Assessment of an electronic patient record system on discharge prescribing errors in a Tertiary University Hospital.
Prescribing error represent a significant source of preventable harm to patients. Prescribing errors at discharge, including omission of pre-admission medications (PAM), are particularly harmful as they frequently propagate following discharge. This study assesses the impact of an educational intervention and introduction of an electronic patient record (EPR) in the same centre on omission of PAM at discharge using a pragmatic design. A survey of newly qualified doctors is used to contextualise findings. Discharge prescriptions and discharge summaries were reviewed at discharge, and compared to admission medicine lists, using a paper-based chart system. Discrepancies were noted, using Health Information and Quality Authority guidelines for discharge prescribing. An educational intervention was conducted. Further review of discharge prescriptions and discharge summaries took place. Following introduction of an EPR, review of discharge summaries and discharge prescriptions was repeated. A survey was administered to recently qualified doctors (interns), and analysed using descriptive statistics and thematic analysis. Omission of PAM as prescribed or discontinued items at discharge occurs frequently. An educational intervention did not significantly change prescribing error rates (U = 1255.5, p = 0.206). EPR introduction did significantly reduce omission of PAM on discharge prescribing (U = 694, p < 0.001), however there was also a reduction in the rate of deliberate discontinuation of PAM at discharge (U = 1237.5, p = 0.007). Survey results demonstrated that multiple sources are required to develop a discharge prescription. Time pressure, access to documentation and lack of admission medicine reconciliation are frequently cited causes of discharge prescribing error. This study verified passive educational interventions alone do not improve discharge prescribing. Introduction of EPR improved discharge prescribing, but negatively impacted deliberate discontinuation of PAM at discharge. This is attributable to reduced access to key sources of information used in formulating discharge prescriptions, and separation of the discontinuation function from the prescribing function on the EPR discharge application.


A biochemical explanation for the fatty liver and kidney syndrome of broilers: its alleviation by the short-term use of dietary fat.
1. Fatty livers and kidney syndrome (FLKS) was induced in young broiler chickens by giving them a diet composed principally of wheat and meat meal. 2. FLKS resulted in reduced growth and increased liver weight; fasting for 18 h increased mortality, liver lipid and the specific activity of hepatic ATP-citrate lyase compared with birds fed on a commercial diet. The specific activities of hepatic fructose-1,6-diphosphate-1-phosphohydrolase and pyruvate carboxylase were reduced in birds suffering from FLKS and fasted for 18 h. 3. Feeding of the FLKS-inducing diet supplemented with 150 g animal tallow/kg for 54 h considerably reduced mortality while restoring liver composition and enzyme activities towards those observed in birds fed a commercial diet. Investigations indicated that the glycerol component of the fat was not responsible for the observed responses. 4. The present results suggest that in FLKS insufficiencies of biotin are induced in specific enzyme systems, but the syndrome may be alleviated without the use of supplementary biotin. 5. The evidence indicates that, when stressed, birds affected by FLKS diet from the hypoglycaemia occurring as a result of a reduced capacity for gluconeogenesis.


Sub-MHz bursts of nanosecond pulses excite neurons at paradoxically low electric field thresholds without membrane damage.
Neuromodulation applications of nanosecond electric pulses (nsEP) are hindered by their low potency to elicit action potentials in neurons. Excitation by a single nsEP requires a strong electric field which injures neurons by electroporation. We bypassed the high electric field requirement by replacing single nsEP stimuli with high-frequency brief nsEP bursts. In hippocampal neurons, excitation thresholds progressively decreased at nsEP frequencies above 20-200 kHz, with up to 20-30-fold reduction at sub-MHz and MHz rates. For a fixed burst duration, thresholds were determined by the duty cycle, irrespective of the specific nsEP duration, rate, or number of pulses per burst. For 100-μs bursts of 100-, 400-, or 800-ns pulses, the threshold decreased as a power function when the duty cycle exceeded 3-5 %. nsEP bursts were compared with single "long" pulses whose duration and amplitude matched the duration and the time-average amplitude of the burst. Such pulses deliver the same electric charge as bursts, within the same time interval. High-frequency nsEP bursts excited neurons at the time-average electric field 2-3 times below the threshold for a single long pulse. For example, the excitation threshold of 139 ± 14 V/cm for a single 100-μs pulse decreased to 57 ± 8 V/cm for a 100-μs burst of 100-ns, 0.25-MHz pulses (p < 0.001). Applying nsEP in bursts reduced or prevented the loss of excitability in multiple stimulation attempts. Stimulation by high-frequency nsEP bursts is a powerful novel approach to excite neurons at paradoxically low electric charge while also avoiding the electroporative membrane damage.


Studies Toward the Syntheses of Pluramycin Natural Products. The First Total Synthesis of Isokidamycin.
We report the first total synthesis of the complex C-aryl glycoside isokidamycin, the epimer of the naturally-occurring pluramycin antibiotic kidamycin. The synthesis features a highly efficientDiels-Alder reaction between a substituted naphthyne and a glycosylatedfuran to form the anthracene core bearing a pendant angolosamine C-glycoside. The regiochemical outcome of the Diels-Alder reaction was controlled by employing a disposable silicon-tether to link the reactive napthyne and the glycosyl furan, rendering the cycloaddition intramolecular. The benzopyranone moietyof the aromatic nucleus was appended by cyclization of a functionalized vinylogous amide onto an advanced anthrol intermediate. The vancosamine amino glycoside was introduced by an O→C-glycoside rearrangement that produced the β-anomer. Subsequent refunctionalizations then led to isokidamycin.


Spermatogonial stem cells and in vitro spermatogenesis.
Spermatogonial stem cells (SSCs) provide the basis for the life-long production of enormous numbers of sperm. The nature of these mysterious cells is being clarified. Although they were regarded to be mostly dormant, dividing rarely and remaining static in a niche, their rather dynamic behavior in the seminiferous tubules has been disclosed. The territories of each colony of SSCs can also quickly change in size. The development of a culture method for SSCs also shed light on their stable, but at the same time, fragile characteristics. In addition, an in vitro system for spermatogenesis was developed which can produce functional sperm from SSCs. These new developments will contribute to reproductive medicine.


CTP:phosphocholine cytidylyltransferase.
CTP:phosphocholine cytidylyltransferase (CCT) catalyzes the synthesis of CDP-choline and is regulatory for phosphatidylcholine biosynthesis. This review focuses on recent developments in understanding the catalytic and regulatory mechanisms of this enzyme. Evidence for the nuclear localization of the enzyme is discussed, as well as evidence suggesting cytoplasmic localization. A comparison of the catalytic domains of CCTs from a wide variety of organisms is presented, highlighting a large number of completely conserved residues. Work implying a role for the conserved HXGH sequence in catalysis is described. The membrane-binding domain in rat CCT has been defined, and the role of lipids in activating the enzyme is discussed. The identification of the phosphorylation domain is described, as well as approaches to understand the role of phosphorylation in enzyme activity. Other possible control mechanisms such as enzyme degradation and gene expression are presented.


Strategic wellness management in Finland: The first national survey of the management of employee well-being.
To examine the scope of strategic wellness management (SWM) in Finland. To measure management of wellness a strategic wellness management index (SWMI) was developed. On the basis of the developed SWM model an Internet questionnaire was conducted for randomly selected employers representing seven business areas and three size categories. Corporate activities and SWMI for each employer and for business area and size groups were calculated. Results highlighted relatively good activity in strategic wellness (SW) processes and fairly low level of SWM procedures. The average values (± SD) of SWMI were 53.6 ± 12.3 for large, 42.8 ± 11.7 for medium-size, and 32.8 ± 12.1 for small companies. SWMI can be a positive new, strong concept to measure SW processes and thus improve both the well-being of the employees and the productivity of the enterprise.


Molecular characterization of a gene encoding a cysteine-rich protein preferentially expressed in anthers of Lycopersicon esculentum.
The tomato (Lycopersicon esculentum Mill.) cDNA clone TomA5B was isolated by differential screening of a cDNA library prepared from anthers at late meiosis to tetrad formation. The 5B gene is present in a single copy in the tomato genome. Expression is developmentally regulated and tissue specific. RNA accumulation was detected from premeiosis through tetrad release in the tapetal cell layer of the anther with low levels of RNA detected in petals and early stages of pistil development. The protein deduced from the DNA sequence analysis is predicted to have a molecular mass of 11.1 kDa and a secretory signal sequence, suggesting it is a secreted protein. The deduced 5B protein has a pattern of cysteine residues that is similar to other proteins that have stamen-specific expression and to a superfamily of seed proteins. The 5B protein is unique in that there is no amino acid sequence similarity to other proteins beyond the similar cysteine motif.


Acetazolamide assisted Tc-99m MAG3 renography to assess renal blood flow reserve.
The present study examines whether or not baseline and acetazolamide (ACZ) Tc-99m MAG3 renography can assess renal blood flow reserve. Renography proceeded for 50 min after sequential injections of 370 MBq Tc-99m MAG3 for baseline renography and 10 min after a 1,000 mg injection of ACZ for ACZ renography. Effective renal plasma flow of renal cortex (cERPF) in each kidney and the percentage change in cERPF of those parameters (deltaERPF) were obtained before and after the administration of ACZ in 10 subjects without hypertension or diabetes (normal group), in 10 with essential hypertension (hypertensive group) and in 10 who had Type 2 diabetes with hypertension (diabetic group). A placebo test was performed in the 10 without hypertension or diabetes using distilled water instead of ACZ (placebo group). The placebo test performed in the 10 without hypertension or diabetes using distilled water instead of ACZ indicated that the parameter variance between the two types of renogram was below 3.2%. The cERPF of baseline and ACZ Tc-99m MAG3 renography and deltaERPF in the normal, hypertensive and diabetic groups were 89 +/- 10 and 110 +/- 10 ml/min, 89 +/- 14 and 117 +/- 22 ml/min, 100 +/- 23 and 112 +/- 23 ml/min, respectively, and 24.5 +/- 13.5%, 26.0 +/- 9.7% and 12.3 +/- 11.1%, respectively. The difference in the cERPF value was significant in the normal and hypertensive groups whereas this did not change in the diabetic group before or after ACZ administration. We suggested that the deltaERPF determined by baseline and ACZ Tc-99m MAG3 renography is a useful parameter for assessing renal blood flow reserve.


A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation.
Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting likelihood of smoking cessation. A systematic review was conducted summarizing evidence of associations between single nucleotide polymorphisms (SNPs) of nAChR genes and smoking cessation. From 24 articles meeting inclusion criteria, summary odds ratios (ORs) for associations between nine SNPs and smoking cessation were calculated from 26 studies (N = 233-29,072) stratified by gene, ancestry, study design, and pharmacotherapy; SNPs in linkage disequilibrium were pooled. Results for a tenth SNP from two GWAS were summarized. People of European ancestry with minor alleles of CHRNA5 rs16969968 and CHRNA3 rs1051730 had longer time to cessation [HR = 0.90, 95 % CI 0.88 - 0.92 (n = 2 studies)] and lower odds of cessation [OR = 0.88, 95 % CI 0.80 - 0.97 (n = 5 cohort studies), OR = 0.64, 95 % CI 0.45 - 0.90 (n = 4 placebo arms)]. Risk of persistent smoking associated with these alleles was attenuated in smokers receiving nicotine replacement therapy (NRT). Recipients of bupropion alone or with NRT with these alleles had higher, though not statistically significant, odds of cessation. Results for CHRNA5 rs588765 and rs680244 were similar to rs16969968/rs1051730 findings. Evidence was limited for other SNPs. Evidence consistently indicates the minor alleles of four SNPs within CHRNA3 or CHRNA5 are risk alleles for cessation failure. Analysis by pharmacotherapy revealed bupropion may be the most efficacious intervention for people with these alleles.


Reassembly of immunoglobulin M heavy and light chains in vitro.
Reduced and alkylated monoclonal IgM was fractionated into mu and light (L) chains by gel chromatography in 1N acetic acid. Equimolar mixtures of the chains formed a noncovalently bonded structure in 0.01M sodium acetate buffer, pH 4.1, that had the properties of a half subunit. The latter reassociated into a subunit-like structure after transfer into 0.08M sodium phosphate buffer, pH 7.5. The similarity of the reconstituted IgM subunit (IgMs) to that of the native molecule was established by its physicochemical and immunochemical properties. Comparable products were obtained on reassembly of the alkylated mu and L chains from several other monoclonal IgM. The presence of active binding sites for IgG on subunits reconstituted from the chains of proteins with anti-IgG activity further indicated correct assembly of the mu and L chains. High yields of subunit-like products were also obtained by assembly of mu chains from one protein and L chains from another. Evidence was obtained that L chains of appropriate specificity can substitute for the homologous chain in the formation of the active site. Heterogeneous mixtures of high molecular weight products were generated from mu and L chains that were not alkylated. Reduction and alkylation demonstrated that the products represented polymers of reconstituted IgMs. Significant levels of anti-IgG activity were detected in the polymeric IgM generated from the chains of active proteins by precipitation with aggregated IgG.


In vivo electrophysiological analysis of lucifer yellow-coupled hippocampal pyramids.
Small transient all-or-none depolarizations (also termed in the literature fast prepotentials, spikelets, pseudospikes, d-spikes, or short latency depolarizations) and their association with lucifer yellow (LY) dye-coupling were analyzed in CA1-CA3 hippocampal pyramidal cells in urethane anesthetized rats. It was found that (a) 15 of the 24 LY-injected pyramidal neurons (63%) showed dye-coupling; (b) spontaneous, anti- and orthodromically evoked spikelets (3-7 ms in duration; 3- to 12-mV peak) were recorded in 40 of 95 cells (42%); (c) there was a significantly higher probability of dye-coupled neurons with spikelets and of uncoupled ones without spikelets; (d) spikelet waveform and amplitude were unaffected by spontaneous or imposed polarizations; (e) large hyperpolarizations could reduce the rate and even prevent spikelets; and (f) spikelets could precede or follow spikes, the latter were more frequent with large depolarizations. Electrophysiological findings, and the association of dye-coupling and spikelets, suggest strongly that at least some spikelets are coupling potentials. This implies that pyramidal cells may be electronically coupled under physiological conditions.


"Pingpong racket" flap model for evaluating flap survival.
Random skin flap is widely used to repair tissue defects; however, it is often accompanied by ischemia and necrosis of the distal flap due to inferior axial vascularity. Even though different drugs, biomaterials, and stem cell therapies have been developed to improve the survival of random flap, evaluating the promotion of flap survival remains a big challenge. Based on successful clinical practice, we designed a "Pingpong racket" shape flap in the rat. Without the predetected blood vessels procedure, the "pingpong racket" flap provides a preferable option to evaluate the function of drugs and biomaterials in promoting flap survival. "Pingpong racket" dorsal flaps with different pedicle lengths were developed in the rats. The survival area was evaluated by digital photography and computer-assisted analysis. The quantitative survival area was considered a useful indicator for analyzing drugs' applicability in improving skin flap survival. A new model with a pedicle width of 1 cm and a flap diameter of 3 cm, in which the length of the pedicle could be tuned, was established. No iliolumbar vessels passed through the pedicle. The necrosis ratio ( round ) of the flap was 29.88% in the 2 cm long pedicle, 74.69% in the 3 cm long pedicle, 95.52% in the 4 cm long pedicle, and in the 5 cm long pedicle; necrotic area could be found in both the round part and in the pedicle. The new 3 cm long pedicle flap is suitable for evaluating the drugs for promoting skin flap survival. Rat dorsal "Pingpong racket" flap can be easily handled, thus avoiding blood vessels' detection. The flap could achieve comparable results to clinical and alleviate the negative influence of the flap's longitudinal contraction. Besides, it is intuitive and aesthetically pleasing.


Medical imaging and computational image analysis in COVID-19 diagnosis: A review.
Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. The disease presents with symptoms such as shortness of breath, fever, dry cough, and chronic fatigue, amongst others. The disease may be asymptomatic in some patients in the early stages, which can lead to increased transmission of the disease to others. This study attempts to review papers on the role of imaging and medical image computing in COVID-19 diagnosis. For this purpose, PubMed, Scopus and Google Scholar were searched to find related studies until the middle of 2021. The contribution of this study is four-fold: 1) to use as a tutorial of the field for both clinicians and technologists, 2) to comprehensively review the characteristics of COVID-19 as presented in medical images, 3) to examine automated artificial intelligence-based approaches for COVID-19 diagnosis, 4) to express the research limitations in this field and the methods used to overcome them. Using machine learning-based methods can diagnose the disease with high accuracy from medical images and reduce time, cost and error of diagnostic procedure. It is recommended to collect bulk imaging data from patients in the shortest possible time to improve the performance of COVID-19 automated diagnostic methods.


Paraoxon toxicity is not potentiated by prior reduction in blood acetylcholinesterase.
The role of blood acetylcholinesterase in moderating the effects of organophosphate challenge in rats was tested. Adult male rats (n = 42) were injected (iv) either with monoclonal antibodies (MAb) to rat acetylcholinesterase (EC 126.96.36.199; AChE) or normal mouse IgG (controls). Two days later, the rats were injected (sc) with either a mild (0.17 mg/kg) or moderate dosage (0.34 mg/kg) of paraoxon or with vehicle. Neurological integrity was assessed by a functional observational battery followed by motor activity, 3 to 4 hr after dosing. Blood, brain, and diaphragm tissues were then collected for determination of AChE activity. MAb treatment reduced whole blood and plasma AChE activity by 32 and 90%, respectively, but did not affect neurobehavioral parameters or the AChE activity of brain or diaphragm. The paraoxon challenge produced dose-related neurobehavioral changes and inhibition of brain and diaphragm AChE activity to the same extent in IgG- and MAb-treated rats. Thus, significant loss in blood AChE alone produced no detectable neurobehavioral deficits and did not alter the subsequent responses to paraoxon challenge.


Unraveling the role of peptidyl-prolyl isomerases in neurodegeneration.
Immunophilins are a family of highly conserved proteins with a peptidyl-prolyl isomerase activity that binds immunosuppressive drugs such as FK506, cyclosporin A, and rapamycin. Immunophilins can be divided into two subfamilies, the cyclophilins, and the FK506 binding proteins (FKBPs). Next to the immunophilins, a third group of peptidyl-prolyl isomerases exist, the parvulins, which do not influence the immune system. The beneficial role of immunophilin ligands in neurodegenerative disease models has been known for more than a decade but remains largely unexplained in terms of molecular mechanisms. In this review, we summarize reported effects of parvulins, immunophilins, and their ligands in the context of neurodegeneration. We focus on the role of FKBP12 in Parkinson's disease and propose it as a novel drug target for therapy of Parkinson's disease.


Use of (35)s nucleotides for DNA sequencing.
DNA sequencing is a technique that has become central to many laboratories engaged in molecular biology. The two basic sequencing methods commonly used are known as the Maxam-Gilbert method of chemical cleavage (1) and the dideoxy chain termination method developed originally by Sanger (2). One of the most critical steps in either of these two methods is the radiolabeling of the DNA such that the sequencing gel "ladder" of reaction products may be obtained after autoradiography of the sequencing gel.


Depalmitoylation rewires FLT3-ITD signaling and exacerbates leukemia progression.
Internal tandem duplication within FLT3 (FLT3-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and correlates with a poor prognosis. Whereas the FLT3 receptor tyrosine kinase is activated at the plasma membrane to transduce PI3K/AKT and RAS/MAPK signaling, FLT3-ITD resides in the endoplasmic reticulum and triggers constitutive STAT5 phosphorylation. Mechanisms underlying this aberrant FLT3-ITD subcellular localization or its impact on leukemogenesis remain poorly established. In this study, we discovered that FLT3-ITD is S-palmitoylated by the palmitoyl acyltransferase ZDHHC6. Disruption of palmitoylation redirected FLT3-ITD to the plasma membrane and rewired its downstream signaling by activating AKT and extracellular signal-regulated kinase pathways in addition to STAT5. Consequently, abrogation of palmitoylation increased FLT3-ITD-mediated progression of leukemia in xenotransplant-recipient mouse models. We further demonstrate that FLT3 proteins were palmitoylated in primary human AML cells. ZDHHC6-mediated palmitoylation restrained FLT3-ITD surface expression, signaling, and colonogenic growth of primary FLT3-ITD+ AML. More important, pharmacological inhibition of FLT3-ITD depalmitoylation synergized with the US Food and Drug Administration-approved FLT3 kinase inhibitor gilteritinib in abrogating the growth of primary FLT3-ITD+ AML cells. These findings provide novel insights into lipid-dependent compartmentalization of FLT3-ITD signaling in AML and suggest targeting depalmitoylation as a new therapeutic strategy to treat FLT3-ITD+ leukemias.


The distribution of alcohol consumption and the prevention paradox in Brazil.
To examine the proportion of self-reported alcohol consumed by different gender and age groups in Brazil over the past year, and to examine whether the 'prevention paradox' applies to Brazilian data on alcohol-related problems. A multi-stage cluster sample, representative of the Brazilian household population. This study was conducted in Brazil between November 2005 and April 2006. Respondents were aged ≥ 14 years (n = 3007). Measures included past year estimates of (i) number of standard drinks, (ii) frequency of binge drinking, and (iii) alcohol-related problems. The survey response rate was 66.4%. The top 2.5% of the drinkers by volume consume 14.9%, the top 5% consume 27.4% and the top 10% consume 44.2% of all alcohol consumed in Brazil. Men consume 77.8% of the total alcohol, and 18-29-year-olds consume 40.3%. Individuals below risky drinking guidelines for weekly volumetric intake account for 49-50% of all problem drinkers and 45-47% of all problem types reported. Individuals who do not binge or who binge infrequently (1-3 times/year) account for 50-51% of all problem drinkers and 45-46% of all reported problem types. Most binge drinkers are low-volume drinkers. Consistent with the prevention paradox literature, most drinking problems in Brazil are associated with low or moderate drinking. Binge drinking accounts more clearly for the distribution of alcohol problems than total volume consumed.


Autoantibodies in healthy subjects of different age groups.
Autoantibody determinations in 1284 healthy Caucasian subjects of various age groups were made by indirect immunofluorescence for anti-nuclear, anti-gastric, and anti-thyroglobulin antibodies. A sex-dependent relationship between age and prevalence of anti-gastric and anti-thyroglobulin antibodies was found. No association was found between age and anti-nuclear antibodies.


[Assessment of the practices and knowledge among cardiologists regarding radiation protection in Tunisia].
interventional cardiology procedures have become complex and expensive in time with a higher risk of exposure to ionizing radiations. The purpose of our study was to assess radiation protection knowledge and practices among Tunisian cardiologists exposed to X-rays. we conducted a descriptive, analytical study in October 2019. An anonymous survey on the knowledge and practices regarding radiation protection was sent to all Tunisian cardiologists exposed to X-rays. among 126 cardiologists exposed to X-rays and having received the survey, 58 physicians responded to the survey (48%), with a male predominance (72%, n=42). Thirty-eight physicians (65%) were public sector workers. Average years of working experience were 12.02 years (SD 6.88 years). Half of doctors had a knowledge score of less than 50%. The average practice score was 43.83 (SD 13.95%). Wearing a lead apron, thyroid shield, dosimeter, lead glasses, lead cap accounted for 100% (n=58), 86.2% (n=50), 30.7% (n=18), 12.1% (n=7) and 1.7% (n=1) respectively. There was no correlation between scores and doctor's age as well as the length of working experience. There was no statistical differences between knowledge scores of males and females (p=0.06) or between public sector and private sector (p=0.9). Practice score was significantly higher among men (0.007) and interventional cardiologists compared to rhythmologists and pediatric cardiologists (p<0.001). the level of knowledge and practices among Tunisian cardiologists regarding radiation protection is generally insufficient. Then, health authorities should implement regular training programs.


New methods for the preparation of the cellular intermediate EAC14.
The cellular intermediate EAC14 was successfully prepared by incubating optimally sensitized sheep erythrocytes (EA) with normal serum diluted in complement diluent buffer containing suitable amounts of inhibitors of EAC142 formation from EAC14 and C2, namely polymyxin E and polymyxin B. EAC14 cells could also be prepared by incubating EA with normal serum diluted in Mg2+ free complement diluent buffer in the presence or absence of sucrose. The cellular intermediates prepared by these methods exhibited characteristic EAC142 formation and decay profiles and were found to be suitable for C2 estimations.


Chemoradiotherapy with Concurrent Regional Arterial Chemotherapy for Locally Bulky Unresectable Rectal Cancer: A Case Series.
We evaluated the feasibility and efficacy of chemoradiotherapy with concurrent regional arterial chemotherapy (CRT/RAC) for locally bulky unresectable rectal cancer (LBURC). We retrospectively reviewed 9 patients with LBURC who received CRT/RAC between January 2012 and December 2018. The regimen consisted of chemoradiotherapy and 3 cycles of regional arterial chemotherapy. Surgery was performed 6 weeks after completion of radiotherapy. The median longest tumor diameter was 10 cm (range 8.2-13.6). Grade 3 toxicity and postoperative complications occurred in 3 and 4 patients, respectively. All patients showed partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST). One patient refused the operation after completion of the scheduled regimen but then had a bowel obstruction and had to undergo urgent surgery. Of the 8 patients who underwent scheduled surgery, all had R0 resection without multivisceral resection; 3 achieved pathological complete response and 5 exhibited good tumor regression. The median follow-up period was 35 months (range 9-63). Recurrences occurred in 3 of 9 patients (pelvic relapses in 2 and lung in 1). CRT/RAC appeared to be beneficial to LBURC, as it achieves remarkable rates of R0 resection, good tumor regression, and pathologic complete response. These preliminary results have to be confirmed in larger cohorts of patients.


Possible involvement of macrophages in embryo--maternal relationships during ovum implantation in the rat.
Distribution of phagocytic cells in the rat endometrium during the estrous cycle and early gestation was examined by histological, electron microscopic, and histochemical techniques. The results show that numerous macrophages emerge around the nidus shortly after the onset of ovum implantation. Such macrophages, however, were not present within the decidua, suggesting that this tissue may be a protective barrier against the migration of phagocytic cells towards the implants. Approximately 48 hours after the onset of implantation, the number of endometrial macrophages decreased dramatically.


Enhanced performance of ZIF-8 nanocrystals hybrid monolithic composites via an in-situ growth strategy for efficient capillary microextraction of perfluoroalkyl phosphonic acids.
Enrichment of perfluoroalkyl phosphonic acids (PFPAs) is of great significance and challenging for environmental monitoring, due to their toxic and persistent nature, highly fluorinated character as well as low concentration. Herein, novel metal-organic frameworks (MOFs) hybrid monolithic composites were prepared via metal oxide-mediated in situ growth strategy and utilized for capillary microextraction (CME) of PFPAs. A porous pristine monolith was initially obtained by copolymerization of the zinc oxide nanoparticles (ZnO-NPs)-dispersed methacrylic acid (MAA) with ethylenedimethacrylate (EDMA) and dodecafluoroheptyl acrylate (DFA). Afterwards, nanoscale-facilitated transformation of ZnO nanocrystals into the zeolitic imidazolate framework-8 (ZIF-8) nanocrystals was successfully realized via the dissolution-precipitation of the embedded ZnO-NPs in the precursor monolith in the presence of 2-methylimidazole. Experimental and spectroscopic results (SEM, N2 adsorption-desorption, FT-IR, XPS) revealed that the coating of ZIF-8 nanocrystals significantly increased the surface area of the obtained ZIF-8 hybrid monolith and endowed the material abundant surface-localized unsaturated zinc sites. The proposed adsorbent showed highly enhanced extraction performance for PFPAs in CME, which was mainly ascribed to the strong fluorine affinity, Lewis acid/base complexing, anion-exchange, and weakly π-CF interaction. The coupling of CME with LC-MS enables effective and sensitive analysis of ultra-trace PFPAs in environment water and human serum. The coupling method demonstrated low detection limits (2.16-4.12 ng L-1) with satisfactory recoveries (82.0-108.0%) and precision (RSDs ≤6.2%). This work offered a versatile route to design and fabricate selective materials for emerging contaminant enrichment in complicated matrices.


Liver injury diagnosed on computed tomography after use of an automated cardiopulmonary resuscitation device.
We report a case of an 89-year-old female with active extravasation and hemoperitoneum from a liver laceration demonstrated on multidetector computed tomography (CT), attributed to the use of an automated mechanical cardiopulmonary resuscitation (CPR) device. Although iatrogenic internal injuries related to manual CPR and CPR devices have previously been reported [1, 2], there has been no reported CT evidence of liver injury related to automated CPR devices to the authors' knowledge. Imaging findings of complications related to the use of automated CPR devices are important to recognize and also help explain the possible mechanisms of injury. Liver injuries with active bleeding following CPR may have devastating consequences related to hemodynamic instability and may have an increased incidence when CPR is performed using an automated chest compression device.


Estimated financial savings associated with health information exchange and ambulatory care referral.
Data and financial models based on an operational health information exchange suggest that health care delivery costs can be reduced by making clinical data available at the time of care in urban emergency departments. Reductions are the result of decreases in laboratory and radiographic tests, fewer admissions for observation, and lower overall emergency department costs. The likelihood of reducing these costs depends on the extent to which clinicians alter their workflow and take into account information available through the exchange from other institutions prior to initiating a treatment plan. Far greater savings can be realized in theory by identifying individuals presenting to emergency departments whose acute and long-term care needs are more suitably addressed at lower costs in ambulatory settings or medical homes. These alternative ambulatory settings can more effectively address the chronic care needs of those who receive most of their care in emergency departments. To support a shift from emergency room care to clinic care, health care information available through the health information exchange must be made available in both emergency department and ambulatory care settings. If practice workflow and patient behavior can be changed, a more effective and efficient care delivery system will be made possible through the secure exchange of clinical information across regional settings. These projections support the case for the financial viability of regional health information exchanges and motivate participation of hospitals and ambulatory care organizations-particularly in urban settings.


Applicability of Transnasal Echography for Identification of Internal Carotid Artery.
To study the applicability of transnasal echography for the internal carotid artery (ICA) imaging during endoscopic procedures, primarily nasopharyngectomy. Non-randomized controlled cohort. The tip of a pediatric transducer for transesophageal echography was inserted into each nostril under endoscopic control and placed in the ipsilateral Rosenmuller's fossa. The ICA's internal diameter and distance between the nasopharyngeal wall and the artery's closest point were measured on each side. Two independent examiners measured the same parameters on the axial plane of the skull base computer tomography (CT). Agreement between CT and echography measurements was estimated by the Bland-Altman approach. Twenty-seven ICAs (sides) were available for the echography-CT agreement analysis. Inter method agreement for both parameters was similar to the inter examiner agreement for the CT measurements. Our first study on endoscopic echography demonstrated that this method is applicable, potentially allowing safer transnasal surgery in the ICA vicinity. 3 Laryngoscope, 132:1184-1188, 2022.


Prevalence of hospital readmissions and related factors in patients with autoimmune diseases.
Autoimmune diseases generate an impact on the morbidity and mortality of patients and are a burden for the health system through hospital admissions and readmissions. The prevalence of readmission of patients with these diseases has not yet been described as a group, but rather as sub-phenotype. The objective of this study is to determine the prevalence of hospital readmissions in a Colombian population with autoimmunity and the factors related to readmission. All patients with autoimmune diseases who were evaluated by the rheumatology service and hospitalized between August 2018 and December 2019 at the Fundación Hospital Infantil Universitario De San José de Bogotá were described. A bivariate analysis was done, and three multivariate logistic regression models were built with the dependent variable being readmission. Of the total 199 admissions, 131 patients were evaluated and 32% were readmitted. The most frequent sub-phenotype in both groups (readmission and no readmission) was SLE (51% and 59%). The most frequent cause of hospitalization and readmission was disease activity (68.7% and 64.3%). History of hypertension was associated with readmission (adjusted OR: 2.98-95% CI: 1.15-7.72). In a second model adjusted for confounding variables, no factor was associated. In a third model analyzing the history of kidney disease and previous use of immunosuppressants (adjusted for confounding variables), the previous use of immunosuppressants was related to readmission (OR: 2.78-95% CI 1.12-6.89). Up to a third of patients with autoimmunity were readmitted and arterial hypertension was an associated factor. This suggested a greater systemic compromise and accumulated damage in patients who have these two conditions that may favor readmission. A history of immunosuppressant use may play a role in readmission, possibly by increasing the risk of developing infections.


Cryptogenic stroke as a working diagnosis: the need for an early and comprehensive diagnostic work-up.
In the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study, the causes of ischemic stroke were identified in 43% of cryptogenic stroke patients monitored with implantable cardiac monitor (ICM), but one-third of these patients had non-cardioembolic causes. These results suggest the need for an early and comprehensive diagnostic work-up before inserting an ICM.


[Genetics in scleroderma].
Systemic sclerosis or scleroderma (SSc) is an autoimmune pathology with a variable clinical expression grouped within genetically complex diseases, in which environmental and genetical factors combine. Genes of the HLA regions were those first associated with susceptibility to present SSc, mainly the HLA-DRB1⁎11/⁎06/⁎16 allelles. However, through association studies, different candidate genes that belong to the triad of autoimmunity, endothelial disfunction and fibrosis have been proposed as genes implicated in the predisposition to disease. In spite of these initial advances, up until recently most studies have had little statistical power, due to the small number of patients included and the lack of reproduction in independent populations. Recently, the development of genotyping platforms and data analysis has allowed for the application of a new type of strategy known as «genome wide association studies» the analysis of the genetics to complex diseases, which are potent tools in the study of these multifactorial diseases. This paper pretends to perform a review of the recent advances in the study of the genetics of scleroderma, presenting results obtained in the analysis of the main candidate genes outside the HLA regions and the contribution of GWAS to the understanding of the molecular mechanisms of this disease.


The synthesis and natural distribution of the major ketone constituents in Echinacea pallida.
The first synthesis of a series of ketones naturally occurring in E. pallida is described. The natural distribution of these ketones among different Echinacea species is also reported.


Quality of acute ischemic stroke care at a tertiary Hospital in Ghana.
Information on the quality of acute ischemic stroke care provided in lower-to-middle income countries is limited. This study was undertaken to examine the quality of acute ischemic stroke care provided at Tamale Teaching Hospital in Ghana. The medical records of patients admitted into the medical ward of the hospital between January to October 2021 were reviewed retrospectively. Extent of compliance to 15 stroke performance indicators were determined. Under the study period, 105 patients were admitted at the hospital with acute ischemic stroke. The mean (±SD) age was 65 ± 12 years; 38.1% were males; 65.7% had National Health Insurance Scheme coverage. Glasgow Coma Scale was the only functional stroke rating scale used by physicians to rate stroke severity. About a quarter of the patients had CT scan performed within 24 h of admission. Less than a quarter of the patients had a last known well time documented. Rate of thrombolytic administration was 0%. Less than a quarter of the patients were prescribed venous thromboembolism prophylaxis on the day of admission or day after. Only 13.8% of patients had documented reasons for not being prescribed venous thromboembolism prophylaxis. Antiplatelet therapy was prescribed to 33.3% of the patients by the end of day 2 of admission. Anticoagulation was prescribed to all patients who had comorbid condition of atrial fibrillation as part of the discharge medications. More than half of the patients were discharged to go home with statin medications. Documented stroke education was provided to 31.4% caretakers or patients. Slightly less than half of the patients were assessed for or received rehabilitation. Less than a quarter had documented dysphagia screening within 24 h of admission. None of the patient had their stroke severity rated with National Institutes of Health Stroke Scale on arrival. No patient obtained carotid imaging assessment by end of day 2. There were several gaps in the quality of acute ischemic stroke care provided to patients at the Tamale Teaching Hospital. With the exception of discharging patients on statin medications, there was poor adherence to all other stroke performance indicators.


Mentoring experience of new surgeons during their transition to independent practice: A nationwide survey.
New surgeons are faced with inadequate mentoring when first entering practice. Our study examined challenges faced by young surgeons during their transition in practice and their mentoring experience when entering practice. An article-based survey was mailed in August 2019 to general, colorectal, vascular, and cardiothoracic surgeons that became members of the American College of Surgeons within the past 5 years. A total of 853 of 2,915 surveys were completed (29.3% response rate). Both female (38%) and male (62%) surgeons participated. The 3 most common challenges during the transition to practice were confidence building (26.0%), adjusting to a new institutional culture (16.9%), and business and administrative aspects of practice (16.3%). First job attrition rate 44.2%, with the mean duration of the first job being 3.28 ± 0.17 years. Nearly one-third (28.3%) of respondents were not mentored when they first entered practice. The proportion of nonmentored young surgeons leaving their first job (64.3%) was almost twice as that of surgeons who received mentoring (36.3%). Furthermore, the mean duration of the first job was significantly shorter in nonmentored versus mentored surgeons (3.16 ± 0.26 vs 3.76 ± 0.25 years; P < .05). A significant number (43.3%) of respondents reported a desire to be mentored by retired surgeons. Our survey highlights the importance of mentoring for young surgeons during their transition into practice. With many young surgeons being enthusiastic about mentoring by retired surgeons, specific programs are necessary to better use their expertise.


Kynureninase-type enzymes and the evolution of the aerobic tryptophan-to-nicotinamide adenine dinucleotide pathway.
Kynureninase-type (L-kynurenine hydrolase, EC 126.96.36.199) activity has been found to be present in the livers of fish, amphibia, reptiles, and birds. In addition to past information concerning this enzyme activity in mammalian liver, it is now clear that all the major classes of vertebrates carry a highly specialized kynureninase-type enzyme, which we have termed a hydroxykynureninase. To compare the reactivities of these enzymes with L-kynurenine and L-3-hydroxykynurenine, ratios of tau values (Km/V) were used. Based on this comparison, the bacterium Pseudomonas fluorescens carries the most efficient kynureninase, whereas the amphibian Xenopus laevis has the most efficient hydroxykynureniase. In these two cases, the ratio of tau values differs by a factor of 38 000. It is hypothesized that the tryptophan-to-nicotinamide adenine dinucleotide biosynthetic pathway evolved from a catabolic system of enzymes, and that the differences observed in the kynureninase-type enzymes between lower and higher organisms reflect the specialization of the function of these enzymes from a strictly catabolic role to an anabolic one during the course of evolution.


Puerarin attenuates cadmium-induced hepatic lipid metabolism disorder by inhibiting oxidative stress and inflammation in mice.
Cadmium (Cd) is a common environmental pollutant with known toxic effects on the liver. Puerarin (PU), a natural flavonoid, has been shown to exert protective effect in numerous pathological processes. However, whether PU affords protection in Cd-induced liver damage is still equivocal. Therefore, 40 mice were treated with Cd and/or PU by gavage for 9 weeks, then the serum and liver samples were collected to verify this issue. In this study, Cd exposure triggered hepatic lipid metabolism disorders and resultant liver damage as evidenced by Oil Red O staining and total cholesterol (TC) and triglyceride (TG) levels in serum and liver, aspartate transaminase (AST) and alanine transaminase (ALT) levels in serum, and histopathology, which were significantly improved by PU. Moreover, PU also normalized the expression of Cd-disturbed lipid metabolism-related proteins to improve lipid accumulation, contributing to the alleviation of liver injury. Moreover, Cd-decreased antioxidative indices superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) as well as glutathione (GSH) in hepatic tissues were significantly attenuated by PU administration, while Cd-elevated hepatic malondialdehyde (MDA) and reactive oxygen species (ROS) levels were markedly down-regulated by PU treatment, demonstrating the antioxidant effect of PU against Cd exposure. In addition, PU supplementation increased the anti-inflammatory potential, and normalized the levels of proinflammatory cytokines during Cd exposure. In conclusion, these observations demonstrate that PU treatment decreases oxidative stress and inflammation response, which may contribute to prevent Cd-induced lipid metabolism disorder and consequent liver damage.


Role of the physician in environmental medicine.
This article describes the role of the medical history and of laboratory findings in diagnosing diseases caused by environmental chemicals. An understanding of routes of exposure is crucial in appropriate diagnosis and in preventing further harm. A listing of potential sources of information is also included.


Identification of cryptic putative IRESs within the ORF encoding the nonstructural proteins of the human rhinovirus 16 genome.
Internal ribosome entry site (IRES)-dependent translation is a mechanism distinct from 5' cap-dependent translation. IRES elements are located mainly in the 5' untranslated regions (UTRs) of viral and eukaryotic mRNAs. However, IRESs are also found in the coding regions of some viral and eukaryotic genomes to initiate the translation of some functional truncated isoforms. Here, five putative IRES elements of human rhinovirus 16 (HRV16) were identified in the coding region of the nonstructural proteins P2 and P3 through fusion with green fluorescent protein (GFP) expression vectors and bicistronic vectors with a hairpin structure. These five putative IRESs were located at nucleotide positions 4286-4585, 5002-5126, 6245-6394, 6619-6718, and 6629-6778 in the HRV16 genome. The functionality of the five IRESs was confirmed by their ability to initiate GFP expression in vitro. This suggests that an alternative mechanism might be used to increase the efficiency of replication of HRV16.


Surviving the crash: transitioning from effector to memory CD8+ T cell.
One outcome of infection is the formation of long-lived immunological memory, which provides durable protection from symptomatic re-infection. In response to infection or vaccination, T cells undergo dramatic proliferation and differentiate into effector T cells that mediate removal of the pathogen. Following pathogen clearance, the majority of effector cells die, restoring lymphocyte homeostasis. However, a small number of antigen-specific cells survive and seed the memory T cell population. Here, we focus on recent advances in identifying the key proteins and transcription factors that allow a portion of effector CD8(+) T cells to persist after contraction of the immune response, forming a memory cell population programmed for long-term self-renewal and survival. We also examine new findings addressing the role of environmental cues such as cytokines and co-stimulatory molecules in CD8(+) memory T cell formation and how the cell-extrinsic cues influence the molecular players of intracellular pathways important for memory formation.


Cost effectiveness analysis of strategies for child health in developing countries.
To determine the costs and effectiveness of selected child health interventions-namely, case management of pneumonia, oral rehydration therapy, supplementation or fortification of staple foods with vitamin A or zinc, provision of supplementary food with counselling on nutrition, and immunisation against measles. Cost effectiveness analysis. Efficacy data came from published systematic reviews and before and after evaluations of programmes. For resource inputs, quantities came from literature and expert opinion, and prices from the World Health Organization Choosing Interventions that are Cost Effective (WHO-CHOICE) database, Cost effectiveness ratios clustered in three groups, with fortification with zinc or vitamin A as the most cost effective intervention, and provision of supplementary food and counselling on nutrition as the least cost effective. Between these were oral rehydration therapy, case management of pneumonia, vitamin A or zinc supplementation, and measles immunisation. On the grounds of cost effectiveness, micronutrients and measles immunisation should be provided routinely to all children, in addition to oral rehydration therapy and case management of pneumonia for those who are sick. The challenge of malnutrition is not well addressed by existing interventions.


Thyroiditis: current views of pathogenesis.
From indirect and circumstantial evidence it would appear that subacute thyroiditis is probably a viral infection of the thyroid gland. The thyroid may respond in the stereotyped manner to any one of a number of viruses. Despite the available evidence, however, the viral theory has yet to be finally proven. Autoimmunity does not appear to be a primary factor in the initiation of subacute thyroiditis, although transient immunologic responses occur as a secondary phenomenon. Autoimmune thyroiditis, on the other hand, is almost certainly a primary immunologic disease, and likely is due to a specific inherited defect in immunologic control. It would appear that both cell-mediated immunity and humoral immunity (i.e., T and B lymphocytes) are necessary for the full expression of this disorder.


Correction of maxillofacial asymmetry using orthognathic surgical methods.
A total of 20 patients with varying degrees of facial asymmetry were followed clinically and radiographically for at least 18 months after undergoing surgical correction. In 12 of the patients, the cause of asymmetry was hemifacial microsomia of varying severity. Infection of the TMJ in early childhood and irradiation damage were other causes of facial growth disturbance. Bimaxillary osteotomy was carried out in all cases and was often combined with resection of the coronoid process in order to lengthen the ramus. A postoperative jaw exercise programme has proved important as a means of maintaining or increasing mouth-opening capacity. The facial asymmetry cases are not easy to correct and are not always in line with expectations. However, they are an important part of maxillofacial reconstructive surgery.


Disruption of joint arthroplasty services in Europe during the COVID-19 pandemic: an online survey within the European Hip Society (EHS) and the European Knee Associates (EKA).
The aim of the present study was to evaluate the impact of the coronavirus (COVID-19) pandemic on joint arthroplasty service in Europe by conducting an online survey of arthroplasty surgeons. The survey was conducted in the European Hip Society (EHS) and the European Knee Associates (EKA). The survey consisted of 20 questions (single, multiple choice, ranked). Four topics were addressed: (1) origin and surgical experience of the participant (four questions); (2) potential disruption of arthroplasty surgeries (12 questions); (3) influence of the COVID-19 pandemic on the particular arthroplasty surgeon (four questions); (4) a matrix provided 14 different arthroplasty surgeries and the participant was asked to state whether dedicated surgery was stopped, delayed or cancelled. Two-hundred and seventy-two surgeons (217 EHS, 55 EKA) from 40 different countries participated. Of the respondents, 25.7% stated that all surgeries were cancelled in their departments, while 68.4% responded that elective inpatient procedures were no longer being performed. With regard to the specific surgical procedures, nearly all primary TJA were cancelled (92.6%) as well as aseptic revisions (94.7%). In most hospitals, periprosthetic fractures (87.2%), hip arthroplasty for femoral neck fractures and septic revisions for acute infections (75.8%) were still being performed. During the current 2020 COVID-19 pandemic, we are experiencing a near-total shutdown of TJA. A massive cutback was observed for primary TJA and revision TJA, even in massively failed TJA with collapse, dislocation, component failure or imminent dislocation. Only life-threatening pathologies like periprosthetic fractures and acute septic TJA are currently undergoing surgical treatment. V.


Smoking, chewing and drinking in Ban Pong. Northern Thailand.
The unusual pattern of oral cavity and respiratory tract cancers in Chiang Mai Province, Northern Thailand led to this descriptive study of smoking, drinking and chewing in a rural community in Chiang Mai Province. A high proportion of adults were smokers and both males and females had very high estimated lifetime tobacco tar exposures. Variation in additive mixed with tobacco in traditional cigars and differences in smoking may be related to different respiratory cancer patterns in males and females. Manufactured cigarettes were little smoked, and then mainly by young men and those of higher socioeconomic status. Betel nut chewing, found commonly in other parts of S.E. Asia was found only among the old, but chewing of miang, a fermented tea-leaf preparation was common in all age groups, and was generally accompanied by smoking. Drinking of alcoholic beverages was rare and infrequent.


Performance of down-flow hanging sponge (DHS) reactor coupled with up-flow anaerobic sludge blanket (UASB) reactor for treatment of onion dehydration wastewater.
In this study, a promising system consisting of up-flow anaerobic sludge blanket (UASB) reactor followed by down-flow hanging sponge (DHS) reactor was investigated for onion dehydration wastewater treatment. Laboratory experiments were conducted at two different phases, i.e., phase (1) at overall hydraulic retention time (HRT) of 11h (UASB reactor: 6h and DHS reactor: 5h) and phase (2) at overall HRT of 9.4h (UASB reactor: 5.2h and DHS reactor: 4.2h). Long-term operation results of the proposed system showed that its overall TCOD, TBOD, TSS, TKN and NH(4)-N removal efficiencies were 92 ± 5, 95 ± 2, 95 ± 2, 72 ± 6 and 99 ± 1.3%, respectively (phase 1). Corresponding values for the 2nd phase were 85.4 ± 5, 86 ± 3, 87 ± 6, 65 ± 8 and 95 ± 2.8%. Based on the available results, the proposed system could be more viable option for treatment of wastewater generated from onion dehydration industry in regions with tropical or sub-tropical climates and with stringent discharge standards.


[The Biomechanics Influence of unilateral laminectomy and discectomy surgery on the adjacent different grades of Disc Degeneration].
To study the stress distribution of the adjacent different grades of disc degeneration underwenting unilateral laminectomy and discectomy surgery using non-linear finite element analysis. Based on the lumbar CT scans, the finite element model (FEM) of lumbar spinal segment (L3-L5) was established. According to L3-L4 intervertebral disc degeneration, different grades of disc degeneration (healthy, mild, moderate and severe) models were established and unilateral laminectomy and discectomy surgery were also established. Physiological action such as flexion, extension, lateral bending and lateral rotation was simulated and the von Mises stress in the nucleus pulposus and annulus fibrosus matrix of L3-L4 disc was investigated. After unilateral laminectomy and discectomy surgery, the extremum value of von Mises stress of nucleus pulposus and annulus fibrosus matrix was maximum during extension and minimus left bending in the healthy intervertebral disc. Compared with healthy disc, the increment of extremum value was found during left bending in the mildly degenerated disc. When the value decreased in the moderately degenerated disc, but still higher than that in the healthy disc. When the adjacent disc is severely degenerated, the extremum value of nucleus pulposus decreased, in addition to axial rotation, and even lower than that of healthy disc. The value of annulus matrix decreased and still higher than that of healthy disc, especially during left bending. After unilateral laminectomy and discectomy surgery, avoiding lateral bending will reduce the abnormal stress in the degenerated disc and decreased the risk of accelerating disc degeneration.


Gastrointestinal Stromal Tumor Masquerading as a Spontaneous Rectal Hematoma.
A 78-year-old Caucasian male with a history of atrial fibrillation and anticoagulation with warfarin presented with a change in bowel habits and weight loss. A computed tomography (CT) scan showed a 3.5 cm rectal mass. After biopsy with colonoscopy and endoscopic ultrasonography, the rectal mass was highly suspicious for rectal hematoma. When the rectal mass did not resolve after 1 month of follow-up, surgery showed the patient to have a rectal gastrointestinal stromal tumor. He is being treated with imatinib and follow-up CT scans. This case illustrates the importance of a high level of suspicion for a gastrointestinal stromal tumor when a rectal mass is found.


99mTc-pyrophosphate bone scans in patients with metastatic carcinoid tumors.
Three patients with foregut (bronchial), hindgut (rectal) or (ovarian) carcinoid tumors had symptomatic bone metastasis with abnormal 99m Tc pyrophosphate bone scans and bone roentgenograms. Six patients with midgut (small intestine or caecal) carcinoid) carcinoid tumors who had no symptoms of bone metastasis had no evidence of bone metastasis on bone scan or bone roentgenographic examination. This study supports the clinical impression that patients with midget carcinoid tumors have a low incidence of bone metastasis.


Median and ulnar nerve conduction in pregnancy.
A prospective, observational study assessed median and ulnar nerve conduction during pregnancy, to identify the optimum test for differentiating physiological effects of pregnancy from pathological carpal tunnel syndrome (CTS). Pregnant women (n=18) and age- and parity-matched non-pregnant controls (n=13) were recruited. Symptomatic and neurophysiological evaluations were performed. Median and ulnar nerve latencies and intrapalmar latency (difference between median and ulnar nerve latencies) were computed. Median nerve distal latency is more prolonged in pregnant women compared with non-pregnant controls. Median nerve latency is more prolonged in pregnant women with symptoms of CTS than in asymptomatic women. The difference between median and ulnar nerve conduction (normal <0.2 ms) discriminates well between symptomatic and asymptomatic pregnant women. Intrapalmar latency is proposed as a useful diagnostic test for classification of carpal tunnel syndrome during pregnancy.


Role of intracellular pH in proliferation, transformation, and apoptosis.
Both cellular proliferation and apoptosis (programmed cell death) have been claimed to be modulated, perhaps even triggered by, changes in intracellular pH. In this review, we summarize the evidence that gave rise to these hypotheses. To facilitate a critical appraisal of the existing data, we briefly review the main pathways involved in cytosolic pH homeostasis and their regulation by mitogens and by apoptosis-inducing agents. The information available at present suggests that cytosolic pH plays a permissive role in cellular growth and proliferation, but is neither a trigger nor an essential step in the mitogenic signal transduction cascade. Concerning apoptosis, it is clear that lowering the pH in vitro can activate DNase II. However, the evidence linking cytosolic acidification with DNA degradation in vivo is presently not convincing. We conclude that the cytosolic pH, an essential physiological parameter that is tightly controlled by multiple, complementary, or redundant systems, is unlikely to play a role in signalling either cell growth or death.


Influence of cadmium ions on endothelin-1 binding and calcium signaling in rat glioma C6 cells.
Cadmium ions did not influence the binding of endothelin-1 (ET-1) to its receptor on the surface of rat glioma C6 and rat aorta A10 cells. This was studied (a) by the binding of 1251-ET-1 to intact cells in the absence or presence of cadmium (Cd2+) and (b) by analysis of the receptor/ET-1 complex after crosslinking with disuccinimidyl suberate (DSS) or ethylene glycol-bis-(succinimidyl succinate) (EGS) on SDS PAGE. Using Fura-2 and Quin-2 loaded C6 rat glioma cells, it was shown that Cd2+ ions strongly interfered with the ET-1 induced Ca(2+)-influx in C6 glioma cells (IC50 approximately 10 microM).


Homocysteine and pregnancy.
Homocysteine is an amino acid that is involved in several key metabolic processes, including the methylation and sulphuration pathways. Blood concentrations of homocysteine are determined by various dietary factors, including folic acid and vitamin B(12), by alteration in physiology, such as renal impairment, and by variation in the activity of enzymes in the various pathways as a result of genetic polymorphisms, some of which are commonly found in the population. Hyperhomocysteinaemia has been associated with vascular disease, although whether it is cause or effect is still a matter of debate. In normal pregnancy, homocysteine concentrations fall. Disturbance of maternal and fetal homocysteine metabolism has been associated with fetal neural tube defects, with various conditions characterized by placental vasculopathy, such as pre-eclampsia and abruption, and with recurrent pregnancy loss. Apart from folate supplementation, which has been clearly shown to halve the risk of fetal neural tube defects, no other strategies have been identified in relation to homocysteine metabolism that will reliably reduce the frequency of these other common obstetric pathologies.


Cytofluorometric quantification of the activity and reaction kinetics of acid phosphatase.
This paper describes how fluorogenic substrates derived from naphthol AS can be used for the microscopic demonstration and cytofluorometric quantification of the activity and reaction kinetics of acid phosphatase in single living cells. A special study has been made of acid naphthol AS-BI phosphatase. However, the method can be extended to other hydrolytic enzymes. The method is sensitive and accurate because: quantification of very low enzyme activity is possible; the reaction kinetics can be evaluated with a good degree of precision inasmuch as the initial reaction velocity is derived over short times; there is an absence of distributional error; and the errors due to extra-cellular diffusion of the hydrolysed substrate, to photodecomposition, and to autofluorescence can be contained within very narrow limits. The procedures for determining enzyme activity and reaction kinetics, and the instrumental characteristics and devices required for carrying out these measurements, are described. Some possible applications are indicated.


Analysis of FCGR3A-p.176Val variants in women with recurrent pregnancy loss and the association with CD16a expression and anti-HLA antibody status.
Natural Killer (NK) cells have been implicated in recurrent pregnancy loss (RPL). The p.Val176Phe (or Val158Phe) Single Nucleotide Polymorphism (SNP) in the FCGR3A gene encoding the FcγRIIIA or CD16a receptor has been associated with an enhanced affinity for IgG and stronger NK-mediated antibody-dependent cellular cytotoxicity. We hypothesized that the presence of at least one p.176Val variant associates with RPL and increased CD16a expression and alloantibodies e.g., against paternal human leukocyte antigen (HLA). In 50 women with RPL, we studied frequencies of the p.Val176Phe FCGR3A polymorphisms. Additionally, CD16a expression and anti-HLA antibody status were analyzed by flowcytometry and Luminex Single Antigens. In woman with RPL, frequencies were: 20% (VV), 42% (VF) and 38% (FF). This was comparable to frequencies from the European population in the NCBI SNP database and in an independent Dutch cohort of healthy women. NK cells from RPL women with a VV (22,575 [18731-24607]) and VF (24,294 [20157-26637]) polymorphism showed a higher expression of the CD16a receptor than NK cells from RPL women with FF (17,367 [13257-19730]). No difference in frequencies of the FCGR3A-p.176 SNP were detected when comparing women with or without class I and class II anti-HLA antibodies. Our study does not provide strong evidence for an association between the p.Val176Phe FCGR3A SNP and RPL.


Characterization of Bacillus subtilis uracil-DNA glycosylase and its inhibition by phage φ29 protein p56.
Uracil-DNA glycosylase (UDG) is a conserved DNA repair enzyme involved in uracil excision from DNA. Here, we report the biochemical characterization of UDG encoded by Bacillus subtilis, a model low G+C Gram-positive organism. The purified enzyme removes uracil preferentially from single-stranded DNA over double-stranded DNA, exhibiting higher preference for U:G than U:A mismatches. Furthermore, we have identified key amino acids necessary for B. subtilis UDG activity. Our results showed that Asp-65 and His-187 are catalytic residues involved in glycosidic bond cleavage, whereas Phe-78 would participate in DNA recognition. Recently, it has been reported that B. subtilis phage φ29 encodes an inhibitor of the UDG enzyme, named protein p56, whose role has been proposed to ensure an efficient viral DNA replication, preventing the deleterious effect caused by UDG when it eliminates uracils present in the φ29 genome. In this work, we also show that a φ29-related phage, GA-1, encodes a p56-like protein with UDG inhibition activity. In addition, mutagenesis analysis revealed that residue Phe-191 of B. subtilis UDG is critical for the interaction with φ29 and GA-1 p56 proteins, suggesting that both proteins have similar mechanism of inhibition.


Monograph series on aging-related diseases: VIII. Non-insulin-dependent diabetes mellitus (NIDDM)
Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia and by disturbances of carbohydrate, fat and protein metabolism. Diabetes mellitus is associated with absolute or relative deficiency in the secretion and/or action of the hormone insulin.


Design of bivalent ligands using hydrogen bond linkers: synthesis and evaluation of inhibitors for human beta-tryptase.
We exploit the concept of using hydrogen bonds to link multiple ligands for maintaining simultaneous interactions with polyvalent binding sites. This approach is demonstrated by the syntheses and evaluation of pseudo-bivalent ligands as potent inhibitors of human beta-tryptase.


Impella5.0 "ILIPELLA" Approach for a Fulminant Myocarditis Patient With a Small Peripheral Artery.
Cardiogenic shock with fulminant myocarditis is a life-threatening diagnosis. Extracorporeal membrane oxygenation (ECMO) with an Impella for left ventricle unloading is often required to maintain the haemodynamics. However, the small peripheral vascularity in small-bodied patients interrupts the upgrade from ECMO to Impella5.0, which usually requires grafting to a femoral artery or subclavian artery of at least 7 mm in size. This report outlines the external iliac artery approach, named the "ILIPELLA" technique, which uses a reconstructed external iliac artery to introduce Impella5.0 in patients with small peripheral vascularity.


Effects of a Mind Map-Based Life Review Program on Anxiety and Depressive Symptoms on Cancer Patients Undergoing Chemotherapy: A Randomized Controlled Trial.
Cancer patients undergoing chemotherapy often experience psychological distress. The mind map-based life review program (MBLRP) offers the potential to reduce patients' negative emotions. However, its effects remain unknown. The objective of this study is to determine the effects of the MBLRP on anxiety and depressive symptoms in cancer patients undergoing chemotherapy. A randomized controlled trial with repeated measures was adopted. Eighty-four cancer patients undergoing chemotherapy were recruited from a general hospital in Fujian, China. Participants were randomly assigned to an experimental group (n = 40) or a control group (n = 44). The participants in the experimental group received the MBLRP plus routine care. The participants in the control group received routine care. Outcomes were measured at baseline, on the second day, and at 4 weeks after the MBLRP. In terms of anxiety, multivariate test statistics showed significant differences in within-group (F = 11.343, P < .001), between-group (F = 8.873, P = .004), and interaction effects (group × time) (F = 19.595, P < .001). For the depressive symptoms, the results showed that the within-group effect (F = 12.385, P < .001), group effect (F = 18.000, P < .001), and group × time effect (F = 26.544, P < .001) were statistically significant, favoring the MBLRP experimental group. The MBLRP has the potential to reduce anxiety and depressive symptoms in cancer patients undergoing chemotherapy. Further research is needed within larger more representative samples. The MBLRP is a nurse-led, nonpharmacological program that could be recommended for cancer patients undergoing chemotherapy and integrated into clinical practice.


Protein Ubiquitination Research in Oncology.
Ubiquitination is a vital posttranslational protein modification involved in the regulation of many eukaryotic signalling pathways. Aberrant ubiquitin signalling is known to be a molecular causality of certain cancer, neurodegenerative, immune system or cardiovascular diseases. The recent development of mass spectrometry methods enables qualitative and quantitative ubiquitination analysis in biological material from cancer patients. Research of ubiquitination may clarify the molecular cause of aberrant changes in the protein level of tumour suppressors or oncogenes. We aim to explain the meaning and importance of ubiquitination in certain molecular processes taking place in the human body. We hereby emphasise the connection between ubiquitination and malignant processes. A literature search is followed by introducing our mass spectrometry platform intended for ubiquitin identification via diglycyl remnants in the CHIP protein sequence. The aim is to introduce tandem mass spectrometry identification of ubiquitin modification, ubiquitination tandem mass spectra validation and the time-dependent manner of CHIP ubiquitination to the reader. A literature search familiarises the reader with known mechanisms of aberrant ubiquitination in malignant diseases. A successfully optimised mass spectrometry platform could serve as a potent tool for determining ubiquitin position in proteins that are a part of real tumour samples.


Prophylactic Medications Taken by Healthcare Workers for COVID-19; A Mixed Methods Study from South India.
COVID-19 is an unprecedented pandemic that has taken the modern world under seize. In spite of lack of solid evidence, certain federal governments had recommended the use of hydroxychloroquine (HCQ), chloroquine, and azithromycin as prophylactic medications either for contacts or for healthcare providers in particular. The objective of this study is to assess the issues related to intake of prophylactic medications in view of COVID-19 and the proportion and pattern of side effects. A descriptive cross-sectional study was conducted using mixed methods approach among healthcare workers in Puducherry, India. HCQ was the prophylactic drug taken by all the participants (n = 26). Of the 26, 15.4% had a baseline ECG, 26.9% took HCQ based on the recommended Day 1 dose of 800 mg and 61.5% of the participants had the drug provided by the hospital where they work. Reasons for taking prophylaxis were sense of vulnerability (due to co-morbidities, lack of PPE kits) and peer practice. However, the participants did not recommend prophylactic medication to others due to lack of evidence, death claims related to prophylactic drugs in media, hospitals not taking responsibility of baseline monitoring and need for long follow-up. The data on assessment of HCQ prophylaxis indicates only minor side-effects, though limited by sample size. Evidence-based recommendations on prophylactic drugs for COVID-19, effective risk communication, peer education and support, accountability, ease of baseline, and follow-up investigations were the need of the hour to improve intake and adherence to prophylactic regime for COVID-19.


Oxygen delivery and consumption in patients with hyperdynamic septic shock.
We analyzed the relationship of increases in oxygen delivery to changes in oxygen consumption in ten patients with hyperdynamic septic shock. Increases in oxygen delivery from 413 +/- 14 (SEM) to 535 +/- 19 ml/min X m2 (p less than .01) were associated with increases in oxygen consumption from 136 +/- 10 to 161 +/- 5 ml/min X m2 (p less than .05). Arterial lactate decreased from 4.6 +/- 1.6 to 2.1 +/- 0.3 mmol/L (p less than .05). These observations suggest that oxygen utilization is perfusion-limited in hyperdynamic septic shock.


Aquatic pollution caused by mercury, lead, and cadmium affects cell growth and pigment content of marine microalga, Nannochloropsis oculata.
The present study investigated the acute (72 h) and sub-acute (14 days) toxicity of mercury, lead, and cadmium to the green microalga, Nannochloropsis oculata. The acute toxicity testing was conducted according to the modified OECD guideline (No. 201). The 72-h IC50 values of Hg, Pb, and Cd exposed to N. oculata were 0.87, 1.81, and 4.97 mg/L, respectively. These results showed that mercury is about twice as toxic as lead and about 5.7 times more toxic than cadmium to this marine microalga. Lead is about 2.7 times more toxic than cadmium. The chlorophyll a content of the microalga decreased in the 10th and 14th days of the sub-acute toxicity test. Although the carotenoid content increased following exposure to the low levels of tested heavy metals (which may show the protective role of carotenoids against oxidative stress), with increased exposure time the total carotenoid reduced compared to control. A regular monitoring program to examine the level of metals in the aquatic ecosystem for protecting microalgae should be implemented.


IL-27 and IL-27-producing CD4+ T cells in human tuberculous pleural effusion.
The objective of the present study was to figure out whether human IL-27-producing CD4(+) T cells represent a distinct T cell subset in tuberculosis pleural effusion (TPE). Distribution, phenotypic features of IL-27-producing CD4(+) T cells in TPE were determined. The required transcription factors and signal transductions for IL-27-producing CD4(+) T cell differentiation were explored. The immune regulation of IL-27 on pleural mesothelial cells was observed. We have determined the presence of a subset of human Th cells that infiltrated into tuberculous pleural effusion, which was characterized by the secretion of IL-27, and somehow IFN-γ, but not of IL-4, IL-9, IL-17, or IL-22. These IL-27-producing CD4(+) T cells were effector memory cells and exhibited a transcription profile clearly separated from those of Th2, Th17, Th9, and Th22 cells. The in vitro experiments showed that IL-1β, IL-2 and IL-12, or their various combinations could promote IL-27(+)CD4(+) T cell differentiation from naive CD4(+) T cells by means of phosphorylation of STAT3, STAT4, or/and STAT5. Transcription factors c-Fos and T-bet were required for IL-27(+)CD4(+) T cell differentiation. By activating STAT3 signaling, IL-27 not only restored a clear epithelial phenotype of pleural mesothelial cells, but also further reversed IFN-γ-induced epithelial-mesenchymal transition of pleural mesothelial cells. These data suggested that human IL-27(+)CD4(+) T cells might represent a distinct human T cell subset with unique expression profiles of transcription factors and proinflammatory cytokines, and these IL-27(+)CD4(+) T cells may play important roles in tuberculosis immunity by affecting pleural mesothelial cells.


A novel risk score for predicting 6-months mortality at the time of hospital discharge in patients admitted with acute coronary syndrome.
In patients with ACS, risk assessment at hospital discharge has not received much consideration in prior risk scoring systems. Hence, there is a need for a reliable and simple tool to identify patients with high mortality risk at discharge form the hospital. In a 1-year observational, prospective study, 1012 patients admitted with ACS were followed up for 6 months after discharge. From 26 potential variables, a new risk score to predict 6-month mortality was developed. A multi-variant Cox regression analysis with forward stepwise variable selection was performed and 10 highly significant independent predictors of 6-month mortality were identified. These include previous history of ACS, higher Killip class at admission, NYHA class at discharge, recurrent ischemia during hospital stay, heart failure, requiring ionotropic supports, requiring hemodialysis, presence of arrhythmia, left ventricular dysfunction detected on echocardiography and elevated admission blood glucose levels. Points were given to each variable and a total score was calculated. A risk score of 0-4 (low risk) predicted a mortality of 3.7%,a risk score of 5-15 (Intermediate risk) predicted a mortality of 16.4% and a risk score of 11-15 predicted a mortality of 32.0% over a 6-month period. The new risk score was noninferior to GRACE risk score in its predictive accuracy of 6-month mortality in the same cohort of patients (p < 0.05). The risk score developed in our study can be easily calculated at the bedside and is aimed at identifying high risk patients who require more intense follow up after discharge.


Ginsenoside Rb1 and Rb2 upregulate Akt/mTOR signaling-mediated muscular hypertrophy and myoblast differentiation.
As a process of aging, skeletal muscle mass and function gradually decrease. It is reported that ginsenoside Rb1 and Rb2 play a role as AMP-activated protein kinase activator, resulting in regulating glucose homeostasis, and Rb1 reduces oxidative stress in aged skeletal muscles through activating the phosphatidylinositol 3-kinase/Akt/Nrf2 pathway. We examined the effects of Rb1 and Rb2 on differentiation of the muscle stem cells and myotube formation. C2C12 myoblasts treated with Rb1 and/or Rb2 were differentiated and induced to myotube formation, followed by immunoblotting for myogenic marker proteins, such as myosin heavy chain, MyoD, and myogenin, or immunostaining for myosin heavy chain or immunoprecipitation analysis for heterodimerization of MyoD/E-proteins. Rb1 and Rb2 enhanced myoblast differentiation through accelerating MyoD/E-protein heterodimerization and increased myotube hypertrophy, accompanied by activation of Akt/mammalian target of rapamycin signaling. In addition, Rb1 and Rb2 induced the MyoD-mediated transdifferentiation of the rhabdomyosarcoma cells into myoblasts. Furthermore, co-treatment with Rb1 and Rb2 had synergistically enhanced myoblast differentiation through Akt activation. Rb1 and Rb2 upregulate myotube growth and myogenic differentiation through activating Akt/mammalian target of rapamycin signaling and inducing myogenic conversion of fibroblasts. Thus, our first finding indicates that Rb1 and Rb2 have strong potential as a helpful remedy to prevent and treat muscle atrophy, such as age-related muscular dystrophy.


Clinical use of the partial saturation and saturation recovery sequences in MR imaging.
The partial saturation (PS) (90 degree-data collection) and saturation recovery (SR) [(90 degree-dephase)n-90 degree-data collection] sequences are described. The early data collection of the PS sequence is of value in demonstrating tissues with a short T2 such as articular cartilage and the annulus fibrosus. The PS sequence also highlights flow and this may provide specific information in vascular lesions. Appropriate choice of echo time enables chemical shift effects to be seen in normal tissues such as breast and bone marrow as well as a variety of diseases such as bone marrow infiltration, pancreatitis, and fatty infiltration of the liver in which there is mixed lipid and water. The SR sequence can be used to control flow effects as well as to calculate values of T1. Although PS and SR sequences display less T1 and T2 dependent contrast than conventional highly T1 and T2 dependent inversion recovery and spin echo sequences, they may still be of clinical value when the mechanism of contrast formation is change in proton density, chemical shift effects, flow effects, or detection of short T2 tissue components.


[Effects of Bruton's tyrosine kinase on the proliferation and differentiation of osteoclasts].
To observe the effect of Bruton's tyrosine kinase (BTK) on the proliferation and differentiation of osteoclasts and to explore the mechanism of BTK on bone destruction in periapical periodontitis. After RAW264.7 cells induced with 100 ng·L⁻¹ receptor activator for nuclear factor-κB ligand (RANKL) for 5 days, osteoclast induction was confirmed by light microscopy, tartrate-resistant acid phosphatase (TRAP) staining, and quantitative real-time PCR (RT-qPCR). Then, BTK-small interfering RNA (BTK-siRNA) was transfected into cells induced for 5 days. After 24 h, the expression of TRAP mRNA was measured using RT-qPCR, and the proliferation and differentiation of osteoclasts were detected using CCK-8 and TRAP activity assay. Statistical analysis was performed. After RAW264.7 was induced with RANKL for 5 days, a large number of round, ellipse, irregularly protuberant, and TRAP-positive macrophages were observed under light microscopy. The expression of TRAP mRNA significantly reduced after 24 h of BTK-siRNA transfection (P<0.05). The detection of CCK-8 and TRAP activities showed that the proliferation and differentiation of osteoclasts significantly decreased (P<0.05). Silencing of BTK can inhibit the proliferation and differentiation of osteoclasts. BTK can be used as a new target for the inhibition of osteoclasts.


Pattern of labeling of rabbit cerebral cortex soluble proteins 24 hours after a single electroconvulsive shock.
The labeling of proteins in the particulate subcellular fractions and in the cell sap was studied in the cerebral cortex of rabbits 24 hours after a single electroconvulsive shock (ECS). To this end the animals were injected with [3H]valine subarachnoidally and sacrificed 30 minutes later. The incorporation of the labeled amino acid into proteins was slightly increased in all subcellular fractions but the increase was significant only for soluble proteins. Referring to the type of soluble polypeptides found in the cortex at this post ECS phase, no modification was found in the SDS electrophoresis pattern of steady state proteins. The fractionation pattern of labeled soluble proteins showed in one third (3 out of 9) of the experiments a remarkable stimulation of the synthesis of two polypeptides (25,000 and 54,000 Dalton MW), which were not labeled in the controls.


The role of 11C-methionine PET in patients with negative diffusion-weighted magnetic resonance imaging: correlation with histology and molecular biomarkers in operated gliomas.
To compare 11C-methionine (11C-METH) PET with diffusion-weighted MRI (DWI-MRI) diagnostic accuracy and prognostic value in patients with glioma candidate to neurosurgery. We collected and analyzed data from 124 consecutive patients (n = 124) investigated during preoperative work-up. Both visual and semiquantitative parameters were utilized for image analysis. The reference standard was based on histopathology. The median follow-up was 14.3 months. Overall, 47 high-grade gliomas (HGG) and 77 low-grade gliomas (LGG) were diagnosed. On visual assessment, sensitivity and specificity for differentiating HGG from LGG were 80.8 and 59.7% for DWI-MRI, versus 95.7 and 41.5% for 11C-METH PET, respectively. On semiquantitative analysis, the sensitivity, specificity, and area under the curve were 78.7, 71.4, and 80.4% for SUVmax, 78.7, 70.1, and 81.1% for SUVratio, and 74.5, 61, and 76.7% for MTB (metabolic tumor burden), respectively. In patients with negative DWI-MRI and IDH-wild type, SUVmax and SUVratio were higher compared to IDH-mutated (P = 0.025 and P = 0.01, respectively). In LGG, patients with 1p/19q codeletion showed higher SUVmax (P = 0.044). In all patients with negative DWI-MRI, median PFS was longer for SUVmax <3.9 (median not reached vs 34.2 months, P = 0.004), SUVratio <2.3 (median not reached vs 21.5 months, P < 0.001), and MTB <3.1 (median not reached vs 45.7 months, P = 0.05). In LGG patients with negative DWI-MRI, only SUVratio <2.3 and MTB <3.1 were associated with longer PFS (P = 0.016 and P = 0.024, respectively). C-METH PET was found highly sensitive for glioma differentiation and molecular characterization. In DWI-negative patients, PET parameters correlated with molecular profile were associated with clinical outcome.


Triacylglycerol hydrolysis by cells isolated from lactating rat mammary gland.
The hydrolysis of exogenous trioleoylglycerol emulsions by suspensions of cells prepared from lactating rat mammary gland has been investigated. Cell integrity remains high throughout short (at least 30 min) incubations, during which extracellular hydrolysis of trioleoylglycerol proceeds at a mean rate (11 preparations) of 1.9 nmol oleate (and 0.6 nmol glycerol) released/min per mg protein. This hydrolysis shows partial dependence upon added serum and partial inhibition by protamine sulphate - both characteristic properties of lipoprotein lipase-catalyzed lipolysis. One of more monoacylglycerol hydrolase enzymes may also contribute to the measured lipolysis. Evidence is presented consistent with the hypothesis that a surface-located lipoprotein lipase is responsible for the observed lipolysis. Very little lipoprotein lipase activity is released from the cell surface by heparin. During trioleoylglycerol hydrolysis, non-esterified oleate does not accumulate in the cells or in the medium in quantities stoicheiometric with glycerol release. Analyses indicate that it passes into the cells without prior equilibration with the extracellular oleate pool(s). Once inside the cells, oleate is rapidly re-esterified into the triacylglycerol fraction. The possible relevance of these findings to the physiological mechanism of fatty acid uptake from triacylglycerol at the capillary endothelium is discussed.


Histamine and TNF-alpha release by rat peritoneal mast cells stimulated with Trichomonas vaginalis.
Mast cells have been reported to be predominant in the vaginal smears of patients infected with T. vaginalis. In this study, we investigated whether T. vaginalis could induce mast cells to migrate and to produce TNF-alpha and histamine. Rat peritoneal mast cells (RPMC), a primary mast cell, were used for the study. T. vaginalis induced an increase in chemotactic migration of the mast cells toward excretory and secretory product (ESP) of T. vaginalis, and the mast cells activated with T. vaginalis showed an increased release of histamine and TNF-alpha. Therefore, mast cells may be involved in the inflammatory response caused by T. vaginalis.


Prediction of residual trophoblastic tissue in first-trimester abortions and low levels of human chorionic gonadotropin beta-subunit.
The clinical data and the histologic report of curettage specimens of 174 patients with first-trimester abortion and human chorionic gonadotropin beta-subunit less than 500 mIU/ml were reviewed. In only 22 (12.6%) were chorionic villi histologically reported. A multivariate analysis showed that increased log human chorionic gonadotropin beta-subunit levels within the range of 20 to 500 mIU/ml, intrauterine tissue demonstrated by ultrasonography, higher gestational age, and active bleeding were significant predictive variables for the presence of villi in curettage specimens. A mathematical formula and a clinical scoring system for the prediction of residual villi in these cases were devised and were applied to the data of our study group. The sensitivity, false-negative rate, and specificity of the scoring system were 90.9%, 2.2%, and 59.2%, respectively; however, the false-positive rate was 75.6%. By use of this scoring system in patients with first-trimester abortion and low human chorionic gonadotropin beta-subunit level, the presence of villi in curettage specimens can thus be predicted with a high sensitivity and as many as 60% of curettage procedures might be prevented.


The effect of nutrition education based on PRECEDE model on iron deficiency anemia among female students.
Iron deficiency anemia disrupts the concentration of adolescent girls; reduces their academic achievement, productivity, and physical strength, and increases the risk of infection. This research aim was to evaluate the effectiveness of the PRECEDE model nutrition education on iron deficiency anemia among female students of Fasa City, Fars Province, Iran. This quasi-experimental study was done on 160 students (80 experimental and 80 control groups) who were selected using a random sampling method in Fasa City, Fars Province, Iran, in 2018-2019. The educational intervention included six sessions based PRECEDE model for 45 or 50 min. A scale of this study consisted of two parts; demographic information, and PRECEDE constructs were used to determine the nutritional behaviors status concluding preventing iron deficiency anemia and hemoglobin, hematocrit, and ferritin blood level in two (before and 4 months after intervention) times. In the experimental group of the students the mean age was 13.85 + 1.72 years and in the controlled group was 13.60 + 1.81 years. Moreover, there was no significant difference in the PRECEDE constructs, and nutritional behaviors preventing iron deficiency anemia before the intervention in two groups of study. However, the experimental group showed a significant increase 4 months after the intervention. Also, there was no significant difference in the mean score of hemoglobin, hematocrit, and ferritin blood level between the two groups before the intervention. However, in ferritin level, a significant increase was shown in 4 months after the intervention in the experiential group. Based on results, the nutrition intervention education base on PRECEDE model has a positive effect to improve iron deficiency anemia preventive behaviors in female students.


Thermodynamic Solubility Profile of Temozolomide in Different Commonly Used Pharmaceutical Solvents.
The solubility parameters, and solution thermodynamics of temozolomide (TMZ) in 10 frequently used solvents were examined at five different temperatures. The maximum mole fraction solubility of TMZ was ascertained in dimethyl sulfoxide (1.35 × 10-2), followed by that in polyethylene glycol-400 (3.32 × 10-3) > Transcutol® (2.89 × 10-3) > ethylene glycol (1.64 × 10-3) > propylene glycol (1.47 × 10-3) > H2O (7.70 × 10-4) > ethyl acetate (5.44 × 10-4) > ethanol (1.80 × 10-4) > isopropyl alcohol (1.32 × 10-4) > 1-butanol (1.07 × 10-4) at 323.2 K. An analogous pattern was also observed for the other investigated temperatures. The quantitated TMZ solubility values were regressed using Apelblat and Van't Hoff models and showed overall deviances of 0.96% and 1.33%, respectively. Apparent thermodynamic analysis indicated endothermic, spontaneous, and entropy-driven dissolution of TMZ in all solvents. TMZ solubility data may help to formulate dosage forms, recrystallize, purify, and extract/separate TMZ.


HLA class II typing using oligonucleotide probes.
A DQ beta locus-specific oligonucleotide probe is used to identify DQ beta alleles present in six insulin-dependent diabetes mellitus (IDDM) multiplex families. Results of genotyping using this technique agree with those from cDNA probes and are often clearer. Allele-specific oligonucleotide probes for the DR beta locus are used to identify subtypes (Dw4 and Dw14) of the DR4 specificity in five IDDM multiplex families. This distinction cannot be made with available cDNA probes.


Contrasting pathogenesis of atopic dermatitis and psoriasis--part II: immune cell subsets and therapeutic concepts.
Atopic dermatitis (AD) and psoriasis are among the most common inflammatory skin diseases. In the first part of this 2-part review, we discussed the similarities and differences between AD and psoriasis with respect to clinical features and pathology. The diseases are characterized by infiltration of skin lesions by large numbers of inflammatory cells; the second part of this review focuses on immune cell subsets that distinguish each disease and the therapeutic strategies that might be used or developed based on this information. We discuss the interactions among different populations of immune cells that ultimately create the complex inflammatory phenotype of AD and compare these with psoriasis. Therapeutic strategies have been developed for psoriasis based on the cytokine network that promotes inflammation in this disease. Antibodies against IL-12 and IL-23p40 antibody and antagonists of TNF are used to treat patients with psoriasis, and studies are underway to test specific antagonists of IL-23, IL-17, IL-17 receptor, IL-20, and IL-22. We discuss how these therapeutic approaches might be applied to AD.


Osteoarticular sporotrichosis in an immunocompetent patient.
Sporotrichosis is a frequent subcutaneous mycosis in Madagascar. Extracutaenous forms are exceptional and are usually seen in immunosuppressed hosts. We report a case of an aggressive clinical evolution of lymphocutaneous sporotrichosis with osteoarticular involvement in an immunocompetent patient. Therapy with oral itraconazole 200 mg twice daily for 12 months improved the lesion. Early diagnosis of Sporothrix schenkii infection is critical to prevent complications including osteoarticular involvement, disseminated forms and death.


Does democracy make taller men? Cross-country European evidence.
We study whether a democracy improves a measure of individual wellbeing: human heights. Drawing on individual-level datasets, we test the democracy and height hypothesis using a battery of eight different measures of democracy and we account for several potential confounders, regional and cohort fixed effects. We document that democracy - or its quality during early childhood - shows a strong and positive conditional correlation with male, but not female, adult stature. Our preferred estimates suggest that being born in a democracy increases average male stature from a minimum of 1.33 to a maximum of 2.4 cm. We also show a positive association when democracy increases from childhood to adolescence, and when we adopt measures of existing democratic capital before birth, and at the end of height plasticity in early adulthood. We also document that democracy is associated with a reduction in inequality of heights distribution. Our estimates are driven by period-specific heterogeneity, namely, early democratizations are associated with taller people more than later ones. Results are robust to the inclusion of countries exposed to communism.


High redox potential promotes oxidation of pyrite under neutral conditions: Implications for optimizing pyrite autotrophic denitrification.
Pyrite autotrophic denitrification (PAD) represents an important natural attenuation process of nitrate pollution and plays a pivotal role in linking nitrogen, sulfur, and iron cycles in a variety of anoxic environments. However, there are knowledge gaps about the oxidation mechanism of pyrite under anaerobic neutral conditions. This study explored the performance of PAD in the presence of EDTA and revealed the mechanism of anaerobic pyrite oxidation and microbial mineral transformation. It was demonstrated that ~200 mV was the electrochemical threshold for converting pyrite into bioavailable forms in PAD conditions, and accelerated pyrite oxidation by Fe3+-EDTA complexes can improve the performance of PAD effectively. Furthermore, genus related to sulfur and nitrogen cycle (Sulfurimonas, Denitrobacter) were found at higher abundances in cultures containing EDTA. The analysis of metagenomic binning showed that the microbial community in PAD culture with EDTA addition exhibited higher levels of functional diversity and redundancy. These results will further the understanding of the oxidation mechanism of pyrite under anaerobic neutral conditions and the corresponding microbial activities, and provide insights into the practical application of PAD.