Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial.
Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. Controlled clinical trial. 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.


Parkinson's disease: in vivo brain metabolomics by MRS.
In vivo brain metabolomics in Parkinson's disease is still in its infancy. This chapter will review brain metabolomics in the human brain as studied noninvasively by magnetic resonance spectroscopy. Although preliminary, the results shed some light on the pathophysiology of Parkinson's disease.


Stabilizing G-quadruplex DNA by methylazacalix[n]pyridine through shape-complementary interaction.
It is found that G-quadruplexes have important functions in biological systems, such as gene expression. Molecules which can stabilize the G-quadruplex structure may have potential application in regulating the expression of gene. A series of methylazacalix[n]pyridine (n=4, 6, 7, 8, 9) has been tested to stabilize the intermolecular human telomeric G-quadruplex (T12 and H12), intramolecular TBA, c-kit and bcl-2 G-quadruplex by CD denaturation experiments. The results showed that only methylazacalix[6]pyridine (MACP6) can stabilize the intermolecular G-quadruplex formed from the 12bp human telomere. Further studies evidenced that the shape-complementary binding mode was what contributed to the interaction between MACP6 and T12 G-quadruplex.


A cannabinoid with cardiovascular activity but no overt behavioral effects.
Abnormal-delta8-tetrahydrocannabinol (ABN-delta8-THC) failed to elicit central nervous system and cardiovascular effects in laboratory animals. Abnormal-cannabidiol (ABN-CBD) was also devoid of overt behavioral effects but produced marked hypotension with only slight bradycardia in anesthesized dogs.


Retracted: Psychological Changes of Social Media on Charitable Cultural Behavior Based on Big Data Technology.
[This retracts the article DOI: 10.1155/2022/5871669.].


Central hubs prediction for bio networks by directed hypergraph - GA with validation to COVID-19 PPI.
Network structures have attracted much interest and have been rigorously studied in the past two decades. Researchers used many mathematical tools to represent these networks, and in recent days, hypergraphs play a vital role in this analysis. This paper presents an efficient technique to find the influential nodes using centrality measure of weighted directed hypergraph. Genetic Algorithm is exploited for tuning the weights of the node in the weighted directed hypergraph through which the characterization of the strength of the nodes, such as strong and weak ties by statistical measurements (mean, standard deviation, and quartiles) is identified effectively. Also, the proposed work is applied to various biological networks for identification of influential nodes and results shows the prominence the work over the existing measures. Furthermore, the technique has been applied to COVID-19 viral protein interactions. The proposed algorithm identified some critical human proteins that belong to the enzymes TMPRSS2, ACE2, and AT-II, which have a considerable role in hosting COVID-19 viral proteins and causes for various types of diseases. Hence these proteins can be targeted in drug design for an effective therapeutic against COVID-19.


A new species of the genus Platycleis Fieber, 1853 (Orthoptera: Tettigoniidae) from the Western and Trans Himalayas, India.
In India, the genus Platycleis was known only from P. kashmira (Uvarov, 1930). A new species, P. rahmoiensis sp. nov., with its type locality in Pulwama, Jammu Kashmir, Western Himalayas is described in this study. Additional specimens collected from the Ladakh region of the Trans Himalayas, India, indicate its broader distribution. The new species is described with detailed external and internal characters together with a dichotomous key for its distinction from P. kashmira. Based on the new species, we also report data on the acoustic signal from the genus for the first time from India.


Comparison of droperidol, haloperidol and prochlorperazine as postoperative anti-emetics.
The results of this study demonstrate that prochlorperazine, haloperidol and droperidol are all effective post-operative anti-emetic compounds when compared to saline but vary in onset of activity and duration of action. Haloperidol has the shortest onset of action, being effective within 30 minutes of intravenous administration. Prochlorperazine has an intermediate onset of action and droperidol is the slowest of the three compounds but the only one to provide significant anti-emesis 4-24 hours following administration. Our data suggest that a combination of haloperidol and droperidol may be more effective as an anti-emetic than any one of the compounds used alone.


[Current diagnosis of pulmonary embolism in Spain: ventilation-perfusion lung scan versus helical CT. Findings from the National Health Service and RIETE Registry].
To analyze the trends in the utilization of ventilation/perfusion pulmonary scintigraphy (V/QSc), spiral CT (sCT) and pulmonary angiography for diagnosis of pulmonary embolism (PE) in Spain, taking in account the information from the National System of Health (NSH) and RIETE Registry. To examine the diagnostic conformities of V/QSc and sCT in RIETE, with special reference to V/QSc of intermediate/indeterminate probability (V/QScIP). We examined annual trends of diagnostic imaging for PE in 5,678 Spanish patients included in RIETE (period 2001-2005) and in those of the NHS Databases (1999-2003 period). In RIETE the agreement between diagnostics was compared in cases with both V/QSc and sCT and angiography and V/QSc or sCT. We observed an increasing trend in sTC use, which overcame to V/QSc in 2002 (RIETE) and 2003 (NHS). In 732 cases with both techniques there was a diagnostic conformity of 53%. In 116 cases with V/QScIP a concomitant sTC was + for PE in 87%. If clinical signs of PE were present, then sTC was + in 95% of cases. In 29 cases with sCT and angiography agreement was 83% and in 31 cases with angiography and V/QSc was 77%. Nowadays in Spain the sTC is the most utilized method to diagnose EP. However, V/QSc studies are also broadly used. In studies V/QScIP it is advisable to look for deep venous thrombosis and, if present, the results of RIETE allow to assure EP coexistence in 87-95% of cases.


Clinical value of capsule endoscopy for detecting small bowel lesions in patients with intestinal Behçet's disease.
To evaluate the clinical value of capsule endoscopy (CE) in patients with intestinal Behçet's disease (BD). The present study was a case-control pilot study conducted in intestinal BD patients and healthy volunteers. A total of 19 patients with intestinal BD (intestinal BD group) and 19 healthy volunteers (control group) matched for age and sex were enrolled. Frequency, number of small bowel lesions per subject, and Lewis score were comparatively evaluated between the two groups. Of the 19 patients with intestinal BD, 18 (94.7%) had reddened lesions, 15 (78.9%) had erosions, and nine (47.4%) had ulcers. There were significant differences in the frequency of reddened lesions (P < 0.0001), erosions (P < 0.0001) and ulcers (P = 0.0011) between the two groups. The difference in the number of small bowel lesions between the two groups was also statistically significant. The median Lewis score in the intestinal BD group was significantly higher than that in the control group (intestinal BD group 237 (0-768) vs. control group 8 (0-135); P < 0.0001). Analysis according to the location in the small bowel revealed that the frequency of ulcers tended to increase towards the distal intestine. This is the first CE study conducted to examine small bowel involvement in intestinal BD patients. Our results suggest that CE evaluation is necessary, in addition to colonoscopy, in all intestinal BD patients.


Theoretical analysis of physicochemical processes occurring during water treatment by ozone and ultraviolet radiation.
The paper presents a kinetic model developed for ozone dissolution in water and taking into account convective and diffusion processes occurring in the vicinity of floating bubbles that contain an ozone-air mixture. It was shown that the gradient of ozone concentration in a convective-diffusion layer and consequently the rate of ozone transfer from bubbles to the solution depended on the rate of ozone decomposition both in its reaction with organic admixtures and in the conditions of exposure to ultraviolet radiation. The obtained kinetic curves of destruction of organic compounds and changes of ozone concentration in water and ozone-air mixture are compared with experimental data for humic acids. The paper also analyzes additional factors affecting the kinetics of ozone dissolution and the rate of resultant reactions.


Unaccompanied mechanosensory domain mediates low expression of glycoprotein Ibα: implications for Bernard-Soulier syndrome.
Disruption of protein folding or inter-subunit interactions in the platelet glycoprotein (GP)Ib-IX complex leads to its abnormally low expression in the plasma membrane, the hallmark of Bernard-Soulier syndrome (BSS). To discover the molecular mechanism by which GPIbα in the absence of GPIbβ and GPIX subunits is targeted for rapid degradation. The expression of GPIbα mutants with deletion or replacement of various domains were measured in transiently transfected Chinese hamster ovary cells. We report evidence to suggest that induction of the unfolded protein response by the unaccompanied mechanosensory domain (MSD) is a major factor for intracellular degradation and low expression of GPIbα. Removal of the MSD produced the first GPIbα variant that, even in the absence of GPIbβ and GPIX, expressed at a level comparable to that of wild-type GPIbα in the GPIb-IX complex, while retaining its native ligand-binding activity. Our finding has important implications on the molecular pathogenesis of BSS and the function of the GPIb-IX complex.


Biologic features and treatment outcome of secondary acute lymphoblastic leukemia--a review of 101 cases.
Secondary acute lymphoblastic leukemia (sALL) is a rare disease and its biologic features are not well characterized. We describe a cohort of seven patients and discuss 94 additional cases from the literature for whom biological parameters were described. Cases with incomplete data were excluded. Hodgkin's disease (HD) was more common in the 18-59 age group while breast and prostate cancers were prevalent only in the >or=18-year-old patients. The time interval to develop sALL was similar among all age groups but was significantly longer for HD and neuroblastoma primary diagnoses and sALL with complex karyotype. T-cell immunophenotype was more common in the <18 age group. Complete remission was infrequent in the >or=60 age group. The overall survival was poor for all sALL regardless of age, primary diagnoses, cytogenetic subgroups, or immunophenotype. Allogeneic transplantation most probably represents the only chance of cure. Better identification of prognostic factors to prevent the occurrence of sALL is indicated.


Characterization of Giardia duodenalis infections in dogs in Trinidad and Tobago.
To our knowledge, the zoonotic potential of Giardia duodenalis has not been assessed in companion animals in Trinidad and Tobago. This report details the first attempt to evaluate the potential zoonotic risk of G. duodenalis in dogs and identify assemblages of G. duodenalis found in dog populations on both islands. Fecal samples were collected from free-roaming dogs and dogs at the Trinidad and Tobago Society for the Prevention of Cruelty to Animals from October 2010 to June 2011. A total of 168 samples were collected of which 104 samples were analyzed for the presence of G. duodenalis by PCR amplification of the ssu-rRNA gene with subsequent assemblage-typing. A subset of samples was also analyzed by ELISA. Twenty-six samples were positive for G. duodenalis by PCR for an overall prevalence of 25%. Four samples were identified as assemblage C (15.4%), 21 as assemblage D (80.8%), and one as assemblage E (3.8%). Puppies were four-times more likely to be infected with G. duodenalis than adult dogs (OR 4.61, 95% CI 1.73-12.2). There was a significant agreement between ELISA and PCR in the detection of the protozoa (κ=0.67). We infer from our results that while the prevalence of G. duodenalis is relatively high in Trinidad and Tobago, the zoonotic risk of infection in humans is low since neither assemblage A nor B was identified in the study population.


Public Interest Report No. 27 : The need for teaching geriatric medicine.
Geriatric medicine, the body of knowledge relating to human aging and associated pathological conditions, must be incorporated systematically and comprehensively into American medical education. Students must be exposed to aging in the context of normal human development and be aware that some diseases present differently in the old.


Risk Factors for Hemorrhagic Stroke among Adults in the Democratic Republic of the Congo: A Hospital-Based Study in a Limited Resource Setting.
The prevalence of stroke is increasing in sub-Saharan Africa. The scarcity of hospital-based stroke data in Lubumbashi (in the Democratic Republic of the Congo) led to the study, which was designed to describe the epidemiology of stroke and identify risk factors associated with hemorrhagic stroke among adult patients in Lubumbashi. This was a cross-sectional study of 158 adult patients admitted for stroke in the internal medicine department of Lubumbashi University Clinics from January 2018 to December 2020. Sociodemographic and clinical features, cardiovascular risk factors, and hospital mortality were collected. A logistic regression has determined the risk of developing a hemorrhagic stroke. Of 9,919 hospitalized patients, 158 had a stroke with a hospital prevalence of 1.6%; 86 (54.4%) patients had a hemorrhagic stroke while 72 (45.6%) had an ischemic stroke. Of which 41.1% (65/158) were women. The mean age was 60.8 ± 13.3 years. Main clinical signs were hemiplegia (63.3%), headache (48.7%), speech disorders (38.6%), and dizziness (38.6%). Hypertension (82.9%) and hyperglycemia (53.2%) were the most common risk factors. Inhospital mortality was 22.8%. After logistic regression, independent predictors for developing hemorrhagic stroke were hypertension (aOR = 8.19; 95% CI: 2.72-24.66; p < 0.0001) and atrial fibrillation (aOR = 4.89; 95% CI: 1.41-16.89; p = 0.012). This study highlights the high stroke mortality in a resource-limited hospital and the burden of hypertension in the development of hemorrhagic stroke. It illustrates the need to establish stroke care setting to improve the quality of stroke care.


Triceps-to-Biceps Tendon Transfer for Restoration of Elbow Flexion in Brachial Plexus Injury.
Restoring elbow flexion is a reconstructive priority in patients with brachial plexus injuries. This study aimed to evaluate the results and assess factors contributing to outcomes of triceps-to-biceps tendon transfer in patients presenting with delayed or chronic upper brachial plexus injury. Patients with traumatic brachial plexus injuries undergoing triceps-to-biceps tendon transfer at a single institution's multidisciplinary brachial plexus center between 2001 and 2021 were retrospectively reviewed. The entire triceps tendon was transferred around the lateral aspect of the arm, secured to the radius with a tenodesis button, and reinforced with a side-to-side tendon transfer to the biceps tendon. Primary outcomes include the modified British Medical Research Council (mBMRC) elbow flexion strength and active elbow range of motion. Twelve patients (eight men and four women; mean age, 45.2 years) were included. The mean follow-up was 10.4 (range, 5-34) months. Nine patients achieved mBMRC ≥3. Five patients achieved mBMRC 4. Average active elbow flexion was 119°, with average extension deficit of 11°. There were three patients with unsatisfactory results, achieving mBMRC 2 elbow flexion. Triceps-to-biceps tendon transfer is an excellent tendon transfer option for restoring elbow flexion in certain patients with an adequately functioning triceps muscle, who present with a delayed or chronic brachial plexus injury. Although most patients achieved mBMRC ≥3 elbow flexion, there was an expected permanent loss of elbow active extension with a residual elbow flexion contracture. Therapeutic IV.


An in vivo clonogenic assay for human tumors using plasma clot diffusion chambers implanted in mice.
A modification of the in vivo tumor clonogenic assay using plasma clot diffusion chambers has been described which allows improved study of the cytological characteristics of the colonies cultured. Seventy-five percent of the tumors derived from malignant ascites could be cultured successfully (more than 30 small and large colonies per diffusion chamber). The cloning efficiency ranged from 0.01 to 10%. The addition of 2-mercaptoethanol, horse serum and insulin to the diffusion chambers did not affect colony formation, whereas the effect of cell-free malignant ascites added to the diffusion chambers was unpredictable. Colony growth was comparable when fresh or cryopreserved tumor cells were cultured. A linear relationship between the number of tumor cells inoculated and the number of colonies cultured was apparent in the range 10(2)-10(4) cells. Colony formation was stimulated by pre-irradiation (8 Gy) of the host animal and by weekly transplantation of the diffusion chambers in new mice. Intravenously administered doxorubicin penetrated the plasma clot and caused inhibition of colony formation in two experiments with melanoma cells.


Surveillance and control of post-transmission schistosomiasis in Jiaxing prefecture, Zhejiang province, China.
A surveillance system has been put in place in the Zhejiang province since achieving there the criteria for transmission interruption of schistosomiasis japonica. Suspected patients and special high-risk groups (e.g. the so called 'floating population' and children under 14 years of age) are screened for Schistosoma japonicum using serological tests. Those with positive serological result are subjected to faecal examination and if S. japonicum eggs are found they are treated with praziquantel and followed by regular re-examination until complete cure, i.e. absence of S. japonicum eggs in faecal samples. Patients with advanced schistosomiasis japonica are continuously followed-up. Implementation of the surveillance system from 1995 to 2002 detected two S. japonicum-infected persons; one came from Anhui province and the other from Jiangsu province, but no new infection occurred among local residents. The number of patients with advanced schistosomiasis japonica decreased from 1524 in 1995 to 906 by the end of 2002; a reduction of 40.6%. However, post-transmission schistosomiasis still continues to weigh on the medial resources. We conclude that the surveillance system in Zhejiang province is effective and a useful means for monitoring the endemic situation of schistosomiasis. Hence, it is recommended to be pursued in the years to come.


Sex-Based Considerations in the Evaluation of Chest Pain and Management of Obstructive Coronary Artery Disease.
Coronary artery disease (CAD) is a major cause of morbidity and mortality globally and poses a threat to both men and women across their lifespans. There is accumulating evidence to support that CAD may present differently in women and men, ranging from the clinical presentation, diagnosis, and management of the disease to underlying differences in the biological and pathophysiological mechanisms. This has called for an expansion of our conventional tools used in the diagnosis and management of obstructive CAD. Understanding these key sex differences will potentially help tailor our diagnostic and treatment strategies and provide equitable and optimal care to both men and women. Numerous studies have consistently shown that women with CAD tend to be older, have a higher burden of co-morbidities, and experience worse outcomes compared to their male counterparts. Women tend to wait longer to seek medical care for cardiovascular symptoms and when they do, they are usually referred late in the disease process and treated less aggressively. Women are significantly underrepresented in most cardiovascular clinical trials, thereby creating an important limitation in the evidence base used for treating cardiovascular disease in women. In this review, we sought to describe the sex-based considerations in evaluation and management of obstructive CAD, underscore the mechanisms behind these considerations, and help develop a more personalized approach according to current paradigms.


Correction to: Intercellular transmission of Seneca Valley virus mediated by exosomes.
An amendment to this paper has been published and can be accessed via the original article.


Immunochemical detection of metallothionein in brain.
Polyclonal and monoclonal antibodies have been used to determine the levels of metallothionein (MT) isoforms in the brain, its regions, and its cellular elements. MT is found abundantly in the astrocytes but not in the oligodendroglia or microglia. The induction of astrocytic metallothionein by cytokines suggests an important role for this protein in providing long-term protection against oxidative damage in tissue injury and inflammation.


Effects of combined inhibition of the Na+-H+ exchanger and angiotensin-converting enzyme in rats with congestive heart failure after myocardial infarction.
1 We investigated the single vs the combined long-term inhibition of Na(+)-H(+) exchanger-1 (NHE-1) and ACE in rats with congestive heart failure induced by myocardial infarction (MI). 2 Rats with MI were randomized to receive either placebo, cariporide (3000 p.p.m. via chow), ramipril (1 mg kg(-1) day(-1) via drinking water) or their combination for 18 weeks starting on day 3 after surgery. 3 Cardiac morphology and function was assessed by echocardiography and by means of a 2.0 F conductance catheter to determine left ventricular (LV) pressure volume relationships. 4 MI for 18 weeks resulted in an increase in LV end-diastolic diameter (LVDed) in the placebo-treated group when compared to sham (placebo: 1.1+/-0.04 cm; sham: 0.86+/-0.01; P<0.05). Combined inhibition of NHE-1 and ACE, but not the monotherapies, significantly reduced LVDed (1.02+/-0.02 cm). 5 Preload recruitable stroke work (PRSW), dp/dt(max) (parameter of systolic function) and end-diastolic pressure volume relationship (EDPVR, diastolic function) were significantly impaired in placebo-treated MI group (PRSW: 39+/-7 mmHg; dp/dt(max): 5185+/-363 mmHg s(-1); EDPVR: 0.042+/-0.001 mmHg microl(-1); all P<0.05). Cariporide treatment significantly improved PRSW (64+/-7 mmHg), dp/dt(max) (8077+/-525 mmHg s(-1)) and EDPVR (0.026+/-0.014 mmHg microl(-1)), and reduced cardiac hypertrophy in rats with MI. Combined inhibition of NHE-1 and ACE had even a more pronounced effect on PRSW (72+/-5 mmHg) and EDPVR (0.026+/-0.014 mmHg microl(-1)), as well as cardiac hypertrophy that, however, did not reach statistical significance compared to cariporide treatment alone. 6 The NHE-1 inhibitor cariporide significantly improved LV remodeling and function in rats with congestive heart failure induced by MI. The effect of cariporide was comparable or tended to be stronger (e.g. systolic function) compared to ramipril. Combined treatment with cariporide and ramipril tended to be more effective on LV remodeling in rats with heart failure than the single treatments. Thus, inhibition of the NHE-1 may be a promising novel therapeutic approach for the treatment of congestive heart failure.


Recombinant Candida utilis for the production of biotin.
Biotin is an important nutritional supplement but is difficult to manufacture effectively. Here we present a trial of biotin production using the food yeast Candida utilis. In this system, we cloned the C. utilis biotin synthase (BIO2) gene, the gene of the rate-limiting enzyme for biotin biosynthesis, and assembled it under the control of a strong promoter. A series of plasmids were constructed to direct the integration of the BIO2 gene, either high-copy integration with 18S rDNA fragment or low-copy integration with URA3 or HIS3 fragment. The BIO2 gene can be successfully integrated into the C. utilis chromosome and can drive biotin production using these plasmids. The biotin yield in this system can reach 100-fold above the endogenous level in a small-scale culture. Although the biotin production is not stable if the selection pressure is removed, this system has the potential to produce biotin-rich feed or food additives directly without the requirement of further purification.


Synthesis of ZnO coated multi-walled carbon nanotubes and their antibacterial activities.
ZnO coated multi-walled carbon nanotubes (ZnO/MWCNTs) were prepared and evaluated for their application potentials as an antimicrobial material for simultaneous concentrating and inactivating pathogenic bacteria. X-ray energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), and X-ray photoelectron spectra (XPS) were used to characterize the ZnO/MWCNTs. Escherichia coli (E. coli) was employed as the target bacterium. Comparing with the raw and the purified MWCNTs (r-MWCNTs and p-MWCNTs), which have been reported to possess antibacterial activity towards E. coli, ZnO/MWCNTs exhibited stronger antibacterial ability. The deposited ZnO was suggested to play an important role in the bactericidal action of ZnO/MWCNTs, while, the r-MWCNTs and p-MWCNTs served as more like adsorbing materials for E. coli.


Characterization of methicillin-resistant Staphylococcus aureus strains colonizing the nostrils of Spanish children.
To characterize the Staphylococcus aureus strains colonizing healthy Spanish children. Between March and July 2018, 1876 Spanish children younger than 14 years attending primary healthcare centers were recruited from rural and urban areas. Staphylococcus aureus colonization of the anterior nostrils was analyzed. MecA and mecC genes, antibiotic susceptibility, and genotyping according to the spa were determined in all strains, and the following toxins were examined: Panton-Valentine leucocidin (pvl), toxic shock syndrome toxin (tst), and exfoliative toxins (eta, etb, etd). Multilocus sequence typing (MLST) and staphylococcal cassette chromosome (SCCmec) typing were performed on methicillin-resistant Staphylococcus aureus (MRSA) strains, as well as pulsed-field gel electrophoresis (PFGE). 619 strains were isolated in 1876 children (33%), and 92% of them were sent for characterization to the Spanish National Centre of Microbiology (n = 572). Twenty (3.5%) of these strains were mecA-positive. Several spa types were detected among MRSA, being t002 the most frequently observed (30%), associating with SCCmec IVc. Among MSSA, 33% were positive for tst, while only 0.73% were positive for pvl. The 20 MRSA strains were negative for pvl, and 6 (30%) harbored the tst gene. methicillin-resistant Staphylococcus aureus nasal colonization in Spanish children is rare, with t002 being the most observed spa type, associated with SCCmec IVc. None of the MRSA strains produced pvl, but up to 30% of S. aureus strains were positive for tst.


Detecting the displacements of spatial beats: a monocular capability.
Sensitivity to the sudden displacement (phase shift) of a single monocularly presented sinusoidal grating is increased when a static grating of similar spatial frequency is presented to the same eye. If the static grating is presented to the other eye instead sensitivity is, at best, halved. This demonstration implies that monocular and binocular visual pathways differ in their sensitivity to spatial variations of contrast. In addition it provides another example in which the monocular visual pathways are more sensitive to spatial displacements than the binocular pathways.


Towards a logical analysis of the immune response.
We present a new way to conceive, formalize and analyse models of the immune network. The models proposed are minimal ones, based essentially on the well-established negative feedback loop between helper and suppressor T cells. The occurrence of T-T interactions in both helper and suppressor circuits. These T-T interactions are represented here by autocatalytic feedback loops on TH and TS. The fact that immature B cells are sensitive to negative signaling, as was originally suggested by Lederberg (1959). There is a functional inactivation of immature B cells encountering antigen or anti-idiotypic antibody. This prevents further differentiation to a stage where the B cells become fully responsive. We describe the role of a logical method in the generation and analysis of the models, and the complementarity between this logical method and the more classical description by continuous differential equations. Logical analysis and numerical simulations of the differential equations show that the emerging model accounts for, the occurrence of multiple steady states (a virgin state, a memory state and a non-responsive state) in the absence of antigen, the kinetics of primary and secondary responses, high dose paralysis, low dose of paralysis. Its fit with real situations is surprisingly good for a model of this simplicity. Nevertheless, we give it as an example of what can now be done in the field rather than as a stable model.


Enhanced bone formation in electrospun poly(L-lactic-co-glycolic acid)-tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide.
To engineer bone tissue, it is necessary to provide a biocompatible, mechanically robust scaffold. In this study, we fabricated an ultrafine nanofiber scaffold by electrospinning a blend of poly(L-lactic-co-glycolic acid), tussah silk fibroin, and graphene oxide (GO) and characterized its morphology, biocompatibility, mechanical properties, and biological activity. The data indicate that incorporation of 10 wt.% tussah silk and 1 wt.% graphene oxide into poly(L-lactic-co-glycolic acid) nanofibers significantly decreased the fiber diameter from 280 to 130 nm. Furthermore, tussah silk and graphene oxide boosted the Young's modulus and tensile strength by nearly 4-fold and 3-fold, respectively, and significantly enhanced adhesion, proliferation in mouse mesenchymal stem cells and functionally promoted biomineralization-relevant alkaline phosphatase (ALP) and mineral deposition. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering.


Effect of imidazolium based ionic liquids on CO-association dynamics and thermodynamic stability of Ferrocytochrome c.
Analysis of kinetic and thermodynamic parameters measured for CO-association reaction of Ferrocytochrome c (Ferrocyt c) under variable concentrations of 1-butyl-3-methylimidazolium with varying anion ([Bmim]X) (X = Cl-, I-, Br-, HSO4-) at pH 7 revealed that the low concentration of [Bmim]X (≤0.5 M) constrains the CO-association dynamics of Ferrocyt c and typically follows the order: [Bmim]HSO4 > [Bmim]Cl > [Bmim]Br > [Bmim]I. At relatively higher concentrations (>0.5), the chaotropic action of [Bmim]+ dominates which consequently increases the thermal-fluctuations responsible to denature the protein and thus accelerates the speed of CO-association reaction. Analysis of thermal denaturation curves of Ferrocyt c measured at different concentrations of [Bmim]X revealed that the [Bmim]X decreases the thermodynamic stability of protein and typically follows the order: [Bmim]I > [Bmim]Br > [Bmim]Cl > [Bmim]CH3COO > [Bmim]HSO4, demonstrating that the effect of [Bmim]X on thermodynamic stability of protein is not in accordance to Hofmeister series effect of anions because instead of increasing the kosmotropic anion carrying [Bmim]X ([Bmim]CH3COO and [Bmim]HSO4) also decreases the thermodynamic stability of protein.


St. Louis encephalitis in Memphis-Shelby County, Tennessee, 1975: epidemiologic aspects of human cases.
An epidemic of St. Louis encephalitis (SLE) occurred in Memphis-Shelby County, Tennessee, in the summer of 1975, as part of an outbreak involving large portions of the Eastern United States. A total of 187 suspected cases were reported, of which 62 were laboratory-confirmed or presumptive SLE. The overall attack rate was 8.1/100,000; rates were higher in lower socioeconomic districts. The case fatality rate was 19.4%. Climatologic data and related factors favoring the occurrence of this outbreak are discussed.


Mutations in and deletions of the Ca2+ channel-encoding gene cacophony, which affect courtship song in Drosophila, have novel effects on heartbeating.
The cacophony (cac) locus of Drosophila melanogaster encodes the a-1 subunit of a voltage gated Ca(2+) channel, termed Dmca1A. A subset of mutations at this locus cause characteristic alterations in the male mating song, manifest as polycyclic pulses with higher than normal amplitude. This phenotype has been postulated to result from disruption of an oscillator involving the cac-encoded channel, nearly identical to a model proposed for the pacemaker of the Drosophila heart. We report here that flies bearing two intragenic mutations that affect song, cac(S) and cac(TS2), cause aberrant heartbeating. Hearts of both cac(S) and cac(TS2) mutants beat significantly more rapidly than wild type and the heartbeat is more regular across temperature. Deletions of the cac gene, heterozygous with cac(+), caused interestingly similar heartbeating anomalies. For the heart phenotypes, the mutations are dominant, unlike the effects of cac(S) on song. In sum, our results establish the hypothesis that the observed effects are a result of a reduced number of functional cac-encoded channels rather than any specific alteration in the protein, and that in addition to Dmca1A, a second Ca(2+) channel with different kinetics is also involved in pacemaking.


Placenta to lamb fetus transfusion in utero during acute hypoxia.
Maternal and fetal hemodynamics, placental blood flow, fetal-placental blood volume, placental blood volume, and fetal blood volumes were measured in six chronic sheep prepartions to evaluate their changes during acute fetal hypoxia induced by maternal hypoxia. During fetal hypoxia, the maternal and fetal arterial blood pressure and heart rate were essentially unchanged. The placental blood flow (control equal to 325 ml.per kilogram per minute) was also unchanged during the hypoxia period. However, the placental blood volume decreased significantly from 65 to 60 and 51 ml. per kilogram at 15 and 30 minutes of hypoxia period, respectively. The fetal blood volume increased reciprocally and significantly from 86 to 109 and 102 ml. per kilogram at the same periods of hypoxia since the fetal-placental blood volumes were unchanged. These blood volume changes persisted for 30 to 60 minutes following the stoppage of hypoxia experiments. The placental vascular resistance measured in six experiments showed a significant increment during hypoxia, suggesting placental vasoconstriction as the responsible mechanism for the reduction of placental blood volume and reciprocal increase in fetal blood volume. The data suggest that significant placental transfusion to the lamb fetus may occur in utero during fetal hypoxia resulting in a higher fetal blood volume before birth.


A targeted activatable NIR-II nanoprobe for positive visualization of anastomotic thrombosis and sensitive identification of fresh fibrinolytic thrombus.
Anastomotic thrombosis prevalently causes anastomosis failure, accompanied with ischemia and necrosis, the early diagnosis of which is restricted by inherent shortcomings of traditional imaging techniques in clinic and lack of appropriate prodromal biomarkers for thrombosis initiation. Herein, a fresh thrombus-specific molecular event, protein disulfide isomerase (PDI) is innovatively chosen as the activating factor, and a thrombosis targeting and PDI-responsive turn-on near infrared II (NIR-II) fluorescence nanoprobe is firstly developed. The supramolecular complex-based nanoprobe IR806-PDA@BSA-CREKA is fabricated by assembling NIR-II emitting cyanine derivative IR806-PDA with bovine serum albumin (BSA), which could ameliorate the stability and pharmacokinetics of the nanoprobe, addressing the contradiction in the balance of brightness and biocompatibility. The NIR-II-off nanoprobe exhibits robust turn-on NIR-II fluorescence upon PDI-specific activation, in vitro and in vivo. Of note, the constructed nanoprobe demonstrates superior photophysical stability, efficient fibrin targeting peptide-derived thrombosis binding and a maximum signal-to-background ratio (SBR) of 9.30 for anastomotic thrombosis in NIR-II fluorescent imaging. In conclusion, the exploited strategy enables positive visualized diagnosis for anastomotic thrombosis and dynamic monitoring for thrombolysis of fresh fibrinolytic thrombus, potentially contributes a novel strategy for guiding the therapeutic selection between thrombolysis and thrombectomy for thrombosis treatment in clinic.


Impact of melatonin on periodontal ligament fibroblasts during mechanical strain.
The endogenous hormone melatonin regulates the circadian rhythm and impacts on bone metabolism. As patient compliance to wear removable orthodontic appliances is generally higher at night, when melatonin release is increased, a boosting effect on tooth movement would be favourable for therapy, whereas an inhibiting effect would indicate daytime wear to be more therapy-effective. We hypothesize that melatonin has either a stimulating or impeding effect on the expression profile of periodontal ligament fibroblasts (PDLF) during simulated orthodontic compressive and tensile strain, which would suggest either an accelerating or inhibiting impact on orthodontic tooth movement in vivo. PDLF were preincubated with melatonin for 24 h and then subjected to tensile or compressive strain to mimic tension and pressure sides in PDL. In addition, the selective melatonin MTNR1B-receptor antagonist 4P-PDOT was used. We investigated melatonin effects on collagen synthesis, expression of inflammatory and bone-remodelling genes/proteins by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and total collagen assays. PDLF-induced osteoclastogenesis was analysed in a coculture model by tartrate-resistant acid phosphatise (TRAP) staining. Expression of melatonin receptors in PDLF was not affected by compressive strain. Melatonin increased expression of inflammatory factors and elevated collagen synthesis during mechanical strain. Melatonin showed no effects on OPG or RANKL expression without mechanical strain, but increased RANKL gene expression during compression. Expression of melatonin receptors by PDLF enable them to detect fluctuating melatonin concentrations in the periodontal ligament. Melatonin increased collagen synthesis and expression of inflammatory mediators, but had no effect on genes involved in bone remodelling. Therefore, we suggest that melatonin has no accelerating effect on PDLF-induced osteoclastogenesis.


Production of monoclonal antibodies to serum antigens in colorectal carcinoma.
Two monoclonal antibodies (mAb) to colorectal cancer were produced using a novel immunization technique. This involved immunizing mice with whole serum obtained from patients with cancer of the colon (three with metastatic disease) and resulted in antibodies which were reactive with colonic tumor tissue by immunoperoxidase testing. Two mAbs (O-1, I-1) were isolated which were non-reactive with normal tissue and with tissues obtained from subjects with benign disease but were reactive with 34/50 (formalin-fixed) colon carcinoma specimens. Further testing on cell lines and other malignant tumors suggested both mAbs detect carcinoembryonic antigen (CEA) as their reactivities were similar to a known anti-CEA antibody, and they reacted with CEA in a solid-phase radioimmunoassay. The two mAbs were found to react with the same or closely associated epitopes on CEA by competitive tests. As the anti-CEA antibodies were made to serum (rather than tissue) CEA, it was possible that unique, highly specific mAb has been produced, particularly as there was a selective reaction of the mAbs for malignant but not normal tissues. A serum test with mAb I-1 was developed which detected raised serum CEA levels in 3/24 patients with benign colonic lesions, 7/19 patients with pancreatic cancer, 5/25 patients with colonic cancer but not in 20 normal individuals. There was direct correlation between these results and a commercially available CEA test kit.


Zonisamide improves wearing off in Parkinson's disease without exacerbating dyskinesia: Post hoc analysis of phase 2 and phase 3 clinical trials.
Although phase 2 and 3 clinical trials in Japan showed that zonisamide improved wearing off in patients with Parkinson's disease (PD), no studies to date have evaluated whether zonisamide improves wearing off in patients with PD without exacerbating dyskinesia. Therefore, we examined this hypothesis in a post hoc analysis of pooled data from the previous phase 2 and 3 trials. Both trials evaluated zonisamide 25 mg and 50 mg versus placebo during a 12-week treatment period. In our analysis, primary efficacy variables were adjusted mean change in wearing off (evaluated as change in "off" time) and dyskinesia from baseline to 12 weeks. Dyskinesia was evaluated using Unified Parkinson's Disease Rating Scale (UPDRS) part 4 items 32 (4-32; duration of dyskinesia) and 33 (4-33; disability of dyskinesia) score. Criteria outcomes included rates of patients meeting specific criteria based on off time plus UPDRS part 4-32 or 4-33. A total of 212 patients were included in this analysis. Zonisamide 50 mg significantly reduced off time and UPDRS part 4-33 score at week 12 versus placebo without increasing UPDRS part 4-32 score. The proportion of patients receiving zonisamide 50 mg who met the criterion "Off time decreased and UPDRS part 4-33 score did not increase" was significantly higher than that of patients receiving placebo. Zonisamide improves wearing off without exacerbating dyskinesia in Japanese patients with PD. Moreover, zonisamide 50 mg may improve dyskinesia. Further studies are needed to prospectively determine the benefits and clinical relevance of zonisamide on dyskinesia.


Pneumococcal infection--low awareness as a potential barrier to vaccination: results of a European study.
Elderly people and adults with chronic disease or compromised immune status are at increased risk of pneumococcal infection, with pneumonia being the most common serious presentation and a significant cause of morbidity and mortality. Most European countries have recommendations for pneumococcal vaccination but vaccination rates have remained low. In the present article, the authors present the results of a European survey that investigated the current level of awareness of pneumococcal infection among primary care physicians and specialists, and attitudes to vaccination in these physicians and members of the general public aged >50 years. Primary care physicians (n = 1,300) and specialists (n = 926) from 13 Western European countries participated in online/face-to-face interviews, and a further 6,534 individuals aged >50 years from a population sample reflecting local socio-demographic structure participated in telephone/face-to-face interviews. Pneumonia was the most well-known of the pneumococcal infections amongst primary care physicians and specialists. However, there was a relatively low awareness of the term invasive pneumococcal disease (IPD), with only 50% of primary care physicians and 71% of specialists reporting knowledge of the term IPD. Key factors influencing a physician's decision to prescribe pneumococcal vaccination were the patient's health condition, recommendations from health authorities, and the tolerability of the vaccine. Perceptions regarding vaccination were good amongst the members of the general public; individuals did not fear vaccines or their side effects. The main drivers for vaccination were recommendations from a healthcare professional and, to a lesser extent, that vaccination provides reassurance against contracting a disease. These findings highlight the low awareness of the term IPD in comparison with individual pneumococcal conditions. Given the importance of physician recommendations in encouraging patients to be vaccinated, primary care physicians need to be vigilant of patients at risk of pneumococcal infections in order to increase vaccination rates.


Carcinoma of the papilla of Vater. A review of fifty-seven cases.
Fifty-seven cases of carcinoma of the papilla of Vater are reviewed. Clinical and pathologic features as well as results of various surgical treatments are summarized. The Whipple operation may be the operation of choice for cancer of the papilla of Vater, offering a chance for cure and obviating further surgery.


The genetic toxicology of putative nongenotoxic carcinogens.
This report examines a group of putative nongenotoxic carcinogens that have been cited in the published literature. Using short-term test data from the U.S. Environmental Protection Agency/International Agency for Research on Cancer genetic activity profile (EPA/IARC GAP) database we have classified these agents on the basis of their mutagenicity emphasizing three genetic endpoints: gene mutation, chromosomal aberration and aneuploidy. On the basis of results of short-term tests for these effects, we have defined criteria for evidence of mutagenicity (and nonmutagenicity) and have applied these criteria in classifying the group of putative nongenotoxic carcinogens. The results from this evaluation based on the EPA/IARC GAP database are presented along with a summary of the short-term test data for each chemical and the relevant carcinogenicity results from the NTP, Gene-Tox and IARC databases. The data clearly demonstrate that many of the putative nongenotoxic carcinogens that have been adequately tested in short-term bioassays induce gene or chromosomal mutations or aneuploidy.


Amine donor protein substrates for transglutaminase activity in Caenorhabditis elegans.
Transglutaminase dependent cross-linking of proteins has been implicated in a wide range of biological phenomena occurring in both extracellular and intracellular compartments. Clarification of the physiological role of transglutaminases requires identification of substrate molecules. Here we report the detection, purification, and identification by mass spectrometry of proteins, the glutamate dehydrogenase, a protein disulfide isomerase, and aldehyde dehydrogenase as amine donor substrates for the transglutaminase activity of the nematode Caenorhabditis elegans utilizing a novel biotinylated oligoglutamine peptide as a substrate. We also purified and identified streptavidin-binding proteins of the worm.


'Lateral Aberrant Thyroid Carcinoma' or 'Thyroglossal Duct Cyst Carcinoma Metastasizing to Neck Node': Can we Decide in this Interesting Case Report?
Lateral aberrant thyroid(LAT) belongs to subset of ectopic thyroid, mostly presenting as asymptomatic lateral neck swelling and are challenging to diagnose without histopathological examination. Malignant transformation in LAT is even rare and is best managed by surgical excision. Here, we report a case of papillary carcinoma of LAT, but with an unusual post-operative finding, revealing papillary carcinoma of thyroglossal duct cyst.


A bibliographic database on economic analysis of natural forest disturbances.
The data presented here are related to the research paper entitled "Economic Analysis of Natural Forest Disturbances: A Century of Research" (Montagné-Huck and Brunette, 2018). Natural disturbances have always affected forest ecosystems, altering or disrupting the flows of goods (wood, non-timber products, etc.) and services (scenic and recreation values, leisure pursuits, clean water, regulation of floods, etc.) provided by forests to human societies. Economic analysis can help private or public decision-makers take forest policy decisions by understanding the causes and consequences of forest disturbances, as well as evaluating tradeoffs in alternative policy scenarios. In consequence, the economic literature about natural disturbances is very rich and diversified. This paper describes a bibliographic database gathering some 340 scientific papers related to the economic analysis of forest natural disturbances. Papers have been inventoried primarily thanks to searches on databases (JSTOR, ScienceDirect, Ingentaconnect and NRC Research Press) using specific keywords and the dataset have been completed by searching through literature-cited sections of papers. Relevant papers have been manually encoded into a database (Excel file) taking into consideration each type of hazard (storm, fire, snow, pests and diseases, etc.) and different economic approaches. Data cover papers published in English from 1916 to 2014.


Heavy Menstrual Bleeding-Visual Analog Scale, an Easy-to-Use Tool for Excessive Menstrual Blood Loss That Interferes with Quality-of-Life Screening in Clinical Practice.
Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss that interferes with quality of life (QoL). The methods for assessing HMB are not suited for clinical practice. We analyzed the validity of a combined visual analog scale (VAS) tool assessing the intensity of menstrual bleeding (VASInt) and its impact on activities of daily living (VASImp) to identify women with HMB. Analysis conducted in the data set used to validate the Spanish HMB screening tool SAMANTA questionnaire. A logistic regression analysis was used to construct the model. Reference standard was the pictorial blood loss assessment chart (PBAC). The performance of the HMB-VAS and the SAMANTA questionnaire was compared. Correlation with SAMANTA questionnaire, PBAC, and other QoL measurements was assessed. The resulting function (HMB-VAS score = 10.86 × VASInt score +2.48 × VASImp score) showed a slightly lower accuracy versus the SAMANTA questionnaire (86.8% vs. 87.9%) but a similar area under the curve: 0.9396 versus 0.943, respectively (p = 0.6605). The cutoff point was established as 700. After rounding the regression coefficients, the resulting function (11 × VASInt +2 × VASImp) showed 87.6% accuracy. The correlation of HMB-VAS with the SAMANTA questionnaire was strong (r: 0.79819; p < 0.0001), whereas the correlation was moderate to strong with the PBAC (0.59299; p < 0.0001) and weak with the QoL (EuroQoL five dimensions five levels questionnaire [EQ-5D-5L]) and well-being (Psychological General Well-Being Index [PGWBI]) scales (EQ-5D-5L VAS and Index: -0.20332 and -0.24384; PGWBI: -0.21680; p < 0.0001 for both). The HMB-VAS shows good performance for HMB screening, providing an easy-to-use alternative to other psychometric tools.


Differential expression of immediate early genes in rubrospinal neurons following axotomy in rat.
Many immediate early genes are rapidly and transiently expressed in the central nervous system following a variety of stimuli. Damage to the axons of peripheral and certain central neurons has been shown to result in a long-term increase in expression of c-Jun in the parent cell bodies. In the peripheral nervous system this increased expression of c-Jun protein and mRNA develops over 24 h following sciatic nerve section and is maintained if the damaged nerve is ligated, but returns to basal levels if the peripheral nerve is allowed to regenerate. Here, we report on the response of rubrospinal neurons to spinal cord hemisection at levels C3 and T10. c-Jun expression was first seen at 12 h post-lesion in a limited number of rubral neurons. The number of positively stained neurons increased up to 10 days post-lesion and then declined over the following weeks. By 7 weeks post-lesion there was still evidence of c-Jun immunoreactivity in both large and other clearly atrophic rubrospinal neurons. c-Fos immunoreactivity was seen only at 12-48 h in a small number of rubrospinal neurons. Evidence from retrograde tracing experiments following fluorogold application to the hemisected cord suggested that all c-Jun-positive neurons projected into the spinal cord. No c-Jun response was seen following a lesion at T10.(ABSTRACT TRUNCATED AT 250 WORDS)


Novel rearrangements in the staphylococcal cassette chromosome mec type V elements of Indian ST772 and ST672 methicillin resistant Staphylococcus aureus strains.
Staphylococcus aureus is a commensal gram positive bacteria which causes severe and non severe infections in humans and livestock. In India, ST772 is a dominant and ST672 is an emerging clone of Staphylococcus aureus. Both cause serious human diseases, and carry type V SCCmec elements. The objective of this study was to characterize SCCmec type V elements of ST772 and ST672 because the usual PCR methods did not amplify all primers specific to the type. Whole genome sequencing analysis of seven ST772 and one ST672 S. aureus isolates revealed that the SCCmec elements of six of the ST772 isolates were the smallest of the extant type V elements and in addition have several other novel features. Only one ST772 isolate and the ST672 isolate carried bigger SCCmec cassettes which were composites carrying multiple ccrC genes. These cassettes had some similarities to type V SCCmec element from M013 isolate (ST59) from Taiwan in certain aspects. SCCmec elements of all Indian isolates had an inversion of the mec complex, similar to the bovine SCCmec type X. This study reveals that six out of seven ST772 S. aureus isolates have a novel type V (5C2) SCCmec element while one each of ST772 and ST672 isolates have a composite SCCmec type V element (5C2&5) formed by the integration of type V SCCmec into a MSSA carrying a SCC element, in addition to the mec gene complex inversions and extensive recombinations.


The Importance of PbtO2 Probe Location for Data Interpretation in Patients with Intracerebral Hemorrhage.
Monitoring of brain tissue oxygen tension (PbtO2) provides insight into brain pathophysiology after intracerebral hemorrhage (ICH). Integration of probe location is recommended to optimize data interpretation. So far, little is known about the importance of PbtO2 catheter location in ICH patients. We prospectively included 40 ICH patients after hematoma evacuation (HE) who required PbtO2-monitoring. PbtO2-probe location was evaluated in all head computed tomography (CT) scans within the first 6 days after HE and defined as location in the healthy brain tissue or perilesional when the catheter tip was located within 1 cm of a focal lesion (hypodense or hyperdense). Generalized estimating equations were used to investigate levels of PbtO2 in relation to different probe locations. Patients were 60 [51-66] years old and had a median ICH-volume of 47 [29-60] mL. Neuromonitoring probes remained for a median of 6 [2-11] days. PbtO2-probes were located in healthy brain tissue in 18/40 (45%) patients and in perilesional brain tissue in 22/40 (55%) patients. In the acute phase after HE (0-72 h), PbtO2 levels were significantly lower (21 ± 12 mmHg vs. 29 ± 10 mmHg, p = 0.010) and brain tissue hypoxia (BTH) was more common in the perilesional area as compared to healthy brain tissue (46% vs. 19%, adjOR 4.0, 95% CI 1.54-10.58, p = 0.005). Episodes of BTH significantly decreased over time in patients with probes in perilesional location (p = 0.001) but remained stable in normal appearing area (p = 0.485). A significant association between BTH and poor functional outcome was only found when probes were located in the perilesional brain tissue (adjOR 6.6, 95% CI 1.3-33.8, p = 0.023). In the acute phase, BTH was more common in the perilesional area compared to healthy brain tissue. The improvement of BTH in the perilesional area over time may be the result of targeted treatment interventions and tissue regeneration. Due to the localized measurement of invasive neuromonitoring devices, integration of probe location in the clinical management of ICH patients and in research protocols seems mandatory.


Sense of meaning and purpose in life and risk of incident dementia: New data and meta-analysis.
A greater sense of meaning and purpose in life is associated with lower dementia risk. The present research examines meaning and incident dementia in the largest sample to date, the UK Biobank, and combines the findings with the published literature on meaning/purpose and dementia risk in a meta-analysis. Participants from the UK Biobank reported on their meaning in life in the 2016/2017 mental health assessment (N=153,445). All-cause and cause-specific dementia were derived from hospital and death records through November 2021. Cox regression was used to test the association between meaning in life and risk of incident dementia. Results from the UK Biobank were combined with published studies identified through a systematic literature review in a random-effect meta-analysis (k=8; total N=214,270). UK Biobank participants were followed up to five years after their assessment of meaning in life; 551 participants developed dementia. For every one-point higher feeling of meaning, there was a 35% decreased risk of all-cause dementia (HR=.74, 95% CI=.67-.82, p<.001). The association was similar controlling for clinical and behavioral risk factors and was not moderated by age, sex, education, or APOE risk status. Similar associations were found for Alzheimer's disease and vascular dementia. The meta-analysis supported the protective association between meaning/purpose and lower dementia risk (HR=.76, 95% CI=.72-.79, p<.001). The present research supports the growing literature that meaning and purpose in life have a robust association with lower risk of developing dementia. Meaning/purpose is a promising intervention target for healthier cognitive outcomes in older adulthood.


In vitro inhibitory effects of plumbagin, the promising antimalarial candidate, on human cytochrome P450 enzymes.
To investigate the propensity of plumbagin to inhibit the three isoforms of human cytochrome P450 (CYP), i.e., CYP1A2, CYP2C19, and CYP3A4 using human liver microsomes in vitro. Inhibitory effects of plumbagin on the three human CYP isoforms were investigated using pooled human liver microsomes. Phenacetin O-deethylation, omeprazole hydroxylation and nifedipine oxidation were used as selective substrates for CYP1A2, CYP2C19 and CYP3A4 activities, respectively. Concentrations of paracetamol, 5-hydroxyomeprazole, and oxidized nifedipine were determined in microsomal incubation mixture using high-performance liquid chromatography. Plumbagin showed significant inhibitory effects on all CYP isoforms, but with the most potent activity on CYP2C19-mediated omeprazole hydroxylation. The IC50 (concentration that inhibits enzyme activity by 50%) values of plumbagin and nootkatone (selective inhibitor) for CYP2C19 were (0.78 ± 0.01) and (27.31 ± 0.66) μM, respectively. The inhibitory activities on CYP1A2-mediated phenacetin O-deethylation and CYP3A4-mediated nifedipine oxidation were moderate. The IC50 values of plumbagin and α-naphthoflavone (selective inhibitor) for CYP1A2 were (1.39 ± 0.01) and (0.02 ± 0.36) μM, respectively. The corresponding IC50 values of plumbagin and ketoconazole (selective inhibitor) for CYP3A4 were (2.37 ± 0.10) and (0.18 ± 0.06) μM, respectively. Clinical relevance of the interference of human drug metabolizing enzymes should be aware of for further development scheme of plumbagin as antimalarial drug when used in combination with other antimalarial drugs which are metabolized by these CYP isoforms.


N6-methyladenosine (m6A) writer KIAA1429 accelerates gastric cancer oxaliplatin chemoresistance by targeting FOXM1.
Chemical modification plays a critical role in regulating human cancer progression, especially N6-methyladenosine (m6A). However, m6A writer KIAA1429-mediated m6A modification in gastric cancer (GC) tumorigenesis remains largely unknown. The levels of mRNA and protein were detected using RT-qPCR and western blot. The half maximal inhibitory concentration (IC50) of oxaliplatin (OXA) resistance is detected using CCK-8 assay. The binding within moleculars was identified using RIP-PCR. Results found that KIAA1429 was upregulated in GC tissue samples and its high expression acted as a prognostic factor of poor survival in patients with GC. Functional assays indicated that KIAA1429 promoted the proliferation of GC cells, besides, KIAA1429 accelerated the half maximal inhibitory concentration (IC50) of oxaliplatin (OXA) resistance. Mechanistically, online prediction found that there was possible m6A modification site on FOXM1 mRNA. KIAA1429 could target the m6A modification site on FOXM1. Notably, KIAA1429 facilitated the GC OXA resistance in GC cells by promoting FOXM1 mRNA stability. Taken together, our study reveals the functions and mechanism for KIAA1429 and exposes KIAA1429 as a key player in GC chemoresistance.


Cor Triatriatum Sinistrum: Classification and Imaging Modalities.
Cor Triatriatum Sinister is a rare congenital abnormality, usually diagnosed in childhood; few cases remain asymptomatic and are diagnosed in adulthood. In this review article we focus on classification and etiologies, clinical manifestations, novel diagnostic modalities and treatment of Cor triatriatum Sinister.


Association between Serum Lipid Profiles and Early Neurological Deterioration in Acute Ischemic Stroke.
Dyslipidemia is associated with chronic cardiovascular disease. However, the effect of dyslipidemia on acute ischemic stroke is unclear. We hypothesized that dyslipidemia could contribute to early neurological deterioration (END) after ischemic stroke. A total of 410 acute ischemic stroke patients who were admitted to our stroke center within 24 hours after ictus were consecutively included in this study. END was defined as any new neurological symptoms/signs or any neurological worsening occurring during the admission and/or within 3 weeks after the index stroke. Multivariable logistic regression was used to examine the independent association between lipid indices and END. Mean age was 68.2 ± 13.3 years, 241 (58.8%) were male, and 78 (19.0%) experienced END. Almost END occurred within 3 days after admission (n = 70, 89.7%), and the majority of END was stroke progression (n = 68, 87.1%). In univariate analysis, high-density lipoprotein (HDL)-cholesterol levels (per 1 mmol/L; odds ratio [OR] .37; 95% CI .17-.80; P = .012) and apolipoprotein B (apoB)/apoA-I ratio (per 1 increase; OR 3.71; 95% CI 1.48-9.29; P = .005) were associated with END. In the multivariable analysis, adjusted ORs of END for the highest quartile of HDL-cholesterol and apoB/apoA-I ratio were .42 (95% CI .19-.94; P = .034) and 2.37 (95% CI 1.02-5.53; P = .045), respectively. The ratio of apoB/apoA-I was associated with END in large artery atherosclerosis stroke but not in other stroke subtypes. Independent association of low HDL-cholesterol and high apoB/apoA-I ratio with END warrants further research to investigate if correction of the lipid profile during the acute period of ischemic stroke could reduce the risk of END.


Absorption of 2-acetylaminofluorene in the guinea-pig colon.
Absorption of the known chemical carcinogen, 2-acetylaminofluorene has been measured in the colon of guinea pigs. Unidirectional influx across the luminal cell membrane was determined in vitro, and transmural absorption across colonic mucosa was evaluated in vivo. The kinetics of unidirectional influx into colon in vitro do not indicate that absorption proceeds by simple diffusion. The observed saturable uptake is indicative of binding of 2-acetylaminofluorene to a cellular component. With 2-acetylaminofluorene present in the lumen in vivo at an initial concentration of 3.5 microM, the rate of absorption decreases over a 20 min period, which also indicates some form of specific interaction between 2-acetylaminofluorene and the intestinal mucosa. We have evaluated the hypothesis that surfactants and a bile salt act as cocarcinogens by increasing the rate of intestinal absorption of 2-acetylaminofluorene. The results lend no support to this possibility.


Decreased glomerular filtration rate is a significant and independent risk for in-hospital mortality in Japanese patients with acute myocardial infarction: report from the Hokkaido acute myocardial infarction registry.
Renal dysfunction is a significant risk factor in the prognosis of patients with cardiovascular diseases. We sought to determine the relationship between estimated glomerular filtration rate (eGFR) values and in-hospital mortality in Japanese acute myocardial infarction (AMI) patients. A total of 2266 consecutive AMI patients admitted to 22 hospitals in Hokkaido were registered. The eGFR values were determined using the following equation: eGFR=194 × (serum creatinine)(-1.094) × (age)(-0.287) ( × 0.739 if female). Patients were classified into four groups according to their eGFR values: ≥60 (n=1304), 30-59 (n=810), 15-29 (n=87) and <15 ml min(-1) per 1.73 m(2) (n=65). A total of 110 patients (4.9%) died during hospitalization. The in-hospital mortality rate was significantly higher in patients with reduced eGFR values at 2.3, 5.4, 24.1 and 23.1% for eGFR values of ≥60, 30-59, 15-29, and <15 ml min(-1) per 1.73 m(2), respectively. The odds ratios for in-hospital all cause death were 8.26 (95% confidence interval (CI): 2.22-30.77) for eGFR<15 ml min(-1) per 1.73 m(2) and 3.42 (95% CI: 1.01-11.61) for eGFR 15-29 ml min(-1) per 1.73 m(2) compared with eGFR ≥60 ml min(-1) per 1.73 m(2). Similarly, the odds ratios for in-hospital cardiac death were 8.43 (95% CI: 1.82-39.05) for eGFR<15 ml min(-1) per 1.73 m(2) and 5.47 (95% CI: 1.51-19.80) for eGFR 15-29 ml min(-1) per 1.73 m(2). In conclusion, the eGFR of <30 ml min(-1) per 1.73 m(2) was a significant and independent risk for in-hospital mortality in abroad cohort of Japanese patients with AMI.


New concepts in the treatment of elderly hypertensive patients.
Present evidence from several secondary and primary prevention trials indicates that if antihypertensive treatment is initiated with a cardioselective beta-blocker such as metoprolol, a better preventive effect on total mortality, cardiovascular mortality, and atherosclerotic complications can be expected than if diuretics are used as initial therapy. Results from a large-scale, multicenter international study have shown that a regimen in which antihypertensive treatment is initiated with metoprolol once daily is effective, safe, and well tolerated in elderly hypertensive patients. This might be of particular importance since a steep increase in cardiovascular mortality and other atherosclerotic complications is seen with age. In many elderly hypertensive patients, symptoms of heart failure might be caused by poor filling in stiff hearts rather than ineffective systolic contractions. By reducing heart rate with use of a cardioselective beta-blocker, diastole will be prolonged; this will improve filling and hence stroke volume and will increase coronary flow. Long-term treatment with metoprolol has also been found to reduce left ventricular systolic wall stress, reverse hypertrophy, improve left ventricular compliance, decrease the stiffness of large arteries, reduce total peripheral resistance, and reduce albuminuria. The improvement in the stiffness of the large arteries might be of particular clinical importance in elderly patients who have isolated systolic hypertension.


Health nurses' experiences and attitudes regarding collaboration with dental personnel.
Collaboration between primary care personnel and dental personnel to prevent early childhood caries has been established in several countries. The purpose of this study was, firstly, to describe health nurses' experiences and attitudes regarding collaboration with dental personnel, and secondly, to identify characteristic of health nurses and health centres associated with the collaboration. Health nurses working with children answered a questionnaire. In total, 163 of 296 health nurses (55 %) reported demographic information, referral routines, frequency of and reasons for referral of young children to dental personnel, contact with dental personnel and satisfaction with the collaboration. Data were analysed using multivariate logistic regression. The majority of health nurses (83 %) were familiar with referral routines and 31 % reported referring children to dental personnel monthly or more often. The most frequent reasons for referral were clinical caries (52 %), dental discolouration (38 %) and dental trauma (34 %). Few health nurses (18 %) had contact with dental personnel monthly or more often. Two-thirds of health nurses (71 %) reported being satisfied with the collaboration with dental personnel. Results of multivariate analysis showed that health nurses were more likely to refer children when the proportion of immigrant children under care in the health centres was high than when proportion of immigrant children was low (OR 6.4, CI 2.7-14.9). Health nurses working in small health centres were more likely to be satisfied with the collaboration than health nurses working in large health centres (OR 3.2, CI 1.4-7.0). Health nurses 45 years or older were more likely to possess knowledge of referral routines than younger health nurses (OR 2.7, CI 1.1-6.4). The results indicated that the majority of health nurses possessed knowledge of collaboration routines and were satisfied with the collaboration. The proportion of immigrant children under care in the health centres, the size of the health centres and the age of health nurses were factors influencing the collaboration between primary care personnel and dental personnel.


Substituting inpatient rehabilitation beds for home-based multidisciplinary rehabilitation: A qualitative study of patient perceptions.
To understand the patients' perspectives of the pilot Better at Home program in order to inform the development of bed substitution rehabilitation services. Prospective qualitative study using semi-structured interviews undertaken 3-6 months following program participation was performed. Interviews were transcribed and themes developed by two independent researchers. Nineteen participants (14 females) were interviewed. Major themes found included high satisfaction with the service and a high regard for the importance of communication both within the team and with the patients. Patients had inconsistent views on the provision of services with some feeling that the program was not specific to their needs, whilst others felt it was focused and flexible. Involvement in decision-making for referral to the service was also not always fully understood. This study provides important information that can be utilised in the development of any bed substitution home-based model of care.


ER-phagy in neurodegeneration.
There are many cellular mechanisms implicated in the initiation and progression of neurodegenerative disorders. However, age and the accumulation of unwanted cellular products are a common theme underlying many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Niemann-Pick type C. Autophagy has been studied extensively in these diseases and various genetic risk factors have implicated disruption in autophagy homoeostasis as a major pathogenic mechanism. Autophagy is essential in the maintenance of neuronal homeostasis, as their postmitotic nature makes them particularly susceptible to the damage caused by accumulation of defective or misfolded proteins, disease-prone aggregates, and damaged organelles. Recently, autophagy of the endoplasmic reticulum (ER-phagy) has been identified as a novel cellular mechanism for regulating ER morphology and response to cellular stress. As neurodegenerative diseases are generally precipitated by cellular stressors such as protein accumulation and environmental toxin exposure the role of ER-phagy has begun to be investigated. In this review we discuss the current research in ER-phagy and its involvement in neurodegenerative diseases.


Juvenile granulosa cell tumor of the testis.
Juvenile granulosa cell tumor of the testis is a rare type of intermediate stromal cell tumor. Only 11 cases of juvenile granulosa cell tumor of the testis have been reported to the national tumor registry as of December 2001. We report an additional case of primary juvenile granulosa cell tumor of the testis. The benign lesion was managed successfully with orchiectomy, and follow-up computed tomography revealed no evidence of recurrence at 6 months. The histopathologic features, treatment, and prognosis of this unusual tumor are reviewed.


Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells.
Notch signalling is essential for the development and maintenance of the colonic epithelium. Its inhibition induces a differentiation phenotype in vivo and reduces adenomas in APCmin mice. Whether Notch signals are also required in colorectal cancer (CRC) has remained elusive. Therefore, 64 CRC cell lines were analysed for the occurrence of proteolytically processed, active Notch. 63 CRC lines contained a fragment with approximately the size of the Notch1 intracellular domain (NICD), which is required for signalling. Subsequent analyses with an antibody that specifically recognises the free Val1744 residue generated by gamma-secretase-mediated cleavage of Notch1 showed that a subset of CRC cells lacks this specific Val1744-NICD. Surprisingly, inhibition of Val1744-NICD signalling with different gamma-secretase inhibitors (GSI) did not lead to substantial effects on CRC cell line growth or survival. However, transient activation of Erk upon GSI treatment was detected. Since cisplatin relies on Erk activation for bioactivity in some cells, platinum compounds were tested together with GSI and enhanced cell killing in a subset of Val1744-NICD-positive CRC cell lines was detected. Erk inhibition ablated this combination effect. We conclude that gamma-secretase inhibition results in activation of the MAP kinases Erk1/2 and, when used in conjunction, enhances cell death induced by platinum compounds in a large subset of colorectal cancer cell lines.Furthermore the activation of Erk appears to be of particular importance in mediating the enhanced effect seen, as its inhibition abrogates the observed phenomenon. These findings do not only highlight the importance of signalling pathway crosstalk but they may also suggest a new avenue of combination therapy for some colorectal cancers.


More evidence required to establish link between premature birth and altered oral development.
PubMed provided the primary data source with references from identified papers being reviewed to find additional studies. Reports were selected of controlled studies that provided quantitative data on the effects of premature birth on jaws, dentition, dental physiology and tooth anomalies, which were published in the English language. Two independent evaluators extracted data describing the year of publication, definition of prematurity, sample size, material and age, methods and measurements, outcomes and authors' conclusions. Correlation between deformity/alteration and prematurity, intubation and sucking habit were considered. Methodological soundness was assessed and the quality of each article categorised as low, medium or high. A total of 13 articles met the inclusion criteria. Quality was judged to be high for three studies, medium for nine studies and low for a single study. The chosen studies described altered palatal morphology (n=5), altered dental maturation (n=5) and altered tooth-crown dimensions (n=3). The limited evidence suggests there may be a correlation between prematurity and altered palate morphology in the short term, with oral intubation as a contributing factor. If corrected age was considered no delay was found in maturation. This systematic review revealed contradictory results and a dearth of longitudinal studies in this subject area. Further well-designed controlled and longitudinal studies are required before any conclusions can be made regarding the consequences of premature birth on oral development.


[Electron-histochemical identification and differentiation of the chemical composition of the supramembranous layer of kidney cells].
The supramembrane layer of cells in various parts of renal nephron in rats and dogs was determined with the help of colloid ferrum. The study of the chemical composition of the supramembrane layer of podocytes, epithelium of the distal tubules, thin segment, collecting tubules and endothelia of blood capillaries revealed in it the presence of carboxyl groups referring to sialic acid, the latter being bound with protein, not with lipids.


Comprehensive feasibility evaluation of small-diameter 3D templated vascular graft via physical characterizations andin-vivoexperiments.
3D printing (3DP) technology for tissue engineering applications has been extensively studied for materials and processes. However, clinical application to the vascular system was limited owing to mechanical inconsistency and toxicity. Here, we characterized 3D templated artificial vascular grafts (3D grafts), which were fabricated by an integrative method involving 3DP, dip coating, and salt leaching method. The as-fabricated grafts were featured with micrometer-scale porosity enabling tissue-mimetic mechanical softness comparable with native blood vessels. In terms of mechanical properties and water permeability, the fabricated 3D grafts exhibited comparable or superior performances compared to the commercialized grafts. Furthermore, thein-vivostability of the 3D graft was validated through a toxicity test, and the small-diameter 3D graft was transplanted into a rat to confirm the implant's performance. Overall, the experimental results demonstrated the clinical feasibility of the 3D graft with retaining the mechanical biocompatibility and also revealed the possibility of patient-specific customization.


A randomised observational study of individualised variations in the start position of the closed-kinetic chain upper extremity stability test.
To assess the reliability, precision and differences between scores produced using the standard 36″ start position and 3 modified start positions of the Closed Kinetic Chain Upper Extremity Stability Test (CKCUEST), towards normalisation to the individual. RCT of 4 conditions. Clinical. Thirty-four asymptomatic individuals. Using an RCT method, variations in CKCUEST starting hand position were tested using hand spacing at standard 36″, 50% height, bi-acromial distance, and bi-acromial distance with reach to 36″. The average number of touches over 3 × 15 s maximal efforts were used to assess the intra-variation reliability, minimum detectable change (MDC) and differences to the standard 36″ start position. The most reliable variation was the 50% height (ICC: 0.93) and with the smallest MDC (14%). 36″ results were second-most reliable (ICC: 0.90), with a low MDC (19%). Significant differences were found between bi-acromial and 50% height to the 36″ standard setup. A setup position where the hand separation is 50% of the individual's height offers excellent repeated measures reliability and the smallest MDC, suggesting it is the most sensitive to change and is a recommendation to clinicians. Conversion calculations between start variations are presented.


Symptoms of posttraumatic stress disorder among targets of school bullying.
The aim of this study was to investigate whether bullying among students is associated with symptoms of posttraumatic stress disorder (PTSD), and whether associations are comparable to other traumatic events leading to PTSD. Data were collected from 219 German children and adolescents: 150 students from grade six to ten and 69 patients from an outpatient clinic for PTSD as a comparison group. Symptoms of PTSD were assessed using the Children's Revised Impact of Event Scale (CRIES) and the Posttraumatic Symptom Scale (PTSS-10). A 2 × 5 factorial analysis of variance (ANOVA) with the factors gender (male, female) and group (control, conflict, moderate bullying, severe bullying, traumatized) was used to test for significant differences in reported PTSD symptoms. Results showed that 69 (46.0%) students from the school sample had experienced bullying, 43 (28.7%) in a moderate and 26 (17.3%) in a severe way. About 50% of the severe bullying group reached the critical cut-off point for suspected PTSD. While the scores for symptoms of PTSD were significantly higher in bullied versus non-bullied students, no significant differences were found between patients from the PTSD clinic and students who experienced severe bullying. Our findings suggest that bullying at school is highly associated with symptoms of PTSD. Thus, prevention of bullying in school may reduce traumatic experiences and consequent PTSD development.


Effect of Ca2+ on the ciliary beat frequency of skinned dog tracheal epithelium.
Beat frequency of dog tracheal ciliated epithelium was measured using a profile projector and a photomultiplier. The preparation, treated with 50 micrograms/ml of saponin for 15 min, lost osmotic behavior and the ciliary beat came to depend on externally applied MgATP2- indicating that ciliated epithelium is skinned with saponin. Beat frequency of skinned cilia did not increase with Ca2+ in 0.1 mM MgATP2- with no ATP-regenerating system. Under 4 mM Mg ATP2- the beat frequency increased with an increase in Ca2+ from 0.3 to 10 microM, although a marked beat continued in the virtual absence of Ca2+ sensitivity and maximum beat frequency increased with the addition of 2.4 microM calmodulin. The effect of calmodulin inhibitor (W-7) on skinned preparations was somewhat weaker than that on intact ones. We concluded that Ca2+, within the physiological range of concentrations, directly activated the ciliary proteins and increased the ciliary beat frequency. The addition of calmodulin augments the effect of Ca2+ but the basal beat frequency is not Ca2+ dependent.


A Qualitative Inquiry About Pruno, an Illicit Alcoholic Beverage Linked to Botulism Outbreaks in United States Prisons.
Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures. We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno. Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno. Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks.


Vasodilator treatment with hydralazine increases blood flow in mdx mice resistance arteries without vascular wall remodelling or endothelium function improvement.
Whereas dystrophin has a key role in striated muscle mechanotransduction, its role in vascular functions is not fully understood. In mice lacking dystrophin (mdx) both flow (shear stress)-mediated dilation (FMD) and vascular wall remodelling are decreased, suggesting a low capacity of the vasculature to adapt to metabolic needs. We assessed the capacity of a systemic vasodilator treatment to improve vascular remodelling and blood flow in mdx mice. We measured vascular structure and function in mesenteric resistance arteries (MRA) from control and mdx mice treated for 1 month with hydralazine. Although hydralazine did not significantly affect blood pressure, mesenteric blood flow was increased in control and mdx mice (150+/-25 to 194+/-30 and 110+/-26 to 143+/-18 microl/min; respectively; n=10/group). MRA (90 microm internal diameter, 75 mmHg) were isolated in vitro in arteriographs. Arterial diameter and FMD were significantly increased by hydralazine in control but not in mdx mice. Hydralazine also increased N-nitro-L-arginine methyl ester (L-NAME)-sensitive FMD in control mice, not in mdx mice. Pressure-, phenylephrine-, serotonin- and calcium-induced contraction, as well as acetylcholine- and sodium nitroprusside-induced dilation, were not affected by hydralazine whatever the strain. This study provides functional evidence that local blood flow could be improve by hydralazine in mdx mice despite a lack of vascular adaptation to flow. This study brings a new insight in the pathophysiology of dystrophin-related myopathies. Nevertheless, the consequences of an increased blood flow in non-adapted arteries remain unknown.


Injury, hospitalization, and operation rates are low in aerial sports.
Aerial sports can cause serious injuries. The rate of injuries is nevertheless reasonably low, contrary to popular belief. This study aimed to evaluate the rate and severity of injuries to ASI patients presented to our Emergency Department (ED). The study was held at a university medical center. The patients who were presented or transferred to the ED in a four year period were retrospectively reviewed. 73.2% of patients were male. The mean age of patients was 28.6. The distribution of injury rates by activity was as follows: 1.46% in parachuting, 0.35% in paragliding, and 0.04% in hang-gliding. 75.6% of patients were trainees. In 82.9% of patients, the injury occurred during the practical session of training. The most common injury is soft tissue and ligamentous (ST/L) injury (41.5%). 25 patients (61%) had isolated lower extremity injuries (13 of them had fractures). Other isolated injuries were head trauma in 2 (4.9%) and vertebral fractures in 3 (7.3%) patients. 4 (9.8%) patients were diagnosed with multiple injuries. The overall rate of hospitalization was 0.07% (0.16% in parachuting, 0.08% in paragliding, and 0.03% in hang-gliding). The need for operation in overall activities was 0.04% (0.08% in parachuting, 0.03% in paragliding, and 0.03% in hang-gliding). The mortality rate was found to be zero in the region. Aerial sports are considered dangerous sports activities, but the injury, hospitalization, and operation rates are low.


Foam elastomer dressing in the management of open granulating wounds: experience with 250 patients.
Our experience in the use of a silicone foam elastomer in the dressing of granulating wounds is described in a series of 250 patients. Among the types of wound treated were a pilonidal sinus, abdominal, perianal and perineal wounds, bed sores and diabetic gangrene of the foot. The technique has marked advantages over conventional packing of wounds in relation to patient comfort and saving of nursing time in hospital, and can eliminate the need for district nursing care in the domiciliary situation. Details of preparation, application and surgical management are given.


COVID-19-Associated Carotid Atherothrombosis and Stroke.
We present a radiology-pathology case series of 3 patients with coronavirus disease 2019 (COVID-19) with acute ischemic stroke due to fulminant carotid thrombosis overlying mild atherosclerotic plaque and propose a novel stroke mechanism: COVID-associated carotid atherothrombosis.


Comparative studies of cardia carcinoma and infracardial gastric carcinoma.
In a part retrospective, part prospective study, 354 carcinomas of the cardia were compared with 1259 infracardial gastric carcinomas with regard to the age and sex of the patients, macroscopic classification, microscopic classifications, depth of invasion, and survival rates. Mortality rates are generally higher in cardia carcinoma than in stomach carcinoma. The difference is due to the significantly poorer survival of cardia carcinoma patients in stage I, while mortality rates in stages II, III, and IV of both types are approximately similar. Highly significant differences were also found with regard to sex ratio, incidence of macro- and microscopic subtypes, and invasive growth. The typical cardia carcinoma occurs preferentially in men, is mostly well-delineated, and is manifested as an ulcerated or polypoid, well-differentiated tumor of expansive growth, corresponding to Laurén's intestinal type. These results confirm the concepts of McPeak and Warren, MacDonald, and Siewert et al., that the carcinoma located in the cardia must be seen as a separate entity of gastric carcinoma.


Enzyme-free fluorescence determination of uric acid by combining CdTe quantum dots with metal-organic framework for signal amplification.
The composite of CdTe quantum dots (QDs) with ZIF-8 was elaborately designed and synthesized as an enzyme-free fluorescent probe for the sensitive determination of uric acid (UA), based on the fluorescence detection property of CdTe QDs and the signal amplification function of ZIF-8. The structure and feature of the composite were characterized with transmission electron microscopy, scanning electron microscopy, powder X-ray diffraction, and fluorescence spectrometry. With adding UA to the composite, the emission of CdTe QDs reduced due to the inner filter and dynamic quenching effects of UA, and the adsorption ability of ZIF-8 toward UA promoted the response signal of CdTe QDs. On this basis, UA was quantified by the composite in the concentration range 0.05 to 10 μM with excitation/emission wavelength at 287/615 nm, and the detection limit of the composite toward UA was 32 nM. The reproducibility of the composite for determining UA was further evaluated, and the relative standard deviations were below 10.2%. The composite also exhibited the merits of enzyme-free analysis such as low testing cost, short analysis time (1 min), and loose pH condition (application in whole physiological pH range, 5.0 - 8.0). The composite was applied to the determination of UA in human urine with recoveries of spiked samples in the range 99 to 113%.


Structure-based computational design of novel covalent binders for the treatment of sickle cell disease.
The quest in finding an everlasting panacea to the pernicious impact of sickle cell disease (SCD) in the society hit a turn of success since the recent discovery of a small molecule reversible covalent inhibitor, Voxelotor. A drug that primarily promotes the stability of oxygenated hemoglobin and inhibit the polymerization of HbS by enhancing hemoglobin's affinity for oxygen has opened a new frontier in drug discovery and development. Despite eminent efforts made to reproduce small molecules with better therapeutic targets, none has been successful. To this end, we employed the use of structure-based computational techniques with emphasis on the electrophilic warhead group of Voxelotor to harness novel covalent binders that could elicit better therapeutic response against HbS. The PubChem database and DataWarrior software were used to design random molecules using Voxelotor's electrophilic functionality. Following the compilation of these chemical entities, a high-throughput covalent docking-based virtual screening campaign was conducted which revealed three (Compound_166, Compound_2301, and Compound_2335) putative druglike candidates with higher baseline energy value compared to the standard drug. Subsequently, in silico ADMET profiling was carried out to evaluate their pharmacokinetics and pharmacodynamics properties, and their stability was evaluated for 1 μs (1 μs) using molecular dynamics simulation. Finally, to prioritize these compounds for further development in drug discovery, MM/PBSA calculations was employed to evaluate their molecular interactions and solvation energy within the HbS protein. Despite the admirable druglike and stability properties of these compounds, further experimental validations are required to establish their preclinical relevance for drug development.


Folie à deux and delusional disorder by proxy in a family.
This report presents a 52-year-old woman who was admitted to nephrology ward with hypernatremia. She shared a persecutory delusion of poisoning with her 22-year-old daughter and did not feed her 8-year-old son due to her delusion.


Acute ascending aortic dissection after MDMA/ecstasy use: A case report.
Acute aortic dissection is rare among young patients in the absence of connective tissue disorders. One of the risk factors associated with aortic dissection among young patients is amphetamine use. We report a case of a 37-year-old female with a past medical history of hypertension presenting with syncope and altered mental status who was found to have an acute DeBakey Type I aortic dissection after ingestion of 3,4-methylenedioxymethamphetamine (MDMA), commonly known as ecstasy. This is the second case in the literature describing aortic dissection in relation to MDMA use. In both cases, the patients were young and had no history of connective tissue disorders or underlying valvular abnormalities. In this case, echocardiography was used to establish the diagnosis early. A transthoracic echocardiogram revealed a possible dissection flap prolapsing in through a normal aortic valve. Subsequently, a transesophageal echocardiogram revealed wide-open aortic regurgitation with several proximal dissection flaps from a normal caliber ascending aorta prolapsing into a normal tricuspid aortic valve. A high index of suspicion is necessary to diagnose and treat aortic dissection in young patients with a history of MDMA use. Recognize MDMA as a risk factor for acute aortic dissection, especially among younger patients with whom clinicians may not often associate aortic dissection.


Flagellin gene fliC of Xanthomonas campestris is upregulated by transcription factor Clp.
Clp, a homologue of cyclic AMP receptor protein (CRP), of Xanthomonas campestris regulates the expression of many genes. In this study, proteomic analysis showed the amounts of several extracellular proteins in a clp mutant to be reduced, including the flagellin encoded by fliC. Transcriptional fusion assay showed that activity of fliC promoter is reduced by 2.3-fold in clp mutant compared to the wild-type, coincident with the protein levels. The clp mutant is slightly reduced in motility; however, electron microscopy showed no significant change in the monotrichous flagellation. A fleQ homologue with conserved Clp-binding site in the upstream region is present in the fully sequenced X. campestris genome, suggesting that regulation of the flagellar genes is similar to that of Pseudomonas aeruginosa in involving Vfr, the CRP homologue, and FleQ in a cascade manner except that Vfr downregulates fleQ. Concomitant loss of flagellum and motility in fliC mutant and absence of a second homologue in the genome sequence suggest that X. campestris possesses a single flagellin gene, fliC. In addition, mutation of this gene does not affect virulence.