B-prolymphocytic leukemia cells that form rosettes with sheep red blood cells through monoclonal surface immunoglobulin.
The neoplastic cells from a patient with B-cell prolymphocytic leukemia exhibited sheep red blood cell (SRBC) rosette formation. Immunochemistries revealed no reactivity with T-cell monoclonal antibodies OKT 3, 4, 8, and 11. However, the neoplastic cells expressed characteristics of B-cells including surface IgM and IgD associated with lambda light chains, Ia-like antigenicity, and reactivity to monoclonal antibodies against B-cell antigens B1, B2, and B4. Inhibition procedures revealed that SRBC rosette formation was the result of binding activity of surface immunoglobulin to SRBC. Pretreatment of the leukemic cells with antihuman IgM or lambda antisera, or pronase or trypsin blocked rosette formation with SRBC. Circulating antibody to SRBC was also suspected by the fact that preincubation of SRBC with heat-inactivated patient's serum resulted in agglutination of the SRBC.


Crystallization of p68 on lipid monolayers and as three-dimensional single crystals.
Two-dimensional crystals of p68, a Ca2+ -binding protein that has homology with members of the lipocortin/calpactin family, were obtained by interaction with a phospholipid monolayer. By measuring surface pressure at constant surface area, p68 was found to interact in a Ca2+ -dependent manner specifically with phosphatidylethanolamine, less so with phosphatidylserine and not at all with phosphatidylcholine. With dimyristoyl-phosphatidylethanolamine, two-dimensional crystalline arrays were formed. Image analysis of electron micrographs of these crystals, which diffracted to about 50 A, revealed p3 symmetry with a unit cell of about 178 A by 178 A; the protein densities showed a two-domain structure giving a cylindrical molecule of about 100 A by 35 A diameter packed as trimers. Three-dimensional microcrystals obtained without lipid or Ca2+ were suitable for electron microscopy and gave a tetragonal unit cell of about 256 A by 68 A. The implications of these observations on the structure and lipid specificity of p68 binding are discussed.


The Tetratricopeptide repeat domain 7 gene is mutated in flaky skin mice: a model for psoriasis, autoimmunity, and anemia.
The flaky skin (fsn) mutation in mice causes pleiotropic abnormalities including psoriasiform dermatitis, anemia, hyper-IgE, and anti-dsDNA autoantibodies resembling those detected in systemic lupus erythematosus. The fsn mutation was mapped to an interval of 3.9 kb on chromosome 17 between D17Mit130 and D17Mit162. Resequencing of known and predicted exons and regulatory sequences from this region in fsn/fsn and wild-type mice indicated that the mutation is due to the insertion of an endogenous retrovirus (early transposon class) into intron 14 of the Tetratricopeptide repeat (TPR) domain 7 (Ttc7) gene. The insertion leads to reduced levels of wild-type Ttc7 transcripts in fsn mice and the insertion of an additional exon derived from the retrovirus into the majority of Ttc7 mRNAs. This disrupts one of the TPRs within TTC7 and may affect its interaction with an as-yet unidentified protein partner. The Ttc7 is expressed in multiple types of tissue including skin, kidney, spleen, and thymus, but is most abundant in germinal center B cells and hematopoietic stem cells, suggesting an important role in the development of immune system cells. Its role in immunologic and hematologic disorders should be further investigated.


Synthesis in vitro of rat brown adipose tissue 32 000 Mr protein.
The synthesis of the mitochondrial inner membrane 32 000 Mr protein from rat brown adipose tissue was examined. Polysomes from the tissue were translated in a reticulocyte lysate protein-synthesizing system and newly-synthesized protein isolated with a monospecific antibody against the 32 000 Mr protein. The newly-synthesized protein had the same relative molecular mass as the mature protein. It was taken up by mitochondria isolated from Chinese hamster ovary cells into a form resistant to trypsin.


Severity of dependence modulates smokers' functional connectivity in the reward circuit: a preliminary study.
Nicotine dependence is characterized as a neural circuit dysfunction, particularly with regard to the reward circuit. Although dependence severity moderates cue reactivity in the brain regions involved in reward processing, the direction of its influence remains controversial. Investigating the functional organization of the reward circuit may provide complementary information. Here, we used resting-state functional connectivity (rsFC) to evaluate the integrity of the reward circuit in smokers with different severities of nicotine dependence. Totals of 65 smokers and 37 non-smokers underwent resting-state functional magnetic resonance imaging (fMRI). The smokers were divided into low-dependent (FTND < 5, n = 26) and high-dependent smoker groups (FTND ≥ 5, n = 39) based on their nicotine-dependence severity (as measured by the Fagerström test for nicotine dependence [FTND]). The region of interest (ROI)-wise rsFC within the reward circuit was compared between smokers and non-smokers as well as between low-dependent and high-dependent smokers and then correlated with smokers' FTND scores. Widespread rsFC attenuation was observed in the reward circuit of smokers compared with non-smokers. Compared with low-dependent smokers, high-dependent smokers showed greater rsFC between the right amygdala and the left nucleus accumbens (NAcc) as well as between the bilateral hippocampus. Furthermore, a positive correlation between the inter-hippocampus rsFC and the severity of nicotine dependence (FTND) was detected among all smokers (r = 0.416, p = 0.001). Our results indicate a dysfunction of the reward circuit in nicotine-dependent individuals. Moreover, our study improves the understanding of the neuroplastic changes that occur during the development of nicotine dependence.


Alison's Story--A Cautionary Tale in the Age of Genomic Medicine.
Alison's story illustrates the disastrous consequences of not securing an accurate family history when evaluating a patient for solid tumor malignancy; this is even more acute when the patient is diagnosed at a young age or has other close relatives affected by the disease. Rapidly advancing genomic technologies directly challenge traditional management practices of referring all patients who may require genetic testing to a genetic counselor or clinical genetics service because next-generation targeted molecular therapies may be indicated based on genomic DNA analysis and may be required urgently to treat life-threatening advanced disease, at times, before genetic counseling.


High-performance asymmetric optical transmission based on coupled complementary subwavelength gratings.
Asymmetric transmission (AT) devices are fundamental elements for optical computing and information processing. We here propose an AT device consisting of a pair of coupled complementary subwavelength gratings. Different from previous works, asymmetric dielectric environment is employed for unidirectional excitation of surface plasmon polaritons (SPPs) and thus asymmetric optical transmission, and near-field coupling effect inherent in the coupled complementary structure is exploited to enhance forward transmission and AT behavior, and determine operation bandwidth as well. The influence of asymmetric dielectric environment, effect of vertical and lateral couplings, interactions of electric- and magnetic-dipole moments and the realization of Kerker conditions, are investigated in depth to unearth the AT mechanism and performance. High-performance AT with large forward transmittance of 0.96 and broad bandwidth of 174 nm is achieved at wavelength 1250 nm. Our work helps people to gain a better understanding of near-filed coupling effect in coupled complementary structures, expand their application fields, and it also offers an alternate way to high-performance AT devices.


Serum levels of 25-hydroxy vitamin D in normal Biozzi and C57BL/6 mice and during the course of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE).
The aim of the study was to examine possible variations in the levels of 25-hydroxy vitamin D [25-(OH)D] in sera from normal Biozzi and C57BL/6 mice and during the course of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE). Serum concentrations of 25-(OH)D were measured in normal male and female Biozzi and C57BL/6 mice, at 3-4 weeks old and 8-10 weeks old, with a minimum of six animals/group. Levels of the vitamin were also determined in CR EAE-inoculated mice, and controls, during the course of the disease using a minimum of six animals/treatment. Cardiac blood was collected from the groups of normal, control and CR EAE-sensitised mice and sera prepared, by centrifugation of clotted samples, and assayed for 25-(OH)D levels by chemiluminescence assay. Normal male and female Biozzi and C57BL/6 mice had significantly higher levels of 25-(OH)D at 8-10 weeks old compared to concentrations at 3-4 weeks of age (P < 0.005). Also, levels of the vitamin were significantly raised in C57BL/6 male and female mice compared to values in samples from corresponding Biozzi mice. In addition, the amounts of 25-(OH)D in sera from female Biozzi and C57BL/6 mice were significantly increased compared to strain and aged-matched male mice. The CR EAE mice with acute stage disease had significantly higher 25-(OH)D levels compared to controls (P < 0.005). Vitamin concentrations fell to within controls values with the progression of CR EAE. Our preliminary studies have revealed marked differences between the amounts of 25-(OH)D in sera from Biozzi and C57BL/6 mice together with clear gender bias. The investigations also show significant, but selective changes, in levels of the vitamin during the course of CR EAE that are not always associated with the neurological disease state.


Evaluation of a Gadolinium-Based Nanoparticle (AGuIX) for Contrast-Enhanced MRI of the Liver in a Rat Model of Hepatic Colorectal Cancer Metastases at 9.4 Tesla.
The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases. 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE = 45/2.5 ms, alpha = 45°, TA = 1: 23 min, FOV = 5.12 × 5.12 cm(2), matrix = 256 × 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i.v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements. Mean SNRliver (Gd-DOTA: 14.6 +/- 0.7; AGuIX: 28.2+/- 2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 +/- 1.2; AGuIX: 29.6 +/- 2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 +/- 0.7; AGuIX: 15.4 +/- 0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 +/- 0.3; AGuIX: 14.0 +/- 0.7, p < 0.001), mean CNR (Gd-DOTA: -2.5 +/- 0.2; AGuIX: -7.5 +/- 1.0, p < 0.001) and LE (Gd-DOTA: 3.8 +/- 0.7; AGuIX: 14.9 +/- 2.8, p = 0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout. AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors. AGuIX provides superior enhancement as compared to the extracellular compound Gd-DOTA at 9.4 T. AGuIX may improve the detection and diagnostic sensitivity of malignant focal liver lesions. The small size of AGuIX allows for fast renal clearance and prevents undesirable accumulation in the body.


Diagnostic value of transferrin.
Despite the growing interest in hepcidin and other relatively new biomarkers, guidelines and clinical pathways continue to recommend traditional markers, such as serum transferrin (Tf) and ferritin, as laboratory tests for the diagnostic evaluation of iron-related disorders. In this study, we aimed to critically evaluate the diagnostic role of Tf relying on the highest level of available evidence by a comprehensive literature search. The role of Tf in iron deficiency (ID) and iron overload (IO) syndrome as well as a risk marker was evaluated. The low accuracy of Tf and Tf saturation (TS) in the diagnosis and management of ID conditions does not permit definitively recommending their use, even if recently published guidelines still consider the TS investigation as a complementary test for ferritin. If a tissue IO is suspected, TS is often used, even if it may not be the best test for detecting this condition. Nevertheless, clinical guidelines strongly recommend the use of TS as a first-level test for performing genetic diagnosis of hereditary hemochromatosis. Recently reported data indicating elevated TS as a risk factor for diabetes mellitus, cancer, and total mortality, may provide useful additions to the debate over whether or not to screen for IO using TS.


[Misdiagnosis of tired fracture of distal segment of femur].
To improve the diagnosis of tired fracture of the distal segment of femur, and to avoid its misdiagnosis. Misdiagnosis of 5 patients with tired fracture of distal segment of the femur was reviewed. Five male patients, aged 18 to 23 years had the lesion for 3 to 6 weeks. They had long tough experience of sports. The lesion was considered at first as osteosarcoma by radiograph and biopsy. It was eventually diagnosed as tired fracture of distal segment of the femur. Symptoms were relieved or disappeared after proper treatment. Follow-up for 7 to 18 months showed good results. The key to avoid misdiagnosis and mistreatment of the fracture is to know its causes, morphological features of fracture healing, and correct pathologic diagnosis.


Effect of Platelet-rich Plasma on the Clinical Success of Alveolar Grafts in Patients With Cleft Lip and Palate: A Systematic Review and Meta-Analysis.
This study assessed the effect of platelet-rich plasma (PRP) on the clinical success of alveolar grafts in patients with cleft lip and palate. In this meta-analysis, a search of the literature was conducted in Medline, Scopus, ISI Web of Science, and Cochrane Central Register of Controlled Trials for randomized clinical trials using PRP or platelet-rich fibrin (PRF) along with autogenous bone for alveolar ridge grafts in patients with cleft lip and palate. The methodological quality of the studies was analyzed using Cochrane's risk of the bias assessment tool. The extracted data underwent meta-analysis using the random-effects model. Of a total of 2256 articles retrieved, 12 met the eligibility criteria and were enrolled; out of which 6 did not undergo meta-analysis due to heterogeneous data. The percentage of defects filled by bone graft was 0.648% (95% confidence interval: -0.15 to 1.45), which was not statistically significant ( P =0.115). Subgroup analysis showed no significant difference based on the use of PRF or PRP ( P =0.28), type of cleft (unilateral/bilateral; P =0.56), or type of radiographic modality (3D/2D; P =0.190). Meta-regression analysis showed that the duration of follow-up and the difference in the mean age of patients did not have a significant effect on the results (R=0, I2: high). The application of PRP/PRF in combination with autogenous bone graft did not have a significant effect on the percentage of alveolar cleft filled by a bone graft. Future clinical studies are required to further elucidate the effect of PRP in the regeneration of alveolar clefts.


The effect of activation of thoracolumbar fascia on the thickness of abdominal muscles: An ultrasonographic study.
This study aims to evaluate the changes in the ultrasonographic thickness of transversus abdominis and internal oblique muscles during bridge with arm extension compared to bridge and abdominal hollowing. Between March 1st, 2019 and March 29th, 2019, a total of 30 healthy individuals (15 males, 15 females; mean age: 28.8±8.1 years; range, 21 to 52 years) among hospital staff were included. Thickness of transversus abdominis, internal, and external oblique muscles of the participants were evaluated using ultrasound during four positions (rest, abdominal hollowing, bridge, and bridge with arm extension). The mean body mass index was 23.8±4.1 kg/m2. The thickness of transversus abdominis and internal oblique muscles increased during all positions (p<0.001), compared to rest. The thickness during bridge with arm extension was greater than abdominal hollowing and bridge. Co-activation of latissimus dorsi and gluteus maximus muscles during abdominal contraction increases the thickness of internal oblique and transversus abdominis muscles greater than abdominal contraction alone or co-activation of gluteus maximus alone. Simultaneous isometric contraction of latissimus dorsi muscle may enhance abdominal muscle function.


Baicalein improves cognitive deficits and hippocampus impairments in temporal lobe epilepsy rats.
Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is a refractory disease. Baicalein possesses various pharmacological activities, including neuroprotection in neurodegenerative disease. However, whether baicalein is protective in the treatment of TLE is not determined. Therefore, the present study investigated the role of baicalein in the treatment of TLE. Baicalein was injected intraperitoneally to TLE rats for two weeks after the onset of spontaneous recurrent seizures (SRS). Rats were observed for the occurrence of SRS, and cognitive and hippocampus injuries were evaluated. Oxidative stress and inflammatory cytokines were measured. Corticosterone and its receptor, actin-associated protein F-actin and cofilin-1 were investigated in the brains of epileptic rats. Baicalein significantly improved cognition and reduced hippocampus damage and mossy fibre sprouting in TLE rats without obvious SRS suppression. Baicalein produced excellent anti-oxidative and anti-inflammatory effects in TLE rats. Baicalein restored the disruption of the glucocorticoid signal pathway and actin-associated protein in TLE rats. These results suggest that the neuroprotective effects of baicalein on cognition and the hippocampus are associated with the suppression of oxidative stress and inflammation and the regulation of the glucocorticoid pathway and actin-associated protein in TLE rats. This evidence supports the use of baicalein as an adjuvant agent for epilepsy treatment.


Green Synthesis of Nanomaterials Using Plant Extract: A Review.
For the last two decades, extensive research is conducted on metal and metal oxide nanoparticles and their application in the field of medical, cosmetics, catalysts, packaging, photonics, agriculture and electronics. However, these nanoparticles show toxicity to the environmental, human and animal health. The toxicity effects of nanoparticles are mainly due to their size, which can easily pass through physiological barriers and also due to the synthesis procedure. The toxicity due to their size cannot be avoided, but toxicity due to the synthesis process can be nullified by adopting the biosynthesis process. Bacteria, fungus, fish scales, plant extracts and algae are used to synthesize metal and metal- oxide nanoparticles such as silver, gold, iron-oxide, zinc-oxide, zirconia, etc. For the last few years, researchers have been working on synthesis methods of plant extracts to produce stable, cost-effective and economical nanoparticles. In this review, we focus on the biosynthesis of nanoparticles using different parts of plant extracts. The review contains a summary of selected papers from 2018-20 with a detailed description of the process of synthesis, mechanism, characterization and their application in various fields of biosynthesized metal and metal oxide nanoparticles.


Cryo-EM structure and rational engineering of a superefficient ochratoxin A-detoxifying amidohydrolase.
Ochratoxin A (OTA) is among the most prevalent mycotoxins detected in agroproducts, posing serious threats to human and livestock health. Using enzymes to conduct OTA detoxification is an appealing potential strategy. The recently identified amidohydrolase from Stenotrophomonas acidaminiphila, termed ADH3, is the most efficient OTA-detoxifying enzyme reported thus far and can hydrolyze OTA to nontoxic ochratoxin α (OTα) and L-β-phenylalanine (Phe). To elucidate the catalytic mechanism of ADH3, we solved the single-particle cryo-electron microscopy (cryo-EM) structures of apo-form, Phe- and OTA-bound ADH3 to an overall resolution of 2.5-2.7 Å. The role of OTA-binding residues was investigated by structural, mutagenesis and biochemical analyses. We also rationally engineered ADH3 and obtained variant S88E, whose catalytic activity was elevated by 3.7-fold. Structural analysis of variant S88E indicates that the E88 side chain provides additional hydrogen bond interactions to the OTα moiety. Furthermore, the OTA-hydrolytic activity of variant S88E expressed in Pichia pastoris is comparable to that of Escherichia coli-expressed enzyme, revealing the feasibility of employing the industrial yeast strain to produce ADH3 and its variants for further applications. These results unveil a wealth of information about the catalytic mechanism of ADH3-mediated OTA degradation and provide a blueprint for rational engineering of high-efficiency OTA-detoxifying machineries.


An unusual case caused by a common reason: Mondor's disease by oral contraceptives.
Mondor's disease (MD) of the breast is a rare condition at breast clinics. We do not have enough data to establish its real prevalence. As a known data, most of the patients that were admitted to breast clinics are not breast cancer. Also MD is a rare entity and diagnosing this entity and informing the patient about it is very important. We present here this case to remind breast clinic practitioners that MD can be seen without trauma (neither surgical nor physical). Also clinical and radiological findings and the treatmentof the MD were discussed. A 35 year old woman was admitted our clinic with cutaneous breast retraction. She had no risk for thrombosis else using oral contraceptives. Mondor's Disease was diagnosed and supported by radiological findings. Rheumatologic and hematologic causes were also explored. Patient healed in four weeks only with non-steroidal anti-inflammatory drug. Mondor's Disease is rarely related with breast cancer. This rare entity can be diagnosed with doubt and patient should be informed about it. Anti-coagulant treatment does not required if disease is idiopathic. Mondor's Disease should be reminded at a patient with retracted breast skin.


A qualitative study of the causes and circumstances of drowning in Uganda.
Drowning is a serious worldwide and preventable injury problem, especially in low- and middle-income countries (LMICs). The aim of this paper is to draw on the results of semi-structured interviews with witnesses, family members and friends of persons involved in fatal and nonfatal drowning incidents to describe the circumstances of drowning in both lakeside and non-lakeside districts and to identify potential contextually appropriate interventions for drowning prevention and surveillance in Uganda. The findings presented in this study were based on data collected from study participants selected through purposive sampling comprising 324 individual face-to-face interviews with drowning witnesses, family members, friends of and survivors of drowning and ten (10) focus group discussions held with community members in 14 districts in Uganda. Data analysis was done using the Framework Analysis Approach with the aid of the Microsoft Atlas ti software (version 8) program. The study results reveal a range of circumstances under which drowning occurs in Uganda, poor record keeping of drowning incidents, fear of reporting drowning incidences to the authorities, challenges in preventing drowning and proposed strategies for mitigating the problem. This study found that there is no specialized record keeping system for drowning cases in Uganda and where such records are kept, the system is entirely manual (in hard copy form) with no electronic storage of data. Secondly, the drowning cases reported to police posts and stations in various parts of the country are not transmitted to the district headquarters and national database. These and other conclusions not only provide valuable insights into understanding of drowning circumstances but also the key policy and programme interventions for water-based economic activities such as fishing and public water transportation in Uganda and other LMICs.


Novel ciprofloxacin and norfloxacin-tetrazole hybrids as potential antibacterial and antiviral agents: Targeting S. aureus topoisomerase and SARS-CoV-2-MPro.
This study was designed to synthesize hybridizing molecules from ciprofloxacin and norfloxacin by enhancing their biological activity with tetrazoles. The synthesized compounds were investigated in the interaction with the target enzyme of fluoroquinolones (DNA gyrase) and COVID-19 main protease using molecular similarity, molecular docking, and QSAR studies. A QSAR study was carried out to explore the antibacterial activity of our compounds over Staphylococcus aureus a QSAR study, using descriptors obtained from the docking with DNA gyrase, in combination with steric type descriptors, was done obtaining suitable statistical parameters ( R 2 = 87.00 , Q L M O 2 = 71.67 , and Q E X T 2 = 73.49 ) to support our results. The binding interaction of our compounds with CoV-2-Mpro was done by molecular docking and were compared with different covalent and non-covalent inhibitors of this enzyme. For the docking studies we used several crystallographic structures of the CoV-2-Mpro. The interaction energy values and binding mode with several key residues, by our compounds, support the capability of them to be CoV-2-Mpro inhibitors. The characterization of the compounds was completed using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR and HRMS spectroscopic methods. The results showed that compounds 1, 4, 5, 10 and 12 had the potential to be further studied as new antibacterial and antiviral compounds.


Remodeling of the myoblast membrane accompanies development.
We have prepared a library of cloned hybridomas that produce monoclonal antibodies reactive with the surface of E63 rat myoblasts. Using immunofluorescence analysis of antigens on single cells we have studied the expression of determinants at distinct stages of development. Conditions were established for quantitative photometry and were used to confirm the diversity in stage-specific expression that accompanies development. The remodeling of the myoblast membrane also involves stage-specific and transient changes in topography and aggregation of many antigens, and the period surrounding fusion is one of particular activity. The localization of antigens on the upper and attached surfaces of myogenic cells was often distinct, and quantitative and spatial stage-specific reorganizations of antigens differed with respect to these two surfaces. This polarity represents an additional level of complexity in the continuous remodeling of the muscle cell membrane. Comparisons of quantitative and topographic analyses of antigens on E63 cells with Rat-1 fibroblasts and developmentally defective (fu-) myoblasts indicate that the outer membranes of these nonmyogenic cells are distinct from differentiating myoblasts. One determinant, H36, is absent on Rat-1 cells and on all fu- lines tested, and undergoes interesting stage-specific changes in expression and topography.


Nutritional prevention of pre-eclampsia--a special role for 1 series prostaglandin precursors?
PGE1 appears to act as a physiological regulator of uteroplacental blood flow. Its vasodilatory, anti-vasopressor, and platelet stabilizing effects could be expected to counteract the placental ischemia, hypertension and excessive coagulation that are seen in pre-eclampsia. Supplementation with efficient essential fatty acid precursors of PGE1 reduces platelet aggregation, has been used with success in the treatment of hypertension and arterial vasospasm, and might offer a nutritional means of reducing the incidence and severity of pre-eclampsia. Assurance of adequate general nutrition also appears to be of importance in this regard.


A Broad-Specificity O-Glycoprotease That Enables Improved Analysis of Glycoproteins and Glycopeptides Containing Intact Complex O-Glycans.
Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis. Recently, several O-glycan-specific endoproteases that can cleave the protein adjacent to the appended glycan have been described. Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias. These factors limit their analytical application. In this study, we examined the capabilities of an immunomodulating metalloprotease (IMPa) from Pseudomonas aeruginosa. Peptide sequence selectivity and its impact on IMPa activity were interrogated using an array of synthetic peptides and their glycoforms. We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid. The enzyme does not cleave between two adjacent O-glycosites, indicating that O-glycosylated serine/threonine is not allowed at position P1. Glycopeptides with as few as two amino acids on either side of an O-glycosite were cleaved by IMPa. Finally, IMPa efficiently cleaved peptides and proteins carrying sialylated and asialylated O-glycans of varying complexity. We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment. In these examples, IMPa enabled both the identification of O-glycosites and the range of complex O-glycan structures at each site.


MicroRNA profile of polyunsaturated fatty acid treated glioma cells reveal apoptosis-specific expression changes.
Polyunsaturated fatty acids (PUFAs) such as γ-linolenic acid (GLA), arachidonic acid (AA) and docosahexaenoic acid (DHA) have cytotoxic action on glioma cells. We evaluated the cytotoxic action of GLA, AA and DHA on glioma cells with specific reference to the expression of miRNAs. Relative expression of miRNAs were assessed by using high throughput nanocapillary real-time PCR. Most of the miRNA target genes that showed altered expression could be classified as apoptotic genes and were up-regulated by PUFA or temozolomide treatment, while similar treatments resulted in repression of the corresponding mRNAs, such as cox2, irs1, irs2, ccnd1, itgb3, bcl2, sirt1, tp53inp1 and k-ras. Our results highlight involvement of miRNAs in the induction of apoptosis in glioma cells by fatty acids and temozolomide.


Endovascular stent-graft exclusion of adult giant patent ductus arteriosus through a hybrid transabdominal approach.
Endovascular stent-graft exclusion has proven to be a safe and effective alternative for adult patients with patent ductus arteriosus. We present a case of a 38-year-old woman with a large, symptomatic ductus. However, her small femoral and iliac arteries limited the access options. The patient underwent laparotomy and end-to-side anastomosis of a Dacron graft to the abdominal aorta. Then, the laparotomy was temporarily closed with the graft externalized, and the patient was transported to the radiology suite for successful stent-graft deployment. This hybrid transabdominal approach may be preferred in patients without suitable peripheral arteries to accommodate the device.


25-Hydroxycholecalciferol receptors in human breast cancer.
Cytosol receptors for 25-hydroxycholecalciferol, oestradiol and progesterone were measured in human mammary carcinomas. Significant positive correlations were found between the concentrations of all three receptors.


Intraspinal delivery of bone marrow stromal cell-derived neural stem cells in patients with amyotrophic lateral sclerosis: A safety and feasibility study.
Stem cells have been used in several studies with different methodologies to treat patients with ALS. In this safety and feasibility study, 11 patients with definite or probable ALS according to El Escorial criteria were selected. 3 patients were excluded due to inadequate bone marrow or safety measures after acquisition of bone marrow. Bone marrow stromal cell-derived neural stem cells were injected in C7-T1 spinal cord under general anesthesia. Patients were followed for 12months after injection with manual muscle testing, ALSFRS-R, quality of life changes, pulmonary function test and electromyography. None of the patients had perioperative mortality or major morbidity. One patient had temporary deterioration in lower extremities after injection which improved after a few weeks. In the 12months post-injection, only one patient died due to pulmonary embolism. From the remaining 7 patients, all had a stable course after 4months and 5 were stable for the first 8months post-injection and deteriorated afterwards. In this study, intraspinal injection of bone marrow derived neural stem cells appears to be safe. Patients experienced a temporary stabilization for the first few months post-injection and then gradually deteriorated.


Russell body apical periodontitis: an unusual case report.
Russell bodies (RBs) changes in chronic apical lesions have rarely been reported in the literature. We describe a case of a periapical lesion abundantly and extensively composed of RB. Microscopic examination showed accumulation of plasma cells containing globular, spherical, polygonal, and eosinophilic structures against fibrous connective tissue. Initial diagnostic considerations based on a smaller magnification included hypersecretory plasmocytoma, although there was no evidence of infiltrative growth, mitotic activity, nuclear atypia, or cellular pleomorphism. Then, a panel of immunohistochemical markers was applied and the cells showed positivity with both kappa and lambda chains demonstrating their polyclonal origin. The extensive accumulation of RBs involving the periapical region represents an unreported and significant histologic change, as it was mimicking a malignant neoplasm.


Quantitative structure-activity relationship studies of a series of non-benzodiazepine structural ligands binding to benzodiazepine receptor.
Heuristic method (HM) and radial basis function neural network (RBFNN) methods were proposed to generate QSAR models for a set of non-benzodiazepine ligands at the benzodiazepine receptor (BzR). Descriptors calculated from the molecular structures alone were used to represent the characteristics of the compounds. The six molecular descriptors selected by HM in CODESSA were used as inputs for RBFNN. Compared with the results of HM, more accurate prediction could be obtained from RBFNN. The correlation coefficients (R) of the nonlinear RBFNN model were 0.9113 and 0.9030 for the training and test sets, respectively. This paper proposed an effective method to design new ligands of BzR based on QSAR.


Articular nodular fasciitis in the glenohumeral joint.
We describe a case of multiple intra-articular masses in the glenohumeral joint of a 15-year-old patient. The patient was treated with arthroscopic excision of the masses and synovectomy. Histological and immunohistochemical studies were consistent with those of a nodular fasciitis. Follow-up examination did not reveal recurrence at 6 months. In this article we report the first case of articular nodular fasciitis in the glenohumeral joint with unusual imaging findings.


Spatiotemporal patterns of PM2.5 elemental composition over China and associated health risks.
Trace metals in atmospheric particulate matter (PM) are a serious threat to public health. Although pollution from toxic metals has been investigated in many Chinese cities, the spatial and temporal patterns in PM2.5 remain largely unknown. Long-term PM2.5 field sampling in 11 cities, combined with a systemic literature survey covering 51 cities, provides the first comprehensive database of 21 PM2.5-bound trace metals in China. Our results revealed that PM2.5 elemental compositions varied greatly, with generally higher levels in North China, especially for crustal elements. Pollution with Cr, As, and Cd was most serious, with 61, 38, and 16 sites, respectively, surpassing national standards, including some in rural areas. Local emissions, particularly from metallurgical industries, were the dominant factors driving the distribution in polluted cities such as Hengyang, Yuncheng, and Baiyin, which are mainly in North and Central China. Elevated As, Cd, and Cr levels in Yunnan, Guizhou Province within Southwest China were attributed to the high metal content of local coal. Diverse temporal trends of various elements that differed among regions indicated the complexity of emission patterns across the country. The results demonstrated high non-carcinogenic risks for those exposed to trace metals, especially for children and residents of heavily cities highly polluted with As, Pb, or Mn. The estimated carcinogenic risks ranged from 6.61 × 10-6 to 1.92 × 10-4 throughout China, with As being the highest priority element for control, followed by Cr and Cd. Regional diversity in major toxic metals was also revealed, highlighting the need for regional mitigation policies to protect vulnerable populations.


Viewpoint dependence in adaptation to facial identity.
We produced morph sequences between identities at a variety of viewpoints, ranging from the three quarter leftward facing view, to the three quarter rightward facing view. We measured the strength of identity adaptation as a function of changing test viewpoint whilst keep the adaptation viewpoint constant, and as a function of adaptation viewpoint whilst keeping test viewpoint constant. Our results show a substantial decrease in adaptation as the angle between adaptation and test viewpoint increases. These findings persisted when we introduced controls for low-level retinotopic adaptation, leading us to conclude that our results show strong evidence for viewpoint dependence in the high-level encoding of facial identity. Our findings support models in which identity is encoded, to a large degree, by viewpoint dependent non-retinotopic neural mechanisms. Functional imaging studies suggest the fusiform gyrus as the most likely location for this mechanism.


A mutational study of Cnu reveals attractive forces between Cnu and H-NS.
Cnu is a small 71-amino acid protein that complexes with H-NS and binds to a specific sequence in the replication origin of the E. coli chromosome. To understand the mechanism of interaction between Cnu and H-NS, we used bacterial genetics to select and analyze Cnu variants that cannot complex with H-NS. Out of 2,000 colonies, 40 Cnu variants were identified. Most variants (82.5%) had a single mutation, but a few variants (17.5%) had double amino acid changes. An in vitro assay was used to identify Cnu variants that were truly defective in H-NS binding. The changes in these defective variants occurred exclusively at charged amino acids (Asp, Glu, or Lys) on the surface of the protein. We propose that the attractive force that governs the Cnu-H-NS interaction is an ionic bond, unlike the hydrophobic interaction that is the major attractive force in most proteins.


Ginkgo biloba in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. A randomized, placebo-controlled, trial.
To evaluate the efficacy of Ginkgo biloba as a complementary therapy for attention-deficit/hyperactivity disorder (ADHD). Children and adolescents with ADHD received methylphenidate (20-30 mg/day) plus either G. biloba (80-120 mg/day) or placebo for 6 weeks. Parent and teacher forms of the ADHD Rating Scale-IV (ADHD-RS-IV) were completed at baseline, week 2, and week 6. Treatment response was defined as 27% improvement from baseline in the ADHD-RS-IV. Compared with placebo, more reduction was observed with G. biloba regarding ADHD-RS-IV parent rating inattention score (-7.74 ± 1.94 vs. -5.34 ± 1.85, P < 0.001) and total score (-13.1 ± 3.36 vs. -10.2 ± 3.01, P = 0.001) as well as teacher rating inattention score (-7.29 ± 1.90 vs. -5.96 ± 1.52, P = 0.004). Response rate was higher with G. biloba compared with placebo based on parent rating (93.5% vs. 58.6%, P = 0.002). The G. biloba is an effective complementary treatment for ADHD. Further studies with longer treatment duration are warranted in this regard. IRCT2014111519958N1.


Impact of Renal Sympathetic Denervation on Left Ventricular Structure and Function at 1-Year Follow-Up.
Catheter-based sympathetic renal denervation (RDN) is a recent therapeutic option for patients with resistant hypertension. However, the impact of RDN in left ventricular (LV) mass and function is not completely established. Our aim was to evaluate the effects of RDN on LV structure and function (systolic and diastolic) in patients with resistant hypertension (HTN). From a single centre prospective registry including 65 consecutive patients with resistant HTN submitted to RDN between July-2011 and April-2015, 31 patients with baseline and 1-year follow-up echocardiogram were included in this analysis. Mean age was 65 ± 7 years, 48% were males, 71% had type 2 diabetes. Most had hypertension lasting for more than 10 years (90%), and were being treated with a median number of 6 anti-hypertensive drugs, including 74% on spironolactone. At 1-year, there was a significant decrease both on office SBP (176 ± 24 to 149 ± 13 mmHg, p<0.001) and DBP (90 ± 14 to 79 ± 11 mmHg, p<0.001), and also in 24h ABPM SBP (150 ± 20 to 132 ± 14 mmhg, p<0.001) and DBP (83 ± 10 to 74 ± 9 mmHg, p<0.001). There was also a significant decrease in LV mass from 152 ± 32 to 136 ± 34 g/m(2) (p<0.001), an increase in LV end diastolic volume (93 ± 18 to 111 ± 27 mL, p = 0.004), an increase in LV ejection fraction (65 ± 9 to 68 ± 9%, p = 0.001) and mitral valve E deceleration time (225 ± 49 to 247 ± 51 ms, p = 0.015) at 1-year follow up. There were no significant changes in left atrium volume index or in the distribution of patients among the different left ventricle geometric patterns and diastolic function subgroups. In this single centre registry of patients with resistant hypertension, renal denervation was associated with significant reduction in both office and ABPM blood pressure and a significant decrease in left ventricle mass evaluated by transthoracic echocardiogram at 1 year follow-up.


Dorsal pallidum as a functional motor output of the corpus striatum.
A major function of the dopamine in the striatum is to control the activity of its efferent systems which contain primarily GABAergic neurons. Direct intracerebral injections of haloperidol into the corpus striatum impaired the performance of rats trained to depress a lever in a sensitive reaction time task. Rats were trained to depress a lever until the presentation of a visual conditioned stimulus and then to release the lever within a time limit of 500 ms to obtain a food reward. The increase in reaction time produced by dopamine blockade of the corpus striatum was mimicked by injection of a GABA agonist muscimol in nanogram quantities into the region of the dorsal pallidum, but not into the substantia nigra reticulata. Injections of a GABA agonist into the substantia nigra impaired performance by increasing the number of anticipatory responses (increased number of lever releases before the conditioned stimulus). These results suggest that the dorsal pallidum may play an important role in the response initiation associated with activation of the corpus striatum, and that the dorsal pallidum may form a significant part of parallel striatal outputs that have different functional significance.


Assessment of Herpes Zoster Risk Among Recipients of COVID-19 Vaccine.
Herpes zoster infection after COVID-19 vaccination has been reported in numerous case studies. It is not known whether these cases represent increased reporting or a true increase in risk. To assess whether COVID-19 vaccination is associated with an increased risk of herpes zoster infection. This cohort study used a self-controlled risk interval (SCRI) design to compare the risk of herpes zoster in a risk interval of 30 days after COVID-19 vaccination or up to the date of the second vaccine dose with a control interval remote from COVID-19 vaccination (defined as 60-90 days after the last recorded vaccination date for each individual, allowing for a 30-day washout period between control and risk intervals). A supplemental cohort analysis was used to compare the risk of herpes zoster after COVID-19 vaccination with the risk of herpes zoster after influenza vaccination among 2 historical cohorts who received an influenza vaccine in the prepandemic period (January 1, 2018, to December 31, 2019) or the early pandemic period (March 1, 2020, to November 30, 2020). Data were obtained from Optum Labs Data Warehouse, a US national deidentified claims-based database. A total of 2 039 854 individuals who received any dose of a COVID-19 vaccine with emergency use authorization (BNT162b2 [Pfizer-BioNTech], mRNA-1273 [Moderna], or Ad26.COV2.S [Johnson & Johnson]) from December 11, 2020, through June 30, 2021, were eligible for inclusion. Individuals included in the SCRI analysis were a subset of the COVID-19-vaccinated cohort who had herpes zoster during either a risk or control interval. Any dose of a COVID-19 vaccine. Incident herpes zoster, defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and a prescription of a new antiviral medication or a dose increase in antiviral medication within 5 days of diagnosis. Among 2 039 854 individuals who received any dose of a COVID-19 vaccine during the study period, the mean (SD) age was 43.2 (16.3) years; 1 031 149 individuals (50.6%) were female, and 1 344 318 (65.9%) were White. Of those, 1451 patients (mean [SD] age, 51.6 [12.6] years; 845 [58.2%] female) with a herpes zoster diagnosis were included in the primary SCRI analysis. In the SCRI analysis, COVID-19 vaccination was not associated with an increased risk of herpes zoster after adjustment (incidence rate ratio, 0.91; 95% CI, 0.82-1.01; P = .08). In the supplementary cohort analysis, COVID-19 vaccination was not associated with a higher risk of herpes zoster compared with influenza vaccination in the prepandemic period (first dose of COVID-19 vaccine: hazard ratio [HR], 0.78 [95% CI, 0.70-0.86; P < .001]; second dose of COVID-19 vaccine: HR, 0.79 [95% CI, 0.71-0.88; P < .001]) or the early pandemic period (first dose of COVID-19 vaccine: HR, 0.89 [95% CI, 0.80-1.00; P = .05]; second dose: HR, 0.91 [95% CI, 0.81-1.02; P = .09]). In this study, there was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.


A possible role of estrogens in carcinogenesis of non-target tissues.
The mitogenic action of the estrogen-receptor complex is supposedly similar in both normal and malignant target tissues. As receptors are present in several types of non-target tissues, in the case of lesions at the nuclear acceptor sites, the complex in those might be able to cause successive mitoses. Estrogen-dependent tumors of non-target tissues have been reported by several investigators. In normal and malignant cells of the breast and some other types of non-endocrine cells, the ability to produce their own estrogens (from circulating precursors) has been shown. The locally formed estrogens might have a role in the initiation of some malignant transformations. Indications of this process are the switching to estrogen production of some neoplastic endocrine or undifferentiated cells, certain ectopic effects displayed by some cancerous tissues, and the possible roles of GH, PRL and cholesterol in the development of some malignancies. The present endocrine system for the synthesis of the sexual hormones might be a specialization of a system at the cellular level. Polypeptide hormones might evolve from regulatory parts of cyclases or phosphodiesterases. Traces of the original biological processes might still be maintained by several cell-types.


The ability of spectrum autocorrelation models to predict the lycopene concentration in foods through visible spectroscopic data.
We developed a novel computerized approach based on lag-k autocorrelation coefficients (LCCs) and linear models (LMs) to estimate the concentration of lycopene in foods by the spectroscopy. The LCCs were calculated using the data obtained using whole visible scans from 400 to 600 nm (vide supra) of lycopene standards and food samples (ketchup, tomato juice and tomato sauce). The chaotic parameter (CP) was then transferred into a LM to estimate the concentration of lycopene compound. The integrated LCC/visible spectroscopy method developed can be considered as a satisfactory analytical technique able to estimate lycopene concentration in food samples in a fast accurate way, with a mean prediction error lower than 5.7% and a mean correlation coefficient higher than 0.957.


Prognostic significance of peritumoural inflammation in invasive urothelial bladder carcinoma.
Peritumoural inflammation consisting of lymphocytes, plasma cells and lymph follicles is present in two thirds of invasive urothelial bladder carcinomas. This type of inflammation is significantly rarer in advanced tumour stages (P3, P/) and its presence is a favourable prognostic factor. The mean survival time in patients with this type of inflammation is 26.1 months compared to only 14.8 months in patients without. All other forms of inflammation e. g. eosinophilic or polymorphonuclear leukocytes have no relation with prognosis. The significant prognostic value of lympho-plasmocytic inflammation may be considered as local expression of immunological host resistance.


Domino metathesis of 2-azanorbornenones: a new strategy for the enatioselective synthesis of 1-azabicyclic compounds.
Domino metathesis of N-alkylated derivatives of (1S)-2-azanorborn-5-en-3-one allowed for the enantioselective synthesis of pyrrolizidine, quinolizidine, pyrrolidinoazepine, and pyrrolidinoazocine derivatives in a straightforward process.


Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data.
The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin's decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one.The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy's values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps.


Families of critically ill patients and the effect of nursing interventions.
Family needs of critically ill individuals and the nursing interventions to meet these needs have spanned 3 decades of research. Researchers have found that interventions appear to meet some family needs, but more can be done to provide family-centered care and improve patient outcomes.


Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7-36 amide] after subcutaneous injection in healthy volunteers. Dose-response-relationships.
Intravenous infusions of glucagon-like peptide 1 (GLP-1) [7-36 amide] are glucose-dependently insulinotropic and glucagonostatic and normalize plasma glucose concentrations in non-insulin-dependent diabetic patients. It was the aim of this study to investigate whether subcutaneous GLP-1 [7-36 amide] also has an influence on insulin and glucagon secretion, and which doses are required for significant effects. Therefore, eight healthy volunteers (24 +/- 2 years, body mass index [BMI] 21.9 +/- 2.3 kg/m2) were studied in the fasting state on five occasions in randomized order. Placebo (0.9% NaCl with 1% human serum albumin) or GLP-1 [7-36 amide] in doses of 0.15, 0.5, 1.5 or 4.5 nmol/kg body weight (volume 1 ml or, at the highest dose, 2 ml) was administered subcutaneously. An intravenous glucose bolus (0.33 g/kg body weight) was injected 30 min later. Blood was drawn for the measurement of glucose, insulin, C-peptide, GLP-1 [7-36 amide], and glucagon using specific radioimmunoassays. There were dose-related increments in GLP-1 [7-36 amide] concentrations (p < 0.0001). However, basal values were reached again after 90-120 min. Before glucose administration, insulin (p < 0.0001) and C-peptide (p < 0.0004) increased, whereas glucagon (p = 0.0018) and glucose (p < 0.0001) decreased in a dose-dependent manner. After glucose stimulation, integrated increments in insulin (p = 0.0007) and C-peptide (p = 0.02) were augmented and kG-values increased (p < 0.0001) in a dose-related fashion. The extent of reactive hypoglycaemia was related to the GLP-1 [7-36 amide] dose.(ABSTRACT TRUNCATED AT 250 WORDS)


Human equality arguments against abortion.
In this paper, I argue that a commitment to a very modest form of egalitarianism-equality between non-disabled human adults-implies fetal personhood. Since the most plausible bases for human value are in being human, or in a gradated property, and since the latter of which implies an inequality between non-disabled adult humans, I conclude that the most plausible basis for human equality is in being human-an attribute which fetuses have.


[New therapeutic guidelines in lower limb arteriopathy].
This article describes the recent therapeutic options for lower limb arteriopathy and, as much as possible, analyzes the medical and surgical treatments according to the recommendations and levels of evidence.


Kampo medicine for the holistic approach to older adults with heart failure.
Heart failure (HF) is a leading cause of hospitalization, morbidity, and mortality in older adults and represents a significant clinical and economic burden on the health care system. However, there are many challenges in assessing and managing HF in elderly patients, who often have coexisting multimorbidity, frailty, and malnutrition. Therefore, it is often difficult to solve these problems with Western medicine alone, and a holistic approach, including Kampo medicine, can be helpful. In particular, managing volume control and frailty by adding Kampo formulas may help improve health-related quality of life and substantially impact prognosis in HF. This review article summarizes the role of Kampo medicine for older patients with HF and frailty.


The activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase in human cerebrospinal fluid.
A method for the determination of cyclic nucleotide phosphatase (CNP) activity in cerebrospinal fluid is presented. In normal CSF the activity of CNP is very low. Comparing CSF from patients with multiple sclerosis to control CSF no significant difference is found, although a small proportion of MS patients has an elevated has an elevated CNP activity in their CSF. It is postulated that similar to other substances the CNP activity in CSF probably does not derive from the central nervous system.


Efficacy of using Maryland forceps versus electrocoagulation hooks in da Vinci robot-assisted thoracoscopic mediastinal tumor resection.
To compare the difference of short-term curative effect between the use of Maryland forceps (MF) and electrocoagulation hooks (EH) in da Vinci robot-assisted thoracoscopic mediastinal tumor resection. Retrospectively analyze 84 patients with mediastinal tumors who underwent robot-assisted thoracoscopic surgery (RATS) at the Department of Thoracic Surgery in Gansu Provincial Hospital from February 2019 to February 2023. Two groups were divided according to the intraoperative use of energy devices, including 41 cases in the MF group and 43 cases in the EH group. Perioperative clinical data was gathered to compare the short-term efficacy of patients in both groups. There were no significant differences in baseline characteristics such as sex (P = 0.685), age (P = 0.165), and tumor size (P = 0.339) between the two groups. Compared with the EH group, patients in the MF group have shorter operative time (P = 0.030), less intraoperative bleeding (P = 0.010), less total postoperative drainage volume (P = 0.001), shorter postoperative drainage time (P = 0.022), shorter hospital stay (P = 0.019), and lower levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and cortisol. No statistically significant differences were found between the two groups in terms of total hospitalization costs (P = 0.123), postoperative visual analog scale (VAS) pain scores (P = 0.064), and postoperative complications (P = 0.431). Using MF in RATS for mediastinal tumor is safe and effective, which can reduce the amount of bleeding, reduce the degree of inflammatory reaction, and conducive to the quick recovery of patients.


Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone.
The purpose of this study was to test the hypothesis that early pregnancy changes in volume homeostasis develop as a consequence of preceding changes in maternal hemodynamics. Maternal cardiovascular function of 10 pregnant women was followed up by Doppler echocardiography. Vascular filling state and volume homeostasis were evaluated by echocardiographic index values, glomerular filtration rate, serum osmolality, and volume-regulating hormones. Studies were performed weekly in early pregnancy, in the second and third trimesters, and post partum. Changes relative to the fifth week and the consistency of changes between weeks 5 and 8 were evaluated by nonparametric statistics. In early pregnancy cardiac output increased and afterload decreased. Concomitant increases in ultrasonic preload index values and glomerular filtration rate were accompanied by decreases in serum renin, Na+, and osmolality. These data support the concept that maternal hemodynamic adaptation to pregnancy is most likely triggered by a primary fall in systemic vascular tone. The resulting rapid fall in preload and afterload leads to a compensatory increase in heart rate and activation of the volume-restoring mechanisms. Subsequently cardiac output increases because of a rise in stroke volume, which develops because the vascular filling state normalizes, whereas the reduced afterload reduction is maintained.


Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS).
The use of hydroxychloroquine or chloroquine (HCQ/CQ) as monotherapy or combined with azithromycin for the treatment of coronavirus disease 2019 (COVID-19) may increase the risk of serious cardiovascular adverse events (SCAEs). Our objective was to describe and evaluate the risk of SCAEs with HCQ/CQ as monotherapy or combined with azithromycin compared with that for therapeutic alternatives. We performed a disproportionality analysis and descriptive case series using the US FDA Adverse Event Reporting System. Compared with remdesivir, HCQ/CQ was associated with increased reporting of SCAEs (reporting odds ratio [ROR] 2.1; 95% confidence interval [CI] 1.8-2.5), torsade de pointes (TdP)/QTc prolongation (ROR 35.4; 95% CI 19.4-64.5), and ventricular arrhythmia (ROR 2.5; 95% CI 1.6-3.9); similar results were found in comparison with other therapeutic alternatives. Compared with lopinavir/ritonavir, HCQ/CQ was associated with increased reporting of ventricular arrhythmia (ROR 10.5; 95% CI 3.3-33.4); RORs were larger when HCQ/CQ was used in combination with azithromycin. In 2020, 312 of the 575 reports of SCAEs listed concomitant use of HCQ/CQ and azithromycin, including QTc prolongation (61.4%), ventricular arrhythmia (12.0%), atrial fibrillation (8.2%), TdP (4.9%), and cardiac arrest (4.4%); 88 (15.3%) cases resulted in hospitalization and 79 (13.7%) resulted in death. In total, 122 fatal QTc prolongation-related cardiovascular reports were associated with 1.4 times higher odds of reported death than those induced by SCAEs; 87 patients received more than one QTc-prolonging agent. Patients treated with HCQ/CQ monotherapy or HCQ/CQ + azithromycin may be at increased risk of SCAEs, TdP/QTc prolongation, and ventricular arrhythmia. Cardiovascular risks need to be considered when evaluating the benefit/harm balance of treatment with HCQ/CQ, especially with the concurrent use of QTc-prolonging agents and cytochrome P450 3A4 inhibitors when treating COVID-19.


Reversion From Mild Cognitive Impairment To Normal Cognition: False-Positive Error Or True Restoration Thanks To Cognitive Control Ability?
Relatively little attention has been paid to the meaning of reversion from mild cognitive impairment (MCI) to cognitively normal (CN), compared to MCI progression studies. The purpose of the study was to investigate the characteristics contributing to reversion from MCI to CN and to identify the associated factors with such reversion. We retrospectively identified 200 individuals who initially diagnosed as MCI and completed the second visit from the National Research Center for Dementia (NRCD) registry in Korea. Participants underwent comprehensive clinical and neuropsychological assessments. Factors associated with reversion were examined by a independent-samples t-test, χ2 test, and logistic regression. Longitudinal change was examined by a repeated measures analysis of variance (rANOVA). Based on the second assessment, 78 (39%) individuals were found to have reverted to CN (rMCI) and 118 (59%) remained with MCI (sMCI). Four (2%) progressed to Alzheimer's disease dementia and they were excluded from further analysis. Over a wide range of socio-demographic, clinical, and neuropsychological variables, group difference was significant only in neuropsychological tests of cognitive control. Both groups showed improvement in several neuropsychological tests, implying a practice effect, but the rMCI group showed greater improvement. Reversion from MCI to CN might not be a false-positive error but a true recovery from cognitive impairment. Our results suggest that cognitive control ability may be a characteristic favorable for the restoration of cognitive function. Therefore, assessment of cognitive control might facilitate the development of appropriate interventions for MCI as well as prognosis evaluation.


Correction of complex nonlinear signal response from a pixel array detector.
The pulsed free-electron laser light sources represent a new challenge to photon area detectors due to the intrinsic spontaneous X-ray photon generation process that makes single-pulse detection necessary. Intensity fluctuations up to 100% between individual pulses lead to high linearity requirements in order to distinguish small signal changes. In real detectors, signal distortions as a function of the intensity distribution on the entire detector can occur. Here a robust method to correct this nonlinear response in an area detector is presented for the case of exposures to similar signals. The method is tested for the case of diffuse scattering from liquids where relevant sub-1% signal changes appear on the same order as artifacts induced by the detector electronics.


Colorado Retinopathy of Prematurity Screening Algorithm (CO-ROP): a validation study at a tertiary care center.
The Colorado Retinopathy of Prematurity Screening Algorithm (CO-ROP) recommends screening for infants meeting the following criteria for retinopathy of prematurity (ROP): gestational age ≤30 weeks, birth weight of ≤1500 g, and net weight gain of ≤650 g between birth and 4 weeks of age. This study was performed to evaluate the validity of CO-ROP in a tertiary referral county hospital. CO-ROP was used to retrospectively analyze the data from consecutive newborns screened for ROP using national screening guidelines at Parkland Hospital, Dallas, Texas, between April 1, 2009, to August 30, 2013. Sensitivities and specificities for identifying ROP were calculated. A total of 374 infants were included, of whom 29 (7.8%) developed type 1 ROP and 12 (3.2%) developed type 2 ROP. The CO-ROP model would have decreased number of infants screened by 34% compared to current national screening criteria. CO-ROP had sensitivity of 93.1% (95% CI, 77.2-99.1) and 92.7% (95% CI, 61.5-99.8) for identifying type 1 and type 2 ROP, respectively. Of 29 patients who developed type 1 ROP, 2 were not identified using CO-ROP. The CO-ROP model significantly reduced total number screened but failed to detect 2 infants with type 1 ROP, suggesting the need for further modification of the algorithm.


Translational research in head and neck cancer: Molecular and immunological updates.
Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Each year, approximately 880,000 patients are newly diagnosed with HNSCC worldwide, and 450,000 patients with HNSCC die. Risk factors for developing HNSCC have been identified, with cigarette smoking, alcohol consumption, and viral infections being the major factors. Owing to the prevalence of human papillomavirus infection, the number of HNSCC cases is increasing considerably. Surgery and chemoradiotherapy are the primary treatments for HNSCC. With advancements in tumor biology, patients are eligible for novel treatment modalities, namely targeted therapies, immunotherapy, and photoimmunotherapy. Because this area of research has rapidly progressed, clinicians should understand the basic biology of HNSCC to choose an appropriate therapy in the upcoming era of personalized medicine. This review summarized recent developments in tumor biology, focusing on epidemiology, genetic/epigenetic factors, the tumor microenvironment, microbiota, immunity, and photoimmunotherapy in HNSCC, as well as how these findings can be translated into clinical settings.


Germline mutational profile of Chinese patients under 70 years old with colorectal cancer.
Inherited susceptibility accounts for nearly one-third of colorectal cancer (CRC) predispositions and has an 80%-100% lifetime risk of this disease. However, there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with CRC. This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC, differences between Chinese and Western patients, and the phenotype-genotype correlation. We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing. A series of bioinformatic analyses, as well as statistical comparisons, were performed. We found that 77 patients (14.6%) harbored functional variants of the 12 genes. The mutation frequencies of the top 5 mutated genes were 6.5% for MutL homolog 1 (MLH1), 5.1% for MutS homolog 2 (MSH2), 1.0% for MSH6, 0.8% for PMS1 homolog 2 (PMS2), and 0.8% for APC regulator of the WNT signaling pathway (APC). Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair (MMR) genes as compared with those in Western populations. Mutations in MLH1, MSH2, and MSH6 were found to be mutually exclusive. Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer (MLH1: 20.6% vs. 8.7%; MSH2: 25.9% vs. 8.6%) and family history of cancer than those without these mutations (MLH1: 73.5% vs. 48.4%; MSH2: 70.4% vs. 48.9%), and the lesions were more prone to occur on the right side of the colon than on the left side (MLH1: 73.5% vs. 29.3%; MSH2: 56.0% vs. 31.0%). The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations (70.6% vs. 50.7%), and the rate of polyps was higher in patients with APC mutations than in those with wild-type APC (75.0% vs. 17.4%). These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.


A pilot clinical study of developing an External Assist Targeting Device for rapid and precise renal calyx access during percutaneous nephrolithotomy.
To design a device to increase the accuracy of the targeting process and reduce the radiation exposure to both the patients and the medical staff. We analyzed the inherent problem and designed the External Assist Targeting Device (EATD) to assist in the alignment of needle targeting on the desired renal calyx under fluoroscopic guidance. The EATD was designed to allow rapid and precise access to calyces at all angles, with a simple two-step puncture protocol developed for puncturing a target renal calyx. We then tested the device in a pilot human trial with four patients. In experiments with phantom models, the time for successful targeting was reduced by 31% using the device. The mean fluoroscopic time was reduced by 40%. In initial human trial, the puncture time was shortened by 66% and the radiation dose was decreased by 65% compared to free-hand technique. No complication was observed during the trial. The EATD was found to be cost effective, portable, simple to set up, and safe to operate for assisting in the percutaneous nephrolithotomy procedures. Our preliminary tests showed high degree of accuracy in gaining precise access to a targeted renal calyx with much shorter time and lesser radiation dose. The EATD also has the potential to be used to access other organs with precision under fluoroscopic guidance.


Real-time monitoring of single ZTP riboswitches reveals a complex and kinetically controlled decision landscape.
RNAs begin to fold and function during transcription. Riboswitches undergo cotranscriptional switching in the context of transcription elongation, RNA folding, and ligand binding. To investigate how these processes jointly modulate the function of the folate stress-sensing Fusobacterium ulcerans ZTP riboswitch, we apply a single-molecule vectorial folding (VF) assay in which an engineered superhelicase Rep-X sequentially releases fluorescently labeled riboswitch RNA from a heteroduplex in a 5'-to-3' direction, at ~60 nt s-1 [comparable to the speed of bacterial RNA polymerase (RNAP)]. We demonstrate that the ZTP riboswitch is kinetically controlled and that its activation is favored by slower unwinding, strategic pausing between but not before key folding elements, or a weakened transcription terminator. Real-time single-molecule monitoring captures folding riboswitches in multiple states, including an intermediate responsible for delayed terminator formation. These results show how individual nascent RNAs occupy distinct channels within the folding landscape that controls the fate of the riboswitch.


The role of concomitant immunosuppressants in impeding the progression of diabetic retinopathy: A pilot study.
Hallmark of Diabetic Retinopathy (DR) is blood-retinal barrier alteration. Vascular endothelial growth factor (VEGF) and inflammation are involved in the pathogenesis of DR. Anti-VEGFs and lasers are effective in treating DR but have numerous drawbacks, hence the need to develop alternative therapies that may delay the onset or progression of DR. Fifteen patients were recruited in each group; the study group was on immunosuppressants for some other coexisting disease and the control group was not on them. Each subject underwent detailed history, ophthalmic examination, and glycosylated hemoglobin (HbA1c) and renal function tests at the time of recruitment and the end of one year. Primary outcome measure was to compare the progression of DR in diabetics on immunosuppressant versus those not on it. Median age in the study and control group was 57 years and 60 years, respectively (P = 0.6). Median duration of diabetes was 11 and 12 years in the study and control group, respectively (P = 0.7). HbA1c for the study and control group for first visit was 7.6% and 8.0%, respectively (P = 0.26) and for second visit was 7.5% and 8.1%, respectively (P = 0.11). Hypertensives in the study and control groups were 9 and 4, respectively (P = 0.065); renal disease in the study and control groups was 4 and 2, respectively (P = 0.361). The control group showed 33.3% progression of DR, and no progression was seen in the study group (P = 0.014). Immunosuppressants seemed to delay the onset and progression of DR in the earlier stages.


Pharmacoenhancement of Low Crizotinib Plasma Concentrations in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer using the CYP3A Inhibitor Cobicistat.
The inhibitor of anaplastic lymphoma kinase (ALK) crizotinib significantly increases survival in patients with ALK-positive non-small cell lung cancer (NSCLC). When evaluating crizotinib pharmacokinetics (PKs) in patients taking the standard flat oral dose of 250 mg b.i.d., interindividual PK variability is substantial and patient survival is lower in the quartile with the lowest steady-state trough plasma concentrations (Cmin,ss ), suggesting that concentrations should be monitored and doses individualized. We investigated whether the CYP3A inhibitor cobicistat increases Cmin,ss of the CYP3A substrate crizotinib in patients with low exposure. Patients with ALK-positive NSCLC of our outpatient clinic treated with crizotinib were enrolled in a phase I trial (EudraCT 2016-002187-14, DRKS00012360) if crizotinib Cmin,ss was below 310 ng/mL and treated with cobicistat for 14 days. Crizotinib plasma concentration profiles were established before and after a 14-day co-administration of cobicistat to construct the area under the plasma concentration-time curve in the dosing interval from zero to 12 hours (AUC0-12 ). Patients were also monitored for adverse events by physical examination, laboratory tests, and 12-lead echocardiogram. Enrolment was prematurely stopped because of the approval of alectinib, a next-generation ALK-inhibitor with superior efficacy. In the only patient enrolled, cobicistat increased Cmin,ss from 158 ng/mL (before cobicistat) to 308 ng/mL (day 8) and 417 ng/mL (day 14 on cobicistat), concurrently the AUC0-12 increased by 78% from 2,210 ng/mL*h to 3,925 ng/mL*h. Neither safety signals nor serious adverse events occurred. Pharmacoenhancement with cobicistat as an alternative for dose individualisation for patients with NSCLC with low crizotinib exposure appears to be safe and is cost-effective and feasible.


53BP1 facilitates long-range DNA end-joining during V(D)J recombination.
Variable, diversity and joining (V(D)J) recombination and class-switch recombination use overlapping but distinct non-homologous end joining pathways to repair DNA double-strand-break intermediates. 53BP1 is a DNA-damage-response protein that is rapidly recruited to sites of chromosomal double-strand breaks, where it seems to function in a subset of ataxia telangiectasia mutated (ATM) kinase-, H2A histone family member X (H2AX, also known as H2AFX)- and mediator of DNA damage checkpoint 1 (MDC1)-dependent events. A 53BP1-dependent end-joining pathway has been described that is dispensable for V(D)J recombination but essential for class-switch recombination. Here we report a previously unrecognized defect in the joining phase of V(D)J recombination in 53BP1-deficient lymphocytes that is distinct from that found in classical non-homologous-end-joining-, H2ax-, Mdc1- and Atm-deficient mice. Absence of 53BP1 leads to impairment of distal V-DJ joining with extensive degradation of unrepaired coding ends and episomal signal joint reintegration at V(D)J junctions. This results in apoptosis, loss of T-cell receptor alpha locus integrity and lymphopenia. Further impairment of the apoptotic checkpoint causes propagation of lymphocytes that have antigen receptor breaks. These data suggest a more general role for 53BP1 in maintaining genomic stability during long-range joining of DNA breaks.


Phosphorylation of cold shock domain/Y-box proteins by ERK2 and GSK3beta and repression of the human VEGF promoter.
The hypoxia responsive region (HRR) of the VEGF promoter plays a key role in regulating VEGF expression. We found that the cold shock domain (Y-box) repressor proteins, dbpA and dbpB/YB-1, bind distinct strands of the human VEGF HRR. We find both dbpA and dbpB are phosphorylated by ERK2 and GSK3beta in vitro, and the binding of dbpB to single-strand VEGF HRR DNA is regulated by this phosphorylation. These findings suggest the ERK/MAPK and PI3K pathways may regulate VEGF expression in part through regulating the action of these repressor proteins.


Food group system of analysis with special attention to type and amount of fat--methodology.
A system for reporting dietary data in terms of food groups is described. The scheme was developed jointly by the National Heart, Lung, and Blood Institute (NHLBI) and the U.S. Department of Agriculture to identify food use patterns in various population groups. The system comprises 14 major groups and 75 minor groups based on major nutrient composition with special attention to fats. One-day dietary recalls from 5,640 participants in the Lipid Research Clinics (LRC) Prevalence Study were analyzed to determine the frequency of food group usage by males and females in age groups 6 to 9, 10 to 19, 20 to 59, and 60 and older. Food group use is reported as percent of the population reporting use as obtained by the dietary recall as well as the average number of times each food group was mentioned by the users. LRC food selection patterns are compared with the Dietary Guidelines. Findings in this report indicate that, for the LRC population, some of the foods emphasized in the guidelines are not eaten with a high degree of frequency.


Human dermal microvascular endothelial cell morphological response to fluid shear stress.
As the cells that line the vasculature, endothelial cells are continually exposed to fluid shear stress by blood flow. Recent studies suggest that the morphological response of endothelial cells to fluid shear stress depends on the endothelial cell type. Thus, the present study characterizes the morphological response of human dermal microvascular endothelial cells (HMEC-1) and nuclei to steady, laminar, and unidirectional fluid shear stress. Cultured HMEC-1 monolayers were exposed to shear stress of 0.3 dyn/cm2, 16 dyn/cm2, or 32 dyn/cm2 for 72 h with hourly live-cell imaging capturing both the nuclear and cellular morphology. Despite changes in elongation and alignment occurring with increasing fluid shear stress, there was a lack of elongation and alignment over time under each fluid shear stress condition. Conversely, changes in cellular and nuclear area exhibited dependence on both time and fluid shear stress magnitude. The trends in cellular morphology differed at shear stress levels above and below 16 dyn/cm2, whereas the nuclear orientation was independent of fluid shear stress magnitude. These findings show the complex morphological response of HMEC-1 to fluid shear stress.


Evaluation of the 16S and 12S rRNA genes as universal markers for the identification of commercial fish species in South Africa.
The development of DNA-based methods for the identification of fish species is important for fisheries research and control, as well as for the detection of unintentional or fraudulent species substitutions in the marketplace. The aim of this study was to generate a comprehensive reference database of DNA sequences from the mitochondrial 16S and 12S ribosomal RNA (rRNA) genes for 53 commercial fish species in South Africa and to evaluate the applicability of these genetic markers for the identification of fish at the species level. The DNA extracted from all target species was readily amplified using universal primers targeting both rRNA gene regions. Sequences from the 16S and 12S rRNA genes were submitted to GenBank for the first time for 34% and 53% of the fish species, respectively. Cumulative analysis of the 16S rRNA gene sequences revealed mean conspecific, congeneric and confamilial Kimura two parameter (K2P) distances of 0.03%, 0.70% and 5.10% and the corresponding values at the 12S level were 0.03%, 1.00% and 5.57%. K2P neighbour-joining trees based on both sequence datasets generally clustered species in accordance with their taxonomic classifications. The nucleotide variation in both the 16S and 12S sequences was suitable for identifying the large majority of the examined fish specimens to at least the level of genus, but was found to be less useful for the explicit differentiation of certain congeneric fish species. It is recommended that one or more faster-evolving DNA regions be analysed to confirm the identities of closely-related fish species in South Africa.


Chemiluminescent detection of DNA: application for DNA sequencing and hybridization.
A non-radioactive DNA detection chemistry is described and its application is shown for DNA hybridization and standard dideoxy DNA sequencing. The method employes a biotin-streptavidin system which binds an enzyme specifically to a target DNA and upon exposure to substrate, the enzyme catalyzes a chemiluminescent reaction. The image is captured within seconds by a Polaroid or X-ray film. The method is capable of detecting DNA in the hundred attomol range.


Evaluation of adrenomedullin and endothelin-1: are they factors in the adaptation of maternal vascular system in normotensive pregnancy.
The aim of our study was to analyse the role of adrenomedullin (AM) and endothelin-1 (ET-1) in the adaptation of the maternal vascular system in normotensive pregnancy. Twenty-eight pregnant women, who were normotensive throughout the duration of their pregnancy, were recruited into the study. Plasma levels of AM and ET-1 at each trimester were measured and the AM/ET-1 ratio was calculated. Our experiment showed a significant decrease in plasma concentrations of AM in the first trimester for the study group (n=28) compared with the non-pregnant control group (n=16). There was also a significant decrease in plasma concentrations of ET-1 in all three trimesters (P<0.05) and a significant increase in the AM/ET-1 ratio in all three trimesters (P<0.05) for the study group compared with the control group. An alteration in vascular equilibrium between AM and ET-1, favouring AM, may be a reason why the physiological adaptation of the maternal vascular system to pregnancy occurs during normotensive pregnancy.


A meta-analysis of the interrelationships between the modes in Roy's adaptation model.
A meta-analysis of nine empirical studies based on Roy's adaptation model was conducted to determine the magnitudes of the interrelationships of the four modes: physiological, self-concept, role function, and interdependence. Small to medium effect sizes between each two modes do support the proposition of Roy's model that the four modes are interrelated. The only exception is the relationship between interdependence and physiological modes, as shown by the non-significant effect size of .04. The present study also discusses several limitations that should be considered when interpreting the findings of this meta-analysis. This study does provide a useful compilation of the Roy model's credible studies and proposes a direction for further research. The results indicate a need for further study to explore the relationship in all response modes to have a clearer understanding of the credibility of Roy's model.


Rapid identification of Escherichia coli with a fluorogenic beta-glucuronidase assay.
We evaluated three fluorogenic methods (MUG; Remel, Lenexa, KS) for the rapid (less than 1 hr) identification of E. coli by detecting beta-glucuronidase activity. The methods included: direct disk inoculation test, tube test, and liquid spot reagent test. Fluorogenic tests were performed on pure cultures of lactose fermenters and compared with identification by Enterotube II (Roche Diagnostics; Nutley, NJ). Organisms yielding disparate results were further analyzed by API 20E (Analytab Products Inc.; Plainview, NY). The tube test was evaluated with isolates subcultured on both MacConkey and blood agars; the direct disk and liquid spot reagent methods were tested with isolates subcultured on blood agar only. All methods were highly specific (greater than 97%). Sensitivity of the beta-glucuronidase tests were method and media dependent, but exceeded 85% in all cases. The direct disk and tube tests also permitted detection of indole formation; results of indole testing, however, contributed little to accurately identifying E. coli.


Differential regional and cellular distribution of dopamine D2-like receptors: an immunocytochemical study of subtype-specific antibodies in rat and human brain.
Dopamine D2-like receptors (D2, D3, and D4) are major targets for action of typical and atypical neuroleptics, commonly used in the treatment of schizophrenia. To understand their individual functional contribution, subtype-selective anti-peptide antibodies were raised against D2, D3, and D4 receptor proteins. The antibodies were shown to be specific on immunoblots of rat brain membranes and immunoprecipitated the solubilized native dopamine receptors in an antibody concentration-dependent manner. In addition, they also bind selectively to the respective recombinant D2, D3, and D4 receptor membrane proteins from cDNA transfected cells. Immunolocalization studies show that the D2-like receptor proteins had differential regional and cellular distribution in the cerebral cortex, hippocampus, basal ganglia, cerebellum, and midbrain, thus providing anatomical substrate for area-specific regulation of the dopamine neurotransmission. In cortical neurons, D4 receptor protein was found in both pyramidal and nonpyramidal cells, whereas D2 and D3 seem to be mostly associated with nonpyramidal interneurons. In rat hippocampus, the expression pattern of D2-like receptors (D4>D3>D2) mirrored that obtained with immunoprecipitation studies. D2 and D4 receptor immunolabeling was observed in the thalamic reticular nucleus, which was negative for the D3 subtype. Species differences were also observed; for example, the D4 subtype receptor is the most highly expressed protein in the rat cortex, whereas it is significantly less in human cortex. Differential patterns of D2, D3, and D4 receptor expression in rat and human brain should shed light on the therapeutic actions of neuroleptic drugs and may lead to the development of more specifically targeted antipsychotic drugs.


Association between single-nucleotide polymorphisms in the endothelial lipase (LIPG) gene and high-density lipoprotein cholesterol levels.
Endothelial lipase (LIPG) is the latest addition to the triglyceride lipase family of genes that includes pancreatic lipase (PL), hepatic lipase (HL), and lipoprotein lipase (LPL). These lipolytic enzymes demonstrate both triglyceride lipase as well as phospholipase activities and are integrally involved in lipid absorption, transport, and metabolism. Several studies have demonstrated that LIPG is important for affecting lipid levels in mice but the data in humans is less complete. To more thoroughly characterize the LIPG gene, we resequenced it from an ethnically diverse population. Thirteen novel single-nucleotide polymorphisms (SNPs) were identified and seven others confirmed. High linkage disequilibrium was found among these SNPs spanning the length of the transcript, allowing interrogation of the entire gene for functional variation. Subjects with either high or low HDL cholesterol were used to investigate its association with LIPG gene variation. Associations were found with the most significant being the intronic variants C+42T/In5 and T+2864C/In8 (P=0.007 and 0.004, respectively). A trend for an association of the same SNPs with fewer myocardial infarctions (P=0.03) was also observed but was not significant after correction for multiple testing. The results of this study provide data linking variation in the human LIPG gene with HDL cholesterol levels as well as further evidence in support of LIPG as a potential target for therapeutic intervention.


Pearls and Pitfalls of Pulsed Field Ablation.
Pulsed field ablation (PFA) was recently rediscovered as an emerging treatment modality for the ablation of cardiac arrhythmias. Ultra-short high voltage pulses are leading to irreversible electroporation of cardiac cells subsequently resulting in cell death. Current literature of PFA for pulmonary vein isolation (PVI) consistently reported excellent acute and long-term efficacy along with a very low adverse event rate. The undeniable benefit of the novel ablation technique is that cardiac cells are more susceptible to electrical fields whereas surrounding structures such as the pulmonary veins, the phrenic nerve or the esophagus are not, or if at all, minimally affected, which results in a favorable safety profile that is expected to be superior to the current standard of care without compromising efficacy. Nevertheless, the exact mechanisms of electroporation are not yet entirely understood on a cellular basis and pulsed electrical field protocols of different manufactures are not comparable among one another and require their own validation for each indication. Importantly, randomized controlled trials and comparative data to current standard of care modalities, such as radiofrequency- or cryoballoon ablation, are still missing. This review focuses on the "pearls" and "pitfalls" of PFA, a technology that has the potential to become the future leading energy source for PVI and beyond.


Effects of soluble aggregates of IgG on the binding, uptake and degradation of the C1q subcomponent of complement by adherent guinea pig peritoneal macrophages.
Earlier studies have indicated that C1q, the first subcomponent of complement component C1, is bound to lymphocytes via specific C1q receptor sites. We have recently shown that adherent guinea pig peritoneal exudate macrophages express specific receptors for C1q (Veerhuis, R. et al., Immunology 1985. 54: 801). The present studies were performed to determine whether binding of 125I-labeled human C1q (125I-C1qhu) to adherent guinea pig peritoneal exudate macrophages would also result in ingestion and subsequent degradation of 125I-C1qhu. The binding of 125I-C1qhu to adherent peritoneal macrophages at 4 degrees C is inhibited fully not only by C1qhu and guinea pig C1q (C1qgp) but also by pepsin fragments of C1qhu. The amount of trichloroacetic acid nonprecipitable radioactivity that appeared in the supernatant was used as a measure for the degradation of 125I-C1qhu. 125I-C1qhu is degraded initially into fragments of 25 kDa, after which it is degraded further into small molecular weight peptides. Ingestion of 125I-C1q by the macrophages occurs before the 125I-C1q is degraded. In the presence of limited amounts of soluble aggregates of guinea pig IgG2 (AIgG), a known activator of C1, part of the C1q is bound to the AIgG and all of the AIgG in turn is bound to the cellular Fc receptors leading to an enhanced binding of 125I-C1q to the cells, a binding that was maximal at near equimolar concentrations of 125I-C1qhu and 131I-AIgG. In the presence of a 30-fold excess of AIgG, however, only a small percentage of the AIgG binds to cellular Fc receptors and the interaction of C1q with its receptor is decreased due to competitive inhibition. The results presented in this report thus suggest that free C1q may be eliminated by specific interaction with C1q receptors present on circulating and tissue phagocytoses and, in addition, that in the presence of immune complexes modulation of elimination of C1q may be encountered.


Phosphorus recovery from artificial wastewater by microbial fuel cell and its effect on power generation.
The effects of ammonium (NH4) and magnesium (Mg) on the precipitation of phosphorus in artificial wastewater by an air-cathode single-chamber microbial fuel cell were investigated. When both NH4 and Mg were added to the wastewater, phosphorus was precipitated as struvite. Almost no precipitation occurred with the addition of only NH4, while phosphorus was precipitated as cattiite with the addition of only Mg. However, the amount of precipitate was less than that observed in experiments in which NH4 was also added. As the amounts of NH4 and Mg were increased, more precipitate was observed. Precipitated phosphorus on the cathode was recovered by dissolution in Milli-Q water and MES buffers. It was discovered that the formation of a precipitate reduced the performance of the cathode. Dissolution treatment caused the performance of the cathodes to increase to their initial level.


Successful plague control in Namibia.
To demonstrate that plague can be successfully controlled. A descriptive study outlining patterns of plague occurrence in relation to variables such as age group, gender, place and time. Two northern districts, namely Engela in Ohangwena region and Onandjokwe in Oshikoto region, an area of 2,000 km2. All patients who presented to the health facilities with signs and symptoms of plague were considered. Diagnosis was made on the basis of clinical symptomatology and laboratory confirmation. A plague control programme was established involving the following components: management capability at the local level, case recognition and management, dusting programme, rodent trapping programme, health education, establishment of plague laboratory, and plague surveillance system. Following the establishment of the control programme plague cases were reduced from 1,092 to zero within 3 years and deaths from 45 to zero within 2 years. The case fatality rate was reduced from 4.12% to 0% over a 3-year period. No cases have been reported in Namibia for the past 3 years. The Namibian experience has demonstrated that plague can be controlled through a combination of strategies taking local conditions into consideration.


Quantitative determination of endogenous sorbitol and fructose in human erythrocytes by atmospheric-pressure chemical ionization LC tandem mass spectrometry.
Evaluation of different extraction methods for quantification of endogenous sorbitol and fructose in human red blood cells (RBCs) and matrix effects in ESI and APCI showed that protein-precipitation followed by mixed-mode solid-phase extraction was more effective extraction method and APCI more effective ionization method. Then the LC/APCI-MS/MS method was fully validated and successfully applied to analysis of clinical RBC samples. The concentrations of endogenous sorbitol and fructose were determined using calibration curves employing sorbitiol-13C6 and fructose-13C6 as surrogate analytes. The method has provided excellent intra- and inter-assay precision and accuracy with a linear range of 50.0-10,000 ng/mL (correlation coefficient >0.999) for sorbitol-13C6 and 250-50000 ng/mL (correlation coefficient >0.999) for fructose-13C6 in human RBCs.