Effect of layer-by-layer polyelectrolyte method on encapsulation of vanillin.
The objective of this work was to microencapsulate vanillin by multilayer emulsion followed by spray drying, aiming to protect it and control its release. An electrostatic layer-by-layer deposition method was used to create the multilayered interfacial membranes around microcapsules with different compositions: (i) one-layer (soy protein isolate); (ii) two-layer (soy protein isolate - OSA starch); (iii) three-layer (soy protein isolate - OSA starch - Chitosan). The morphology of the microcapsules was analyzed by scanning electronic microscopy. The hygroscopicity, solubility, particle size, encapsulation efficiency, Fourier transform infrared spectroscopy and release into water (37°C and 80°C) were also examined. FTIR confirmed the interaction between the wall materials. All microcapsules were not very water-soluble or hygroscopic while three-layer microcapsules compared to one and two layer microcapsules have lower moisture content and predominantly shriveled surfaces. The results indicated it was possible to encapsulate vanillin with the techniques employed and that these protected the vanillin even at 80°C. The reduced solubility and low release rates indicated the enormous potential of the vehicle developed in controlling the release of the vanillin into the food and pharmaceuticals.


Urinary titin N-fragment as a predictor of decreased skeletal muscle mass in patients with interstitial lung diseases.
This study aimed to examine the validity of urinary N-terminal titin fragment/creatinine (urinary N-titin/Cr) reflecting muscle damage biomarker in patients with interstitial lung disease. This retrospective study enrolled patients with interstitial lung disease. We measured urinary N-titin/Cr. Furthermore, we measured the cross-sectional areas of the pectoralis muscles above the aortic arch (PMCSA) and erector spinae muscles of the 12th thoracic vertebra muscles (ESMCSA) to assess muscle mass until 1 year. We examined the correlation between urinary N-titin/Cr and the change in muscle mass. We plotted receiver operating characteristic curves to estimate the cut-off points for urinary N-titin/Cr for distinguishing the greater-than-median and smaller-than-median reduction of muscle mass after 1 year. We enrolled 68 patients with interstitial lung disease. The median urinary N-titin/Cr value was 7.0 pmol/mg/dL. We observed significant negative correlations between urinary N-titin/Cr and changes in the PMCSA after 1 year (p < 0.001) and changes in the ESMCSA after 6 months (p < 0.001) and 1 year (p < 0.001). The cut-off points for urinary N-titin/Cr were 5.2 pmol/mg/dL and 10.4 pmol/mg/dL in the PMCSA and ESMCSA, respectively. In summary, urinary N-titin/Cr may predict muscle loss in the long-term and act as a clinically useful biomarker reflecting muscle damage.


Pemphigoid Gestationis and adverse pregnancy outcomes: A literature review.
Pemphigoid gestationis (PG), also known as gestational pemphigoid, as it is specifically associated with a pregnancy event, is among the rare pregnancy-related dermatoses, characterised by the formation of autoantibodies against Bullous Pemphigoid antigens 180 and 230 (BP180 and BP230), causing significant damage to the basement membrane of the skin, resulting in marked pruritus and blisters on the abdomen and extremities. Diagnosis of PG is basically made by the characteristic clinical picture and confirmed by immunofluorescence studies and histopathology of a skin biopsy. Treatment, just as for other autoimmune dermatoses, is achieved by corticosteroids with the risk of relapses in subsequent pregnancies. Fetal growth restriction and pre-maturity are potential fetal complications associated with the disease, hence the recommended combined antenatal care by a dermatologist as well as an obstetrician, however, this disease is unlikely to be a source of significant maternal morbidity or mortality.


A new method for selecting sites for soil sampling, coupling global weighted principal component analysis and a cost-constrained conditioned Latin hypercube algorithm.
Analysing spatial patterns of soil properties in a landscape requires a sampling strategy that adequately covers soil toposequences. In this context, we developed a hybrid methodology that couples global weighted principal component analysis (GWPCA) and cost-constrained conditioned Latin hypercube algorithm (cLHC). This methodology produce an optimized sampling stratification by analysing the local variability of the soil property, and the influence of environmental factors. The methodology captures the maximum local variances in the global auxiliary dataset with the GWPCA, and optimizes the selection of representative sampling locations for sampling with the cLHC. The methodology also suppresses the subsampling of auxiliary datasets from areas that are less representative of the soil property of interest. Consequently, the method stratifies the geographical space of interest in order to adequately represent the soil property. We present results on the tested method (R2 = 0.90 and RMSE = 0.18 m) from the Guinea savannah zone of Ghana. •It defines the local structure and accounts for localized spatial autocorrelation in explaining variability.•It suppresses the occurrence of model-selected sampling locations in areas that are less representative of the soil property of interest.


Targeting TFIIH to inhibit host cell transcription by Rift Valley Fever Virus.
In the February 20 issue of Cell, report that Rift Valley Fever Virus (RVFV) targets cellular transcriptional apparatus to inhibit RNA polymerase II-mediated transcription. Unlike polio and vesicular stomatitis viruses, both of which target the TATA binding protein (TBP), RVFV appears to target the basal transcription factor THIIH to induce shut-off of host cell transcription.


Development: How the Reissner Fiber Keeps Our Back Straight.
Two new studies elegantly identify a missing link between idiopathic scoliosis and the Reissner fiber.


Highly enantioselective borane reduction of heteroaryl and heterocyclic ketoxime ethers catalyzed by novel spiroborate ester derived from diphenylvalinol: application to the synthesis of nicotine analogues.
An asymmetric synthesis for the preparation of nonracemic amines bearing heterocyclic and heteroaromatic rings is described. A variety of important enantiopure thionyl and arylalkyl primary amines were afforded by the borane-mediated enantioselective reduction of O-benzyl ketoximes using 10% of catalyst 10 derived from ( S)-diphenylvalinol and ethylene glycol with excellent enantioselectivity, in up to 99% ee. The optimal condition for the first asymmetric reduction of 3- and 4-pyridyl-derived O-benzyl ketoxime ethers was achieved using 30% of catalytic loading in dioxane at 10 degrees C. ( S)- N-ethylnornicotine ( 3) was also successfully synthesized from the TIPS-protected ( S)-2-amino-2-pyridylethanol in 97% ee.


Toxic effects of perfluorocaproic acid (PFHxA) on crucian carp (Carassius auratus) and the response of the intestinal microbial community.
Perfluorocaproic acid (PFHxA), a short-chain substitute for the emerging contaminant perfluorinated compounds, has been detected in the aquatic environment. However, its aquatic toxicity and health risk assessment are mainly unknown. In this study, we compared the toxic doses of 0 mg/L, 5 mg/L, 15 mg/L, 45 mg/L and 135 mg/L on the pathological damage to tissue sections, antioxidant indexes and inflammatory factor expressions in liver, spleen, kidney, Prosogaster, Mid-gut, Hid-gut as well as the changes of IgM, C3, C4, LZM, GOT, GPT in serum of crucian carp. We determined the response of the intestinal microbial community to PFHxA stress by 16S. The results showed that the growth performance of crucian carp was slowed with the increase of PFHxA dose, which caused different degrees of damage to the tissues. Meanwhile, the indexes of SOD, GSH-Px, T-AOC, ACP, AKP and LZM in each tissue were reduced, and the indexes of IgM, C3, C4 and LZM in serum were reduced. The levels of MDA, GOT and GPT in tissues and GOT and GPT in serum were promoted. In addition, IL-1β, TNF-α, NF-KB, and KEAP-1 in each tissue increased compared with the control group. The levels of IL-10, Nrf2, CAT, and GPx were decreased. The 16S rRNA gene sequencing results showed that PFHxA significantly reduced the abundance and diversity of the gut microbiota. It is suggested that PFHxA is likely to cause different degrees of damage to various tissues by disrupting the diversity of the intestinal flora. These results provide insights to facilitate the risk assessment of PFHxA contaminants in the aquatic environment.


Role of Preoperative Patient Expectations in Adult Cochlear Implant Outcomes.
Preoperative expectations affect patient outcomes in many health conditions, but expectations are rarely assessed in adult cochlear implant (CI) users. This study is a first step in assessing the contribution of preoperative expectations to postoperative CI outcomes, including speech recognition, CI quality of life (CIQOL), and CI satisfaction. Cross-sectional study. Tertiary medical center. Fourty one adult CI patients. Preoperative expectation questionnaire results, pre- and postoperative speech recognition (CNC and AzBio) scores, postoperative CIQOL domain scores and global scores, and CI satisfaction scores using a visual analog scale (VAS). Cohen's d was used to express effect size. Overall, patients with lower preoperative CI performance expectations showed higher postoperative QOL. This effect was large for the emotional, entertainment, and social domains (d = 0.85-1.02) of the CIQOL-35 and medium for the communication, listening effort domains, and the Global score (d = 0.55-0.63). Preoperative performance expectations showed minimal associations with preoperative versus postoperative change in CNC (d = -0.26; -0.69-0.18) or AzBio scores (d = -0.28; -0.72-0.15). Determining the extent to which preoperative expectations played a role in postoperative satisfaction with CIs was limited by the clustering of satisfaction scores in the upper range of the scale (VAS mean 81.1). This study provides preliminary evidence that patients' expectations before cochlear implantation may influence their postoperative quality of life and other outcomes, but not postoperative speech recognition. This suggests that an increased emphasis should be placed on measuring and counseling expectations in CI candidates. This assumption needs to be confirmed with additional research with larger sample sizes, more sensitive satisfaction measures, and a prospective design.


Thiopyrano[2,3-d]thiazole structures as promising scaffold with anticancer potential.
Seven chromeno[4',3':4,5]thiopyrano[2,3-d]thiazole derivatives were synthesized and screened for their cytotoxic effects on different lines of mammalian leukemia, breast adenocarcinoma, glioblastoma, and pseudo-normal and normal cells. The derivative 3 demonstrated toxicity towards tumor cells of Jurkat, K562, U251, HL-60, MCF-7, and MDA-MB-231 lines. At the same time, this compound possessed low toxicity (IC50 > 100 μM) towards cells, used as control, representing non-tumor, somatic cells: HaCaT, HEK293 cells as well as murine Balb/c 3T3 and J774.2 cells, mink Mv1Lu cells, and normal mitogen-activated human blood lymphocytes. The derivative 3 induced apoptosis in human leukemia Jurkat T-cells and glioblastoma U251 cells via mitochondria-dependent pathway and inhibition of the DNA reparation enzyme PARP-1. This compound triggered pro-apoptotic morphological changes in Jurkat and U251 cells, namely chromatin condensation, nuclei fragmentation, and membrane blebbing. However, the DNA damaging effects of compound 3 were significantly lower in normal human lymphocytes, compared with such results in tumor Jurkat and U251 cells. The DNA damaging effects of compound 3 were unrelated to its DNA-binding and/or DNA-intercalating abilities. This compound induced the accumulation of endogenous reactive oxygen species (ROS), namely superoxide radicals, in human leukemia and glioblastoma cells. Our finding indicated that compound 3 inhibited the viability of human leukemia T-cells and glioblastoma cells via induction of DNA damage and apoptosis through ROS-mediated mitochondrial pathway.


Organophosphate di- and tri-esters in indoor and outdoor dust from China and its implications for human exposure.
Organophosphate (OP) esters are emerging environmental contaminants, but little is known about their occurrence in dust. In this study, 19 OP triesters and their 11 diester degradation products were measured in indoor dust and outdoor dust collected from China. ∑OP triester concentrations in indoor dust (median: 2380 ng/g dry weight [dw]) were an order of magnitude higher than those in outdoor dust (446 ng/g dw). The median concentrations of ∑OP diesters in indoor and outdoor dust were 260 and 96.8 ng/g dw, respectively. Dust samples collected from eastern and southern China contained higher concentrations of ∑OP di- and tri-esters than those from the other regions. Dust from the most urbanized areas in China including Beijing, Shanghai, and Guangzhou exhibited the highest concentrations of ∑OP di- (>1000 ng/g dw) and triesters (>4000 ng/g dw). We also found notable concentrations of emerging aryl-OP triesters in dust (3.85-10.6 ng/g dw). Significant correlations existed between the concentrations of bis(2-ethylhexyl) phosphate (BEHP) and tris(2-ethylhexyl) phosphate (TEHP) (rho = 0.672-0.691, p < 0.01), as well as DPHP and triphenyl phosphate (TPHP) (rho = 0.537-0.766, p < 0.01) in dust samples, indicating that OP diesters originated from the degradation of triesters. High molar concentration ratios of DEP to triethyl phosphate (TEP) and DPHP to TPHP/ethylhexyl diphenyl phosphate (EHDPP) suggested that these OP triesters degrade readily. Significant correlations were found between the concentrations of ∑OP di- (R2 = 0.390, p < 0.05) and tri-esters (R2 = 0.475, p < 0.01) in paired indoor-outdoor dust samples, which suggested that indoor dust was the source of OP esters to the outdoor environment. The estimated daily intake (EDI) of ∑OP diesters through dust ingestion was 0.21 ng/kg bw/d for adults and 2.59 ng/kg bw/d for children. The exposure levels of OP diesters, DEP and DPHP, were comparable to those of their parent triester compounds.


A simple and rapid method for isolating small myotoxins from rattlesnake venoms.
Many rattlesnake venoms (family Crotalidae) contain small, highly basic toxins which cause contracture and necrosis of skeletal muscle in experimental animals. Isolation of these myotoxins requires several chromatographic steps taking several days to complete. We report the isolation of crotamine, myotoxin a, and myotoxin a-like molecules from whole venom of three species of rattlesnakes using a Hydrazide Avidchrom Cartridge. Milligram amounts of highly purified and biologically active myotoxin can be obtained in 30 min to 2 hr.


Neurodevelopmental follow-up at five years corrected age of extremely low birth weight infants after postnatal replacement of 17β-estradiol and progesterone.
Extremely low birth weight (ELBW) infants are prone to impaired neurodevelopment. The aim was to determine long-term neurodevelopmental outcome in ELBW infants after postnatal 17β-estradiol (E2) and progesterone (P) replacement. At 5-yr corrected age, ELBW infants were assessed for standardized cognitive and neurological outcome after postnatal randomized E2 and P replacement or placebo administration. The follow-up examination was performed in a neuropediatric ambulatory care center. Sixty-one of 71 surviving infants (86%) were available for follow-up. Cognitive and neurological outcome was evaluated using the Kaufmann Assessment Battery for Children, the Gross Motor Function Classification Scale, and clinical neurological examination. No significant differences were found between the replacement and placebo groups for the Gross Motor Function Classification Scale, presence of paresis, cerebral palsy, spasticity, and ametropia. However, a significant time-response relationship was found with E2 and P replacement. Every day of treatment reduced the risk for cerebral palsy (P=0.03), spasticity (P=0.01), and ametropia (P=0.01). Postnatal E2 and P replacement may have potential in improving neurodevelopmental outcome in ELBW infants. Larger trials are needed to test this new hypothesis.


Pre- and post-operative differences between genders in idiopathic macular holes.
To compare idiopathic macular holes (IMHs) between male and female before and after surgery. Patients with IMHs of stage 3 and stage 4 who underwent 23-gauge vitrectomy were retrospectively enrolled. Pre-operative clinical features like age of onset, and best-corrected visual acuity (BCVA) were reviewed. Optical coherence tomography parameters including minimum linear diameter (MLD), central macular thickness and some other indexes were measured and calculated. Main surgical outcomes included the primary closure rate, the highest BCVA during follow-up, and the recovery duration. All the metrics mentioned above were compared between genders with appropriate statistical methods. A total of 298 eyes from 280 patients (male: 51; female: 229) were enrolled. Compared with men, women demonstrated a significantly higher ratio of stage3/stage4 (P = 0.045), larger horizontal MLD (P = 0.009), but similar surgical outcomes except for a relatively longer recovery duration (P = 0.024). For stage 3 IMHs, women exhibited significantly younger age of onset (P = 0.023), larger MLD (P = 0.003), and smaller height of the hole (P = 0.029). However, for stage 4 IMHs, all the pre- and post-operative metrics showed no differences between genders. Female IMHs seem to demonstrate an earlier age of onset and larger size of hole, especially in IMHs of stage 3. However, these differences, which may owe to normal gender-related variations, have limited influence on the surgical outcomes.


The quantitative detection of herpes simplex virus, varicella zoster virus, and cytomegalovirus DNAs in recipient corneal buttons.
We detected herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) DNAs in recipient corneal buttons taken at the time of penetrating keratoplasty. Twenty-seven corneal buttons were obtained from 27 patients (10 men and 17 women), 7 of whom had a history of HSV keratitis. Excised corneal buttons were immediately frozen in liquid nitrogen in the operating theater and then stored at -80°C until DNA extraction. The detection of HSV-1, HSV-2, VZV, and CMV DNAs was carried out by a nested polymerase chain reaction (PCR) method. The genome copy numbers for the nested PCR-positive samples were subsequently quantified by real-time PCR. HSV-1, HSV-2, VZV, and CMV DNAs were detected in 10, 1, 9, and 2 of the 27 recipient corneal buttons, respectively. HSV-1 or HSV-2 DNAs were also detected in 5 of 7 patients with a history of HSV keratitis. Both CMV-positive patients (patients 2 and 3) had ocular pemphigoid. Among the nested PCR-positive samples, 2 HSV-1, 1 HSV-2, 1 VZV, and 1 CMV sample could be quantified by real-time PCR. Copy numbers ranged from 19 to 928 copies. All 4 herpesviruses, including CMV, were detected in the corneal buttons. The relationship between CMV in the cornea and ocular diseases of the anterior segment should be further evaluated.


A survey of UK parental attitudes to the MMR vaccine and trust in medical authority.
Contested reports associating the MMR vaccine with autism have resulted in diminished confidence and uptake of the vaccine in the UK. This postal survey of parent's decisions, attitudes and use of information about MMR immunisation was constructed from questions derived from in-depth qualitative work. The setting was a Primary Care Trust in northeast England (N=996). Both MMR-accepting and refusing parents were supportive of immunisation, yet the high level of concern about the safety of the vaccine expressed even by parents who had immunised their children is worrying in its implications for public confidence and trust in health care. The findings suggest that the ability of practitioners to provide effective professional advice about MMR vaccine could be undermined if a government were to directly promote the vaccine to parents. Practitioners should continue to provide parents with accurate information, while communicating respect for parents' intentions to protect their children's health.


Percutaneous embolization of persistent low-output enterocutaneous fistulas.
To present and retrospectively evaluate the technique of percutaneous embolization of chronic enterocutaneous fistulas (ECFs) using n-butyl-2-cyanoacrylate and Lipiodol under fluoroscopic guidance. Six patients with a total of seven post-operative low-output ECFs of the large intestine were treated. After fistulography a hydrophilic guide wire and a catheter were advanced through the ECF into the intestine. After dilation of the bowel with saline and contrast medium, the catheter was withdrawn into the enteric orifice and glue together with Lipiodol was injected while simultaneously pulling the catheter. Complete closure of all seven fistulas was achieved. There were no peri-procedural complications. In one patient 1 month following embolization a low-output enteric discharge was observed, but the ECF spontaneously healed 5 days later. In one patient 18 months after the embolization a new perforation due to diverticulitis close to the embolization site occurred and resection of the sigmoid colon was performed. One patient needed reoperation due to a recurrence of rectal carcinoma. In our series of patients, the presented technique of percutaneous embolization proved to be efficacious and easy to perform. It may have potential as a first-line treatment of low-output ECFs but a prospective study with a larger series of patients and a longer follow-up is required.


Hummelsheim procedure combined with medial rectus recession in complete sixth nerve palsy and esotropic Duane Retraction Syndrome.
To evaluate the effect of half tendon vertical rectus muscle transposition (HVRT) combined with medial rectus muscle recession (MRrec) in complete sixth nerve palsy (CSNP) and esotropic Duane Retraction Syndrome (eDRS). A retrospective study of patients with unilateral CSNP or eDRS who underwent HVRT combined with medial rectus recession over the course of 18 years. The patients with previous strabismus surgery and follow up less than 3 months were excluded. Overcorrection was defined as any amount of exotropia, and undercorrection was defined as residual esotropia of ⩾10 prism diopter (PD). A total of 39 patients were enrolled including 22 CSNP and 17 eDRS patients. Esotropia improved from 45.8 ± 22 and 22.5 ± 6.4 PD to 0.8 ± 2.5 and 0.3 ± 1 PD in CSNP group and eDRS group respectively. The angle of face turn improved from 34.3 ± 8.4° and 26.5 ± 9° to 0.6 ± 2.4° and 0.8 ± 1.6° in the CSNP group and eDRS group respectively. Abduction limitation improved from -4.5 ± 0.5 and -4 ± 0 units to -2.9 ± 0.5 and -2.7 ± 0.5 units in CSNP group and eDRS group respectively. No patient developed a new vertical deviation. An overcorrection occurred in one patient of the eDRS group who improved after botulinum toxin injection in the ipsilateral lateral rectus muscle. Undercorrection was seen in two patients. HVRT combined with MRrec is an effective procedure to improve esotropia, face turn, and abduction limitation in CSNP and eDRS.


Ablation of atrioventricular-nodal-reentrant- tachycardia in a patient with left-sided superior vena cava and dilated coronary sinus.
Atrioventricular (AV)-nodal-reentrant-tachycardia is a rare association in a patient with persistent left-sided superior vena cava and dilated coronary sinus. There are a few inherent difficulties in ablation in this condition, viz., difficulty in localization of good site for ablation and difficulty in stabilization of the ablation catheter at the designated site, making it difficult to produce transmural lesions and increasing risk of producing AV block. We hereby present a case highlighting the difficulties and possible solutions for them.


Wrapping in Ascending Aortic Aneurysms as an Alternative for Replacement: Is It Beneficial?
Prosthetic replacement of aneurysms of the ascending aorta is the gold standard in terms of long-term stability. Wrapping seems to be a less invasive procedure. It has not yet been shown if it is as safe in terms of long-term outcome. We present a single-center analysis of our experience over 13 years. We retrospectively analyzed data from patients who received either aortic prosthetic wrapping (AW) or aortic prosthetic replacement (AR) with or without aortic valve replacement and assessed them through phone calls. We used propensity score matching to adjust the baseline of the groups. Before propensity matching, 144 patients received AW and 91 patients underwent AR. Mean age was 64 ± 11.8 years. After propensity score matching and adjusting for significant differences in age, gender, body mass index, logistic EuroSCORE I, and left ventricular function, 69 patients in each group remained for further analysis. Rate of early reoperation due to tamponade, inhospital mortality, and survival rates did not differ. In both groups, the surgically treated aortic segment did not show enlargement, whereas the nontreated aortic arch showed comparable aneurysmatical progression. AW is safe and feasible and can be used in elderly or frail patients in order to avoid an AR. Progression of the remaining native aortic segments occurs, thus requiring strict life-long follow-up to ensure an elective and thus safe approach for appropriate consecutive surgical measures, if required.


1H NMR relaxation investigation of acetylcholinesterase inhibitors from huperzine A and derivative.
The binding properties of huperzine A (1) with Torpediniforms Nacline acetylcholinesterase (TnAChE) were investigated by (1)H NMR methods. The noselective, selective and double-selective spin-lattice relaxation rates were acquired in absent and present of TnAChE at a ratio [ligand]/[protein]=1:0.005. The selective relaxation rates shown protons of 1 had dipole-dipole interaction with protein active site protons. The motional correlation time of bound ligand was calculated by double-selective relaxation rate at 1 tau(2,3)=40.5 ns at 298 K, which showed 1 had high affinity with TnAChE. The experiments give a possible method to use TnAChE to locate the new huperzine A derivatives as AChE inhibitors.


Streptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008.
An association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD) in South Africa. IPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV) introduction, from 2003-2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR)) as referent. Among 3953 IPD cases, CFR was 55% (641/1166) for meningitis and 23% (576/2484) for bacteremia (p<0.001). Serotype 19F had the highest CFR (48%, 100/207), followed by serotype 23F (39%, 99/252) and serotype 1 (38%, 246/651). On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1-3.5) and 19F (OR 2.9, 95%CI 1.4-6.1) vs. serotype 4; increasing age (25-44 years, OR 1.8, 95%CI 1.0-3.0; 45-64 years, OR 3.6, 95%CI 2.0-6.4; ≥65 years, OR 5.2, 95%CI 1.9-14.1; vs. 15-24 years); meningitis (OR 4.1, 95%CI 3.0-5.6) vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0-2.8). On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases. Mortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization.


Epithelial and mesenchymal fate decisions in Wolffian duct development.
Wolffian ducts (WDs) are the paired embryonic structures that give rise to internal male reproductive tract organs. WDs are initially formed in both sexes but have sex-specific fates during sexual differentiation. Understanding WD differentiation requires insights into the process of fate decisions of epithelial and mesenchymal cells, which are tightly coordinated by endocrine, paracrine, and autocrine signals. In this review, we discuss current advances in understanding the fate-decision process of WD epithelial and mesenchymal lineages from their initial formation at the embryonic stage to postnatal differentiation. Finally, we discuss aberrant cell differentiation in WD abnormalities and pathologies and identify opportunities for future investigations.


The sugarless mutation affects the expression of the white eye color gene in Drosophila melanogaster.
Investigation of a modifier locus displaying a darker eye phenotype in white-apricot flies led to the isolation of the gene encoding UDP-glucose dehydrogenase (UDPGDH). The P-element insertion l(3)05007 occurs upstream of the transcription start site of the sugarless (sgl) gene and greatly reduces its transcription at various developmental stages. A single abundant sgl transcript shows a ubiquitous distribution and encodes a 53-kDa protein which is 64% identical in sequence to bovine UDP-glucose dehydrogenase. Overexpression of sgl in E. coli resulted in synthesis of a protein with high levels of UDPGDH activity. Expression of three genes that participate in pigment deposition, white, scarlet and brown, was significantly affected in populations segregating for sgl, suggesting that it is the decrease in UDPGDH level that produces the modifying effect observed. In addition, genetic effects on white-apricot were observed in sgl-wingless and sgl-hedgehog double mutants. Recent data have indicated an effect of UDPGDH on cell surface glycosaminoglycans (GAGs) which modulate the activity of growth factors, and in particular wingless signaling. Our results suggest that the levels of GAGs are rate limiting for cell-cell signaling pathways which mediate changes in gene expression.


Tropomyosin receptor kinases B and C are tumor progressive and metastatic marker in colorectal carcinoma.
Members of the tropomyosin receptor kinase (Trk) family have a high affinity for neurotrophins and regulate neuronal survival. The role of Trks in cancer is still controversial. The expression and role of TrkB and TrkC were examined in colorectal cancer (CRC). Immunohistochemical analysis of TrkB and TrkC was performed in 133 patients with CRC. Using human CRC cell lines, expression of vascular endothelial growth factor (VEGF) and transforming growth factor β, cell growth, invasion, and apoptosis were examined by knockdown methods. Immunohistochemistry showed positive results of TrkB and TrkC (23.3% and 12.8%, respectively). TrkB expression was associated with local progression (P = .0284), clinical stage (P = .0026), nodal metastasis (P = .0068), and peritoneal metastasis (P = .0026). TrkC expression was only related to liver metastasis (P = .0001). Coexpression of TrkB or TrkC and their ligands was found in 80.6% and 82.4% of cases, respectively. In vitro analysis using human CRC cells showed that TrkB positively regulated gene expression of VEGF-A (P < .05) and VEGF-C (P < .05), whereas TrkC suppressed transforming growth factor β expression (P < .05). TrkB and TrkC induced cell growth (P < .05) and invasion (P < .05), respectively. Both TrkB and TrkC showed antiapoptotic effect (P < .05). These results suggest that TrkB and TrkC have a tumor progressive function and may be a useful diagnostic and therapeutic target in CRC.


Thymus algeriensis and Thymus fontanesii exert neuroprotective effect against chronic constriction injury-induced neuropathic pain in rats.
We have previously demonstrated that the Thymus algeriensis and Thymus fontanesii extracts have powerful anti-inflammatory, antipyretic, and analgesic effects against acute pain models. We profiled their chemical composition and found many phenolic acids, flavonoids, and phenolic diterpenes. In this work, we investigated their antioxidant properties on HaCaT cells exposed to UVA-induced oxidative stress and examined their effects against chronic neuropathic pain and the underlying mechanisms. Through a rat chronic constriction injury (CCI) model, we induced chronic neuropathic pain by placing 4 loose ligatures around the right sciatic nerve for 14 days. Thermal and mechanical hyperalgesia in addition to cold and dynamic allodynia were tested on the day before surgery and on the 7th and 14th post-surgery days. Key markers of the nitrosative and oxidative stresses, in addition to markers of inflammation, were measured at day 14 post surgery. Histopathological examination and immunostaining of both synaptophysin and caspase-3 of sciatic nerve and brain stem were also performed. Results of this study showed that T. algeriensis extract suppresses UVA oxidative stress in HaCaT cells via activation of the Nrf-2 pathway. Both extracts attenuated hyperalgesia and allodynia at 7- and 14-days post-surgery with more prominent effects at day 14 of surgery. Their protective effects against neuropathic pain were mediated by inhibiting NOX-1, iNOS, by increasing the enzyme activity of catalase, and inhibition of inflammatory mediators, NF-κB, TNF-α, lipoxygenase, COX-2 enzymes, and PGE2. Furthermore, they improved deleterious structural changes of the brainstem and sciatic nerve. They also attenuated the increased caspase-3 and synaptophysin. The data indicate that both extracts have neuroprotective effects against chronic constriction injury-induced neuropathic pain. The observed protective effects are partially mediated through attenuation of oxidative and nitrosative stress and suppression of both neuroinflammation and neuronal apoptosis, suggesting substantial activities of both extracts in amelioration of painful peripheral neuropathy.


Review of developmental toxicity of nitrophenolic herbicide dinoseb, 2-sec-butyl-4,6-dinitrophenol.
The present review paper summarizes the data available in the literature concerning prenatal exposure to dinoseb (2-sec-butyl-4,6-dinitrophenol; CAS No. 88-85-7), evaluating reported developmental toxicity in experimental animals. In particular, we have focused on the variable factors in the manifestation of the developmental toxicity of dinoseb. In this review, we showed that developmental toxicity of dinoseb was remarkably different between animal species used in experiments. Teratogenicity was detected in rats fed a diet containing dinoseb, in mice given dinoseb by gavage, intraperitoneally or subcutaneously, and in rabbits given dinoseb by gavage or dermally. Teratogenicity in rats given dinoseb by gavage was influenced by the dietary composition used in the experiments. We postulated that evaluation of the developmental toxicity after exposure by anticipated routes of human exposure would be important for risk assessment in humans.


Ovarian proteomic study reveals the possible molecular mechanism for hyperprolificacy of Small Tail Han sheep.
Small Tail Han sheep is a widely bred farm animal in China which has attracted lots of attention due to their high prolificacy and year-round estrus. However, the molecular mechanism of its fecundity remains unrevealed. The FecB gene polymorphism has been found to be associated with the ovulation rate and litter size of sheep. In the present study, we constructed an iTRAQ-based quantitative proteomics analysis to compare the ovarian proteomes of FecB+FecB+ genotype Small Tail Han sheep ewes (Han ++), FecB(B)FecB(B) Han ewes (Han BB) and Dorset ewes (Dorset). Hundreds of differentially expressed proteins between each two groups were identified; GO and KEGG pathway analysis indicated that the expressions of those proteins involved in ribosome assembly, protein translation and mTOR pathway between Dorset and both Han groups were highly different. Between Han ++ and Han BB groups, higher level of protein expressions were related to mitochondrial oxidation functions such as oxidoreductase activity, cytochrome-c oxidase activity and electron carrier activity. This was identified in Han BB group, which may contribute to the elevated ovulation rate of Han BB ewes. In conclusion, our work provided a prospective understanding of the molecular mechanism for high prolificacy of Small Tail Han sheep.


[Diagnostics of intraocular tumors with the radiophosphorus test (author's transl)].
The author reports about the radio-phosphorus-test as an additional method in diagnostics of intraocular tumors in 62 examinations. The conformity between 49 histologically examined cases and the positive test-results amounted to 90%.


Functional Molecular Crystals from the Arylation of a Halogenoplatinum Complex: Stimuli Responsiveness, Comproportionation, and π-Bridged Dimerization.
A chloroplatinum complex was arylated to obtain stimuli-responsive molecular crystals. The resulting arylplatinum complex showed polymorph-dependent emission, mechano- and thermochromic luminescence as well as comproportionation and π-bridged dimerization. Simple mixing of structurally similar arylplatinum complexes at room temperature resulted in the transfer of their aryl groups (comproportionation), which allowed their mechanochromic profiles to be tuned. We also found that recrystallization of the complex afforded a dimerized product in which two platinum ions are bridged by aryl groups resulting in a very short (3.0466(10) Å) Pt-Pt distance.


Survey of microbial populations within Lake Michigan nearshore waters at two Chicago public beaches.
Lake Michigan is a critical resource for the residents of Chicago, providing drinking water to its 9+ million area residents. Along Chicago׳s 26 miles of public beaches the populous urban environment and this freshwater environment meet. While city-led monitoring initiatives investigate pathogenic bacteria in these nearshore waters, very little is known about other microbial species present. We collected surface water samples from two Chicago public beaches - Montrose Beach and 57th Street Beach - every ten days from June 5 through August 4, 2013 as well as once in early Fall (October 4, 2013). Sixteen bacterial communities in total were surveyed through targeted sequencing of the V4 16S rRNA gene. Taxa were identified using Mothur. Raw sequence data is available via NCBI׳s SRA database (part of BioProject PRJNA245802). OTU calls for each read are also available at our online repository: www.lakemichiganmicrobes.com/bacteria/.


Site-directed spin labeling of membrane proteins.
EPR spectroscopy of site-directed spin labeled membrane proteins is at present a common and valuable biophysical tool to study structural details and conformational transitions under conditions relevant to function. EPR is considered a complementary approach to X-ray crystallography and NMR because it provides detailed information on (1) side chain dynamics with an exquisite sensitivity for flexible regions, (2) polarity and water accessibility profiles across the membrane bilayer, and (3) distances between two spin labeled side chains during protein functioning. Despite the drawback of requiring site-directed mutagenesis for each new piece of information to be collected, EPR can be applied to any complex membrane protein system, independently of its size. This chapter describes the state of the art in the application of site-directed spin labeling (SDSL) EPR to membrane proteins, with specific focus on the different types of information which can be obtained with continuous wave and pulsed techniques.


Epithelial-mesenchymal transition and metastatic ability of CD133+ colorectal cancer stem-like cells under hypoxia.
Although CD133 is a representative cancer stem cell marker, its function in tumor aggressiveness under hypoxia remains unclear. Therefore, the present study aimed to investigate the associations between CD133, the epithelial-mesenchymal transition and distant metastasis in colorectal cancer. CD133+ and CD133- cells were isolated from a single colorectal cancer cell line LoVo, and their adhesive and migratory properties were compared under hypoxic conditions. Immunostaining analysis was performed to determine CD133 expression in clinical samples of primary tumors, as well as liver and peritoneal metastases. Under hypoxia, the expression levels of hypoxia-inducible factor (HIF)-1α and the epithelial-mesenchymal transition markers N-cadherin and vimentin were significantly higher in the CD133+ compared with those in the CD133- cells. Furthermore, the migratory ability of the CD133+ cells was higher compared with that of the CD133- cells under hypoxia. By contrast, the expression levels of β1 integrin were significantly lower in the CD133+ cells under hypoxia compared with those in the CD133- cells. Immunohistochemical analysis of clinical samples revealed that the levels of CD133 expression in metastatic tissues from the liver were significantly higher compared with those in the corresponding primary tumors, whereas CD133 expression levels in peritoneal metastatic tissues were significantly lower compared with those in the corresponding primary tumors. In conclusion, compared with the CD133- cells, the CD133+ colorectal cancer cells exhibited enhanced levels of HIF-1α expression and tumor cell migration during hypoxia. This was associated with an increased ability of epithelial-mesenchymal transition, possibly leading to the acquisition of an increased hematogenous metastatic potential and eventually resulting in liver metastasis. High β1 integrin expression levels in the CD133- cells under hypoxia may serve a key role in cell adhesion to the peritoneum, resulting in peritoneal metastasis.


Using the Drosophila melanogaster D17-c3 cell culture system to study cell motility.
Cultured Drosophila melanogaster S2 and S2R+ cell lines have become important tools for uncovering fundamental aspects of cell biology as well as for gene discovery. Despite their utility, these cell lines are nonmotile and cannot build polarized structures or cell-cell contacts. Here we outline a previously isolated, but uncharacterized, Drosophila cell line named Dm-D17-c3 (or D17). These cells spread and migrate in culture, form cell-cell junctions and are susceptible to RNA interference (RNAi). Using this protocol, we describe how investigators, upon receiving cells from the Bloomington stock center, can culture cells and prepare the necessary reagents to plate and image migrating D17 cells; they can then be used to examine intracellular dynamics or observe loss-of-function RNAi phenotypes using an in vitro scratch or wound healing assay. From first thawing frozen ampules of D17 cells, investigators can expect to begin assaying RNAi phenotypes in D17 cells within roughly 2-3 weeks.


Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties, clinical development and applications.
Hepatobiliary contrast agents with uptake into hepatocytes followed by variable biliary excretion represent a unique class of cell-specific MR contrast agents. Two hepatobiliary contrast agents, mangafodipir trisodium and gadobenate dimeglumine, are already clinically approved. A third hepatobiliary contrast agent, Gd-EOB-DTPA, is under consideration. The purpose of this review is to provide an overview on the properties, clinical development and application of these three hepatobiliary contrast agents. Bolus injectable paramagnetic hepatobiliary contrast agents combine established features of extracellular agents with the advantages of hepatocyte specificity. The detection and characterisation of focal liver disease appears to be improved compared to unenhanced MRI, MRI with unspecific contrast agents and contrast-enhanced CT. To decrease the total time spent by a patient in the MR scanner, it is advisable to administer the agent immediately after acquisition of unenhanced T1-w MRI. After infusion or bolus injection (with dynamic FS-T1-w 2D or 3D GRE) of the contrast agent, moderately and heavily T2w images are acquired. Post-contrast T1-w MRI is started upon completion of T2-w MRI for mangafodipir trisodium and Gd-EOB-DTPA as early as 20 min following injection, while gadobenate dimeglumine scans are obtained >60 min following injection. Post-contrast acquisition techniques with near isotropic 3D pulse sequences with fat saturation parallel the technical progress made by MSCT combined with an unparalleled improvement in tumour-liver contrast. The individual decision that hepatobiliary contrast agent one uses is partly based on personal preferences. No comparative studies have been conducted comparing the advantages or disadvantages of all three agents directly against each other.


The efficacy and safety of Jinwu Gutong capsule in the treatment of knee osteoarthritis: A meta-analysis of randomized controlled trials.
The Jinwu Gutong (JWGT) capsule is a Chinese patent medicine that is widely used in the treatment of knee osteoarthritis (KOA) and osteoporosis in China and is considered to have the potential for good clinical efficacy. The purpose of this study was to systematically evaluate the clinical efficacy and safety of JWGT in the treatment of KOA. We searched the China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, PubMed, Embase and Cochrane Library databases to identify clinical trials that explore the use of JWGT only or JWGT combined with Western drugs (JWGT group) compared with the use of conventional Western drugs (Western drugs group) for the treatment of KOA. The clinical trials, that were retrieved from each database from the inception of the database to December 2021, were screened. We used the risk of bias assessment tool recommended by Cochrane to evaluate the quality of the included literature and RevMan 5.3 software for data analysis. A total of 17 clinical randomized controlled trials (RCTs) were included in this study, with a total of 1930 participants, including 1015 people in the experimental group and 915 people in the control group. The results of the meta-analysis showed that the JWGT group exhibited better efficacy than the Western drug group with respect to WOMAC score (WMD = -6.25, 95% CI = -8.09 to -4.41, P < 0.001), VAS score (WMD = -1.36, 95% CI = -2.17 to -0.55, P = 0.001), KSS score (WMD = 23.01, 95% CI = 21.42 to 24.59, P < 0.001), IL-6 (SMD = -3.30, 95% CI = -4.84 to -1.76, P < 0.001), TNF-α (SMD = -1.70, 95% CI = -2.02 to -1.38, P < 0.001). The effective rate (OR = 2.56, 95% CI = 1.83 to 3.57, P < 0.001) and incidence of adverse reactions was significantly lower in the JWGT group than in the control group (OR = 0.13, 95% CI = 0.07 to 0.21, P < 0.001). Subgroup analysis showed that JWGT + NSAIDs had more advantages in regard to efficacy (OR = 2.05, 95% CI = 1.35 to 3.12, P < 0.001), and reducing adverse reactions (OR = 0.10, 95% CI = 0.06 to 0.18, P < 0.001), VAS score (WMD = -1.00, 95% CI = -1.93 to -0.07, P = 0.04), KSS score (WMD = 17.39, 95% CI = 15.39 to 19.39, P < 0.001), WOMAC score (WMD = -2.84, 95% CI = -10.75 to 5.08, P < 0.001), IL-6 (SMD = -1.42, 95% CI = -2.08 to -0.75, P < 0.001) and TNF-α (SMD = -1.68, 95% CI = -1.93 to -1.43, P < 0.001) than NSAIDs alone. Compared with hyaluronic acid (HA) alone, JWGT + HA had better clinical efficacy (OR = 3.08, 95% CI = 1.48 to 6.40, P < 0.001). Compared with glucosamine (GS) alone, JWGT + GS significantly reduced the Lequesne index score (WMD = -0.53, 95% CI = -0.85 to -0.21, P = 0.001) and the serum TNF-α level (SMD = -1.68, 95% CI = -1.93 to -1.43, P < 0.001), but it had no significant advantage in reducing the serum IL-6 level (SMD = -4.53, 95% CI = -10.13 to 1.07, P = 0.11). JWGT is considered effective and safe in the treatment of KOA and is worthy of clinical application. In addition, the application of JWGT combined with NSAIDs, HA or GS can significantly improve the clinical efficacy of the latter agents in KOA treatment.


The role of guanidine hydrochloride in graphitic carbon nitride synthesis.
Graphitic carbon nitride (CN) was synthesized from guanidine hydrochloride (G), melamine (M) and dicyandiamide (DCDA). The CN materials synthetized from the pure precursors and their mixtures were characterized by common methods, including thermal analysis, and their photocatalytic activities were tested by the degradation of selected organic pollutants, such as amoxicillin, phenol, Rhodamine B (RhB). Remarkable changes in their texture properties in terms of particle sizes, specific surface areas (SSA) and consequently their photocatalytic activity were explained by the role of guanidine hydrochloride in their synthesis. The SSA increased due to the release of NH3 and HCl and its complex reactions with melamine and DCDA forming structure imperfections and disruptions. The photocatalytic activity of the CN materials was found to be dependent on their SSA.


11B and 1H-11B HMBC NMR as a Tool for Identification of a Boron-Containing Nucleoside Dimer.
Boron-containing compounds are commonly used in synthetic chemistry and are known to play important roles in biology. Despite the widespread relevance of boronated compounds, there have been limited methods to discover, characterize, and study them. Here, we describe the use of 11B NMR, including 1H-11B HMBC, for the isolation and characterization of the boron-containing natural product diadenosine borate. Utilizing synthetic standards, we optimized coupling parameters for 1H-11B HMBC experiments to allow for the analysis of small quantities (∼1 mg) of boron-containing compounds. This work can facilitate the broader application of 11B NMR to the study of boron in a range of applications, from synthetic chemistry to the role of boron in naturally occurring systems.


Application of delayed luminescence measurements for the identification of herbal materials: a step toward rapid quality control.
Herbal materials are widely used as medicinal products, dietary supplements, food, and spices. With increased consumption, the safety, quality, and efficacy of herbal materials are becoming more relevant. The authenticity of herbal materials plays an important role in herbal quality control, and there is an urgent need to develop a simple, direct, objective, rapid, and inexpensive measurement tool for the identification of herbal materials for the purpose of quality control. Delayed luminescence (DL) was used to measure authentic and counterfeit herbal materials. A hyperbolic function was used to extract four properties from the DL curves of the herbal materials. Statistical tools, including Student's t test and Principal Component Analysis, were used to differentiate authentic and counterfeit herbal materials based on the DL properties. Our results showed that authentic and counterfeit herbal materials could be identified based on the DL properties as follows: (a) authentic versus counterfeit materials; (b) authentic versus adulterated materials; (c) authentic versus sulfur-fumigated materials; as well as (d) authentic versus dyed materials. The simple, direct, rapid, and inexpensive measurements offered by DL potentially offer a novel technique for the identification of Chinese herbal materials. However, the establishment of a valid database will be the next step toward the possible application of this technique, which would contribute significantly to the development of a novel digital tool for the quality control of herbal materials.


Biochemical characterization of two new Aspergillus niger aspartic proteases.
Two new aspartic proteases, PepAb and PepAc (encoded by pepAb and pepAc), were heterologously expressed and biochemically characterized from Aspergillus niger F0215. They possessed a typical structure of pepsin-type aspartic protease with the conserved active residues D (84, 115), Y (131, 168) and D (281, 326), while their identity in amino acid sequences was only 19.0%. PepAb had maximum activity at pH 2.5 and 50 °C and PepAc at 3.0 and 50 °C. The specific activities of PepAb and PepAc toward casein were 1368.1 and 2081.4 U/mg, respectively. Their activities were significantly promoted by Cu2+ and Mn2+ and completely inhibited by pepstatin. PepAb exhibited higher catalytic efficiency (k cat/K m) toward soy protein isolates than casein, while PepAc showed higher catalytic efficiency toward casein. The hydrolysis capacities of PepAb and PepAc on soy protein isolates were slightly lower than that of previously identified A. niger aspartic protease, PepA (aspergillopepsin I), while the resultant peptide profiles were remarkably different for all three proteases.


Temperature-controlled molecular weight of hyaluronic acid produced by engineered Bacillus subtilis.
To produce high-, medium- and low-molecular-weight hyaluronic acid (HA) at different temperatures using engineered Bacillus subtilis expressing hyaluronidase (HAase) from leech. By overexpressing the HAase gene hya in the HA-producing strain WmB using temperature-sensitive plasmid pKSV7, the engineered strain WmB-PYh produced HA with different molecular weights (8.61 kDa at 32 °C, 0.615 MDa at 42 °C, and 6.19 MDa at 47 °C). In this study, the molecular weight of HA was regulated by using leech HAase expressed from a temperature-sensitive plasmid. We thus obtained different molecular weight HAs by using a single bacterial strain at different culture temperatures.


Are ADHD gender patterns moderated by sample source?
To examine whether ADHD gender patterns with respect to social-demographic characteristics, comorbidity, and impairment vary as a function of service use for emotional or behavioral problems. Two hundred and seventy-nine males and 119 females meeting ADHD symptom criteria identified in a nationally representative sample of Australian youth ages 6 to 17 are stratified according to whether they had attended a service in the previous 6 months. ADHD gender patterns vary across service use on only 2 of the 31 comparisons made. The two exceptions were child's age at interview (females were older than males among service attendees but younger among nonattendees) and depressive disorders (females had higher rates than males among service attendees but lower rates among nonattendees). Systematic differences in methods of case identification rather than sample source may be responsible for the discrepant ADHD patterns found between clinic and community-based studies.


EPSPs Measured in Proximal Dendritic Spines of Cortical Pyramidal Neurons.
EPSPs occur when the neurotransmitter glutamate binds to postsynaptic receptors located on small pleomorphic membrane protrusions called dendritic spines. To transmit the synaptic signal, these potentials must travel through the spine neck and the dendritic tree to reach the soma. Due to their small size, the electrical behavior of spines and their ability to compartmentalize electrical signals has been very difficult to assess experimentally. In this study, we developed a method to perform simultaneous two-photon voltage-sensitive dye recording with two-photon glutamate uncaging in order to measure the characteristics (amplitude and duration) of uncaging-evoked EPSPs in single spines on the basal dendrites of L5 pyramidal neurons in acute brain slices from CD1 control mice. We were able to record uncaging-evoked spine potentials that resembled miniature EPSPs at the soma from a wide range of spine morphologies. In proximal spines, these potentials averaged 13.0 mV (range, 6.5-30.8 mV; N = 20) for an average somatic EPSP of 0.59 mV, whereas the mean attenuation ratio (spine/soma) was found to be 25.3. Durations of spine EPSP waveforms were found to be 11.7 ms on average. Modeling studies demonstrate the important role that spine neck resistance (Rneck) plays in spine EPSP amplitudes. Simulations used to estimate Rneck by fits to voltage-sensitive dye measurements produced a mean of 179 MΩ (range, 23-420 MΩ; N = 19). Independent measurements based on fluorescence recovery after photobleaching of a cytosolic dye from spines of the same population of neurons produced a mean R eck estimate of 204 MΩ (range, 52-521 MΩ; N = 34).


Exploring the relationship between medical student basic psychological need satisfaction, resilience, and well-being: a quantitative study.
There is increasing acknowledgment that medical training is stressful for students and can impact their well-being. An important aspect of this is self-determination and basic psychological need satisfaction. A better understanding of how medical student perceptions of the learning environment impacts their basic psychological needs for motivation, resilience, and well-being may help to create learning environments that support the needs of medical students and help them become better healthier physicians. We aim to add to the literature on this topic by examining this relationship through the lens of Self-Determination Theory. A total of 400 students from all 4 years of the medical program at our institution were invited to complete an anonymous online survey, measuring basic need satisfaction/frustration (autonomy, competence, relatedness) within the learning environment, resilience, and psychological well-being. We used analysis of variance to assess the effect of gender, age, and year on all variables, with t-tests to compare subgroups. Structural equation modelling was performed to test a hypothesized model in which support of medical students' basic needs would positively relate to their resilience and well-being. The response rate was 183/400 (46%). After data cleaning, 160 remained: 67 males (42%) and 93 females (58%). There were 67 first years (42%), 35 second years (22%), 30 third years (19%), and 28 fourth years (18%). The sample mean age was 25.8 years (SD = 4.1). A well-fitting model was confirmed to fit the data, χ2 = 3.15, df = 3, p = 0.369, RMSEA = 0.018, SRMR = 0.022, CFI = 0.999. Autonomy and relatedness satisfaction exerted direct effects on well-being. Competence satisfaction did so indirectly, through its direct effect on resilience. Female medical students had lower resilience scores compared to their male peers. When medical students perceived their learning environment as supportive to their basic needs, it was associated with an increase in their psychological well-being. Satisfaction of competence, but not autonomy or relatedness, predicted an increase in their resilience. Fostering medical students' basic needs for motivation, especially competence, is recommended to support their resilience and well-being. Further research is required to generalize these results further.


Salmonella typhimurium mitogen induces proliferation of human B lymphocytes.
The maturation of human B lymphocytes can be described as a sequence of activation, proliferation, and differentiation into immunoglobulin-secreting cells. A variety of mitogens which are T cell dependent or independent have been employed to study this process. These moieties generally induce B-cell activation and proliferation followed by differentiation, making the study of initial events difficult. This study characterizes the mitogenic activity of Salmonella typhimurium mitogen (STM), a protein fraction of S. typhimurium. Glass-nonadherent peripheral blood lymphocytes were rosetted with affinity-purified rabbit anti-human F(ab')2-coupled ox erythrocytes and separated on a Ficoll-Hypaque gradient. This population of B lymphocytes, when cultured in dilutions of STM showed dose-dependent proliferation by [3H]thymidine incorporation. Maximal proliferation occurred on Day 7 using STM at 100 micrograms/ml (control, 5692 +/- 1704 cpm; STM, 58,541 +/- 5655 cpm). On Day 7 the percentage of blast cells by Giemsa stain was 14 +/- 4% in control cultures and 52.5 +/- 8.7% with STM. ELISA quantitation of IgG and IgM in culture supernatants revealed no secretion above unstimulated controls. When B lymphocytes were enriched by a negative selection technique, significant proliferation was not observed. STM is a novel B lymphocyte mitogen which induces proliferation but not activation or differentiation of human B lymphocytes into immunoglobulin-secreting cells.


Renal cell carcinoma with tumor thrombus growing against the direction of venous return: an indicator of complicated surgery and poor prognosis.
To explore the effect of tumor thrombus growing against the direction of venous return (GADVR) tumor thrombus on the choice of surgical approach, the impact on the complexity of the surgery and the prognosis. We retrospectively analyzed the clinicopathological data of 213 patients, who underwent surgery in a single center of Peking University Third Hospital between January 2016 and June 2020. For right renal cell carcinoma (RCC) and venous tumor thrombus (VTT), imaging revealed a filling defect in the left renal vein, which was significantly enhanced in enhanced imaging, suggesting that the tumor thrombus grew against the direction of venous return into the left renal vein. For left RCC and VTT, at least one of the left renal vein branches has tumor thrombus. The branches include the left adrenal vein, the left gonadal vein (testicular vein or ovarian vein), and the left ascending lumbar vein. The patients were divided into two groups according to whether they were GADVR tumor thrombus, and we compare the clinicopathological characteristics of GADVR tumor thrombus and non-GADVR tumor thrombus. Univariate and multivariate Cox regression analyses were performed to explore the risk factors that affect the prognosis of patients with RCC and VTT. Kaplan-Meier plots were conducted to evaluate the effect of GADVR on progression-free survival (PFS). Compared with non-GADVR tumor thrombus, patients with GADVR tumor thrombus had a higher proportion of open surgery (76.2% vs. 52.1%, P = 0.035), a higher proportion of tumor thrombus adhering to the inferior vena cava (IVC) vessel wall (81% vs. 45.8%, P = 0.002), a higher proportion of segmental resection of the IVC vessel wall (61.9% vs. 15.6%, P < 0.001); higher preoperative serum creatinine value (110.0 μmol/L vs. 91.0 μmol/L, P = 0.015), a higher proportion of tumor thrombus combined with bland thrombus (non-tumor thrombus) (57.1% vs. 19.8%, P < 0.001). In terms of surgical complexity, patients with GADVR tumor thrombus had a longer median operation time (379 min vs. 308 min, P = 0.038), more median surgical blood loss (1400 mL vs. 600 mL, P = 0.018), and more postoperative complications (52.4% vs. 30.7%, P = 0.045). Multivariate Cox regression analysis showed that GADVR tumor thrombus, symptoms, postoperative serum creatinine, distant metastasis, sarcomatoid feature, pathological type, lymph node dissection were independent risk factors for PFS. Patients with GADVR tumor thrombus's median survival time was 14.0 months, while patients with non-GADVR tumor thrombus were 32.0 months (P = 0.016). GADVR tumor thrombus is an independent risk factor for PFS in patients with RCC and VTT. GADVR tumor thrombus is a characteristic feature of tumor thrombus, with an incidence of 9.9%. It has a higher proportion of open surgery and higher surgical complexity, which is an independent risk factor for PFS.


Efficient transfected liposomes co-loaded with pNrf2 and pirfenidone improves safe delivery for enhanced pulmonary fibrosis reversion.
Pulmonary fibrosis (PF) is an interstitial lung disease with complex pathological mechanism, and there is currently a lack of therapeutics that can heal it completely. Using gene therapy with drugs provides promising therapeutic strategies for synergistically reversing PF. However, improving the intracellular accumulation and transfection efficiency of therapeutic nucleic acids is still a critical issue that urgently needs to be addressed. Herein, we developed lipid nanoparticles (PEDPs) with high transfection efficiency coloaded with pDNA of nuclear factor erythroid 2-related factor 2 (pNrf2) and pirfenidone (PFD) for PF therapy. PEDPs can penetrate biological barriers, accumulate at the target, and exert therapeutic effects, eventually alleviating the oxidative stress imbalance in type II alveolar epithelial cells (AECs II) and inhibiting myofibroblast overactivation through the synergistic effects of Nrf2 combined with PFD, thus reversing PF. In addition, we systematically engineered various liposomes (LNPs), demonstrated that reducing the polyethylene glycol (PEG) proportion could significantly improve the uptake and transfection efficiency of the LNPs, and proposed a possible mechanism for this influence. This study clearly reveals that controlling the composition ratio of PEG in PEDPs can efficiently deliver therapeutics into AECs II, improve pNrf2 transfection, and synergize with PFD in a prospective strategy to reverse PF.


Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis.
We performed a meta-analysis of cross-sectional studies on serum 25(OH)D status globally. Serum 25(OH)D levels on average were 54 nmol/l, were higher in women than men, and higher in Caucasians than in non-Caucasians. There was no trend in serum 25(OH)D level with latitude. Vitamin D deficiency was widespread. We studied vitamin D status (expressed as serum 25-hydroxy-vitamin D [25(OH)D]) in native subjects worldwide. Meta-analysis and meta-regression of studies reporting on 25(OH)D in healthy subjects retrieved from Pubmed, Embase and Web of Science using the terms "serum", "25-hydroxy-vitamin D", "cholecalciferol", and "human". A total of 394 studies were included. The mean 25(OH)D level was 54 nmol/l (95% CI: 52-57 nmol/l). Women had borderline significantly higher 25(OH)D levels than men, and Caucasians had higher levels than non-Caucasians. 25(OH)D levels were higher in subjects aged >15 years than in younger subjects. Unadjusted there was no significant decrease in 25(OH)D with latitude (slope of curve -0.03 +/- 0.12 nmol/l per degree latitude north or south of equator, p = 0.8). There was a significant decline with latitude for Caucasians (-0.69 +/- 0.30 nmol/l per degree, p = 0.02), but not for non-Caucasians (0.03 +/- 0.39 nmol/l per degree, p = 0.14). After adjustment for age, gender, and ethnicity, no overall correlation was present between 25(OH)D and latitude (-0.29 +/- 0.24 nmol/l per degree, p = 0.23). There was no overall influence of latitude on 25(OH)D. However, in separate analyses 25(OH)D decreased with latitude in Caucasians but not in non-Caucasians. A widespread global vitamin D insufficiency was present compared with proposed threshold levels.


Current perspectives on the drug treatment of neonatal respiratory distress syndrome.
Respiratory distress syndrome (RDS) in preterm neonates is caused by a lack of alveolar surfactant, which leads to decreased pulmonary compliance and increased work of breathing. Effective therapy for RDS has reduced mortality at the expense of increasing the number of preterm survivors with chronic lung disease. Drugs such as corticosteroids, proterelin (thyrotropin-releasing hormone) and ambroxol have all been administered to mothers to promote fetal lung maturation, but of these only corticosteroids have been proven to be of benefit. The management of RDS includes assisted ventilation and surfactant replacement therapy. There are several surfactant preparations, some synthetic and others derived from animal lungs, and recent research has been directed at finding which, if any, is superior. The timing of the first dose has also been studied. Prophylactic surfactant administration within the first 15 minutes of life appears to be more efficacious than later treatment for very preterm babies, but could lead to some neonates being treated unnecessarily and perhaps being exposed to adverse effects. Newer treatments for neonates with RDS are aimed at reducing the pulmonary inflammation that occurs as a result of ventilatory barotrauma and oxygen toxicity. Superoxide dismutase, along with other antioxidants, may be beneficial as a free radical scavenger to reduce oxygen toxicity. Inhaled nitric oxide may reduce oxygen requirements by reducing ventilation-perfusion mismatching, and early treatment with corticosteroids may reduce pulmonary inflammation. All of these treatments are currently undergoing clinical trials.


Insulin resistance by unprocessed insulin proreceptors point mutation at the cleavage site.
Failure to cleave the interconnecting site between alpha- and beta-subunit produced insulin proreceptors in the plasma membranes which had markedly low affinity to insulin, leading to extreme insulin resistance in a patient. We performed cDNA sequence analysis of the cleavage site of the insulin proreceptor from the patient. Polymerase chain reaction was used to obtain large amount of cDNA coding for the region including the interconnecting site. A thermostable DNA polymerase, Taq polymerase, successfully produced enough amount of cDNA of the region to be sequenced. The results showed AGG (Arg) to AGT (Ser) point mutation, resulting in the change of interconnecting sequence of the two subunits from -Arg-Lys-Arg-Arg- to -Arg-Lys-Arg-Ser-. These results suggest that the tertial structure change of the cleavage site leads to production of unprocessed insulin proreceptors.


Emergency Department and Hospital Use Among Adolescents With Justice System Involvement.
Adolescents with justice system involvement have high rates of physical and behavioral health disorders and are potentially high users of costly health care services. We examined emergency department (ED) and hospital use among a national sample of adolescents with various levels of justice involvement. Cross-sectional analysis using the 2009 to 2014 National Survey on Drug Use and Health. We included adolescents aged 12 to 17 and used multivariable logistic and negative binomial regression models, adjusting for sociodemographic and health differences, to compare ED and hospital use among adolescents with and without justice involvement. Our sample included 1375 adolescents with past year arrest, 2450 with past year probation or parole, 1324 with past year juvenile detention, and 97 976 without past year justice involvement. In adjusted analyses, adolescents with any justice system involvement, compared to those without, were more likely to have used the ED (38.5%-39.5% vs 31.0%; P < .001) or been hospitalized in the past 12 months (7.1%-8.8% vs 4.8%; P < .01). After adjustment, adolescents with justice involvement also had more ED visits per 100 person-years (77.7-92.9 vs 62.8; P < .01) and hospital nights per 100 person-years (43.3-53.7 vs 18.0; P < .01). Use was highest among adolescents with justice involvement who reported fair or poor health, an illicit drug use disorder, or a mood disorder. Adolescents with justice involvement had substantially higher rates of ED and hospital use. Providing comprehensive support services to adolescents with justice involvement may improve health care use patterns and reduce health care spending.


Construction of a minimum-size functional flagellin of Escherichia coli.
Various deletions were introduced into the central region of Escherichia coli flagellin (497 residues) without destroying its ability to form flagellar filaments. The smallest flagellin retained only the N-terminal 193 residues and the C-terminal 117 residues, which are suggested to be the domains essential for filament formation.


Mifepristone increases AQP1 mRNA expression, angiogenesis, and cell permeability through the ERK MAPK pathway.
The purpose of this study was to investigate the mechanism of mifepristone serves as an anti-implantation contraceptive drug on aquaporins 1 (AQP1) expression. Human umbilical vein endothelial cells (HUVECs) were used to detect the effects of different concentrations of mifepristone (0, 0.065, 0.2, and 1 μmol/L) on the activity of angiogenesis and AQP1 expression. The expression of AQP1 was tested by the real-time PCR. The angiogenesis and penetration function of HUVECs was investigated by Matrigel lumen formation and trans-well assay, respectively. The expression of AQP1, angiogenesis and cell permeability were significantly higher than control groups in HUVECs treatment with mifepristone at 1 μmol/L for 12 h. Estrogen and progesterone decreased the up-regulation of AQP1 and cell permeability, not angiogenesis, induced by mifepristone. Mifepristone increased protein levels of p-ERK, not p-p38 or p-JNK, and pre-treatment with ERK MAPK-specific inhibitor significantly inhibited the up-regulation of AQP1 mRNA expression, angiogenesis and cell permeability induced by mifepristone. si-AQP1 significantly reduced the up-regulation of angiogenesis, cell permeability and p-ERK/ERK ratio expression induced by mifepristone treatment. Overexpression of AQP1 enhanced the increase of expression ratio of p-ERK/ERK induced by mifepristone. Low-dose mifepristone increased cell permeability, angiogenesis and AQP1 expression, which was involved in MAPK pathways. This provides new insights into the molecular mechanism of mifepristone serves as an anti-implantation contraceptive drug.


Opioid Dosage Levels, Concurrent Risk Factors and Self-Perceptions among Chronic Pain, Opioid-Managed Individuals at Elevated Risk for Opioid Overdose.
While current opioid prescribing guidelines highlight a dose-response relationship between therapeutic management and overdose risk, other concurrent risk factors have also been identified. However, there is little data in assessing the relationship between risk factor prevalence, associated provider communication, and subsequent perceptions of overdose risk among chronic pain, opioid-managed (CPOM) patients. An online questionnaire was distributed in June 2020 to a sample of CPOM individuals (n = 190) treated with an opioid prescription at or above 50 daily MME, or any dosage alongside benzodiazepines. CPOM individuals reported a mean daily MME of 470, with half (52.6%) receiving a concurrent benzodiazepine prescription. All patients reported past month alcohol use, and 67.4% indicated a risk-elevating diagnosed medical condition. In assessing provider communication, 41.6% reported no discussion focusing on the risks of one's opioid therapy. Subsequently, 62.1% perceived themselves as having "no risk", and 60.0% were "not at all concerned" (60.0%) about experiencing an opioid overdose. Organizational policies should focus on implementing consistent methods of patient education regarding overdose risk, as well as assessments of behaviors or characteristics that my increase an individual's risk of opioid overdose. These policies should also include other forms of evidence-based overdose risk prevention such as co-prescriptions of naloxone.


A Review on Alaria alata, Toxoplasma gondii and Sarcocystis spp. in Mammalian Game Meat Consumed in Europe: Epidemiology, Risk Management and Future Directions.
Game meat is increasingly appreciated and consumed in Europe, also due to the growing population of wild ungulates. In addition to interesting nutritional properties and market opportunities, game meat is characterized by some specific public health issues. This review focuses on the etiology, epidemiology, public health aspects and risk management along the supply chain, including parasite detection at slaughtering and inactivation in meat, of three selected foodborne parasitic hazards (Alaria alata, Toxoplasma gondii and Sarcocystis spp.) in the main mammalian game meat species in the EU: wild boar (Sus scrofa), red deer (Cervus elaphus), roe deer (Capreolus capreolus), fallow deer (Dama dama), Alpine chamois (Rupicapra rupicapra), moose (Alces alces), hare (Lepus europaeus) and wild rabbit (Oryctolagus cuniculus). The presented data point out the main issues, and knowledge gaps as well as the potential for improved control in order to contribute to the risk analysis process. To pursue an effective management of these parasitic zoonoses, awareness raising should involve all figures in the supply chain, including hunters, restaurateurs and consumers. Human behaviour and the lack of knowledge regarding meat borne parasitic zoonoses and the health risks they pose seem to be the most important factors responsible for human infections. However, detection methods, starting from the sampling procedure, should be further developed and standardized in order to improve the collection of accurate and up-to-date epidemiological data.


The consensus on the monitoring, treatment, and prevention of leukemia relapse after allogeneic hematopoietic stem cell transplantation in China.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important curative therapy for patients with leukemia. However, relapse remains the leading cause of death after transplantation. In recent years, substantial progress has been made by Chinese physicians in the field of establishment of novel transplant modality, patient selection, minimal residual disease (MRD) monitoring, and immunological therapies, such as modified donor lymphocyte infusion (DLI) and chimeric antigen receptor T (CART) cells, as well as MRD-directed intervention for relapse. Most of these unique systems are distinct from those in the Western world. In this consensus, we reviewed the efficacy of post-HSCT relapse management practice from available Chinese studies on behalf of the HSCT workgroup of the Chinese Society of Hematology, Chinese Medical Association, and compared these studies withthe consensus or guidelines outside China. We summarized the consensus on routine practices of post-HSCT relapse management in China and focused on the recommendations of MRD monitoring, risk stratification directed strategies, and modified DLI system. This consensus will likely contribute to the standardization of post-HSCT relapse management in China and become an inspiration for further international cooperation to refine global practices.


Protection of evolving myocardial infarction and failed PTCA.
Acute myocardial infarction is caused by acute coronary occlusion and is the major cause of death in Europe and the United States. In-hospital mortality is due principally to cardiogenic shock because of extensive ischemic muscle damage. Previous surgical results of coronary artery bypass grafting for left ventricular power failure have been disappointing because intraoperative ischemic injury is superimposed on severe damage already sustained by the myocardium. Surgical revascularization has, in general, been restricted to patients with acute occlusion after elective percutaneous transluminal coronary angioplasty with or without thrombolytic therapy. During the last years new knowledge has been gained in the pathophysiology of acute coronary occlusion on ischemic and nonischemic (remote) myocardium that has evolved in a new surgical strategy for revascularization of patients with evolving myocardial infarctions and failed percutaneous transluminal coronary angioplasty. Studies of the natural history of acute regional ischemia have shown that acute occlusion of a coronary artery not only affects the ischemic myocardium but causes structural, functional, and metabolic alterations in the remote and adjacent myocardium. These changes in the remote myocardium are even more severe if the remote myocardium is supplied by a stenotic coronary artery. Furthermore, many experimental and clinical studies have shown that normal blood reperfusion of myocardium injured previously by ischemia leads to additional damage (reperfusion injury).(ABSTRACT TRUNCATED AT 250 WORDS)


Eaton agent--science and scientific acceptance: a historical commentary.
The three classical papers published in 1944 and 1945 by Monroe A. Eaton and colleagues deal with the etiology of primary atypical pneumonia (PAP) and with the properties of a filterable agent (subsequently and for a number of years known as Eaton agent) from the sputum or lung of patients with PAP using cotton rats, hamsters, and chick embryos as laboratory hosts. The present review is first and foremost a tribute to Monroe Eaton and his colleagues for their trail-blazing discovery of a major cause of the atypical pneumonia syndrome and their steadfast vision of its importance. The organism was finally identified and designated Mycoplasma pneumoniae some 20 years after their papers first appeared in the Journal of Experimental Medicine.


Potential applications of DNA methylation testing technology in female tumors and screening methods.
DNA methylation is a common epigenetic modification, and the current commonly used methods for DNA methylation detection include methylation-specific PCR, methylation-sensitive restriction endonuclease-PCR, and methylation-specific sequencing. DNA methylation plays an important role in genomic and epigenomic studies, and combining DNA methylation with other epigenetic modifications, such as histone modifications, may lead to better DNA methylation. DNA methylation also plays an important role in the development of disease, and analyzing changes in individual DNA methylation patterns can provide individualized diagnostic and therapeutic solutions. Liquid biopsy techniques are also increasingly well established in clinical practice and may provide new methods for early cancer screening. It is important to find new screening methods that are easy to perform, minimally invasive, patient-friendly, and affordable. DNA methylation mechanisms are thought to have an important role in cancer and have potential applications in the diagnosis and treatment of female tumors. This review discussed early detection targets and screening methods for common female tumors such as breast, ovarian, and cervical cancers and discussed advances in the study of DNA methylation in these tumors. Although existing screening, diagnostic, and treatment modalities exist, the high morbidity and mortality rates of these tumors remain challenging.


Characterization of progesterone 11 alpha-hydroxylase of Aspergillus ochraceus TS: a cytochrome P-450 linked monooxygenase.
The monooxygenase of Aspergillus ochraceus TS capable of 11 alpha-hydroxylation of progesterone has been resolved into three components and characterized as (i) cytochrome P450, (ii) NADPH-cytochrome P450-reductase and (iii) phosphatidyl choline. The 11 alpha-hydroxylase was observed to be NADPH dependent, and hydroxylation was enhanced by a NADPH regenerating system. This fungal monooxygenase has many features in common with that of mammalian liver microsomes. The role of mammalian cytochrome P450 inducers were tested for induction of 11 alpha-hydroxylase in Aspergillus ochraceus TS. The reductase has been partially purified.


EVALUATION OF THE INCLUSION OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN A TELEMEDICINE DIABETIC RETINOPATHY SCREENING PROGRAM: A Real Clinical Practice.
To evaluate whether combining spectral domain optical coherence tomography with monoscopic fundus photography using a nonmydriatic camera (MFP-NMC) improves the accuracy of diabetic macular edema (DME) referrals in a teleophthalmology diabetic retinopathy screening program. We conducted a cross-sectional study with all diabetic patients aged 18 years or older who attended screening from September 2016 to December 2017. We assessed DME according to the three MFP-NMC and the four spectral domain optical coherence tomography criteria. The sensitivity and specificity obtained for each criterion were estimated by comparing them with the ground truth of DME. This study included 3,918 eyes (1,925 patients; median age, 66 years; interquartile range, 58-73; females, 40.7%; once-screened, 68.1%). The prevalence of DME ranged from 1.22% to 1.83% and 1.54% to 8.77% on MFP-NMC and spectral domain optical coherence tomography, respectively. Sensitivity barely reached 50% in MFP-NMC and less for the quantitative criteria of spectral domain optical coherence tomography. When macular thickening and anatomical signs of DME were considered, sensitivity increased to 88.3% and the false DMEs and non-gradable images were reduced. Macular thickening and anatomical signs showed the highest suitability for screening, with a sensitivity of 88.3% and a specificity of 99.8%. Notably, MFP-NMC alone missed half of the true DMEs that lacked indirect signs.


Genome-wide identification, characterization and expression analysis of calmodulin-like (CML) proteins in tomato (Solanum lycopersicum).
Calcium (Ca(2+)) has emerged as a significant secondary messenger that regulates the activities of hormonal and environmental signals that are associated with biotic and abiotic stresses. Ca(2+) binding proteins typically contain a Ca(2+) binding EF-hand (a helix-loop-helix structure) motif. In this study, tomato genes encoding calmodulin-like (CML) proteins that possess EF-hand motifs and no other identifiable functional domains were analyzed. Using genome analysis and BLAST searches in database, 52 CML genes were identified in tomato. Comprehensive analyses, including evolutionary relationships, gene structures, chromosomal locations, functional annotations, and gene duplications, were performed. Distribution mapping exhibited that 52 SlCML proteins containing different intron/exon patterns were unevenly distributed among ten chromosomes. In addition, 24 SlCML proteins were predicted as segmentally duplicated. Conserved motifs, promoter cis-regulatory elements, organ-based expression patterns and expression analyses indicated the potential responsiveness of SlCML proteins to abiotic stresses and phytohormones. These results illustrate the complexity of the CML gene family and indicate a potential vital role for these molecules in tomato growth and development as Ca(2+) signal transducers.


Case of ehrlichiosis induced Guillain-Barre Syndrome in a 71 year-old female.
Guillain-Barre Syndrome (GBS) is a rare autoimmune demyelinating polyradiculoneuropathy that causes an ascending paralysis and flaccid weakness. Tick paralysis is a mimic of GBS as symptoms include generalized weakness and paralysis. However, symptom onset and timing as well as lab findings can distinguish between them. We present a case of a 71-year-old female who complained of generalized weakness and dizziness starting three weeks prior to admission. During that time, she had fevers and chills and a questionable insect bite. Her lab values indicated thrombocytopenia and elevated liver enzymes. PCR titers were positive for ehrlichiosis and she was started on doxycycline then discharged. She returned over a week later with worsening symptoms despite treatment. There was concern she may had Heartland or Bourbon virus but titers were negative. Her neurological exam showed numbness and areflexia in her lower extremities which progressed since her first encounter. She was given IVIG and her symptoms improved and recovered slowly. Although ehrlichiosis is not a common cause for GBS, the pathogenesis is like Lyme disease or Campylobacter jejuni. This patient had clinical symptoms that were like tick-borne illness yet as her disease progressed, it illustrated the need for an expanded differential diagnosis. There is very little literature about ehrlichia inducing GBS. It is important to keep a broad differential as sometimes common syndromes do not always come from common pathogens and with the COVID-19 pandemic having similar results, we are learning new things that may potentially be new standards in medical education.


Modulation of TLR2, TLR4, TLR5, NOD1 and NOD2 receptor gene expressions and their downstream signaling molecules following thermal stress in the Indian major carp catla (Catla catla).
Toll-like receptors (TLRs) and nucleotide binding and oligomerization domain (NOD) receptors are pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and play crucial role in innate immunity. In addition to PAMPs, PRRs recognize endogenous molecules released from damaged tissue or dead cells [damage-associated molecular patterns (DAMPs)] and activate signaling cascades to induce inflammatory processes. In the aquatic environment, large variation in seasonal and diurnal water temperature causes heat and cold stresses in fish, resulting in tissue injury and mortality of fish. In the Indian subcontinent, catla (Catla catla) is an economically important freshwater fish species and is prone to thermal stresses. To investigate the response of pattern recognition receptors in thermal stress, we analyzed TLRs (TLR2, TLR4 and TLR5) and NOD (NOD1 and NOD2) receptors gene expression in catla following heat and cold stress. Analysis of tissue samples (gill, liver, kidney and blood) of the thermal stressed and control fish by quantitative real-time PCR (qRT-PCR) assay revealed significant (p < 0.05) induction of TLR2, TLR4 and NOD2 gene expression in majority of the tested tissues of the treated fish as compared to the control. The expression of TLR5 and NOD1 gene was also induced in the heat and cold stressed fish, but mostly restricted in the blood. The downstream signaling molecule of TLR and NOD signaling pathway viz., MyD88 (myeloid differentiation primary response gene 88) and RICK (receptor interacting serine-threonine protein kinase-2) was also induced in the thermal stressed fish suggesting the engagement of TLR and NOD signaling pathway during thermal stress.


Long-term results of stomach-conserving therapy in gastric MALT lymphoma.
To evaluate long-term results of stomach-conserving therapy and to assess the value of histological probable minimal residual disease (pMRD) in predicting outcome in patients with gastric MALT lymphoma. We studied 115 patients with stage I-II(2) gastric MALT lymphoma treated between 1975 and 2002. Initially, first-line treatment consisted of radiotherapy only. Since 1994 most patients were primarily treated with Helicobacter pylori eradication; radiotherapy was used in case of eradication failure. To assess the value of pMRD, first follow-up biopsy samples classified as compete remission (CR) according to classical clinico-pathological criteria and biopsy samples 1 year after assessment of histological CR were reviewed; results were related to outcome. Following radiotherapy only (n=56) 96% achieved a clinical CR; 10-year cancer-specific survival rate was 94%. Following H. pylori eradication only (n=35) CR-rate was 43% and after additional treatment 89%; 5-year cause-specific survival was 93%. There was no difference in relapse rate following initial histological CR or pMRD. Patients with early stage gastric MALT lymphoma have a favorable long-term outcome following conservative treatment. Outcome after H. pylori eradication followed by delayed radiotherapy on indication was excellent. In our series pMRD was not associated with increased risk of recurrence.


Saturation transfer difference NMR studies on substrates and inhibitors of succinic semialdehyde dehydrogenases.
Saturation transfer difference (STD) NMR experiments on Escherichia coli and Drosophila melanogaster succinic semialdehyde dehydrogenase (SSADH, EC184.108.40.206) suggest that only the aldehyde forms and not the gem-diol forms of the specific substrate succinic semialdehyde (SSA), of selected aldehyde substrates, and of the inhibitor 3-tolualdehyde bind to these enzymes. Site-directed mutagenesis of the active site cysteine311 to alanine in D. melanogaster SSADH leads to an inactive product binding both SSA aldehyde and gem-diol. Thus, the residue cysteine311 is crucial for their discrimination. STD experiments on SSADH and NAD(+)/NADP(+) indicate differential affinity in agreement with the respective cosubstrate properties. Epitope mapping by STD points to a strong interaction of the NAD(+)/NADP(+) adenine H2 proton with SSADH. Adenine H8, nicotinamide H2, H4, and H6 also show STD signals. Saturation transfer to the ribose moieties is limited to the anomeric protons of E. coli SSADH suggesting that the NAD(+)/NADP(+) adenine and nicotinamide, but not the ribose moieties are important for the binding of the coenzymes.


The effect of time since stroke, gender, age, and lesion size on thalamus volume in chronic stroke: a pilot study.
Recent stroke studies have shown that the ipsi-lesional thalamus longitudinally and significantly decreases after stroke in the acute and subacute stages. However, additional considerations in the chronic stages of stroke require exploration including time since stroke, gender, intracortical volume, aging, and lesion volume to better characterize thalamic differences after cortical infarct. This cross-sectional retrospective study quantified the ipsilesional and contralesional thalamus volume from 69 chronic stroke subjects' anatomical MRI data (age 35-92) and related the thalamus volume to time since stroke, gender, intracortical volume, age, and lesion volume. The ipsi-lesional thalamus volume was significantly smaller than the contra-lesional thalamus volume (t(68) = 13.89, p < 0.0001). In the ipsilesional thalamus, significant effect for intracortical volume (t(68) = 2.76, p = 0.008), age (t(68) = 2.47, p = 0.02), lesion volume (t(68) = - 3.54, p = 0.0008), and age*time since stroke (t(68) = 2.46, p = 0.02) were identified. In the contralesional thalamus, significant effect for intracortical volume (t(68) = 3.2, p = 0.002) and age (t = - 3.17, p = 0.002) were identified. Clinical factors age and intracortical volume influence both ipsi- and contralesional thalamus volume and lesion volume influences the ipsilesional thalamus. Due to the cross-sectional nature of this study, additional research is warranted to understand differences in the neural circuitry and subsequent influence on volumetrics after stroke.


Derivation and Validation of a Simplified Clinical Prediction Rule for Identifying Children at Increased Risk for Clinically Important Traumatic Brain Injuries Following Minor Blunt Head Trauma.
To develop a simplified clinical prediction tool for identifying children with clinically important traumatic brain injuries (ciTBIs) after minor blunt head trauma by applying machine learning to the previously reported Pediatric Emergency Care Applied Research Network dataset. The deidentified dataset consisted of 43 399 patients <18 years old who presented with blunt head trauma to 1 of 25 pediatric emergency departments between June 2004 and September 2006. We divided the dataset into derivation (training) and validation (testing) subsets; 4 machine learning algorithms were optimized using the training set. Fitted models used the test set to predict ciTBI and these predictions were compared statistically with the a priori (no information) rate. None of the 4 machine learning models was superior to the no information rate. Children without clinical evidence of a skull fracture and with Glasgow Coma Scale scores of 15 were at the lowest risk for ciTBIs (0.48%; 95% CI 0.42%-0.55%). Machine learning algorithms were unable to produce a more accurate prediction tool for ciTBI among children with minor blunt head trauma beyond the absence of clinical evidence of skull fractures and having Glasgow Coma Scale scores of 15.


Optimization of Process Parameters for Production of Pectinase using Bacillus Subtilis MF447840.1.
Pectinase enzyme has immense industrial prospects in the food and beverage industries. In our investigation, we find out the optimum process parameters suitable for better pectinase generation by Bacillus subtilis MF447840.1 using submerged fermentation. 2% (OD600 nm = 0.2) of pure Bacillus subtilis MF447840.1 bacterial culture was inoculated in sterile product production media. The production media components used for this study were 1 g/l of pectin, 2 g/l of (NH4)2SO4, 1 g/l of NaCl, 0.25 g/l of K2HPO4, 0.25 g/l of KH2PO4 and 1 g/l of MgSO4 for pectinase generation. We reviewed all recent patents on pectinase production and utilization. The various process parameters were observed by changing one variable time method. The optimum fermentation condition of different parameters was noticed to be 5% inoculums, 25% volume ratio, temperature (37°C), pH (7.4) and agitation rate (120 rpm) following 4 days incubation. Maximum pectinase generation was noticed as 345 ± 12.35 U following 4 days incubation.


3-Hydroxyterphenyllin, a new metabolite of Aspergillus candidus. Structure elucidation by H and C nuclear magnetic resonance spectroscopy.
A new compound isolated from cultures of Aspergillus candidus Link is shown to be 3-hydroxyterphenyllin. The structure was assigned by comparing the 1H and 13C nmr spectra of the metabolite and its acetate derivative with those of terphenyllin and terphenyllin triacetate.


Effects of submicron magnetite particles on granulation of flocculent sludge and process stability in upflow anaerobic sludge blanket reactor.
Promoting direct interspecies electron transfer (DIET) with conductive additives is considered a promising approach to enhance methanogenesis. This study investigated the effects of adding submicron magnetite particles on sludge granulation and methanogenic performance in upflow anaerobic sludge blanket reactors inoculated with flocculent sludge. The reactor supplemented with magnetite was more stable and resilient than the no-magnetite control, with higher degree of granulation (up to 26.6-fold) and biomass retention. Magnetite addition to unstable reactors improved the methane yield in both reactors (1.2-1.3-fold). Electroactive Deltaproteobacteria bacteria, including Geobacter and Syntrophobacter, were enriched in the presence of magnetite. Methanogenic functional genes involved in DIET-based syntrophy were more abundant under magnetite-supplemented conditions. However, the improvement of methanogenic performance and granulation was limited, and inducing the self-embedment of magnetite into mature sludge granules rather than granulating flocculent sludge with magnetite appears to be a better strategy for engineering DIET in anaerobic granular sludge systems.


Brain stem projections to the cerebral cortex in the rat.
By means of the HRP method it was shown that the entire cerebral cortex, but in greater proportion the frontal and posterior temporo-parietal regions, receive fibres from the dorsal and medial raphe nuclei and from the locus coeruleus. In contrast, the pars compacta substantiae nigrae and the tegmental area send projections to the motor and cingular areas respectively.