Latent Tuberculosis Infection and Associated Factors in Patients with Systemic Lupus Erythematosus: a Multicenter, Cross-Sectional Study.
The objectives of this study were to screen for latent tuberculosis infection (LTBI) among patients with systemic lupus erythematosus (SLE) using the T-SPOT.TB assay and to identify factors affecting the assay results. SLE patients were enrolled from 13 tertiary hospitals in eastern, central, and western China from September 2014 to March 2016 and were screened using the T-SPOT.TB assay to detect LTBI. Basic information about the subjects was collected, including gender, age, body mass index (BMI), course of disease, evidence of previous tuberculosis, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, and the use of glucocorticoids and immunosuppressants. Univariate analysis and multivariable logistic regression were performed to identify factors affecting the results of the T-SPOT.TB assay. In all, 2,229 SLE patients were screened using the T-SPOT.TB assay, of whom 334 patients tested positive, yielding a positivity rate of 15% (95% confidence interval [CI], 13.5% to 16.5%). The positivity rate was higher in male than female patients and had an increasing trend with age. Multivariable logistic regression analysis showed that patients over 40 (odds ratio [OR], 1.65; 95% CI, 1.29 to 2.10) and with evidence of previous tuberculosis (OR, 4.43; 95% CI, 2.81 to 6.99) were more likely to have positive T-SPOT.TB results, while patients with a SLEDAI-2K score of ≥10 (OR, 0.61; 95% CI, 0.43 to 0.88), a glucocorticoid dose of ≥60 mg/d (OR, 0.62; 95% CI, 0.39 to 0.98), leflunomide (LEF) treatment (OR, 0.51; 95% CI, 0.29 to 0.88), or tacrolimus (FK506) treatment (OR, 0.40; 95% CI, 0.16 to 1.00) were more likely to have negative T-SPOT.TB results. The frequencies of CFP-10-specific gamma interferon (IFN-γ)-secreting T cells were significantly lower in SLE patients with severe disease activity or high-dose glucocorticoids (P < 0.05). The positivity rate of the T-SPOT.TB assay was 15% among SLE patients. Severe, active SLE disease and the use of high-dose glucocorticoids and some types of immunosuppressants are likely to result in negative T-SPOT.TB results. For SLE patients with the above conditions, diagnosing LTBI based on a positive T-SPOT.TB result may lead to underestimation of the prevalence. IMPORTANCE The burden of tuberculosis and systemic lupus erythematosus in China ranks among the top three in the world. Therefore, active screening for LTBI and preventive intervention in SLE patients are of great significance in China. In view of the lack of relevant data in a large sample, we conducted a multicenter, cross-sectional study using T-SPOT.TB as a screening method for LTBI, to investigate the prevalence of LTBI and analyze the factors affecting the results of the T-SPOT.TB assay in SLE patients. Our study showed that the overall positivity rate of the T-SPOT.TB assay in SLE patients was 15.0%, which was lower than the estimated LTBI prevalence in the general population in China (~20%). For SLE patients with severe, active disease, high-dose glucocorticoids, and some types of immunosuppressants, a diagnosis of LTBI based on only positive T-SPOT.TB results may lead to underestimation of the prevalence.


Effects of carbamazepine on male reproductive hormones.
Reproductive endocrine disorders and sexual dysfunction are common among men with epilepsy. We investigated sexual hormone serum levels among men with newly diagnosed epilepsy, before starting any antiepileptic drug (AED), and then after starting carbamazepine (CBZ), to determine the role and effects of epilepsy versus CBZ in creating reproductive endocrine disorders. In this prospective study, male patients 20 to 40 years of age who due to new-onset seizure(s) were referred to the outpatient epilepsy clinic at Shiraz University of Medical Sciences from 2009 through 2012 were studied. A blood sample was obtained to evaluate the serum levels of follicle stimulating hormone, luteinizing hormone, prolactin, testosterone, free-testosterone, dehydroepiandrosterone sulfate and sex hormone binding globulin. CBZ was started after blood works. After at least three months of taking CBZ, another blood sample was obtained to determine the serum levels of those hormones again. Twenty patients were included. Their mean age (± standard deviation) was 28 years (± 5). The statistical analysis with paired sample tests did not show any significant changes in serum levels of sex hormones before and after CBZ therapy. Despite the fact that, sexual dysfunction and reproductive disorders are common among men with epilepsy, the exact pathophysiology of these problems is not clear yet. Further studies are required to determine the exact role of epilepsy itself, AEDs, and other possible determinants.


[The importance of comorbidity in nephrologists' assessment of acute renal failure].
To study the features of acute renal failure (ARF) in our hospital and to determine prognosis and mortality associated factors. Retrospective study of ARF episodes during a two years period (2005-2007). ARF was considered when a sudden rise in serum creatinine concentration was more than 0,5 mg/dl in patients with normal renal function and more than 1 mg/dl in patients with previous mild to moderate chronic renal failure. We analyzed epidemiologic, clinical, laboratories results, therapeutics and prognosis factors. Two hundred and one patients were evaluated (62,7% males; Age= 67,35 16,38 years (63,68%>65 years); Comorbility Index of Charlson 3,49 2,43). 115 episodes presented in patients with previous renal failure. ARF was pre-renal in 52,7%, renal in 34,8% and post-renal in 8,5%. 35,8% of ARF patients had oliguria or anuria. The mean duration of ARF/hospitalization was 22,47 days (22,47 21,83). The percentage of resolved ARF was 70,1%. Mortality was 30,8%. The univariated analysis showed comorbility Index of Charlson, oliguria, low serum albumin and cholesterol, and anemia were significantly associated with mortality (p<0,05). The lineal regression analysis found three factors associated to the mortality rate: Comorbility Index of Charlson, oliguria and low serum cholesterol. Mortality predictive model was carried out. Highest basal comorbility of patients, oliguria and malnutrition-inflammation dates are princess prognosis and mortality factors in ARF today A new approach is needed in ARF because this new type/class of population.


Intraprocedural angiographic CT as a valuable tool in the course of endovascular treatment of direct sinus cavernous fistulas.
This investigation aimed to demonstrate the potential of intraprocedural angiographic CT in monitoring complex endovascular coil embolization of direct carotid cavernous fistulas. Angiographic CT was performed as a dual rotational 5 s run with intraarterial contrast medium injection in two patients during endovascular coil embolization of direct carotid cavernous fistulas. Intraprocedural angiographic CT was considered helpful if conventional 2D series were not conclusive concerning coil position or if a precise delineation of the parent artery was impossible due to a complex anatomy or overlying coil material. During postprocessing multiplanar reformatted and dual volume images of angiographic CT were reconstructed. Angiographic CT turned out to be superior in the intraprocedural visualization of accidental coil migration into the parent artery where conventional 2D-DSA series failed to reliably detect coil protrusion. The delineation of coil protrusion by angiographic CT allowed immediate correct coil repositioning to prevent parent artery compromising. Angiographic CT can function as a valuable intraprocedurally feasible tool during complex coil embolizations of direct carotid cavernous fistulas. It allows the precise visualization of the cerebral vasculature and any accidental coil protrusion can be determined accurately in cases where conventional 2D-DSA series are unclear or compromised. Thus angiographic CT might contribute substantially to reduce procedural complications and to increase safety in the management of endovascular treatment of direct carotid cavernous fistulas.


A History of Cancer Research: Tumor Viruses.
Early studies of transmissible tumors in chickens provided evidence that viruses such as avian leukosis virus (ALV) and Rous sarcoma virus (RSV) can cause cancer in these animals. Doubts about the relevance to human tumors and failures to replicate some early work meant the field of tumor virology followed a bumpy course. Nevertheless, viruses that can cause cancers in rodents and humans were ultimately identified, and several Nobel prizes were awarded for work in this area. In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at the early history of tumor virus research, from some of the early false starts and debates, to discovery of reverse transcriptase, and identification of human papilloma virus (HPV) as the major cause of cervical cancer.


Inhibition of the active principle of the weak opioid tilidine by the triazole antifungal voriconazole.
To investigate in vivo the influence of the potent CYP2C19 and CYP3A4 inhibitor voriconazole on the pharmacokinetics and analgesic effects of tilidine. Sixteen healthy volunteers received voriconazole (400 mg) or placebo together with a single oral dose of tilidine (100 mg). Blood samples and urine were collected for 24 h and experimental pain was determined by using the cold pressor test. Noncompartimental analysis was performed to determine pharmacokinetic parameters of tilidine, nortilidine and voriconazole, whereas pharmacodynamic parameters were analysed by nonparametric repeated measures ANOVA (Friedman). Voriconazole caused a 20-fold increase in exposition of tilidine in serum [AUC 1250.8 h*ng ml(-1), 95% confidence interval (CI) 1076.8, 1424.9 vs. 61 h*ng ml(-1), 95% CI 42.6, 80.9; P < 0.0001], whereas the AUC of nortilidine also increased 2.5-fold. After voriconazole much lower serum concentrations of bisnortilidine were observed. The onset of analgesic activity occurred later with voriconazole, which is in agreement with the prolonged t(max) of nortilidine (0.78 h, 95% CI 0.63, 0.93 vs. 2.5 h, 95% CI 1.85, 3.18; P < 0.0001) due to the additional inhibition of nortilidine metabolism to bisnortilidine. After voriconazole the AUC under the pain withdrawal-time curve was reduced compared with placebo (149 s h(-1), 95% CI 112, 185 vs. 175 s h(-1), 95% CI 138, 213; P < 0.016), mainly due to the shorter withdrawal time 0.75 h after tilidine administration. Voriconazole significantly inhibited the sequential metabolism of tilidine with increased exposure of the active nortilidine. Furthermore, the incidence of adverse events was almost doubled after voriconazole and tilidine.


The Distinctive Activation of Toll-Like Receptor 4 in Human Samples with Sepsis.
Clinical success of Toll-Like receptor-4 (TLR-4) antagonists in sepsis therapy has thus far been lacking. As inhibition of a receptor can only be useful if the receptor is active, stratification of patients with active TLR-4 would be desirable. Our aim was to establish an assay to quantify phosphorylated TLR-4 using the proximity ligation assay (PLA). HEK293 TLR4/MD2/CD14 as well as THP-1 cells were stimulated with LPS and the activation of TLR-4 was measured using the PLA. Furthermore, peripheral blood mononuclear cells (PBMCs) from 25 sepsis patients were used to show the feasibility of this assay in clinical material. Activation of TLR-4 in these samples was compared to the PBMCs of 11 healthy individuals. We could show a transient activation of TLR-4 in both cell lines. Five min after the LPS stimulation, the signal increased 6.7-fold in the HEK293 cells and 4.3-fold in the THP-1 cells. The assay also worked well in the PBMCs of septic patients. Phosphorylation of TLR-4 at study inclusion was 2.9 times higher in septic patients compared to healthy volunteers. To conclude, we established a diagnostic assay that is able to quantify the phosphorylation of TLR-4 in cell culture and in clinical samples of sepsis patients. This makes large-scale stratification of sepsis patients for their TLR-4 activation status possible.


[Compartment syndrome after impact trauma from a car bumper].
A 67-year-old woman, having been hit in the lower leg by a car bumper in a road accident, developed a compartment syndrome in the lower leg without any bone injury. In the following weeks typical contractures of the affected muscles occurred with talipes equinus and clawfoot deformities. In addition there developed insertion tendinitis of the affected muscle groups of the anterior tibia. A year later magnetic resonance imaging (with normal radiological findings) revealed fatty degeneration and muscle fibrosis. The patient complained of pain at rest and on movement in the proximal tibia, and there was definite pain on pressure over the proximal end of the tibia. Conservative treatment having failed, the Achilles tendon and the long flexor muscle of the toes were lengthened by operation. Both signs and symptoms then improved. A compartment syndrome may develop after blunt trauma even in the absence of bony injury. If there are the appropriate clinical signs, intracompartmental pressure measurement is the procedure of choice to confirm the diagnosis quickly and thus avoid sequelae.


Single-shot antithrombin in human pancreas-kidney transplantation: reduction of reperfusion pancreatitis and prevention of graft thrombosis.
Reperfusion pancreatitis and graft thrombosis often induce early graft loss in simultaneous pancreas-kidney (SPK) transplantation. Antithrombin (AT) is a coagulatory inhibitor with pleiotropic activities that reduces experimental ischemia/reperfusion injury. This study retrospectively analyses prophylactic high-dose AT application in patients with first SPK. In an university transplantation center, 53 consecutive patients with SPK were studied without randomization. In one group, 3000 IU of AT was given intravenously before pancreatic reperfusion (AT, n = 24). Patients receiving standard therapy including postoperative AT supplementation (controls, n = 29) served as controls. Daily blood sampling was performed as a part of the clinical routine during four postoperative days. There were no differences in demographic and laboratory parameters [donor/recipient age, ischemia time, perfusion solution, body weight, mismatches] between both groups. Baseline creatinine values were lower in the control group versus AT group (P < 0.05). Coagulatory parameters and bleeding incidence were not influenced by AT, while incidence of graft thrombosis was reduced (control: 7/29; AT: 4/24; relative reduction of risk: -33%; P < 0.05). Single-shot AT application during SPK modulated serum lipase activity on postoperative days 2 and 3, and minimized risk for graft thromboses without increasing perioperative bleeding. This new concept should deserve testing in a prospective clinical trial.


In Vitro SARS-CoV-2 Infection of Microvascular Endothelial Cells: Effect on Pro-Inflammatory Cytokine and Chemokine Release.
In the novel pandemic of Coronavirus Disease 2019, high levels of pro-inflammatory cytokines lead to endothelial activation and dysfunction, promoting a pro-coagulative state, thrombotic events, and microvasculature injuries. The aim of the present work was to investigate the effect of SARS-CoV-2 on pro-inflammatory cytokines, tissue factor, and chemokine release, with Human Microvascular Endothelial Cells (HMEC-1). ACE2 receptor expression was evaluated by western blot analysis. SARS-CoV-2 infection was assessed by one-step RT-PCR until 7 days post-infection (p.i.), and by Transmission Electron Microscopy (TEM). IL-6, TNF-α, IL-8, IFN-α, and hTF mRNA expression levels were detected by RT-PCR, while cytokine release was evaluated by ELISA. HMEC-1 expressed ACE2 receptor and SARS-CoV-2 infection showed a constant viral load. TEM analysis showed virions localized in the cytoplasm. Expression of IL-6 at 24 h and IFN-α mRNA at 24 h and 48 h p.i. was higher in infected than uninfected HMEC-1 (p < 0.05). IL-6 levels were significantly higher in supernatants from infected HMEC-1 (p < 0.001) at 24 h, 48 h, and 72 h p.i., while IL-8 levels were significantly lower at 24 h p.i. (p < 0.001). These data indicate that in vitro microvascular endothelial cells are susceptible to SARS-CoV-2 infection but slightly contribute to viral amplification. However, SARS-CoV-2 infection might trigger the increase of pro-inflammatory mediators.


Pathological findings in harbour porpoises (Phocoena phocoena) from Norwegian and Icelandic waters.
A study of 37 by-caught harbour porpoises from Icelandic and Norwegian waters showed that most were in good or moderate nutritional condition and none was severely emaciated. Mild infection with lungworms (Halocercus invaginatus, Pseudalius inflexus, Torynurus convolutus) was found in 84% of the Icelandic and 91% of the Norwegian animals, usually associated with bronchopneumonia which was rarely severe. Most (91%) of the animals had parasites in the stomach and intestine (Anisakis simplex, Contracaecum osculatum, Pholeter gastrophilus), and Campula oblonga was present in the liver and pancreas of 88 and 21%, respectively. Oesophagitis, gastritis, cholangitis, pericholangitis, pancreatitis and lymphadenitis were almost exclusively associated with parasitic infection and usually mild. Bacterial isolates were obtained from 50 to 55% of the animals but were not considered to be clinically significant. There was no indication of morbillivirus infection. Icelandic and Norwegian animals showed a thicker blubber layer and a lower incidence of severe lesions, especially in the respiratory tract, as compared with reports of by-caught animals from the Baltic Sea.


METTL3 regulates breast cancer-associated alternative splicing switches.
Alternative splicing (AS) enables differential inclusion of exons from a given transcript, thereby contributing to the transcriptome and proteome diversity. Aberrant AS patterns play major roles in the development of different pathologies, including breast cancer. N6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNA, influences tumor progression and metastasis of breast cancer, and it has been recently linked to AS regulation. Here, we identify a specific AS signature associated with breast tumorigenesis in vitro. We characterize for the first time the role of METTL3 in modulating breast cancer-associated AS programs, expanding the role of the m6A-methyltransferase in tumorigenesis. Specifically, we find that both m6A deposition in splice site boundaries and in splicing and transcription factor transcripts, such as MYC, direct AS switches of specific breast cancer-associated transcripts. Finally, we show that five of the AS events validated in vitro are associated with a poor overall survival rate for patients with breast cancer, suggesting the use of these AS events as a novel potential prognostic biomarker.


Off-road recreational motor vehicle accidents: hospitalization and deaths.
There is increasing concern over the unregulated use of recreational off-road motor vehicles. A review of 207 patients admitted to a tertiary care hospital over a 5-year period, as well as deaths due to use of recreational vehicles, elicited the following information. Recreational accidents predominantly involved men in their mid-twenties. Children younger than 16 years were more frequently involved in all-terrain vehicle (ATV) or dirt-bike accidents and constituted more than one-third of the total. There was a ninefold increase in ATV accidents over the study period, so that by 1985 ATVs were the primary cause of off-road injuries (52%). The musculoskeletal system was most frequently injured (66%) followed by the head and face (25%). There was permanent disability in 10.6%, and 33% of the recreational deaths were in children younger than 16 years. The inherent instability of ATVs was confirmed by the finding that in 60% of accidents the vehicle had rolled or flipped. Stricter licensing requirements should be implemented, and public education is required to draw attention to the danger of these vehicles, particularly to children. There is a need for proper safety equipment and driver training. The issue of vehicle design must also be addressed by the industries concerned.


Physico-chemical characteristics of breeding habitats of Anopheles dirus (Diptera:Culicidae) in Assam, India.
Larval ecology of Anopheles dirus, the main vector of forest malaria in north-eastern region of India, was studied in relation to physico-chemical characteristics of its breeding habitats in a rain forest area of Assam, India. Shady stream side pools, positive for the breeding of An. dirus, had significantly higher amounts of total hardness (P < 0.024) in comparison to negative pools of similar type. When compared with An. dirus negative breeding habitats, in hot-wet as well as in cool-dry seasons, An. dirus positive shady ground pools showed higher mean values of total alkalinity, hardness and chloride content, whereas lower pH, dissolved oxygen along with higher total alkalinity and hardness were possessed by An. dirus positive stream side pools. Specificity of breeding habitats of An. dirus in relation to its ecology has been discussed.


Radioisotopic techniques for noninvasive detection of platelet deposition in bovine-tissue mitral-valve prostheses and in vitro quantification of visceral microembolism in dogs.
Platelet deposition on bovine pericardial-tissue mitral-valve prostheses in 11 dogs was observed noninvasively by use of 111In-labeled platelets and quantified after sacrifice at one (n = 3), 14 (n = 3), and 30 (n = 5) days postimplantation (300-400 microCi of labeled platelets having been injected 24 hours previously). Thrombosis on the sewing ring and pericardial leaflets at one and 14 days and on the leaflets at 30 days was delineated in scintiphotos. In vitro quantification (% injected dose) indicated that the leaflets, sewing ring, and perivalvular tissue retained 0.904% of labeled platelets at one day postimplantation, 0.198% at 14 days, and 0.040% at 30 days. Platelet half-life was reduced to 38 hours at 21 days postimplantation but returned toward the normal (50 hours) with fibrous ingrowth in the sewing ring. Microembolism in lung and kidney, as measured by tissue/blood radioactivity ratio, also was decreased significantly at 30 days. 111In-labeled platelets thus provide a sensitive marker for noninvasive imaging and in vitro quantification of platelet deposition on valvular prostheses and microemboli trapped in viscera, although histochemical confirmation will be necessary to correlate the increase in tissue/blood ratio with the presence of microembolism.


[Injuries of the small and large intestine].
While laparotomy is always mandatory for penetrating injuries of the intestine, its indication for blunt trauma is still difficult because of diagnostic problems. Late interventions are responsible for a poor prognosis in these patients. While the operative management of small bowel ruptures is mostly unproblematic injury of the large intestine demands more differential treatment. In cases of contaminated abdominal cavity and the necessity of bowel resection a so-called anastomosis stoma should be used if possible. In case of major trauma of the rectosigmoid, a Hartmann procedure may be necessary. Profuse drainage and colostomy are required in cases of trauma of the extraperitoneal part of the rectum.


Crystal structure of (E)-2-fluoro-benz-aldehyde (pyridin-2-yl)hydrazone.
The title compound, C12H10FN3, is approximately planar: the dihedral angles between the mean plane of the central N-N=C spacer unit and the fluoro-benzene and pyridine rings are 14.50 (13) and 4.85 (15)°, respectively, while the dihedral angle between the aromatic rings is 16.29 (6)°. The F atom lies at the same side of the mol-ecule as the N atom of the pyridine ring. In the crystal, inversion dimers linked by pairs of N-H⋯N hydrogen bonds generate R 2 (2)(8) loops. Mol-ecules related by translation in the a direction are linked by two π-π stacking inter-actions involving pairs of benzene rings and pairs of pyridine rings. In each case, the ring-centroid separation is 3.8517 (9) Å. Two chains of this type pass through each unit cell, but there are no direction-specific inter-actions between adjacent chains.


A Biatrial Myxoma with Triple Ripples.
Cardiac myxoma is a benign tumor, but it is known for its space-occupying effect at the site of origin and frequent systemic embolization. This case report highlights a biatrial myxoma of interatrial septum who presented with significant tricuspid valve regurgitation, atrial fibrillation, and cardioembolic stroke of the left parietal lobe, i.e., a biatrial myxoma with triple ripples.


Comparative brain analysis of wild and hatchery reared Mahseer (Tor putitora) relative to their body weight and length.
The present study was aimed at comparing the brain size of mahseer (Tor putitora) in relation to their body weight and standard length, to investigate the potential impact of rearing environment on brain development in fish. The weight of the brain and three of its subdivisions cerebellum (CB), optic tectum (OT), and telencephalon (TC) were measured for both wild and hatchery-reared fish. The data was analysed using multiple analysis of covariance (MANCOVA), analysis of covariance (ANCOVA), and discriminate function analysis (DFA). We found the fish reared under hatchery conditions exhibit smaller brain size related to body weight, when compared to the wild ones. A significant (p<0.5) difference was observed in the length of CB and OT concerning the standard body length while no significant difference was found in TC of the fish from both the origins. The results of the current study highlight a logical assumption that neural deficiency affects the behaviour of fish, that's why the captive-reared fish show maladaptive response and face fitness decline when released to the natural environment for wild stock enhancement. The current study concluded that hatchery-reared fish exhibit variations in gross brain morphology as compared to their wild counterpart.


What is the feasibility of imaging coronary arteries during routine echocardiograms in children?
Abnormalities of coronary artery (CA) origins may be associated with sudden death. No data exist regarding the feasibility of routine echocardiographic imaging of CA in pediatrics. Our aim was to determine the feasibility of imaging CA origins during routine echocardiograms. One hundred randomly selected children without clinical evidence of heart disease were studied. The mean age was 13.8 +/- 6.4 years. Location of CA origins were tallied with clock-face reference. The left CA origin was imaged in 98% with the origin most commonly at 3:30 o'clock. The right CA origin was imaged in 95% with the origin most commonly at 11 o'clock. Four abnormalities of CA were discovered: right CA origin from the left coronary sinus n = 2, circumflex from right CA origin n = 1, and small left CA origin to pulmonary artery fistula n = 1. We conclude that imaging of CA origins during routine pediatric echocardiograms is feasible with a potentially life-saving result.


Obesity epidemic: time to swallow the frog.
Mark Twain once said, "If you have to swallow a frog, don't stare at it too long." I believe that members of the healthcare community have been staring at the obesity epidemic for too long.


[Chiral selectivity in differentiation of lung cancer A549 cell to vascular endothelial cells after drug resistance induced by D-or L-methotrexate enantiomers].
To study the chiral selectivity in vascular endothelial differentiation in drug resistant lung cancer cells induced by high-dose L- or D-methotrexate (MTX) enantiomer. Human lung cancer cells of the line A549 were co-cultured with high-dose (15 micromol/L) L- or D-MTX enantiomer so as to develop cancer cells resistant to MTX. MTT method was used to detect the drug resistant index. Flow cytometry was used to detect the expression of CD44, a transmembrane glycoprotein reflecting the migration ability of cells, CD31, a marker of vascular endothelium, and P-170 protein. Fifteen BALB/c nude mice were inoculated with the parent A549 cells, L-MTX-resistant A549 cells induced by L-MTX enantiomer, and D-MTX-resistant A549 cells induced by D-MTX enantiomer. Four weeks later the mice were killed to take out the tumor masses. Immunohistochemistry with CD34 staining was used to detect the microvascular density (MVD). The drug resistant index of the D-MTX induced drug resistant A549 cells was 20.1 +/- 2.3, significantly higher than that of the L-MTX-induced cells (12.4 +/- 1.2, P = 0.000). The CD44 positive rate of the D-MTX induced A549 cells was 97.0% +/- 0.9%, not significantly different from that of the L-MTX-induced A549 cells (96.7% +/- 1.4%, P = 0.544). The CD31 positive rate of the D-MTX induced A549 cells was 91.9% +/- 3.2%, significantly higher than that of the L-MTX-induced A549 cells (32.9% +/- 8.0%, P = 0.000). The P-170 protein positive rate of the parent cells was 85.5% +/- 4.6%, and the P-170 protein positive rate of the D-MTX-induced A549 cells was 87.0% +/- 8.9%, significantly higher than that of the L-MTX-induced cells (71.5% +/- 8.2%, P = 0.002). The MVD of the D-MTX-induced cells was 55.9 +/- 11.9, significantly higher than that of the L-MTX-induced cells (7.2 +/- 1.7, P = 0.000). MVD was significantly positively correlated with the CD31 level (r = 0.462, P = 0.007), and not correlated with P-170 protein and CD34 levels. The MTX enantiomers have different chiral selectivity on human lung cancer cell, D-MTX resistant cells shows a potential of differentiation from cancer cells to vascular endothelial cells. D-MTX is not be regarded just as a pollutant in the drug MTX, MTX with single enantiomer (L-MTX) should be selected clinically so as to decrease the side effects of D-MTX.


Risperidone versus placebo for schizophrenia.
Risperidone is the first new generation antipsychotic drug made available in the market in its generic form. To examine the clinical effects of oral risperidone for people with schizophrenia and schizophrenia-like psychoses in comparison with placebo. We searched the Cochrane Schizophrenia Group's Register (February 2008), references of all included studies, and contacted industry and authors of included studies for relevant studies and data. Randomised clinical trials comparing oral risperidone with placebo treatments for people with schizophrenia and/or schizophrenia-like psychoses. Two reviewers independently inspected citations and/or abstracts, ordered papers, re-inspected and assessed the quality of results and extracted data. For dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). One study (n=599) compared risperidone against placebo but the attrition rate was 60% over a period of six weeks rendering most of the efficacy and global improvement data unusable. The attrition rate was higher for placebo compared with risperidone (n=1363, 10 RCTs, RR 0.70 CI 0.57 to 0.86, NNT 13 CI 9 to 29) and less participants left the trial in the risperidone arm due to lack of efficacy (n=888, 5 RCTs, RR 0.38 CI 0.20 to 0.73, NNT 7 CI 5 to 15). Risperidone was no better than placebo on the CGI global score (n=397, 3 RCTs, RR 0.80 CI 0.55 to 1.15) but significantly more number of participants in risperidone arm had more than 20% reduction in their BPRS/PANSS score (n=856, 7 RCTs, RR 0.43 CI 0.32 to 0.58, NNT 7 CI 6 to 10). Data became considerably more homogeneous (and positive) when the one study independent of industry funding was removed (I(2) 75% to 55%). Despite poor reporting, it is clear that around 24% of all participants receiving either risperidone or placebo developed some form of extrapyramidal effects (n=723, 5 RCTs, RR 1.40 CI 0.93 to 2.10). Three people on risperidone had prolonged QTc (n=198, 1 RCT, RR 7.5 CI 0.4 to 144), more on risperidone gained weight (n=303, 2 RCTs, RR 5.14 CI 1.79 to 14.73, NNH 10 CI 3 to 51) and had a raised prolactin (n=323, 2 RCTs, RR 12.54 CI 5.11 to 30.79, NNH 3 CI 2 to 5). Fewer in the risperidone arm needed an additional psychotropic during the trial period (n=186, 1 RCT, RR 0.62 CI 0.45 to 0.85, NNT 10 CI 7 to 28). Risperidone appears to have a marginal benefit in terms of clinical improvement compared with placebo in the first few weeks of treatment but data are limited, poorly reported and probably biased in favour of risperidone. The margin of improvement chosen by the researchers as their outcome may not be clinically meaningful. Even after so much use of this drug, we feel that further independent trials can be justified.


Effect of Nitrogen Concentration on the Biosynthesis of Citric Acid, Protein, and Lipids in the Yeast Yarrowia lipolytica.
Yarrowia lipolytica yeast is well known to be able to synthesize citric acid (CA) in large amounts. This study deals with CA biosynthesis, the production of biomass, as well as the accumulation and composition of proteins and lipids in Y. lipolytica VKM Y-2373 grown in media with glucose at different concentrations of ammonium sulfate (from 2 to 10 g/L). It was found that these concentrations of nitrogen source are limiting for the growth of Y. lipolytica and that nitrogen deficiency is the main cause of CA excretion. At the high concentration of (NH4)2SO4 (10 g/L), the accumulation of cell biomass, biomass yield (YX/S), and protein concentration was higher than in the medium with 2 g/L ammonium sulfate by 4.3 times, 143%, and 5.1 times, respectively. CA was accumulated in meaningful quantities only in media containing 3-10 g/L (NH4)2SO4 with the maximum concentration of CA (99.9 g/L) at 4 g/L ammonium sulfate. Also of interest is the technological mode with 6 g/L (NH4)2SO4, which is characterized by high productivity (1.11 g/L × h). It should be noted that biomass contains large amounts of essential amino acids and unsaturated fatty acids and can be used in food biotechnologies and agriculture.


Detection of Adulterants and Contaminants in Liquid Foods-A Review.
Milk and fruit juices have paramount importance in human diet. Increasing demand of these liquid foods has made them vulnerable to economic adulteration during processing and in supply chain. Adulterants are difficult to detect by consumers and thus necessitating the requirement of rapid, accurate and sensitive detection. The potential adulterants in milk and fruit juices and their limits set by different regulatory bodies have been briefly described in this review. Potential advantages and limitations of various techniques such as physicochemical methods, chromatography, immunoassays, molecular, electrical, spectroscopy with chemometrics, electronic nose, and biosensors have been described. Spectroscopy in combination with chemometrics has shown potential for rapid, precise, and sensitive detection of potential adulterants in these liquid foods.


Bafilomycin A1 inhibits the action of tetanus toxin in spinal cord neurons in cell culture.
Tetanus toxin (TeNT) is one of the clostridial neurotoxins that act intracellularly to block neurotransmitter release. However, neither the route of entry nor the mechanism by which these toxins gain access to the neuronal cytoplasm has been established definitively. In murine spinal cord cell cultures, release of the neurotransmitter glycine is particularly sensitive to blockade by TeNT. To test whether TeNT enters neurons through acidic endosomes or is routed through the Golgi apparatus, toxin action on potassium-evoked glycine release was assayed in cultures pretreated with bafilomycin A1 (baf A1) or brefeldin A (BFA). baf A1, which inhibits the vacuolar-type H(+)-ATPase responsible for endosome acidification, diminishes the staining of acidic compartments and interferes with the action of TeNT in a dose-dependent manner. TeNT blockade of evoked glycine release is inhibited by 50 and 90% in cultures pretreated with 50 and 100 nM baf A1, respectively, compared with cultures treated with the inhibitor alone. The effects of baf A1 are fully reversible. In contrast, BFA, which disrupts Golgi function, has no effect on TeNT action. These findings provide evidence that TeNT enters the neuronal cytoplasm through baf A1-sensitive acidic compartments and that TeNT is not trafficked through the Golgi apparatus before its translocation into the neuronal cytosol.


Prognostic value of abnormal vasoreactivity of epicardial coronary arteries to sympathetic stimulation in patients with normal coronary angiograms.
We aimed to evaluate prospectively whether patients with normal coronary angiogram but abnormal epicardial vasoreactivity to cold pressor test (CPT) are at increased risk for cardiovascular events. Vasoreactivity in response to CPT and dilation of epicardial arteries to intracoronary application of nitroglycerin were assessed quantitatively (percent change of luminal area, DeltaLA%) in 130 patients with normal coronary angiograms. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 45+/-9 months. Based on their vascular responses to CPT, patients were assigned into the following 3 groups: group 1, patients with normal vasodilator response (DeltaLA >0%; n=37); group 2, patients with moderate vasoconstrictor response (DeltaLA between 0% and -15%; n=42); and group 3, patients with severe vasoconstrictor response (DeltaLA < or =-15%; n=51). Although patients from groups 2 and 3 had significantly increased vasoconstrictor response to CPT (group 2, DeltaLA -6+/-3% and group 3, DeltaLA -24+/-6% versus group 1, DeltaLA 11+/-9%; P< or =0.0001), they showed normal endothelial-independent epicardial vasodilation to intracoronary application of nitroglycerin similar to patients from group 1 (DeltaLA 39+/-16% and 34+/-14% versus 41+/-14%; P=NS, respectively). During follow-up, none of the patients from group 1 developed cardiac events. However, 7 cardiovascular events occurred in group 2 and 30 occurred in group 3 in 4 and 22 patients, respectively (P< or =0.0001, univariate by log-rank test). After adjustment for known risk factors for coronary artery disease, impaired epicardial coronary vasoreactivity to CPT remained significantly associated with the risk of developing cardiovascular events (P=0.040, multivariate by Cox regression model). In patients with normal coronary angiogram, abnormal vasoreactivity of epicardial coronary arteries in response to sympathetic stimulation is associated with the risk of developing cardiovascular events.


Metabolic acidosis.
Acute metabolic acidosis is frequently encountered in critically ill patients. Metabolic acidosis can occur as a result of either the accumulation of endogenous acids that consumes bicarbonate (high anion gap metabolic acidosis) or loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic or normal anion gap metabolic acidosis). The cause of high anion gap metabolic acidosis includes lactic acidosis, ketoacidosis, renal failure and intoxication with ethylene glycol, methanol, salicylate and less commonly with pyroglutamic acid (5-oxoproline), propylene glycole or djenkol bean (gjenkolism). The most common causes of hyperchloremic metabolic acidosis are gastrointestinal bicarbonate loss, renal tubular acidosis, drugs-induced hyperkalemia, early renal failure and administration of acids. The appropriate treatment of acute metabolic acidosis, in particular organic form of acidosis such as lactic acidosis, has been very controversial. The only effective treatment for organic acidosis is cessation of acid production via improvement of tissue oxygenation. Treatment of acute organic acidosis with sodium bicarbonate failed to reduce the morbidity and mortality despite improvement in acid-base parameters. Further studies are required to determine the optimal treatment strategies for acute metabolic acidosis.


Blood velocity waveforms in the fetal aorta and umbilical artery as predictors of fetal outcome: a comparison.
In 139 pregnancies in which intrauterine growth retardation (IUGR) was suspected at routine ultrasound screening at 32 weeks of gestation, blood velocity in the fetal aorta and umbilical artery was recorded by a pulsed Doppler ultrasound every second week until delivery. The maximum blood flow velocity waveforms (FVWs) were analyzed for pulsatility index (PI) and blood flow class (BFC). In both vessels, an abnormal PI (greater than mean + 2 SD of the normal population) and abnormal BFC at the final antenatal examination were significantly associated with the occurrence of IUGR (birthweight less than or equal to mean - 2 SD) (p less than 0.001), operative delivery for fetal distress (p less than 0.001), and a low 1-minute Apgar score (less than or equal to 7). PI in the umbilical artery was a better predictor of fetal outcome than was the aortic PI, but the BFC was similarly predictive of fetal outcome in both vessels. The data indicate that a simple umbilical artery examination, which can be performed blindly with the Doppler ultrasound instrument without the help of a real-time scanner, is a reliable method for monitoring fetal status in pregnancies when IUGR is suspected.


Perception of musical tension for nontonal orchestral timbres and its relation to psychoacoustic roughness.
Can tension in nontonal music be expressed without dynamic or rhythmic cues? Perceptual theories of tonal harmony predict that psychoacoustic roughness plays an important role in the perception of this tension. We chose a set of orchestrated chords from a nontonal piece and investigated listeners' judgments of musical tension and roughness. Paired comparisons yielded psychophysical scales of tension and roughness. Two experiments established distinct levels of these two attributes across chords. A model simulation reproduced the experimental roughness measures. The results indicate that nontonal tension could be perceived consistently on the basis of timbral differences and that it was correlated with roughness, the correlation being stronger as the perceptual salience of other attributes (such as high-pitched tones or tonal intervals) was reduced.


Heritability of beef cow metabolizable energy for maintenance.
Most of the metabolizable energy that a cow uses during a production year is for maintenance; however, less is known about the heritability of maintenance compared to other traits that can be measured directly. Feed intake is a heritable trait in the mature cow and most of the feed consumed is used for maintenance. We hypothesized that maintenance energy was a heritable trait. Individual feed intake was measured for 84 or 85 d on 5 yr old pregnant cows (N = 887) from a pedigreed population of cattle that represent prominent breeds in the United States. Phenotypic mean (± SD) values were 654 ± 68 kg for cow body weight, 0.21 ± 0.24 kg/d for average daily gain, and 175 ± 17 d for midpoint fetal age. Dry matter intake averaged (± SD) 10.84 ± 1.41 kg/d. Metabolizable energy for maintenance was estimated by subtracting the metabolizable energy used for conceptus growth and tissue accretion from metabolizable energy intake. Metabolizable energy for maintenance averaged (± SD) 139 ± 18 ME kcal/d/BW kg0.75 and had a heritability of 0.31 ± 0.11. Cows have a moderate heritability for maintenance suggesting an opportunity for selection.


The 26 S proteasome: from basic mechanisms to drug targeting.
The regulated degradation of proteins within eukaryotes and bacterial cells is catalyzed primarily by large multimeric proteases in ATP-dependent manner. In eukaryotes, the 26 S proteasome is essential for the rapid destruction of key regulatory proteins, such as cell cycle regulators and transcription factors, whose fast and tuned elimination is necessary for the proper control of the fundamental cell processes they regulate. In addition, the 26 S proteasome is responsible for cell quality control by eliminating defective proteins from the cytosol and endoplasmic reticulum. These defective proteins can be misfolded proteins, nascent prematurely terminated polypeptides, or proteins that fail to assemble into complexes. These diverse activities and its central role in apoptosis have made the proteasome an important target for drug development, in particular to combat malignancies.


[Cellular immunity in breast cancer patients].
84 breast cancer patients were examined prior to surgery regarding cellular immunity. 47 patients were free from secondary tumors, 37 already had axillary lymph node metastases, but no other secondary growth. 37 healthy women formed a control group. With reference to the total leukocyte count and to the percentage of T cells in the total lymphocyte count, there was no difference between the control group and the cancer patients. The latter, however, showed a significantly increased lymphocyte count compared with that of the control group. Despite an increase in the number of lymphocytes in cancer patients, there was a significant decrease in their ability to be stimulated by concanavalin A. In breast cancer patients with regional metastases the ability to be stimulated by phytohemagglutinin was decreased, too.


Multiple acute parasitization by Anisakis simplex.
Hypersensitivity to Anisakis is an increasingly prominent medical problem throughout the world, due to a better understanding of diseases induced by parasites and to modern culinary habits of eating raw or undercooked fish. We describe the case of a patient who presented epigastric pain, wheals, erythema, and pruritus 3 hours after the ingestion of fish. More than 200 larvae were obtained by endoscopy. However, the patient only developed an immune response with specific immunoglobulin E and eosinophilia peaking at day 18 and decreasing during the 17-month follow-up. Only eosinophilia reached normal limits.


Multiple Patterns of FHIT Gene Homozygous Deletion in Egyptian Breast Cancer Patients.
Fragile histidine triad (FHIT) gene encodes a putative tumour suppressor protein. Loss of Fhit protein in cancer is attributed to different genetic alterations that affect the FHIT gene structure. In this study, we investigated the pattern of homozygous deletion that target the FHIT gene exons 3 to 9 genomic structure in Egyptian breast cancer patients. We have found that 65% (40 out of 62) of the cases exhibited homozygous deletion in at least one FHIT exon. The incidence of homozygous deletion was not associated with patients' clinicopathological parameters including patients' age, tumour grade, tumour type, and lymph node involvement. Using correlation analysis, we have observed a strong correlation between homozygous deletions of exon 3 and exon 4 (P < 0.0001). Deletions in exon 5 were positively correlated with deletions in exon 7 (P < 0.0001), Exon 8 (P < 0.027), and exon 9 (P = 0.04). Additionally, a strong correlation was observed between exons 8 and exon 9 (P < 0.0001).We conclude that FHIT gene exons are homozygously deleted at high frequency in Egyptian women population diagnosed with breast cancer. Three different patterns of homozygous deletion were observed in this population indicating different mechanisms of targeting FHIT gene genomic structure.


Three-dimensional mesoporous PtM (M = Co, Cu, Ni) nanowire catalysts with high-performance towards methanol electro-oxidation reaction and oxygen reduction reaction.
Alloying with transition elements is proven to be an effective way to improve the methanol electro-oxidation reaction (MOR) and oxygen reduction reaction (ORR) activities of Pt catalysts for direct methanol fuel cells (DMFCs). Through a process of rapid solidification and two-step dealloying, we have successfully fabricated three-dimensional mesoporous PtM (M = Co, Cu, Ni) nanowire catalysts, which show much enhanced electrocatalytic properties towards MOR and ORR in comparison with the commercial Pt/C catalyst. Electrochemical tests indicate that alloying with Cu presents the best ORR activities, the half-wave potential of which is 42 mV positively shifted compared with the commercial Pt/C (0.892 V vs. RHE). Meanwhile, the PtM nanowire catalysts also possess good CO tolerance as well as stability for 10 000 cycles of cyclic voltammetry scanning. This convenient preparation method is promising for the development of high performance electrocatalysts for MOR and ORR in DMFCs.


Evaluation of an Audio-Visual Novela to Improve COVID-19 Knowledge and Safe Practices Among Spanish-Speaking Individuals with Schizophrenia.
In the United States, the health and economic consequences of the COVID-19 pandemic have disproportionately affected the Latinx community. Within the Latinx community, people with schizophrenia-spectrum disorders are more susceptible to exposure to the virus. Given their increased risk of contracting and getting sick from the virus, efforts targeting the Latinx population should focus on increasing knowledge and safe practices associated with COVID-19. We developed a 10 min animated, Spanish-language audio-visual novela designed to improve knowledge, attitudes, and behaviors regarding COVID-19. Latinx adults with schizophrenia (N = 100) at a community mental health center in Los Angeles were randomly assigned to watch the novela or a non-COVID video (control group). Participants completed surveys immediately before and one month after viewing the material. One month after watching the audio-visual novela, subjects endorsed a greater likelihood of seeking a COVID-19 vaccine than control subjects. No other significant differences were observed between the two conditions. The findings of this study suggest that the presentation of health information in a relevant, engaging, and appealing manner may be useful way to improving salutary health behaviors of Latinx people with schizophrenia-spectrum disorders.


cd1 Mutation in Drosophila Affects Phenoxazinone Synthase Catalytic Site and Impairs Long-Term Memory.
Being involved in development of Huntington's, Parkinson's and Alzheimer's diseases, kynurenine pathway (KP) of tryptophan metabolism plays a significant role in modulation of neuropathology. Accumulation of a prooxidant 3-hydroxykynurenine (3-HOK) leads to oxidative stress and neuronal cell apoptosis. Drosophila mutant cardinal (cd1) with 3-HOK excess shows age-dependent neurodegeneration and short-term memory impairments, thereby presenting a model for senile dementia. Although cd gene for phenoxazinone synthase (PHS) catalyzing 3-HOK dimerization has been presumed to harbor the cd1 mutation, its molecular nature remained obscure. Using next generation sequencing, we have shown that the cd gene in cd1 carries a long deletion leading to PHS active site destruction. Contrary to the wild type Canton-S (CS), cd1 males showed defective long-term memory (LTM) in conditioned courtship suppression paradigm (CCSP) at days 5-29 after eclosion. The number of dopaminergic neurons (DAN) regulating fly locomotor activity showed an age-dependent tendency to decrease in cd1 relative to CS. Thus, in accordance with the concept "from the gene to behavior" proclaimed by S. Benzer, we have shown that the aberrant PHS sequence in cd1 provokes drastic LTM impairments and DAN alterations.


Diversity of cAMP-dependent protein kinase isoforms and their anchoring proteins in mouse ventricular tissue.
Using a chemical proteomics approach, we efficiently enriched for the generally low abundant cAMP signaling proteins, and their interactors, directly from mouse ventricular tissue. The presence of undesired contaminating (noncyclic) nucleotide-binding proteins was diminished using a tailored sequential elution protocol. Through further optimization of this affinity purification and elution protocol, we were able to detect all known protein kinase A regulatory isoforms (PKA-R). Furthermore, 11 different A-kinase anchoring proteins (AKAPs) were detected. A proposed fusion protein of paralemmin 2 and AKAP2 could be decisively established as a novel AKAP at the protein level in ventricular tissue. When comparing this dataset of cAMP-affinity purified proteins with earlier data obtained with immobilized cGMP from rat ventricular tissue, we observe a large overlap in the retained proteins but also some clear differences. Furthermore, implementation of an in-depth analysis of in vivo phosphorylation sites on PKA-R revealed the presence of several differentially phosphorylated PKA-R isoforms. This illustrates yet another layer of functional regulation in cyclic nucleotide signaling. In general, our improved chemical proteomics screen offers a broad, but detailed, view on nature's complex diversity in cyclic nucleotide signaling mechanisms. Possibly different AKAP-isoforms may direct differentially phosphorylated PKA-R isoforms to different cellular compartments, providing a multifaceted platform for just this kinase.


Mixed foods are similarly categorized by 8-13 year old children.
Food search in a computerized 24h dietary recall (24hdr) for children should be easiest when the categories reflect children's categorization of foods, in contrast to professional categories. This study assessed how 8-13 year old children categorized and labeled mixed foods (e.g. fried rice, lasagna), and how these were influenced by child characteristics. A set of 48 cards with pictures and names of mixed foods from 14 professionally defined food groups was sorted by each child into piles of similar foods. Participants (n=146), including 8-13 year old 130 English speaking, and 16 Spanish speaking children, attended data collection in the summer, 2006. One way ANOVA, pairwise comparisons and Robinson matrices for identification of clusters were used. Children created an average of 10.5 (+/-5.5) piles with 6.0 (+/-4.1) cards per pile. No substantial differences in Robinson clustering were detected across subcategories for each of the demographic characteristics, body mass index, or 6-n-propylthiouracil sensitivity. For the majority of the piles, children provided "taxonomic-professional" (26.0%) labels, such as vegetables, sandwiches and drinks, or "specific-food item" (23.0%) labels, i.e. the name of the food. These categories may be used to facilitate mixed food search in a computerized 24hdr for children in this age group.


Glaucoma drainage implants: a critical comparison of types.
The purpose of this review is to critically compare the various glaucoma drainage implants in popular use. Glaucoma drainage implants are being increasingly utilized in the surgical management of glaucoma. Comparisons between the various drainage implants are difficult because most clinical data are derived from retrospective studies with different study populations, follow-up periods, and criteria defining success. The type of glaucoma under treatment is a major factor influencing surgical outcomes. The resistance to aqueous flow through glaucoma drainage implants occurs across the fibrous capsule around the end plate, and the major determinants of the final intraocular pressure are capsular thickness and filtration surface area. The use of antifibrotic agents as adjuncts to drainage implant surgery has not proven effective in modulating capsular thickness. Valved implants appear to reduce, but do not eliminate, the risk of hypotony. Bleb encapsulation is more frequently seen with the Ahmed valve implant than other drainage implants. Diplopia was a common complication with the Baerveldt glaucoma implant after its introduction, but design modifications have markedly reduced the incidence of this complication. There are several glaucoma drainage implants that are currently available, and all have been shown to be safe and effective in reducing intraocular pressure. Greater pressure reduction may be achieved with implants with larger end plates, and valved implants appear to reduce the risk of postoperative hypotony.


Effect of various hydrocolloids on the physical and fermentation properties of dough.
Sixteen hydrocolloids (12 carbohydrate-origin and 4 protein-origin hydrocolloids) at several concentrations were added to dough and their rheological, pasting and fermentation properties were studied. We found that 0.2-1% guar gum (GG) and locust bean gum (LBG) resulted in more strengthened doughs. But 0.2-1% pectin and konjac glucomannan (KGM) yielded weaker dough. The chemical interactions study suggested that pectin and KGM induced highest content of chemical bonds. In the fermentation studies, it was found that pectin, GG and agaric gum (AG) had positive effects, resulting in higher stability of dough pore space and gas retention. All protein hydrocolloids exhibited a negative effect on dough quality. Overall, polysaccharide based hydrocolloids with linear chain and higher viscosity have a remarkable effect on the enhancing gluten network. The interaction between hydrocolloids and gluten proteins was also crucial for dough properties, as exceptionally strong interactions caused disaggregation and instability of gluten network.


The structure and aminoacylation of a temperature-sensitive tRNATrp (Escherichia coli).
A temperature-sensitive (t.s.) tRNATrp from Escherichia coli has a single base change from the wild type (w.t.) species, which results in the loss of a base pair at the bottom of the CCA stem of the cloverleaf structure. Thermodynamic studies on this t.s. tRNA show that it is more susceptible to denaturation than the w.t. due to a larger change in the entropy of denaturation. Correlated with this thermodynamic result is the finding that the denatured t.s. tRNA's T psi C loop is more susceptible to digestion by T1 RNase, suggesting that it has greater freedom than the corresponding structure on the denatured w.t. molecule. In contrast, the native form of the t.s. tRNATrp is very similar to the w.t. with regard to aminoacylation, T1 RNase susceptibility, and column chromatographic mobility, despite the fact that it necessarily has one less base pair. In addition, the well known denaturation-dependent shift in column chromatographic mobility, which is observed for both the t.s. and w.t. molecules, depends on a modification in the anticodon loop, since tRNATrp lacking that modification does not shift when denatured. Thus, though it is not usually thought to be implicated, denaturation probably affects the conformation of the anticodon loop. The lethal phenotype of the mutant at high temperature, defective attenuation of the tryptophan biosynthetic operon in the mutant, and some aspects of the denatured state are clarified by these findings.


Purification and characterization of pepsinogens and a unique pepsin from rat stomach.
Four pepsinogens (1, 2, 3 and 4) (zymogens of pepsin A, EC 188.8.131.52, or pepsin C, EC 188.8.131.52) were purified from the fundic mucosa of rat stomach to homogeneous states as judged by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and a unique pepsin was purified from pepsinogen 1. The molecular weights of pepsinogens 1, 2, 3 and 4 were 42 000, 40 000, 40 500 and 39 000, respectively, and those of the respective activated pepsins (1, 2, 3 and 4) were 35 500, 40 000, 35 500 and 37 000, respectively, as estimated by polyacrylamide gel electrophoresis. The amino acid compositions of these four zymogens differed, but resembled those of pepsinogen Cs from various animal species. Rabbit antiserum prepared against pepsinogen 1 reacted with pepsinogen 2, but not with pepsinogens 3 or 4. The precipitin line against pepsinogen 1 fused completely with that against pepsinogen 2. Purified pepsin 1 was a unique pepsin showing remarkable stability in alkali. It resembled pepsin A with respect to inhibition by pepstatin and pepsin C with respect to its amino acid composition, but had properties intermediate between those of pepsin A and C with respect to its optimal pH (2.1 to 3.1) with hemoglobin and activity on N-acetyl-L-phenylalanyl-L-diiodotyrosine.


Laparoscopic repair of ventral and incisional hernias: our experience in 150 patients.
Incisional hernias develop in 2 to 20% of laparotomy incisions. Approximately 100,000 ventral hernias are operated on each year in the United States. The reported recurrence rates for open repair are 25-52% for primary and 12.5-19% for mesh repair. Compared to the open technique, laparoscopic repair has low rates of complications and recurrence, greater patient acceptance, and shorter hospital stay. Between April 1999 and April 2004, we treated 150 patients (111 female, 39 male) with ventral and incisional hernias laparoscopically. Data concerning the age and sex of patients, the location, number, and size of fascial defects, the type of hernias and their contents, the size and type of meshes used in repair, operative time, length of hospital stay, and postoperative complications were collected. Of the 150 patients, 92 had incisional hernias and 58 had umbilical hernias. Polypropylene was used in 85 cases, dual mesh in 40 cases, and composite mesh in 25 cases. The mean age of the patients was 56.0 years (range, 33-81 years). Mean operative time was 63 minutes (range, 30-125 minutes). Mean postoperative hospital stay was 2.5 days (range, 1-15 days). The postoperative complication rate was 8.6% (seroma, paralytic ileus, small bowel injury, and suture-site neuralgia). The mean follow-up period was 32 months (range, 4-60 months). There was a 3% recurrence rate. Three subileus cases were detected during follow-up. The laparoscopic approach to ventral and incisional hernias is safe, feasible, and a good alternative to the open approach. Our results are comparable with those of other reports in the literature.


Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty?
We investigated the reliability of the cobalt-chromium (CoCr) synovial joint fluid ratio (JFR) in identifying the presence of a severe aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response and/or suboptimal taper performance (SOTP) following metal-on-metal (MoM) hip arthroplasty. We then examined the possibility that the CoCr JFR may influence the serum partitioning of Co and Cr. For part A, we included all revision surgeries carried out at our unit with the relevant data, including volumetric wear analysis, joint fluid (JF) Co and Cr concentrations, and ALVAL grade (n = 315). Receiver operating characteristic curves were constructed to assess the reliability of the CoCr JFR in identifying severe ALVAL and/or SOTP. For part B, we included only patients with unilateral prostheses who had given matched serum and whole blood samples for Co and Cr analysis (n = 155). Multiple regression was used to examine the influence of JF concentrations on the serum partitioning of Co and Cr in the blood. A CoCr JFR > 1 showed a specificity of 83% (77% to 88%) and sensitivity of 63% (55% to 70%) for the detection of severe ALVAL and/or SOTP. In patients with CoCr JFRs > 1, the median blood Cr to serum Cr ratio was 0.99, compared with 0.71 in patients with CoCr JFRs < 1 (p < 0.001). Regression analysis demonstrated that the blood Cr to serum Cr value was positively associated with the JF Co concentration (p = 0.011) and inversely related to the JF Cr concentration (p < 0.001). Elevations in CoCr JFRs are associated with adverse biological (severe ALVAL) or tribocorrosive processes (SOTP). Comparison of serum Cr with blood Cr concentrations may be a useful additional clinical tool to help to identify these conditions.Cite this article: D. J. Langton, S. Natu, C. F. Harrington, J. G. Bowsher, A. V. F. Nargol. Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty? Bone Joint Res 2019;8:146-155. DOI: 10.1302/2046-3758.83.BJR-2018-0049.R1.


Association of Motor and Nonmotor Symptoms With Health-Related Quality of Life in a Large Online Cohort of People With Parkinson Disease.
There is growing interest in health-related quality of life (HRQOL) as a comprehensive view of the patient's well-being, guiding concept for the treating clinician, and therapeutic trial outcome measure for patients with Parkinson disease (PwPD). The key determinants of HRQOL have not been investigated in large populations of PwPD. Our objective was to evaluate correlates of HRQOL in a large, online cohort of PwPD. As part of an ongoing online cohort study, we performed a cross-sectional analysis at enrollment of 23,058 PwPD. We conducted univariate and stepwise multivariate linear regression analyses of HRQOL as measured by the EQ-5D-5L tool. In addition, we performed an interaction analysis to evaluate heterogeneity of the effect of motor symptoms on HRQOL and Spearman correlation analysis to evaluate the association of nonmotor symptoms with HRQOL. In the multivariate linear regression model, participants with moderate or severe depression, more severe motor symptoms, and a higher burden of medical comorbidities had the most substantially decreased HRQOL as measured by the EQ index (β -0.11, -0.18, -0.02, -0.01, respectively; p < 0.001 for all). An interaction analysis showed that more severe motor symptoms had a higher effect on individuals with female sex, lower educational level, lower income, more severe depression, or more severe cognitive impairment (p ≤ 0.01 for interaction terms). Neuropsychiatric symptoms and falls had the most negative associations with HRQOL (ρ -0.31 to 0.37; p < 0.0001). Potentially treatable motor and nonmotor symptoms, particularly neuropsychiatric symptoms, account for a large amount of the variation in HRQOL in PwPD. Motor symptoms may have differential effects on HRQOL in different demographic and clinical subpopulations, highlighting important areas for future health disparities research. Our findings provide targets for clinician intervention and future research on symptom management to optimize HRQOL in PD. This study provides Class II evidence that motor and neuropsychiatric symptoms are associated with HRQOL in PwPD.


Improving the detection of illicit substance use in preoperative anesthesiological assessment.
Illicit substance use (ISU) is a worldwide burden, and its prevalence in surgical patients has not been well investigated. Co-consumption of legal substances, such as alcohol and tobacco, complicates the perioperative management and is frequently underestimated during routine preoperative assessment. The aim of this study was to compare the anesthesiologists' detection rate of ISU during routine preoperative assessment with a computerized self-assessment questionnaire. In total, 2,938 patients were included in this study. Prior to preoperative assessment, patients were asked to complete a computer-based questionnaire that addressed ISU, alcohol use disorder (AUDIT), nicotine use (Fagerström) and socio-economic variables (education, income, employment, partnership and size of household). Medical records were reviewed, and the anesthesiologists' detection of ISU was compared to the patients' self-reported ISU. Seven point five percent of patients reported ISU within the previous twelve months. ISU was highest in the age group between 18 and 30 years (26.4%; P<0.01). Patients reporting ISU were more often men than women (P<0.01), smokers (P<0.01) and tested positive for alcohol use disorder (P<0.01). Anesthesiologists detected ISU in one in 43 patients, whereas the computerized self-assessment reported it in one in 13 patients. The detection was best in the subgroup self-reporting frequent ISU (P<0.01). Anesthesiologists underestimate the prevalence of ISU. Computer-based self-assessment increases the detection of ISU in preoperative assessment and may decrease perioperative risk. More strategies to improve the detection of ISU as well as brief interventions for ISU are required in preoperative assessment clinics.


Distribution of autistic traits and their association with sociodemographic characteristics in Japanese workers.
This study aimed to confirm whether autistic traits are normally distributed across a population and to describe their association with the sociodemographic characteristics of Japanese workers. The participants were 2075 workers aged 23-65 years from various parts of Japan. Autistic traits were measured using an abridged Japanese version of the Autism-Spectrum Quotient (AQ-Short). The AQ-Short comprises five subcomponents assessing a fascination for numbers and patterns (numbers/patterns), difficulties with imagination, a preference for routine, difficulties with social skills, and difficulties with switching attention. The five subcomponents of the autistic phenotype as well as the overall autistic phenotype itself were continuously distributed across the sample population of Japanese workers. Men had significantly higher AQ-Short scores than women. AQ-Short scores were not associated with age. Except for the numbers/patterns scores, workers of a lower socioeconomic status had significantly higher AQ-Short scores than their respective counterparts. For the numbers/patterns trait, workers of a higher socioeconomic status scored higher. Workers with low general physical activity had or tended to have higher scores for total and all subcomponent traits, except for the numbers/patterns trait. Generally, the autistic phenotype was more prevalent in workers of a low socioeconomic status, while a particular trait was prevalent among workers of a high socioeconomic status.


Rapid prototyping of nanotube-based devices using topology-optimized microgrippers.
Nanorobotic handling of carbon nanotubes (CNTs) using microgrippers is one of the most promising approaches for the rapid characterization of the CNTs and also for the assembly of prototypic nanotube-based devices. In this paper, we present pick-and-place nanomanipulation of multi-walled CNTs in a rapid and a reproducible manner. We placed CNTs on copper TEM grids for structural analysis and on AFM probes for the assembly of AFM super-tips. We used electrothermally actuated polysilicon microgrippers designed using topology optimization in the experiments. The microgrippers are able to open as well as close. Topology optimization leads to a 10-100 times improvement of the gripping force compared to conventional designs of similar size. Furthermore, we improved our nanorobotic system to offer more degrees of freedom. TEM investigation of the CNTs shows that the multi-walled tubes are coated with an amorphous carbon layer, which is locally removed at the contact points with the microgripper. The assembled AFM super-tips are used for AFM measurements of microstructures with high aspect ratios.


Cellular contractility requires ubiquitin mediated proteolysis.
Cellular contractility, essential for cell movement and proliferation, is regulated by microtubules, RhoA and actomyosin. The RhoA dependent kinase ROCK ensures the phosphorylation of the regulatory Myosin II Light Chain (MLC) Ser19, thereby activating actomyosin contractions. Microtubules are upstream inhibitors of contractility and their depolymerization or depletion cause cells to contract by activating RhoA. How microtubule dynamics regulates RhoA remains, a major missing link in understanding contractility. We observed that contractility is inhibited by microtubules not only, as previously reported, in adherent cells, but also in non-adhering interphase and mitotic cells. Strikingly we observed that contractility requires ubiquitin mediated proteolysis by a Cullin-RING ubiquitin ligase. Inhibition of proteolysis, ubiquitination and neddylation all led to complete cessation of contractility and considerably reduced MLC Ser19 phosphorylation. Our results imply that cells express a contractility inhibitor that is degraded by ubiquitin mediated proteolysis, either constitutively or in response to microtubule depolymerization. This degradation seems to depend on a Cullin-RING ubiquitin ligase and is required for cellular contractions.


The representation of the body surface in somatosensory area I of the grey squirrel.
Microelectrode mapping methods were used to determine the organization of primary somatosensory cortex, SmI, in grey squirrels. A systematic representation of the contralateral body surface was found within somatic konicortex. This primary representation differs from maps of SmI in other mammals in at least two significant ways. The first way in which SmI of squirrels differs from the organization reported for other mammals is that SmI of squirrels contains a double representation of the hand and parts of the forearm. The glabrous skin of the digits is represented twice in a mirror image fashion joined at the finger tips. The hairy skin of the digits, wrist, and parts of the forearm are also represented twice, once on each side of the joined representations of the glabrous skin. A second unique feature of SmI of squirrels is that there is a small region of cortex completely surrounded by SmI that was unresponsive to light cutaneous stimuli under our recording conditions. This unresponsive zone is easily identified in brain sections by architectonic features that deviate from sensory koniocortex and approach motor cortex. A third significant finding was that the back is rostral to the belly in the representation of the trunk in SmI of squirrels. This is the reverse of the orientation reported elsewhere for SmI of mammals, but corresponds to the orientation of the trunk representation in Area 3b of owl monkeys (Kaas et al., '78; Merzenich et al., '78). This similarity supports an earlier contention that the representation of the body in Area 3b of primates is the homolog of SmI in other mammals (Merzenich et al., '78).


A radiological survey of the Eğrigöz granitoid, Western Anatolia/Turkey.
A radiological survey of the granitoid areas throughout Western Anatolia was conducted during 2007-14. As a part of this radiological survey, this article presents results obtained from Eğrigöz pluton, which lies in the northeastern region of Western Anatolia. In the investigated area, the activity measurements of the natural gamma-emitting radionuclides ((226)Ra, (232)Th and (40)K) in the granitic rock samples and soils have been carried out by means of the NaI(Tl) gamma-ray spectrometry system. The activity concentrations of the relevant natural radionuclides in the granite samples appeared in the ranges as follows: (226)Ra, 28-95 Bq kg(-1); (232)Th, 50-122 Bq kg(-1) and (40)K, 782-1365 Bq kg(-1), while the typical ranges of the (226)Ra, (232)Th and (40)K activities in the soil samples were found to be 7-184, 11-174 and 149-1622 Bq kg(-1), respectively. Based on the available data, the radiation hazard parameters associated with the surveyed rocks/soils are calculated. The corresponding absorbed dose rates in air from all those radionuclides were always much lower than 200 nGy h(-1) and did not exceed the typical range of worldwide average values noted in the UNSCEAR (2000) report. Furthermore, the data are also used for the mapping of the surface soil activity of natural radionuclides and the corresponding gamma dose rates of the surveyed area.


Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer.
Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A-T, we produced gene-targeted pigs with mutations in the ATM gene by somatic cell nuclear transfer. The disrupted allele in the ATM gene of cloned piglets was confirmed via PCR and Southern blot analysis. The ATM gene-targeted pigs generated in the present study may provide an alternative to the current mouse model for the study of mechanisms underlying A-T disorder and for the development of new therapies.


Lower-pole fluoroscopy-guided percutaneous renal access: which calix is posterior?
When obtaining fluoroscopy-guided lower-pole percutaneous renal access, knowledge of which calix is posterior is of paramount importance. Textbooks and peer-reviewed articles consistently refer to the most medial calix seen on fluoroscopy as posterior. We undertook this study to determine the orientation of the lower-pole calices to define the optimal site for lower-pole percutaneous renal access via a posterior calix. A retrospective review was performed of 101 renal units for patients who underwent routine contrast-enhanced abdomen/pelvic CT with delayed images for the workup of microscopic hematuria. Delayed images of the renal collecting system that were performed with patients in the supine position were analyzed for the study. Axial and coronal CT scans were evaluated by two observers, and the anatomic details of the lower pole were collected. Specifically, the number of minor calices in the lower pole (ie, two or three), the orientation of each minor calix (anterior facing, posterior facing), and the relative orientation of the minor calices (ie, which calix is most anterior, which calix is most posterior) were recorded. Exclusion criteria were: History of nephrolithiasis, history of renal surgery (open, laparoscopic, endoscopic, percutaneous), CT evidence of ipsilateral renal parenchymal or collecting system lesion. CT scans were analyzed for 101 renal units (50 left, 51 right). For the lower pole, 42 (41.6%) renal units had two calices and 59 (58.4%) renal units had three calices. The most medial calix on coronal imaging was anterior facing in 95 (94.1%) kidneys, was the most anterior positioned calix in 84 (83.2%) kidneys, and was the most posterior positioned calix in 9 (8.9%) kidneys. Kidneys were then stratified by number of lower pole calices (two vs three). For the 42 renal units with two lower pole calices, the most medial calix on coronal imaging was anterior facing in 41 (95.2%) kidneys, was the most anterior positioned calix in 39 (92.9%) kidneys, and was the most posterior positioned calix in 2 (7.1%) kidneys. Of the 59 renal units with three lower-pole calices, the most medial calix on coronal imaging was anterior facing in 55 (93.2%) kidneys, was the most anterior positioned calix in 49 (84%) kidneys, and was the most posterior positioned calix in 4 (6.8%) kidneys. For percutaneous lower-pole renal access, the most medial calix on coronal CT imaging and therefore retrograde opacification using fluoroscopy is almost always anterior facing and is the most anterior positioned in the majority of kidneys. Percutaneous lower-pole puncture should be directed at the more lateral calices because their posterior position and orientation provides optimal access to the collecting system for most cases. This anatomic understanding is critical for successful percutaneous nephrolithotomy.


Sex differences in sympathy for attempted suicides.
In a sample of 115 undergraduates, women expressed more sympathy for hypothetical attempted suicides than did men, but not more empathy or agreement with the actions. A history of considering suicide was not associated with judgments about attempting suicide.


Multichannel near-infrared spectroscopy as a tool for assisting intra-arterial fasudil therapy for diffuse vasospasm after subarachnoid hemorrhage.
Diffuse cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) refractory to medical management can be treated with intra-arterial administration of vasodilators, but valid bedside monitoring for the diagnosis and therapeutic assessment is poorly available. We demonstrate the successful application of regional cerebral oxygen saturation (rSO(2)) monitoring with multichannel near-infrared spectroscopy (NIRS) in assisting intra-arterial infusions of fasudil hydrochloride to a patient suffering from post-SAH vasospasm in the distal vascular territories. A 63-year-old man presented with SAH and intracerebral hematoma due to ruptured right middle cerebral artery aneurysm developed aphasia and right-sided weakness on day 9 after SAH onset. Delayed cerebral ischemia attributable to diffuse vasospasm in the distal territories of the left anterior and middle cerebral arteries was suspected. Since the symptoms persisted despite maximal hyperdynamic therapy with dobutamine, intra-arterial fasudil treatment in the setting of rSO(2) monitoring including the spasm-affected vascular territory with four-channel flexible NIRS sensors was subsequently performed. Decreased and fluctuating rSO(2) in angiographically documented vasospastic territories increased immediately after intra-arterial fasudil infusion in accordance with relief of vasospasm that correlated with neurological improvement. The procedure was repeated on day 11 since the effect was transient and neurological deterioration and reduction of rSO(2) recurred. The deficits resolved accompanied by uptake and maintenance of rSO (2) following the intra-arterial fasudil, resulting in favorable functional outcome. Continuous rSO(2) monitoring with multichannel NIRS is a feasible strategy to assist intraarterial fasudil therapy for detecting and treating the focal ischemic area exposed to diffuse vasospasm.


[Severe combined immune deficiency with hypereosinophilia. Immunologic study of 5 cases].
We herein report five new cases of severe combined immunodeficiency with hypereosinophilia, the so-called familial reticuloendotheliosis first described by Omenn. It is characterized by erythroderma, polyadenopathy, hepatosplenomegaly, severe and repeated infections, protracted diarrhoea with failure to thrive. There is marked eosinophilia as well as a profound immunodeficiency. The immunologic abnormalities consist of an increase in T cell number, a B cell lymphopenia and a complete lack of humoral and cellular immune responses to antigens. A deficiency of lymphocytes 5'-nucleotidase has been inconstantly found. Histologic findings are characteristic, consisting of severe T and B lymphocyte depletion in lymphoid organs with infiltration by histiocytes and, to a lesser extent, eosinophils. The outcome was uniformly fatal within the first year of life. Treatment by a combination of parenteral nutrition, steroids and epipodophyllotoxin was effective in obtaining the complete remission of clinical manifestations due to the histiocytic and eosinophilic infiltration in two patients. However, the treatment failed to correct the immunologic defect. These results indicate that the histiocytic infiltration is possibly not responsible for the immunologic detect observed in this condition.


Etv2-miR-130a-Jarid2 cascade regulates vascular patterning during embryogenesis.
Remodeling of the primitive vasculature is necessary for the formation of a complex branched vascular architecture. However, the factors that modulate these processes are incompletely defined. Previously, we defined the role of microRNAs (miRNAs) in endothelial specification. In the present study, we further examined the Etv2-Cre mediated ablation of DicerL/L and characterized the perturbed vascular patterning in the embryo proper and yolk-sac. We mechanistically defined an important role for miR-130a, an Etv2 downstream target, in the mediation of vascular patterning and angiogenesis in vitro and in vivo. Inducible overexpression of miR-130a resulted in robust induction of vascular sprouts and angiogenesis with increased uptake of acetylated-LDL. Mechanistically, miR-130a directly regulated Jarid2 expression by binding to its 3'-UTR region. Over-expression of Jarid2 in HUVEC cells led to defective tube formation indicating its inhibitory role in angiogenesis. The knockout of miR-130a showed increased levels of Jarid2 in the ES/EB system. In addition, the levels of Jarid2 transcripts were increased in the Etv2-null embryos at E8.5. In the in vivo settings, injection of miR-130a specific morpholinos in zebrafish embryos resulted in perturbed vascular patterning with reduced levels of endothelial transcripts in the miR-130a morphants. Further, co-injection of miR-130a mimics in the miR-130a morphants rescued the vascular defects during embryogenesis. qPCR and in situ hybridization techniques demonstrated increased expression of jarid2a in the miR-130a morphants in vivo. These findings demonstrate a critical role for Etv2-miR-130a-Jarid2 in vascular patterning both in vitro and in vivo.


Modelling the physiological status of yeast during wine fermentation enables the prediction of secondary metabolism.
Saccharomyces non-cerevisiae yeasts are gaining momentum in wine fermentation due to their potential to reduce ethanol content and achieve attractive aroma profiles. However, the design of the fermentation process for new species requires intensive experimentation. The use of mechanistic models could automate process design, yet to date, most fermentation models have focused on primary metabolism. Therefore, these models do not provide insight into the production of secondary metabolites essential for wine quality, such as aromas. In this work, we formulate a continuous model that accounts for the physiological status of yeast, that is, exponential growth, growth under nitrogen starvation and transition to stationary or decay phases. To do so, we assumed that nitrogen starvation is associated with carbohydrate accumulation and the induction of a set of transcriptional changes associated with the stationary phase. The model accurately described the dynamics of time series data for biomass and primary and secondary metabolites obtained for various yeast species in single culture fermentations. We also used the proposed model to explore different process designs, showing how the addition of nitrogen could affect the aromatic profile of wine. This study underlines the potential of incorporating yeast physiology into batch fermentation modelling and provides a new means of automating process design.


An Intramuscular DNA Vaccine for SARS-CoV-2 Decreases Viral Lung Load but Not Lung Pathology in Syrian Hamsters.
The 2019 novel coronavirus, SARS-CoV-2, first reported in December 2019, has infected over 102 million people around the world as of February 2021 and thus calls for rapid development of safe and effective interventions, namely vaccines. In our study, we evaluated a DNA vaccine against SARS-CoV-2 in the Syrian hamster model. Hamsters were vaccinated with a DNA-plasmid encoding the SARS-CoV-2 full length spike open reading frame (ORF) to induce host cells to produce spike protein and protective immune responses before exposure to infectious virus. We tested this vaccine candidate by both intranasal (IN) and intramuscular (IM) routes of administration and complexing with and without an in vivo delivery reagent. Hamsters receiving prime-boost-boost IM-only vaccinations recovered body weight quicker, had decreased lung viral loads, and increased SARS-CoV-2-specific antibody titers compared to control vaccinated animals but, surprisingly, lung pathology was as severe as sham vaccinated controls. The IM/IN combination group showed no efficacy in reducing lung virus titers or pathology. With increasing public health need for rapid and effective interventions, our data demonstrate that in some vaccine contexts, significant antibody responses and decreased viral loads may not be sufficient to prevent lung pathology.


Smartphone-compatible, CRISPR-based platforms for sensitive detection of acute hepatopancreatic necrosis disease in shrimp.
Acute Hepatopancreatic Necrosis Disease (AHPND), caused by bacterial isolates expressing PirAB binary toxins, represents the severest and most economically destructive disease affecting penaeid shrimp. Its rapid disease progression and associated massive mortalities call for vigilant monitoring and early diagnosis, but molecular detection methods that simultaneously satisfy the requirements of sensitivity, specificity, and portability are still scarce. In this work, the CRISPR-Cas12a technology was harnessed for the development of two fluorescent assays compatible with naked-eye visualization. The first assay, AP4-Cas12a, was based on the OIE-recommended AP4 two-tubed nested PCR method and was designed to bypass the time-consuming and potentially hazardous agarose gel electrophoresis step. Using AP4-Cas12a, the detection limit of 10 copies per reaction could be achieved within less than 30 minutes post-PCR. The second assay, RPA-Cas12a, utilized recombinase polymerase amplification (RPA) to rapidly and isothermally amplify the target DNA, followed by amplicon detection by Cas12a, resulting in a protocol that can be completed in less than an hour at a constant temperature of 37°C. The detection limit of RPA-Cas12a is 100 copies of plasmid DNA or 100 fg of bacterial genomic DNA per reaction. Importantly, we validated that both assays are compatible with a previously reported smartphone-based device for facile visualization of fluorescence, thereby providing an affordable option that requires less consumables than lateral flow detection. Using this portable device for readouts, the AP4-Cas12a and RPA-Cas12a methods showed excellent concordance with the AP4-agarose gel electrophoresis approach in the evaluation of clinical samples. Therefore, the developed Cas12a assays have the potential to streamline both in-laboratory and onsite diagnosis of AHPND.


GARBAN II: an integrative framework for extracting biological information from proteomic and genomic data.
Genomic and proteomic analyses generate a massive amount of data that requires specific bioinformatic tools for its management and interpretation. GARBAN II, developed from the previous GARBAN platform, provides an integrated framework to simultaneously analyse and compare multiple datasets from DNA microarrays and proteomic studies. The general architecture, gene classification and comparison, and graphical representation have been redesigned to ensure a user-friendly feature and to improve the capabilities and efficiency of this system. Additionally, GARBAN II has been extended with new applications to display networks of coexpressed genes and to integrate access to BioRag and MotifScanner so as to facilitate the holistic analysis of users' data.


Women's perceptions of femininity after craniopharyngioma: a qualitative study.
Previous quantitative studies have shown a reduced quality of life in patients treated for craniopharyngioma (CP). However, few have assessed their sexual quality of life and other issues related to patient intimacy have not yet been addressed. Standardized questionnaires limit the approach to sexuality and the exploration of patient experiences. A qualitative study, which allows in-depth analysis, may represent an interesting approach to explore intimacy in women with a history of CP. To assess the impact of a CP history on femininity and relationships in women. A qualitative study with semi-structured interviews was conducted with 15 adult women treated for CP during childhood, adolescence or at childbearing age up to 40 years of age. Interviews were audio recorded, anonymized and transcribed literally. Data analysis was carried out with an inductive approach according to the grounded theory method. Three main themes were identified: (a) apparent changes leading to altered self-perception that may impact on femininity and generate lower self-esteem; (b) managing the hidden disabilities of the disease inducing a need for permanent control; and (c) building parenthood and couple relationships: coping with sexual dysfunction and infertility. Our study highlighted alterations in self-perception and femininity due to body change and disability resulting from CP treatment, impacting both couple and social relationships. Interviewing women who underwent CP surgery at different ages highlighted specific needs and different expectations of medical professionals which emphasize the importance of offering both global and personalized care.


Minimally invasive spine surgery: systematic review.
Minimally invasive procedures in spine surgery have undergone significant development in recent times. These procedures have the common aim of avoiding biomechanical complications associated with some traditional destructive methods and improving efficacy. These new techniques prevent damage to crucial posterior stabilizers and preserve the structural integrity and stability of the spine. The wide variety of reported minimally invasive methods for different pathologies necessitates a systematic classification. In the present review, authors first provide a classification system of minimally invasive techniques based on the location of the pathologic lesion to be treated, to help the surgeon in selecting the appropriate procedure. Minimally invasive techniques are then described in detail, including technical features, advantages, complications, and clinical outcomes, based on available literature.


Associations of objectively assessed physical activity and sedentary time with health-related quality of life among lung cancer survivors: A quantile regression approach.
No studies have examined objectively assessed physical activity, sedentary time, and patient-reported outcomes among lung cancer survivors. The objective of this study was to determine associations of objectively assessed moderate-to-vigorous intensity physical activity (MVPA) and sedentary time with health-related quality of life (HRQoL) and fatigue among lung cancer survivors. Lung cancer survivors in Southern Alberta (N = 540) were invited to complete a mailed survey that assessed HRQoL [Functional Assessment of Cancer Therapy-Lung (FACT-L)], physical and functional well-being [Trial Outcome Index (TOI)], and fatigue [Fatigue Scale (FS)]. Physical activity and sedentary time data was collected using an Actigraph® GT3X+ accelerometer that was worn on the hip for seven consecutive days. Quantile regression was used to examine associations of HRQoL and fatigue with physical activity and sedentary time at the 25th, 50th, and 75th HRQoL and fatigue percentiles. A total of 127 lung cancer survivors participated for a 24% response rate (Mean age = 71 years; Mean time since diagnosis = 75 months). Total MVPA minutes was positively associated with fewer fatigue symptoms at the 25th percentile (β = 0.16, p = 0.046). Total sedentary time was inversely associated with HRQoL at the 75th percentile (β = -0.07, p = 0.014) and inversely associated with fatigue symptoms at the 50th percentile (β = -0.04, p = 0.009). Total sedentary time was also inversely associated with physical and functional well-being scores at the 25th (β = -0.07, p = 0.045), 50th (β = -0.07, p = 0.004) and 75th (β = -0.04, p = 0.035) percentiles. Across the HRQoL, fatigue, and physical and functional well-being distributions, sedentary time was inversely associated with HRQoL, fatigue, and physical and functional well-being in lung cancer survivors. Small associations were observed between MVPA and fatigue, but no associations emerged with HRQoL or physical and functional well-being.


Inflammatory reaction and collagen accumulation in an experimental model of open wounds in the rat. A comparison between gauze and Debrisan treatment.
Debrisan treatment was compared with the use of gauze in an experimental model of open wounds in the rat. The amounts of exudate absorbed by the gauze and by Debrisan were measured daily during the post-wounding period and the myeloperoxidase (MPO) activity in the exudate was determined. Blood flow, water content and accumulation of the collagen amino acid hydroxyproline in the granulation tissue were measured on days 3, 5, 7 and 10 post-wounding. The amount of exudate absorbed both by gauze and by Debrisan reached a peak on post-wounding days 4-5 and was greater in Debrisan-treated wounds. MPO activity in the Debrisan-absorbed exudate, on the other hand, was lower throughout the study period than in the exudate absorbed by gauze. Granulation tissue blood flow and water content reached maximum values on day 7 post-wounding, irrespective of treatment. Blood flows were 39% and 40% lower in the Debrisan-treated wounds on post-wound days 3 and 7, respectively, than in the gauze-treated wounds, whereas the water contents of the former wounds were 23% and 15% lower on days 3 and 10, respectively. The hydroxyproline content of the granulation tissue increased continuously from day 3 to day 10 and was similar in the two wounds. These results suggest that Debrisan is more effective than gauze for absorbing wound exudate, when applied on an openly secreting wound. In addition, the inflammatory reaction taking place in Debrisan-treated wounds seems to be less severe than in wounds treated with gauze.


A c.3037G>A mutation in FBN1 gene causing Marfan syndrome with an atypically severe phenotype.
Marfan syndrome is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, mostly caused by mutations in the FBN1 gene, which is located on chromosome 15q21.1 and encoding fibrillin 1. We report a case of Marfan syndrome presenting with severe ocular and systemic manifestations, such as cardiac congenital anomalies. The patient underwent a multidisciplinary approach and his clinical diagnosis was associated with a c.3037G>A mutation in the FBN1 gene. Identification of this genetic alteration should instigate a prompt multidisciplinary assessment and monitoring, in order to prevent devastating consequences such as cardiac and ocular phenotype. Molecular modeling of the mutation highlighted the importance of the preservation of the calcium-dependent structure of an epidermal- growth-factor-like domain of fibrillin-1 and consequently the microfibrillar formation process. This report aims to highlight the importance of an early clinical and molecular diagnosis and once more, the importance of the multidisciplinary approach of this genetic entity.