors and physical activity patterns on the development of OLF.


Brain isoenzyme of creatine kinase. III. Active and inactive forms in dystrophic muscle of vitamin E-dificient rabbit.
Rabbits were fed a vitamin E-deficient diet for 7 weeks. Control rabbits, paired for weight, were pair-fed an identical diet supplemented with vitamin E. After 3 weeks the expermental animals showed a rise in serum creatin kinase activity which was attributable to the muscle isoenzyme (MM). No rise in creatine kinase activity or appearance of MM was noted in the serum of the control rabbits. Total creatine kinase activity and MM activity were reduced in the gastrocnemii of the experimental animals while the activities of the brain (BB) and hybird (MB) isoenzymes were increased. The specific activity of BB based on immunochemically determined BB protein was not different from normal in either the experimental or control group. Activation of pre-existing inactive BB is probably not the explanation for increased BB activity in the gastroncnemii of the experimental group.


Bioinformatic analysis of key pathways and genes shared between endometriosis and ovarian cancer.
The purpose of the study is to identify potential key genes and pathways, using bioinformatics, underlying the potentially common molecular mechanisms between endometriosis (EMS) and ovarian cancer (OC). Two datasets were collected from the Gene Expression Omnibus database, and the limma package identified common differentially expressed genes (DEGs) in the EMS and OC groups compared to controls. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene interaction network, and module analyses identified the enriched pathways associated with DEGs. A protein-protein interaction (PPI) network was then constructed, and the CytoHubba plugin of Cytoscape was used to calculate the degree of connectivity for proteins in the PPI network. A total of 571 overlapping DEGs were identified between EMS and OC (vs. controls). Enriched DEGs were associated with 36 gene ontology terms and 7 Kyoto Encyclopedia of Genes and Genomes pathways, which were mainly associated with deactivation of the p53 signaling pathway. The Kaplan-Meier plotter platform confirmed the expression of the identified hub genes, and survival analysis suggested that CCNB1, CCNB2, BUB1B, CCNA2, KIF2C, and TOP2A are associated with decreased survival and disease-free survival rates of OC. The key pathways identified herein elucidate the possible mechanism by which EMS evolves into OC; further, the identified hub genes may serve as potential biomarkers to predict OC occurrence and prognosis.


Acute painless paraparesis due to bilateral femoral artery occlusion.
Acute peripheral arterial occlusion is a medical emergency manifesting with pain, pallor, absence of pulse, paralysis, and paresthesia. Neurological deficits have occasionally been described as the presenting symptoms of acute arterial ischemia. We report a patient with acute bilateral occlusion of the femoral arteries and an underlying severe atherosclerotic aorto-iliac disease who presented with acute painless paraplegia and anesthesia in the lower extremities. The patient underwent arterial thrombectomy of the right and left femoral artery, followed by angioplasty and stent insertion of the right and left common iliac artery within 5 h from the onset of his symptoms. Subsequent physical therapy resulted in rapid improvement in the strength of his lower extremities and the patient was able to walk unaided after two weeks.


Analysis of altered capillary pressure and permeability after thermal injury.
In order to investigate the effects of thermal injury on microvascular hemodynamics and permeability, hindpaw arterial (PA), venous (PV), and capillary (PC) pressures, blood (QB) and lymph (QL) flows, and lymph (CL) and plasma (CP) total protein concentrations were measured before and for 3 hr after a 10-sec 100 degrees C scald burn in 11 dogs. Prior to injury in eight experiments (Group I--permeability analysis) venous pressure was elevated by outflow restriction until the minimal CL/CP was obtained. In three experiments (Group II--hemodynamic analysis) outflow was not restricted. Lymph and plasma protein fractions ranging in size from 37 to 120 A were measured using gradient gel electrophoresis and capillary equivalent pore sizes were calculated. In the early postburn period, PC increased from 24 +/- 2 (mean +/- SE) to 47 +/- 5 mm Hg (P less than 0.05) and precapillary resistance (RA) decreased from 6.6 +/- 0.2 to 2.5 +/- 0.2 mm Hg/ml/min/100 g (P less than 0.05) while postcapillary resistance (RV) remained unchanged. Pre- to postcapillary resistance (RA/RV) fell by 74%. The reflection coefficient for total proteins (calculated as sigma = 1 - CL/CP) decreased from 0.87 +/- 0.01 to 0.45 +/- 0.02 (P less than 0.01). Permeability of the postburn capillary endothelium was described by using two populations of equivalent pores. Preburn pore radii were 50 and 300 A with 13% of the capillary filtrate passing through the large pores. Pore radii increased after injury to 70 and 400 A with 49% of the filtrate passing through the large pores. The postburn total tissue filtration coefficient (Kf) increased to 2.4 times the control. Over the first 3 hr postburn, 53% of the increase in capillary filtration was attributable to increased capillary pressure and 47% to increased permeability. We conclude that the early rapid edema formation following thermal injury is the result of marked increases in both capillary filtration pressure and filtration through large nonsieving pores.


Morphological and transmitter release properties are changed when sympathetic neurons are cultured in low Ca2+ culture medium.
The stimulated elevation of [Ca2+]i can either promote neuronal survival or lead to Ca(2+)-mediated neurotoxicity. Similarly, growth cone mobility and neurite outgrowth may be promoted or arrested by elevated [Ca2+]i. We examined survival, development and transmitter release properties of chick sympathetic neurons maintained in culture medium containing varying concentrations of Ca2+. Neurons maintained in medium with no added Ca2+ or as low as 0.1 mM external Ca2+ show a dramatic change in growth and development compared to neurons kept in 1-2 mM Ca(2+)-containing medium. Furthermore, neurons in Ca(2+)-free medium (+ 100 microM EGTA) survived up to 24 h and, following change to 0.1 mM Ca2+, grew neurites and survived for several weeks. Neurons grown in high Ca2+ medium (0.6-2 mM) exhibited thick neurites, aggregated cell bodies, and neurites began to detach after six to eight days in culture. Neurons in low Ca2+ medium (no added Ca2+ to 0.3 mM) grew as single cells with extensive, thin branching neurites, remained firmly attached to the substrate and survived for several weeks. Neurons initially plated in 0.1 mM Ca2+ (or 2 mM Ca2+) medium and switched over to 2 mM (or 0.1 mM) Ca2+ medium after two days acquired the characteristic morphology of high (and low) Ca2+ medium over the next six days, demonstrating the plasticity of effects of external Ca2+. The above characteristic changes in growth of sympathetic neurons in low Ca2+ medium occurred when neurons were supported by 35 mM KCl or 30 nM phorbol 12,13-dibutyrate instead of nerve growth factor. The uptake and retention of tritiated norepinephrine in neurons grown in low or high Ca2+ medium were similar. However, basal release of [3H]norepinephrine in neurons maintained in low Ca2+ medium was one-third of that in neurons kept in high Ca2+ medium. Furthermore, electrically stimulated (10 pulses at 1 or 10 Hz) [3H]norepinephrine release from neurons grown in high Ca2+ had a high fractional release (> 1%) which did not change during six days in culture. On the other hand, fractional release in neurons grown in low Ca2+ medium for six to 10 days decreased about 50% and 75%, respectively, compared to release after two days in culture. The resulting low fractional release (< 0.5%) is characteristic of sympathetic neurons in neuroeffector organs.(ABSTRACT TRUNCATED AT 400 WORDS)


Phylogeny and chronology of the major lineages of New World hystricognath rodents: insights on the biogeography of the Eocene/Oligocene arrival of mammals in South America.
The hystricognath rodents of the New World, the Caviomorpha, are a diverse lineage with a long evolutionary history, and their representation in South American fossil record begins with their occurrence in Eocene deposits from Peru. Debates regarding the origin and diversification of this group represent longstanding issues in mammalian evolution because early hystricognaths, as well as Platyrrhini primates, appeared when South American was an isolated landmass, which raised the possibility of a synchronous arrival of these mammalian groups. Thus, an immediate biogeographic problem is posed by the study of caviomorph origins. This problem has motivated the analysis of hystricognath evolution with molecular dating techniques that relied essentially on nuclear data. However, questions remain about the phylogeny and chronology of the major caviomorph lineages. To enhance the understanding of the evolution of the Hystricognathi in the New World, we sequenced new mitochondrial genomes of caviomorphs and performed a combined analysis with nuclear genes. Our analysis supports the existence of two major caviomorph lineages: the (Chinchilloidea + Octodontoidea) and the (Cavioidea + Erethizontoidea), which diverged in the late Eocene. The Caviomorpha/phiomorph divergence also occurred at approximately 43 Ma. We inferred that all family-level divergences of New World hystricognaths occurred in the early Miocene. The molecular estimates presented in this study, inferred from the combined analysis of mitochondrial genomes and nuclear data, are in complete agreement with the recently proposed paleontological scenario of Caviomorpha evolution. A comparison with recent studies on New World primate diversification indicate that although the hypothesis that both lineages arrived synchronously in the Neotropics cannot be discarded, the times elapsed since the most recent common ancestor of the extant representatives of both groups are different.


Directed cell growth in multi-zonal scaffolds for cartilage tissue engineering.
Articular cartilage serves as a low-friction cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature and the low cell density, the tissue has a limited ability to regenerate, and damage due to injury, wear and tear, or disease usually requires surgical intervention. While articular cartilage had been predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Here we report the fabrication of multi-layer polymer nanocomposite scaffolds that mimic the structural design, chemical cues, and mechanical characteristics of mature articular cartilage. These scaffolds guide the morphology, orientation, and phenotypic state of cultured chondrocytes in a spatially controlled manner, support the growth of tissue with features that are reminiscent of the natural analogue, and promote localized hydroxyapatite formation to permit integration with the subchondral bone.


Isotope dilution-thermal ionisation mass spectrometric analysis for tin in a fly ash material.
Isotope dilution-thermal ionisation mass spectrometry (ID-TIMS) analysis has been applied to the determination of tin in a fly ash sample supplied by the EC Joint Research Centre (Ispra, Italy). The proposed procedure includes the silica gel/phosphoric acid technique for tin thermal ionisation activation and a strict heating protocol for isotope ratio measurements. Instrumental mass discrimination factor has been previously determined measuring a natural tin standard solution. Spike solution has been prepared from 112Sn-enriched metal and quantified by reverse isotope dilution analysis. Two sample aliquots were spiked and tin was extracted with 4.5M HCl during 25 min ultrasound exposure time. Due to the complex matrix of this fly ash material, a two-step purification stage using ion-exchange chromatography was required prior TIMS analysis. Obtained results for the two sample-spike blends (10.11+/-0.55 and 10.50+/-0.64 micromol g(-1)) are comparable, both value and uncertainty. Also a good reproducibility is observed between measurements. The proposed ID-TIMS procedure, as a primary method and due to the lack of fly ash reference materials certified for tin content, can be used to validate more routine methodologies applied to tin determination in this kind of samples.


The role of adherence to human mononuclear phagocytes in the destruction of red cells sensitized with non-complement binding IgG antibodies.
In patients with IgG incomplete non-complement binding warm autoantibodies, the subclass composition of the antibodies was studied in relation to the occurrence of increased haemolysis in vivo and the adherence of the patients red cells to peripheral blood monocytes (PBM) in vitro. The presence of IgG3 autoantibodies was almost always accompanied by haemolytic anaemia, but the presence of IgG1 autoantibodies only in some patients but not in others. IgG2 and IgG4 autoantibodies were not associated with increased red cell destruction. A relation identical to that between subclass composition and increased haemolysis was found between subclass composition and adherence of the patients erythrocytes to PBM and thus a strong correlation between positive adherence in vitro and increased red cell destruction in vivo. These results support an important role of adherence to mononuclear phagocytic cells in the destruction of red cells sensitized with non-complement binding IgG antibodies. Strong indications were found that IgG1 autoantibodies are of two kinds, only one of which causes adherence to phagocytes and thus increased red cell destruction.


Synthetic menthyl α/β-(1→6)-diglucopyranosides-induced cell death in human leukemia cells is dependent on caspases.
A series of alkyl α/β-(1→6)-diglucopyranosides 1-12 were synthesized and assessed for cytotoxicity against HL-60, U937, Molt-3 and MCF-7 cancer cell lines. The menthyl derivatives displayed strong cytotoxic properties showing IC(50) values between 6 and 16 μM. Furthermore, we demonstrated that the selected synthetic (+)-menthyl β-(1→6)-diglucopyranoside 5 induces apoptotic cell death in human leukemia cells through a mechanism that involves activation of multiple caspases. Cell death was completely prevented by the non-specific caspase inhibitor z-VAD-fmk and found to be associated with the release of cytochrome c, an increase in the expression of Bax levels and a decrease in the generation of reactive oxygen species.


Peptic (contact ulcer) granuloma of the larynx.
Review of published work and analysis of clinical data and pathology of four biopsy specimens from two patients with laryngeal contact granuloma showed that its peptic origin was derived from a gastro-oesophago-laryngeal reflux. It is proposed that the term "peptic granuloma" should be given to this phenomenon. This term is given further support on account of the spectacular recovery of the laryngeal lesion following antacid and antireflux treatment, rather than the traditional method of using vocal rest and speech therapy, assumed to be the best way of treating a result of mechanical irritation, the previously accepted cause of laryngeal contact granuloma.


Generation and characterization of oligodendrocytes from lineage-selectable embryonic stem cells in vitro.
Oligodendrocytes develop from proliferating oligodendrocyte precursor cells (OPCs), which arise in germinal zones, migrate throughout the developing white matter and divide a limited number of times before they terminally differentiate. Thus far, it has been possible to purify OPCs only from the rat optic nerve, but the purified cells cannot be obtained in large enough numbers for conventional biochemical analyses. Moreover, the central nervous system stem cells that give rise to OPCs have not been purified, limiting the ability to study the earliest stages of commitment to the oligodendrocyte lineage. Pluripotent mouse embryonic stem (ES) cells can be propagated indefinitely in culture and induced to differentiate into various cell types. We describe protocols for culture conditions in which neural precursor cells, OPCs, and oligodendrocytes can be efficiently produced from genetically modified ES cells. This strategy should be useful for study of the intracellular and extracellular factors that direct central nervous system stem cells down the oligodendrocyte pathway and influence subsequent oligodendrocyte differentiation. It may also be useful for producing OPCs and oligodendrocytes from human ES cells for cell therapy and drug screening.


Sulpiride and paroxetine in the treatment of chronic tension-type headache. An explanatory double-blind trial.
Drugs influencing monoaminergic pathways are of potential use in the treatment of pain. A serotonin re-uptake inhibitor, paroxetine (20-30 mg daily), and a dopamine antagonist, sulpiride (200-400 mg daily) were compared in a randomized, double-blind, response-conditional cross-over pilot study in 50 non-depressed patients with chronic tension-type headache. Headache was scored daily on a 5-point verbal scale during 4-weeks baseline and during 8 weeks of treatment for each drug. A 5-point 'Global' assessment was obtained for each drug. In both treatment groups headache score decreased compared to baseline. Group comparison of 24 patients first treated with paroxetine and 24 patients first treated with sulpiride showed a non-significant trend in favor of sulpiride by 'Global' evaluation and by evaluation of the available diary records (18 paroxetine-treated and 19 sulpiride-treated). Cross-over analysis of 'Global' records from 20 patients treated with paroxetine followed by sulpiride and 17 patients treated in the reverse order showed better relief from sulpiride compared to paroxetine in patients having tested both drugs (P = .03). A similar difference was reflected in available headache scores (13 and 10 patients respectively; P = .03). Predominant side effects were sedation and depression, for paroxetine also nausea and head pain. None of the drugs improved headache more than one score-point on average. A placebo controlled trial of sulpiride may be warranted.


Huge right ventricular mass lesion associated with genital malignant tumor: a case report.
Primary heart tumors are rare, whereas metastatic heart tumors occur more frequently. We report a case of a 75-year-old Japanese woman who had metastatic heart tumors of the right ventricle. Although she initially received antibiotic therapy following a diagnosis of pneumonia and pleuritis, her symptoms worsened, and she developed dyspnea and bilateral lower limb edema. Echocardiography showed a huge mass lesion occupying the entire right ventricle. Because the patient's tumor markers were elevated, we used computed tomography to search for the primary lesion, which was located in the vagina or the uterus. Histology demonstrated the presence of basaloid squamous cell carcinoma in the vaginal tissue. Chemotherapy with paclitaxel and carboplatin was initiated. These data suggest that the tumor in the right ventricle metastasized from the genital organs.


Phanerochaete chrysosporium inoculation shapes the indigenous fungal communities during agricultural waste composting.
Inoculation with exogenous white-rot fungi has been proven to be an efficient method to promote lignocellulose biodegradation during agricultural waste composting. Indigenous fungal communities, the most important organisms responsible for mineralization and decomposition of lignocellulosic materials in composts, can be affected by sample properties and other biotic factors. This research was conducted to determine the effects of the Phanerochaete chrysosporium inoculation on the indigenous fungal communities during agricultural waste composting. Fungal communities in samples with different inoculation regimes were investigated by sequencing and quantitative PCR. Results showed that P. chrysosporium inoculants produced significant negative effects on the indigenous fungal community abundance during the thermophilic stage. Samples inoculated during Phase II contained higher proportion of Acremonium chrysogenum and Galactomyces geotrichum, while those non-inoculated samples were dominated by Coprinopsis cinerea and Scytalidium thermophilum. Moreover, the indigenous fungal community abundance was significantly correlated with the C/N ratio, water soluble carbon and moisture content (P < 0.05). Redundancy analysis indicated that the most variation in distribution of indigenous fungal community structure was statistically explained by nitrate, C/N ratio, and moisture content, factors which solely explained 29.6 % (F = 30.316, P = 0.002), 25.6 % (F = 26.191, P = 0.002) and 10.0 % (F = 10.249, P = 0.002) of the variation in the indigenous fungal community structure, respectively.


[Exercise and physical training as interventions in gerontopsychiatry].
The treatment of mental disorders in older adults is often restricted by limitations in efficacy and tolerability of pharmacologically dominated standard therapeutic strategies. Therefore, nonpharmacological therapeutic alternatives and supplements play a crucial role in these patients. Structured exercise and training are interventions that are associated with a high level of evidence in prevention and treatment of mental and cognitive disorders. This article is based on a selective search of the literature and provides an overview of the current scientific evidence with respect to the mechanisms of action, the effects on frequently occurring clinical disorders and modalities of the exercise interventions.


Is exercise protective against influenza-associated mortality?
Little is known about the effect of physical exercise on influenza-associated mortality. We collected information about exercise habits and other lifestyles, and socioeconomic and demographic status, the underlying cause of death of 24,656 adults (21% aged 30-64, 79% aged 65 or above) who died in 1998 in Hong Kong, and the weekly proportion of specimens positive for influenza A (H3N1 and H1N1) and B isolations during the same period. We assessed the excess risks (ER) of influenza-associated mortality due to all-natural causes, cardiovascular diseases, or respiratory disease among different levels of exercise: never/seldom (less than once per month), low/moderate (once per month to three times per week), and frequent (four times or more per week) by Poisson regression. We also assessed the differences in ER between exercise groups by case-only logistic regression. For all the mortality outcomes under study in relation to each 10% increase in weekly proportion of specimens positive for influenza A+B, never/seldom exercise (as reference) was associated with 5.8% to 8.5% excess risks (ER) of mortality (P<0.0001), while low/moderate exercise was associated with ER which were 4.2% to 6.4% lower than those of the reference (P<0.001 for all-natural causes; P = 0.001 for cardiovascular; and P = 0.07 for respiratory mortality). Frequent exercise was not different from the reference (change in ER -0.8% to 1.7%, P = 0.30 to 0.73). When compared with never or seldom exercise, exercising at low to moderate frequency is beneficial with lower influenza-associated mortality.


Gaps exist between patients' experience and clinicians' awareness of symptoms after chemotherapy: CINV and accompanying symptoms.
Correlating patients' chemotherapy-induced nausea and vomiting (CINV) experience with clinicians' understanding of the symptom severity and the patients' and clinicians' symptom management goals would aid in advancing symptom management. Identifying rankings of symptom severity after chemotherapy would help prioritizing symptom management. The purpose of this study was to investigate and compare patients' CINV experience and clinicians' awareness of symptoms and symptom management goals. The study also aimed to identify and compare rankings of the severity of symptoms after chemotherapy by patients and clinicians. A prospective observational study was conducted. Cancer patients starting the first adjuvant highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) (n = 313), and oncology clinicians at two university hospitals (n = 73) in Korea participated in the study. The Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT) items and 20-symptom list were used to generate a symptom diary and survey questions. Descriptive statistics with a 95 % confidence interval and the Mann-Whitney U test were used to analyze the data. In general, clinicians overestimated the patients' CINV experience. Patients' symptom experiences and clinicians' estimates only corresponded for delayed nausea after the second cycle MEC. For symptom management goals, patients aimed for absolute vomiting control and avoiding significant nausea. Patients' symptom management goals exceeded the clinicians' goals for CINV control except for the goal for delayed nausea control. Clinicians rated chemotherapy-induced nausea as the most problematic symptom followed by vomiting; however, fatigue and loss of appetite were the top rated symptoms by patients. Gaps exist between patients' symptom experience and clinicians' symptom awareness. Clinicians overestimated the patients' CINV experience and set less stringent symptom control goals. Enhancing clinicians' understanding of patients' symptom experience and retargeting the CINV management goals are the next steps for advancing symptom management. Symptoms other than CINV require more attention to set symptom management priorities reflecting patient experience and clinical significance.


[BRCA1 protein expression in sporadic breast and its clinical significance].
To study BRCA1 gene expression in sporadic breast cancer in Han nationality and its relations to clinical pathological parameters. Immunohistochemical method was used to detect the BRCA1 protein in paraffin embedded breast cancer tissue of 51 patients. The relationship between BRCA1 protein and clinical pathological features was analysed. BRCA1 protein was located in the nuclear of breast cancer cells. The rate of its down regulation of expression was 49.0% (25/51), which correlated reversely with c-erbB-2 protein, but did not correlate with histological grading, tumor size, lymph node involvement and patient age. The detection of BRCA1 protein expression may be a reflection of its gene alteration. So it may be a primary method for screening the susceptibility to breast cancer.


Metabolic associations with archaea drive shifts in hydrogen isotope fractionation in sulfate-reducing bacterial lipids in cocultures and methane seeps.
Correlation between hydrogen isotope fractionation in fatty acids and carbon metabolism in pure cultures of bacteria indicates the potential of biomarker D/H analysis as a tool for diagnosing carbon substrate usage in environmental samples. However, most environments, in particular anaerobic habitats, are built from metabolic networks of micro-organisms rather than a single organism. The effect of these networks on D/H of lipids has not been explored and may complicate the interpretation of these analyses. Syntrophy represents an extreme example of metabolic interdependence. Here, we analyzed the effect of metabolic interactions on the D/H biosignatures of sulfate-reducing bacteria (SRB) using both laboratory maintained cocultures of the methanogen Methanosarcina acetivorans and the SRB Desulfococcus multivorans in addition to environmental samples harboring uncultured syntrophic consortia of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing Deltaproteobacteria (SRB) recovered from deep-sea methane seeps. Consistent with previously reported trends, we observed a ~80‰ range in hydrogen isotope fractionation (ε(lipid-water)) for D. multivorans grown under different carbon assimilation conditions, with more D-enriched values associated with heterotrophic growth. In contrast, for cocultures of D. multivorans with M. acetivorans, we observed a reduced range of ε(lipid-water) values (~36‰) across substrates with shifts of up to 61‰ compared to monocultures. Sediment cores from methane seep settings in Hydrate Ridge (offshore Oregon, USA) showed similar D-enrichment in diagnostic SRB fatty acids coinciding with peaks in ANME/SRB consortia concentration suggesting that metabolic associations are connected to the observed shifts in ε(lipid-water) values.


Modeling risky decision making in rodents.
Excessive risk taking is a hallmark of various psychopathological disorders. We have developed a task that models such risky decision making in rats. In this task, rats are given choices between small, safe rewards and large rewards accompanied by a risk of punishment (footshock). The risk of punishment increases throughout the test session, which allows the quantification of risky decision making at different degrees of risk for each subject. Importantly, this task yields a consistently wide degree of reliable individual variability, allowing the characterization of rats as "risk taking" or "risk averse." This task has been demonstrated to be effective for testing the effects of pharmacological agents on risk taking, and the individual variability (which mimics the human population) allows assessment of neurobiological distinctions between subjects based on risk-taking profile.


Psychiatric diseases.
The traditional boundary between primary psychiatric disorders, as "diseases of the mind", and neurological conditions, as "diseases of the brain", has been challenged since advances in brain imaging techniques have allowed the correlation of functional and structural brain abnormalities with the presence and severity of psychopathological symptoms in psychiatric illnesses, thus suggesting a neural basis for their onset and progression and providing an in vivo pathological anatomy of psychiatric diseases.


Sensory nerves enhance triple-negative breast cancer invasion and metastasis via the axon guidance molecule PlexinB3.
In breast cancer, nerve presence has been correlated with more invasive disease and worse prognosis, yet the mechanisms by which different types of peripheral nerves drive tumor progression remain poorly understood. In this study, we identified sensory nerves as more abundant in human triple-negative breast cancer (TNBC) tumors. Co-injection of sensory neurons isolated from the dorsal root ganglia (DRG) of adult female mice with human TNBC cells in immunocompromised mice increased the number of lung metastases. Direct in vitro co-culture of human TNBC cells with the dorsal root ganglia (DRG) of adult female mice revealed that TNBC cells adhere to sensory neuron fibers leading to an increase in migration speed. Species-specific RNA sequencing revealed that co-culture of TNBC cells with sensory nerves upregulates the expression of genes associated with cell migration and adhesion in cancer cells. We demonstrated that lack of the semaphorin receptor PlexinB3 in cancer cells attenuate their adhesion to and migration on sensory nerves. Together, our results identify a mechanism by which nerves contribute to breast cancer migration and metastasis by inducing a shift in TNBC cell gene expression and support the rationale for disrupting neuron-cancer cell interactions to target metastasis.


Antigenic escape selects for the evolution of higher pathogen transmission and virulence.
Despite the propensity for complex and non-equilibrium dynamics in nature, eco-evolutionary analytical theory typically assumes that populations are at equilibria. In particular, pathogens often show antigenic escape from host immune defences, leading to repeated epidemics, fluctuating selection and diversification, but we do not understand how this impacts the evolution of virulence. We model the impact of antigenic drift and escape on the evolution of virulence in a generalized pathogen and apply a recently introduced oligomorphic methodology that captures the dynamics of the mean and variance of traits, to show analytically that these non-equilibrium dynamics select for the long-term persistence of more acute pathogens with higher virulence. Our analysis predicts both the timings and outcomes of antigenic shifts leading to repeated epidemics and predicts the increase in variation in both antigenicity and virulence before antigenic escape. There is considerable variation in the degree of antigenic escape that occurs across pathogens and our results may help to explain the difference in virulence between related pathogens including, potentially, human influenzas. Furthermore, it follows that these pathogens will have a lower R0, with clear implications for epidemic behaviour, endemic behaviour and control. More generally, our results show the importance of examining the evolutionary consequences of non-equilibrium dynamics.


Studies on pulmonary and systemic Aspergillus fumigatus-specific IgE and IgG antibodies in horses affected with chronic obstructive pulmonary disease (COPD).
Inhalant exposure to Aspergillus fumigatus (Asp. f.) antigens induces marked inflammatory and immunological alterations in the lungs of horses affected with chronic obstructive pulmonary disease (COPD). In this study we investigated the role of specific allergen(s) present in Asp. f. on systemic and pulmonary IgE and IgG responses in control and COPD-affected horses, using an enzyme-linked immunosorbent assay (ELISA) and immunoblotting techniques. Compared with controls, horses affected with COPD had significantly higher levels of BALF IgE and IgG to somatic Asp. f. antigens as well as to the allergen 1/a (Asp. f. 1/a). Serum levels of IgE and IgG against these antigens did not differ between control and COPD-affected horses. Antigen specific IgE and IgG levels did not correlate between BALF and serum. Scanning of Asp. f. and IgE and IgG blots revealed bands that are recognised by both IgE- and IgG-specific antibodies. Additionally, all horses responded with BALF IgE- and IgG-specific for 93, 35, 31 and 23 kDa allergens, suggesting that these antigens are involved in the induction of airway IgE and IgG responses. These allergens may have the potential to be used as biomarkers for the diagnosis of Asp. f. related exacerbations of equine COPD.


Resistance and aerobic exercises do not affect post-exercise energy compensation in normal weight men and women.
Previous research has reported no effect of exercise modality (aerobic vs. resistance) on energy intake (EI). However, the relatively low energy cost of resistance training, the absence of total energy expenditure (TEE) measurements and the short duration of these studies justify further investigation. To evaluate the effects of exercise modality on EI, TEE, non-exercise activity thermogenesis (NEAT) and post-exercise energy compensation (PEEC) measured acutely, as well as for 10 and 34 h following exercise. Eight men and 8 women participated in three randomized crossover sessions: aerobic-based exercise, resistance-based exercise, and sedentary control. Exercise energy expenditure (ExEE) was continuously measured (indirect calorimetry) throughout the exercise sessions, which were designed to produce an isocaloric ExEE of 4 kcal/kg body weight. TEE and EI were monitored for 34 h post-exercise with biaxial accelerometers and a validated food menu, respectively. There were no differences in EI between exercise modalities acutely, as well as 10 and 34 h following exercise. However, a modality by sex interaction was noted for acute EI. Men ate more after the resistance than after the aerobic session (1567±469; 1255±409 kcal, respectively; P=0.034), while no differences were seen in women (568±237; 648±270 kcal, respectively; P=NS). No differences in TEE, NEAT and PEEC were found 10h and 34 h post-exercise, while a positive correlation (r=0.897; P<0.01) was found between both modalities across participants for PEEC. Exercise modality does not impact PEEC when ExEE is controlled. Our results also show that within-individual PEEC seems to be relatively constant across exercise modality.


Rest tremor in Parkinson's disease: Body distribution and time of appearance.
To assess body distribution and timing of appearance of rest tremor in Parkinson's disease. Information was obtained by a computerized database containing historical information collected at the first visit and data collected during the subsequent follow-up visits. Information on rest tremor developed during the follow-up could be therefore obtained by our own observation in a proportion of patients. Among 289 patients, rest tremor was reported at disease onset in 65.4% of cases and detected at last follow-up examination in 74.4% of patients. Analysis of patients who did not report rest tremor at disease onset indicated that 26% of such patients (9% in the overall population) manifested rest tremor over the disease course. Rest tremor spread to new sites in 39% of patients who manifested rest tremor at disease onset. Regardless of tremor presentation at disease onset or during the follow-up, upper limb was the most frequent tremor localization. Over the follow-up, rest tremor developed faster in the upper limb than in other body sites. The risk of developing rest tremor during the follow-up was not affected by sex, side of motor symptom onset and site of tremor presentation. However, age of disease onset >63years was associated with an increased risk of rest tremor spread. This study provides new information about body distribution and timing of rest tremor appearance during the course of early stages of Parkinson's disease that may help clinicians in patients' counselling.


Description of two new species of Clivina Latreille (Coleoptera, Carabidae, Clivinini) from southeastern United States.
Two new species of the genus Clivina Latreille are described. One, Clivina choatei Bousquet & Skelley, belongs to the nominotypical subgenus and is known from six specimens collected in northern Florida. The species is structurally similar to Clivina myops Bousquet, known only from the holotype found in North Carolina, but differs among others by its smaller size and wider elytral striae. The second species, Clivina alabama Bousquet, belongs to the subgenus Antroforceps Barr and is known from two specimens collected in north-central Alabama. The species is structurally most similar to Clivina sasajii Ball, known only from Latimer County in Oklahoma, but differs among others in the absence of eyes and in having the pronotum and elytra proportionally wider.


Association of body composition and surgical outcomes in patients with early-stage breast cancer.
Breast cancer is a disease that requires multimodality treatment, and surgical resection of the tumor is a critical component of curative intent treatment. Obesity, defined as a body mass index (BMI) > 30, has been associated with increased surgical complications. Additionally, sarcopenia, a condition of gradual loss of muscle mass, has been associated with worse breast cancer treatment outcomes. Sarcopenia occurs with increased age, inactivity, and poor diet leading to patient frailty, which can increase medical treatment complications. Even patients with high BMI can have sarcopenia (termed sarcopenic obesity). We investigated the association of sarcopenia with surgical complications for breast cancer. A retrospective review was performed of patients diagnosed with breast cancer who received bioelectrical impedance spectrometry analysis of skeletal muscle mass and had surgery at our institution. Patient characteristics, treatment data, surgical type and complications were obtained from medical records. Multivariate logistic regression models were used to associate sarcopenia status and BMI with surgical complications, adjusted for other patient characteristics. We analyzed 682 patients with stage I to III breast cancer. On multivariable logistic regression controlling for age, BMI, comorbidities, and types of surgeries (lumpectomy, mastectomy with or without reconstruction), sarcopenia (p = 0.66) was not associated with surgical complications. Obesity was associated with a higher rate of surgical complications in patients who received mastectomy with reconstruction (p = 0.01). More complex surgical approaches were associated with a higher risk of surgical complications in our series. Compared with those undergoing lumpectomy or mastectomy without reconstruction, patients undergoing mastectomy with reconstruction were more likely to experience postoperative complications and obesity was associated with higher risk of complication in the latter group. We did not identify a correlation between sarcopenia and rate of adverse surgical outcomes.


Comparison of the effects of different anti-inflammatory drugs on synovial fluid prostanoid concentrations in patients with rheumatoid arthritis.
The effects of one-day treatment with nine nonsteroidal anti-inflammatory drugs and prednisolone on human synovial fluid concentrations of prostanoids were studied. The doses were calculated so as to be approximately equipotent according to clinical experience and the recommendations of the manufacturers. Most of the drugs used reduced clearly PGE2 and TxB2 levels in synovial fluid, but only a slight diminution in 6-keto-PGF1 alpha values was found. Carprofen, diclofenac, indomethacin, naproxen and tolfenamic acid reduced significantly the synovial fluid PGE2 concentrations. Diclofenac and indomethacin also reduced significantly the synovial TxB2 concentrations.


Integration of Comprehensive Genomic Analysis and Functional Screening of Affected Molecular Pathways to Inform Cancer Therapy.
To select optimal therapies based on the detection of actionable genomic alterations in tumor samples is a major challenge in precision medicine. We describe an effective process (opened December 1, 2017) that combines comprehensive genomic and transcriptomic tumor profiling, custom algorithms and visualization software for data integration, and preclinical 3-dimensiona ex vivo models for drug screening to assess response to therapeutic agents targeting specific genomic alterations. The process was applied to a patient with widely metastatic, weakly hormone receptor positive, HER2 nonamplified, infiltrating lobular breast cancer refractory to standard therapy. Clinical testing of liver metastasis identified BRIP1, NF1, CDH1, RB1, and TP53 mutations pointing to potential therapies including PARP, MEK/RAF, and CDK inhibitors. The comprehensive genomic analysis identified 395 mutations and several structural rearrangements that resulted in loss of function of 36 genes. Meta-analysis revealed biallelic inactivation of TP53, CDH1, FOXA1, and NIN, whereas only one allele of NF1 and BRIP1 was mutated. A novel ERBB2 somatic mutation of undetermined significance (P702L), high expression of both mutated and wild-type ERBB2 transcripts, high expression of ERBB3, and a LITAF-BCAR4 fusion resulting in BCAR4 overexpression pointed toward ERBB-related therapies. Ex vivo analysis validated the ERBB-related therapies and invalidated therapies targeting mutations in BRIP1 and NF1. Systemic patient therapy with afatinib, a HER1/HER2/HER4 small molecule inhibitor, resulted in a near complete radiographic response by 3 months. Unlike clinical testing, the combination of tumor profiling, data integration, and functional validation accurately assessed driver alterations and predicted effective treatment.


Transcriptome analysis of Panax zingiberensis identifies genes encoding oleanolic acid glucuronosyltransferase involved in the biosynthesis of oleanane-type ginsenosides.
Oleanolic acid glucuronosyltransferase (OAGT) genes synthesizing the direct precursor of oleanane-type ginsenosides were discovered. The four recombinant proteins of OAGT were able to transfer glucuronic acid at C-3 of oleanolic acid that yields oleanolic acid 3-O-β-glucuronide. Ginsenosides are the primary active components in the genus Panax, and great efforts have been made to elucidate the mechanisms underlying dammarane-type ginsenoside biosynthesis. However, there is limited information on oleanane-type ginsenosides. Here, high-performance liquid chromatography analysis demonstrated that oleanane-type ginsenosides (particularly ginsenoside Ro and chikusetsusaponin IV and IVa) are the abundant ginsenosides in Panax zingiberensis, an extremely endangered Panax species in southwest China. These ginsenosides are derived from oleanolic acid 3-O-β-glucuronide, which may be formed from oleanolic acid catalyzed by an unknown oleanolic acid glucuronosyltransferase (OAGT). Transcriptomic analysis of leaves, stems, main roots, and fibrous roots of P. zingiberensis was performed, and a total of 46,098 unigenes were obtained, including all the identified homologous genes involved in ginsenoside biosynthesis. The most upstream genes were highly expressed in the leaves, and the UDP-glucosyltransferase genes were highly expressed in the roots. This finding indicated that the precursors of ginsenosides are mainly synthesized in the leaves and transported to different parts for the formation of particular ginsenosides. For the first time, enzyme activity assay characterized four genes (three from P. zingiberensis and one from P. japonicus var. major, another Panax species with oleanane-type ginsenosides) encoding OAGT, which particularly transfer glucuronic acid at C-3 of oleanolic acid to form oleanolic acid 3-O-β-glucuronide. Taken together, our study provides valuable genetic information for P. zingiberensis and the genes responsible for synthesizing the direct precursor of oleanane-type ginsenosides.


[Structural-functional organization of the incompatibility group P plasmid pBS221].
Plasmid pBS221 was physically mapped for restriction endonucleases EcoRI, BamHI, BglII, HindIII. The regions essential for the plasmid existence and participating in replication (oriV trfA*) and mobilization (mob) were cloned. The tet determinant and oriV trfA* regions were localized on the physical map of the plasmid. A DNA sequence homologous to genes of Tn501 mer operon was detected in this plasmid. The studies on homology of plasmids RP4 (IncP alpha), R751 (IncP beta) and pBS221 plasmid suggest that the latter belongs to the IncP beta subgroup.


Contribution of prophylactic administration of flurbiprofen for mesenteric traction syndrome to postoperative leakage or bleeding in gastrointestinal surgery: a retrospective observational study.
Mesenteric traction syndrome (MTS) sometimes occurs during abdominal surgery. Prophylactic administration of flurbiprofen, a non-steroidal anti-inflammatory drug, prevents the development of MTS. However, administration of non-steroidal anti-inflammatory drugs for postoperative pain increases the incidence of postoperative bleeding. Our aim was to examine the effect of prophylactic flurbiprofen administration on postoperative leakage or bleeding after gastrointestinal surgery. A retrospective observational study on patients who underwent open or laparoscopic abdominal surgery was conducted. Perioperative, anesthesia and medical records were reviewed. Patients who did (Flurbio-Group) or did not receive (Control-Group) prophylactic flurbiprofen administration were compared. Then, the Flurbio-Group and Control-Group were each divided into two groups according to whether the patients did or did not develop MTS (Flurbio-MTS-Group and Flurbio-no-MTS-Group, respectively, Control-MTS-Group and Control-no-MTS-Group, respectively). This study included 188 patients (Flurbio-MTS-Group, 1 patient; Flurbio-no-MTS-Group, 31 patients; Control-MTS-Group, 59 patients; Control-no-MTS-Group, 97 patients). Seventeen patients developed postoperative leakage or bleeding. Eleven Flurbio-MTS-Group patients (18.6%), 4 Flurbio-no-MTS-Group patients (12.9%, 4/31), and only 2 Control-no-MTS-Group patients (2%, 2/97) developed postoperative leakage or bleeding. Multivariate logistic regression analysis demonstrated that there was a qualitative interaction effect between prophylactic administration of flurbiprofen and the development of MTS on postoperative leakage or bleeding. Prophylactic flurbiprofen administration increased the risk of postoperative leakage or bleeding among patients who did not develop MTS.


A direct test of Listing's law--II. Human ocular torsion measured under dynamic conditions.
Ocular torsion was recorded with a scleral search coil technique in five normal subjects. The dynamic aspects of torsion were investigated during monocular fixation, blinking, smooth pursuit and saccades. Torsion near the primary position showed considerable short-term (SD about 0.25 deg) and a much larger long-term fluctuation (SD about 2.3 deg). During saccades between diagonally opposite tertiary positions torsion transiently reached values approximating those in the sustained primary position. During smooth pursuit across the primary position, the minimal values of torsion varied with the direction and the trajectory of pursuit, in violation of Donder's law. Changes in torsion associated with horizontal and vertical saccades and during the aftermath of blinks often had a sluggish, exponential time course. During eye movements around a circular or square trajectory torsion showed hysteresis. During clockwise pursuit the right eye showed relative intorsion compared to counterclockwise pursuit. It is proposed that central nervous control of torsion is usually imprecise, and that the eye follows Listing's and Donder's laws only approximately.


The organization that has our backs.
A dentist with 16 years of practice experience who participated in the ADA's New Dentist program ticks off the benefits of participation in the American Dental Association: discounts, insurance, CE, publications, leadership opportunities, political voice, patient benefits, product testing, and more.


Diffusion tensor imaging of the superior longitudinal fasciculus and working memory in recent-onset schizophrenia.
Structural and functional abnormalities in frontal-parietal circuitry are thought to be associated with working memory (WM) deficits in patients with schizophrenia. This study examines whether recent-onset schizophrenia is associated with anatomical changes in the superior longitudinal fasciculus (SLF), the main frontal-parietal white matter connection, and whether the integrity of the SLF is related to WM performance. We applied a novel registration approach (Tract-Based Spatial Statistics [TBSS]) to diffusion tensor imaging data to examine fractional anisotropy (FA) in the left and right SLF in 12 young adult patients with recent-onset schizophrenia and 17 matched control subjects. Schizophrenia patients showed lower FA values than control subjects across the entire SLF, with particular deficits on the left SLF. Fractional anisotropy values were correlated with performance on a verbal WM task in both patient and control groups in the left but not right SLF. Recent-onset schizophrenia patients show deficits in frontal-parietal connections, key components of WM circuitry. Moreover, the integrity of this physiological connection predicted performance on a verbal WM task, indicating that this structural change may have important functional implications. These findings support the view that schizophrenia is a disorder of brain connectivity and implicate white matter changes detectable in the early phases of the illness as one source of this dysfunction.


Surgical indications in children with cerebral palsy.
We have presented our approach to the surgical consideration for the upper extremities of a child with cerebral palsy. This is basically a coordinated approach involving many team members, and is the only way to achieve predictable postoperative results.


Vitiligo-like lesions in patients with advanced breast cancer treated with cycline-dependent kinases 4 and 6 inhibitors.
Introduction of cyclin-dependent inhibitors was a milestone in therapeutics for patients with estrogen receptor+/HER2- metastatic breast cancer. Despite the wide use of such agents and remarkable improvement of survival rates, drug-related adverse events are not yet fully characterized. We describe vitiligo-like lesions as a new adverse event occurring in patients with advanced breast cancer treated with cyclin-dependent inhibitors. We performed an international retrospective study including patients with advanced breast cancer who developed vitiligo-like lesions during treatment with cyclin-dependent kinases 4 and 6 inhibitors, in the period January 2018-December 2019. Patients > 18 years, both males and females, were recruited at six Dermatology Departments located in Italy (3), France (1) and Greece (2). We evaluated epidemiological and clinical characteristics, impact on quality of life and outcome of vitiligo-like lesions in patients treated with cyclin-dependent 4 and 6 inhibitors. The percentage of skin involved by vitiligo-like lesions was assessed using the Body Surface Area (BSA) score. Changes in patients' quality of life were investigated through the evaluation of the Dermatology Life Quality Index (DLQI) questionnaire. Sixteen women (median age: 62.5 years; range 40-79 years) treated with cyclin-dependent kinases 4 and 6 inhibitors for advanced breast cancer presented with vitiligo-like lesions during follow-up visits. Cutaneous lesions consisted of white, irregular macules and patches located mainly on sun-exposed areas in 11/16 patients or diffuse to the entire body surface in 5/16. Cutaneous lesions clearly impaired the quality of life of patients tested (DLQI ≥ 10). We present for the first time, to our knowledge, a case series of vitiligo-like lesions developing in patients with advanced breast cancer treated with cyclin-dependent kinases 4 and 6 inhibitors. We showed that such lesions further impair the patients' quality of life and their treatment is challenging.


Production of uroporphyrinogen III, which is the common precursor of all tetrapyrrole cofactors, from 5-aminolevulinic acid by Escherichia coli expressing thermostable enzymes.
Uroporphyrinogen III (urogen III) was produced from 5-aminolevulinic acid (ALA), which is a common precursor of all metabolic tetrapyrroles, using thermostable ALA dehydratase (ALAD), porphobilinogen deaminase (PBGD), and urogen III synthase (UROS) of Thermus thermophilus HB8. The UROS-coding gene (hemD₂) of T. thermophilus HB8 was identified by examining the gene product for its ability to produce urogen III in a coupled reaction with ALAD and PBGD. The genes encoding ALAD, PBGD, and UROS were separately expressed in Escherichia coli BL21 (DE3). To inactivate indigenous mesophilic enzymes, the E. coli transformants were heated at 70 °C for 10 min. The bioconversion of ALA to urogen III was performed using a mixture of heat-treated E. coli transformants expressing ALAD, PBGD, and UROS at a cell ratio of 1:1:1. When the total cell concentration was 7.5 g/l, the mixture of heat-treated E. coli transformants could convert about 88 % 10 mM ALA to urogen III at 60 °C after 4 h. Since eight ALA molecules are required for the synthesis of one porphyrin molecule, approximately 1.1 mM (990 mg/l) urogen III was produced from 10 mM ALA. The present technology has great potential to supply urogen III for the biocatalytic production of vitamin B₁₂.


The DNAJB6 and DNAJB8 protein chaperones prevent intracellular aggregation of polyglutamine peptides.
Fragments of proteins containing an expanded polyglutamine (polyQ) tract are thought to initiate aggregation and toxicity in at least nine neurodegenerative diseases, including Huntington's disease. Because proteasomes appear unable to digest the polyQ tract, which can initiate intracellular protein aggregation, preventing polyQ peptide aggregation by chaperones should greatly improve polyQ clearance and prevent aggregate formation. Here we expressed polyQ peptides in cells and show that their intracellular aggregation is prevented by DNAJB6 and DNAJB8, members of the DNAJ (Hsp40) chaperone family. In contrast, HSPA/Hsp70 and DNAJB1, also members of the DNAJ chaperone family, did not prevent peptide-initiated aggregation. Intriguingly, DNAJB6 and DNAJB8 also affected the soluble levels of polyQ peptides, indicating that DNAJB6 and DNAJB8 inhibit polyQ peptide aggregation directly. Together with recent data showing that purified DNAJB6 can suppress fibrillation of polyQ peptides far more efficiently than polyQ expanded protein fragments in vitro, we conclude that the mechanism of DNAJB6 and DNAJB8 is suppression of polyQ protein aggregation by directly binding the polyQ tract.