Phenotypic characterization and genome analysis of a novel Salmonella Typhimurium phage having unique tail fiber genes.
Salmonella enterica serovar Typhimurium is a foodborne pathogen causing occasional outbreaks of enteric infections in humans. Salmonella has one of the largest pools of temperate phages in its genome that possess evolutionary significance for pathogen. In this study, we characterized a novel temperate phage Salmonella phage BIS20 (BIS20) with unique tail fiber genes. It belongs to the subfamily Peduovirinae genus Eganvirus and infects Salmonella Typhimurium strain (SE-BS17; Acc. NO MZ503545) of poultry origin. Phage BIS20 was viable only at biological pH and temperature ranges (pH7 and 37 °C). Despite being temperate BIS20 significantly slowed down the growth of host strain for 24 h as compared to control (P < 0.009). Phage BIS20 features 29,477-base pair (bp) linear DNA genome with 53% GC content and encodes for 37 putative ORFs. These ORFs have mosaic arrangement as indicated by its ORF similarity to various phages and prophages in NCBI. Genome analysis indicates its similarity to Salmonella enterica serovar Senftenberg prophage (SEStP) sequence (Nucleotide similarity 87.7%) and Escherichia virus 186 (~ 82.4% nucleotide similarity). Capsid genes were conserved however those associated with tail fiber formation and assembly were unique to all members of genus Eganvirus. We found strong evidence of recombination hotspot in tail fiber gene. Our study identifies BIS20 as a new species of genus Eganvirus temperate phages as its maximum nucleotide similarity is 82.4% with any phage in NCBI. Our findings may contribute to understanding of origin of new temperate phages.


Allergic contact dermatitis from fluocortolone, flucocortolone pivalate and fluocortolone caproate.
Two patients with contact allergy to Ultralan preparations are reported. Each Ultralan preparation contains two of three related fluocortolone derivatives. The first patient reacted to all three derivatives. The second patient reacted to flucortolone and when retested 4 months later also to fluocortolone pivalate but ot to flucortolone caproate. The negative reaction to fluocortolone pivalate at the first examination was probably false negative due to a low test concentration. In order to avoid false negative patch test reactions the fluorinated steroids should possibly be applied in concentrations higher than 1%. No cross sensitivity to the other steroids for topical use was found.


The ret finger protein-like 4 gene, Rfpl4, encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells.
Using an in silico (electronic database) subtraction, we identified a new member of the Ret Finger Protein-Like gene family, Rfpl4. Rfpl4 encodes a 287 amino acid putative E3 ubiquitin-protein ligase with a RING finger-like domain and a B30.2 motif. Reverse transcriptase polymerase chain reaction and Northern blot analyses reveal that Rfpl4 encodes a 1.7kb mRNA detectable exclusively in the gonads of adult mice. In situ hybridization localizes Rfpl4 transcripts within the ovary to oocytes of primary and later stage follicles and in the testis to elongating spermatids. The Rfpl4 gene comprises three exons and maps to mouse chromosome 7. We have identified the human ortholog, which maps to 19q13.4. These studies suggest that RFPL4 mediates protein degradation pathways important for gametogenesis or early embryonic development.


Pseudomonas aeruginosa improved the phytoremediation efficiency of ryegrass on nonylphenol-cadmium co-contaminated soil.
The effect of Pseudomonas aeruginosa (P. aeruginosa) on the phytoremediation efficiency of ryegrass on soil contaminated with nonylphenol (NP) and cadmium (Cd) was investigated by pot experiments. Pseudomonas aeruginosa application stimulated the adsorption of Cd by ryegrass and facilitated the biodegradation of NP in the soil. Exogenous P. aeruginosa inoculation increased the activities of urease, dehydrogenase, and polyphenol oxidase in the soil of the T4 treatment by 38.5%, 50.0%, and 56.5% compared to that of the T2 treatment, respectively. There was a significant positive correlation between the activities of dehydrogenase and polyphenol oxidase and the NP removal rate (P < 0.001). The relative abundances of beneficial microorganisms (such as Sphingomonas, Lysobacter, Streptomyces, Chloroflexia, Deltaproteobacteria, and Alphaproteobacteria) were increased as a result of P. aeruginosa inoculation. These microorganisms play important roles in nutrient cycling, Cd adsorption, and NP degradation. Additionally, P. aeruginosa was not the dominate bacterial species at the end of the experiment. According to this study, P. aeruginosa application improved the phytoremediation efficiency of ryegrass on soil contaminated with NP and Cd, with a minimal risk of alien microbial invasion.


Contribution of spinal 5-HT1A and 5-HT7 receptors to locomotor-like movement induced by 8-OH-DPAT in spinal cord-transected mice.
Growing evidence from in vitro studies suggests that spinal serotonin (5-HT) receptor subtypes 5-HTR(1A) and 5-HTR(7) are associated with an induction of central pattern generator activity. However, the possibility of a specific role for these receptor subtypes in locomotor rhythmogenesis in vivo remains unclear. Here, we studied the effects of a single dose (1 mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT), a potent and selective 5-HTR(1A/7) agonist, in mice spinal cord transected at the low-thoracic level (Th9/10). The results show that 8-OH-DPAT acutely induced, within 15 min, hindlimb movements that share some characteristics with normal locomotion. Paraplegic mice pretreated with the selective 5-HTR(1A) antagonists, WAY100,135 or WAY100,635, displayed significantly less 8-OH-DPAT-induced movement. A similar reduction of 8-OH-DPAT-induced movements was found in animals pretreated with SB269970, a selective 5-HTR(7) antagonist. Moreover, a near complete blockade of 8-OH-DPAT-induced movement was obtained in wild-type mice pretreated with 5-HTR(1A) and 5-HTR(7) antagonists, and in 5-HTR(7)-/- mice pretreated with 5-HTR(1A) antagonists. Overall, these results clearly demonstrate that 8-OH-DPAT potently induces locomotor-like movement in the previously paralysed hindlimbs of low-thoracic-transected mice. The results, with selective antagonists and knockout animals, provide compelling evidence of a specific contribution of both receptor subtypes to spinal locomotor rhythmogenesis in vivo.


Complete Pathologic Response Prediction by Radiomics Wavelets Features of Unenhanced CT Simulation Images in Locally Advanced Rectal Cancer Patients after Neoadjuvant Chemoradiation.
For locally advanced rectal cancer patients a watch-and-wait strategy is an acceptable treatment option in cases of complete tumor response. Clinicians need robust methods of patient selection after neoadjuvant chemoradiation. To predict pathologic complete response (pCR) using computer vision. To analyze radiomic wavelet transform to predict pCR. Neoadjuvant chemoradiation for patients with locally advanced rectal adenocarcinoma who passed computed tomography (CT)-based simulation procedures were examined. Gross tumor volume was examind on the set of CT simulation images. The volume has been analyzed using radiomics software package with wavelets feature extraction module. Statistical analysis using descriptive statistics and logistic regression was performed was used. For prediction evaluation a multilayer perceptron algorithm and Random Forest model were used. In the study 140 patients with II-III stage cancer were included. After a long course of chemoradiation and further surgery the pathology examination showed pCR in 38 (27.1%) of the patients. CT-simulation images of tumor volume were extracted with 850 parameters (119,000 total features). Logistic regression showed high value of wavelet contribution to model. A multilayer perceptron model showed high predictive importance of wavelet. We applied random forest analysis for classifying the texture and predominant features of wavelet parameters. Importance was assigned to wavelets. We evaluated the feasibility of using non-diagnostic CT images as a data source for texture analysis combined with wavelets feature analysis for predicting pCR in locally advanced rectal cancer patients. The model performance showed the importance of including wavelets features in radiomics analysis.


NMR monitoring of the SELEX process to confirm enrichment of structured RNA.
RNA aptamers are RNA molecules that bind to a target molecule with high affinity and specificity using uniquely-folded tertiary structures. RNA aptamers are selected from an RNA pool typically comprising up to 1015 different sequences generated by iterative steps of selection and amplification known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Over several rounds of SELEX, the diversity of the RNA pool decreases and the aptamers are enriched. Hence, monitoring of the enrichment of these RNA pools is critical for the successful selection of aptamers, and several methods for monitoring them have been developed. In this study, we measured one-dimensional imino proton NMR spectra of RNA pools during SELEX. The spectrum of the initial RNA pool indicates that the RNAs adopt tertiary structures. The structural diversity of the RNA pools was shown to depend highly on the design of the primer-binding sequence. Furthermore, we demonstrate that enrichment of RNA aptamers can be monitored using NMR. The RNA pools can be recovered from the NMR tube after measurement of NMR spectra. We also can monitor target binding in the NMR tubes. Thus, we propose using NMR to monitor the enrichment of structured aptamers during the SELEX process.


A survey of the microbial community in the rhizosphere of two dominant shrubs of the Negev Desert highlands, Zygophyllum dumosum (Zygophyllaceae) and Atriplex halimus (Amaranthaceae), using cultivation-dependent and cultivation-independent methods.
Plant roots comprise more than 50% of the plant's biomass. Part of that biomass includes the root microbiome, the assemblage of bacteria and fungi living in the 1-3 mm region adjacent to the external surface of the root, the rhizosphere. We hypothesized that the microorganisms living in the rhizosphere and in bulk soils of the harsh environment of the Negev Desert of Israel had potential for use as plant-growth-promoting bacteria (PGPB) to improve plant productivity in nutrient-poor, arid soils that are likely to become more common as the climate changes. • We used cultivation-dependent methods including trap experiments with legumes to find nitrogen-fixing rhizobia, specialized culture media to determine iron chelation via siderophores and phosphate-solubilizing and cellulase activities; cultivation-independent methods, namely 16S rDNA cloning and sequencing; and also community-level physiological profiling to discover soil microbes associated with the Negev desert perennials Zygophyllum dumosum and Atriplex halimus during the years 2009-2010. • We identified a number of PGPB, both epiphytes and endophytes, which fix nitrogen, chelate iron, solubilize phosphate, and secrete cellulase, as well as many other bacteria and some fungi, thereby providing a profile of the microbiomes that support the growth of two desert perennials. • We generated a snapshot of the microbial communities in the Negev Desert, giving us an insight in its natural state. This desert, like many arid environments, is vulnerable to exploitation for other purposes, including solar energy production and dry land farming.


Pharmacological studies on tandamine hydrochloride, a potential heterocyclic antidepressant.
Tandamine, a potential heterocyclic antidepressant, was compared with imipramine for its ability to modify: (a) the contractions induced by noradrenaline (NA) and 5-hydroxytryptamine (5-HT) on the normal and chronically denervated nictitating membrane of the cat, (b) the neuron blocking effect induced by guanethidine in the guinea pig vas deferens, (c) the electroencephalograph and the physostigmine arousal in the rabbit and (d) the sleep pattern of the rat. Both tandamine and imipramine potentiated the NA and 5-HT induced contractions of the normalnictitating membrane and antagonized the effects of gaunethidine on the vas deferens. The potentiation by tandamine and imipramine of the NA and 5-HT contraction of the nictitating membrane disappeared after chronic denervation of the membrane. These results are consistant with the ability of the substances to block the neural uptake of catechol- and indoleamines. Tandamine did not induce EEG synchronization and did not affect the arousal reaction induced by physostigmine. Tandamine also reduced or abolished REM (rapid eye movement) sleep with a concomitant decrease in NREM (non-rapid eye movement) sleep.


Population-based investigation of familial undescended testis and its association with other urogenital anomalies.
Up to now, observation of familial undescended testis (UDT) has been confined to the description of individual cases. The aim of our study was to evaluate the frequency of a positive family history and of associated urological anomalies in family members, and to calculate the risk of newborn male individuals having UDT if a family member is affected. A total of 374 patients who underwent surgery because of UDT and 374 controls without UDT were interviewed by means of a special questionnaire. We asked for a family history of UDT, as well as for other urogenital anomalies (varicocele, hydrocele, hypospadias, testicular cancer, renal anomalies). For statistical analysis the odds ratio was calculated. Of the analysed patients, 85 (22.73%) had family members with UDT versus 7.5% of the control group. Of these 85 cases, brothers were involved in 37.3%, fathers in 35.2%, uncles in 23.5%, cousins in 16.5%, great-cousins in 8.2% and grandfathers in 7.1%. The risk of UDT in a newborn male is 3.6-fold overall, and 6.9-fold if a brother and 4.6-fold if the father is affected. The rate of family members with UDT and/or other urogenital anomalies in the patient group was nearly 2-fold higher than in the control group. Due to the increased familial risk and the higher percentage of a positive family history for UDT and other urogenital anomalies in patients with UDT, a genetic predisposition seems probable.


New ways of treatment of fractures of the humeral shaft: does the combination of intramedullary nail osteosynthesis and cerclage improve the healing process?
The humeral shaft fracture is a rare fracture of the long bones with various treatment options. Dreaded complications such as lesions of the radial nerve or non-unions make the decision for what kind of therapy option more difficult. Biomechanically the upper arm is mostly exposed to rotational forces, which affect intramedullary nail osteosynthesis. Additive cerclage may compensate for these in spiral fractures. The aim of this study is to investigate what effect a combination of intramedullary nail osteosynthesis and limited invasive cerclage has on the rate of healing. In addition, this study addresses the question if complications arise as a result of cerclage. In this retrospective study, 109 patients were evaluated, who, during a period of 6 years, underwent operative treatment of a humerus shaft fracture with a combination of intramedullary nail osteosynthesis and additive cerclage. The primary end point was to establish the rate of healing. A secondary end point was to evaluate complications such as infections and damage to the nerve. This was followed by an examination of patient files and X-ray images and a statistical analysis with SPSS. The healing process shows a non-union rate of 2.6%, and complications such as secondary radial nerve lesions of 4.6%. The antegrade intramedullary nail osteosynthesis with limited invasive, additive cerclage reduces the risk of non-union and does not lead to an increased risk of iatrogenic damage to the radial nerve. Wound healing was not impaired and there were no infections through the cerclage in our patient cohort.


Cognitive disturbances in schizophrenics: what are they, and what is their origin?
Cognitive disorders are neither a unique nor a constant phenomenon in schizophrenia. Among the dysfunctions that may be observed at times, primarily during acute phases and in patients with a non-paranoid symptomatology, certain disturbances in attention-focusing and information processing seem to be most conspicuous. Some of these cognitive dysfunctions may have been transmitted from parent(s) to the patient, either genetically or through simple forms of learning. the empirical evidence for this assumption is to be found in the fact that some of the same cognitive deficits as those found in schizophrenic patients also found in their first-degree relatives, although usually in a milder form. Other forms of cognitive dysfunction may have developed as complementary strategies in response to communication deviances and cognitive behavior found in their parents. A developmental model, in which genetic, physiological and environmental factors are included is described as a way of illustrating how predisposing factors, as well as intermediating and stress factors, contribute to the debut and maintenance of cognitive disorders in schizophrenics.


Association Between Hearing Loss And Cauliflower Ear in Wrestlers, a Case Control Study Employing Hearing Tests.
According to anecdotal findings, some wrestling coaches and wrestlers believe that cauliflower ear might lead to hearing loss. Our preliminary study showed that the prevalence of hearing loss reported by the wrestlers with cauliflower ear is significantly higher than this rate among wrestlers without cauliflower ear. To the best of our knowledge, no other study has confirmed this finding employing hearing tests. To evaluate and to compare the prevalence of hearing loss among wrestlers with and without cauliflower ears employing hearing tests. The subjects were randomly selected form 14 wrestling clubs in Tehran. Subjects were 201 wrestlers with cauliflower ears (100 wrestlers with one cauliflower ear and 101 wrestlers with two cauliflower ears) and 139 wrestlers without cauliflower ears. All the participants in this study were interviewed to collect information on demographic factors and medical history of risk factors and diseases related to hearing loss. The subjects in both groups underwent otoscopic and audiologic examinations. Audiometric examination results at the frequency range of 0.5 - 8 KHz showed that the prevalence of hearing loss among cauliflower ears was higher than this rate among non-cauliflower ears. Also, the percentage of positive history of ear infections among cauliflower ears (8.4%) was about two times more than this finding among non-cauliflower ears (4.9%). This difference tended to be significant (OR: 1.86, P = 0.06, 95% CI: 0.98 - 3.53). To the best of our knowledge, this is the first study showing that the prevalence of hearing loss among cauliflower ears is higher than this rate among non-cauliflower ears confirmed by audiological tests. This emphasizes that, more preventive measures such as mandatory ear gear for wrestlers are required.


Unnecessary investigations in patients with acute pancreatitis: arterial blood sampling and serum biochemistry.
Most patients admitted with acute pancreatitis undergo arterial blood gas sampling (ABG) to calculate the modified Glasgow score (MGS) and serum amylase and liver function tests (LFTs) are requested frequently during admission. This study aims to assess the necessity of these investigations. A retrospective study of all patients attending a district general hospital with a diagnosis of acute pancreatitis (AP) between November 2005 and November 2006 was performed. Patients were identified from clinical coding data, excluding those with serum amylase levels of < 5501 U/l thereby increasing the likelihood of correct diagnosis. Demographic data and ABC reports were retrieved from the case notes. Criteria were defined for necessity of amylase and LFT requests. Data were retrieved for 63 patients with 227 amylase requests, 329 LFT requests, 95 ABGs and 80 MGSs. Eight ABGs were found to have PaO2 values less than 8kPa, a result that could be predicted in all cases by pulse oximeter-derived oxygen saturations of less than 95%. When the MGS excluding the PaO2 parameter was two, only one patient out of 22 (4.5%) was upgraded to a score of three due to a PaO2 of less than 8 kPa and this could have been predicted by pulse oximeter-derived oxygen saturations of 92%. The MGS excluding the PaO2 parameter was always three or more in cases where acid-base disturbance exhibited more than a mild metabolic acidosis. One hundred and sixty-two unnecessary amylase requests and 168 unnecessary LFT requests were made according to our defined criteria, equating to 2.6 unnecessary amylase requests and 2.7 unnecessary LFT requests per admission at a cost of pounds 83.40 (pounds 1.32 per admission). We propose not performing ABGs if the MCS excluding the PaO2 component totals two or less. Clinical judgment would have to be exercised. Unnecessary serum biochemistry requests are frequent but at little financial expense.


Risk factors for acute, moderate to severe donor reactions associated with multicomponent apheresis collections.
Legitimate concerns exist over the safety of donors during multicomponent apheresis collections (MACs), when large volumes of red blood cells (RBCs) and plasma are removed. This study evaluates the predictive value of various donor- and procedure-related variables for moderate to severe donor acute adverse events (AAEs). Data on all apheresis donation procedures performed at a large university hospital-based donor center over a 2-year period were obtained by a review of adverse event forms and procedure logs (Trima Accel 5.1, Gambro BCT). Various donor- and procedure-related variables were compared between procedures that resulted in moderate to severe AAEs and those that did not. Moderate to severe AAEs occurred in 53 (0.47%) of 11,333 apheresis donation procedures. The majority of events (96.2%) had predominantly features of vasovagal reactions (VVRs). Females were at significantly higher risk (odds ratio [OR] = 2.8, p < 0.0003) compared to males. Donors who experienced AAEs had significantly lower predonation total blood volume (TBV) and hematocrit (Hct) and higher total RBC loss and net fluid loss at the end of the procedures. Total plasma loss alone was not significantly different between the two groups. Total blood loss was significantly higher among donors who experienced AAEs as a percentage of the donor's TBV. Apheresis collections are well tolerated even when multiple components are collected, with a very low overall incidence of moderate to severe AAEs (0.47%). Small, female donors with lower predonation Hct are at higher risk, especially when RBCs are collected.


Acacia mearnsii gum: A residue as an alternative gum Arabic for food stabilizer.
Acacia mearnsii gum is not commercially exploited, being characterized as residue from A. mearnsii cultivation. This work investigated the A. mearnsii gum polysaccharide composition, its cytotoxicity and the technological effect as a stabilizer in ice cream. A. mearnsii gum showed a similar chemical structure to commercial gum Arabic and did not decrease the viability and proliferation of fibroblast cells (Balb/3T3) and hepatocarcinoma (HepG2). Rheological tests showed that the ice cream stabilized by the A. mearnsii gum had a more structured system (more interactions between the mixture components) and the same melting characteristics as the ice cream samples made with commercial gum Arabic. The results showed that A. mearnsii gum, which is actually an agro-industrial residue from tannin production for industry, is a potential stabilizing gum for the food industry, contributing to the economic development of the exploitation chain of A. mearnsii products and by-products.


Synthesis of new head-activator analogues and their application for improved radioimmunoassays.
New analogues of head activator were produced for receptor and radioimmunoassay studies. The precursor molecules [(4'-I)Phe11] head activator and [Tyr11] head activator were synthesised for catalytic tritiation and iodination, respectively. With the tracer [(3,5-125 I2)Tyr11] head activator the sensitivity range of the radioimmunoassay was 5-100 fmol.


Acaricidal activity of aqueous extract and synthesized silver nanoparticles from Manilkara zapota against Rhipicephalus (Boophilus) microplus.
Traditional parasite control is primarily based on the use of chemical acaricides, which unfortunately have many negative side effects. The aim of the present study was to evaluate the effect of plant synthesized silver nanoparticles (AgNPs) using aqueous leaf extract of Manilkara zapota to control Rhipicephalus (Boophilus) microplus. The synthesized AgNPs were characterized by UV-vis spectrum, scanning electron microscopy (SEM), Fourier transform infrared and X-ray diffraction. The UV-vis spectrum of the aqueous medium containing silver nanostructures showed a peak at 421 nm corresponding to the surface plasmon resonance band of AgNPs. SEM supports the biosynthesis and characterization of AgNPs with spherical and oval in shape and size of 70-140 nm. Acaricidal activity of aqueous leaf extract of M. zapota and synthesized AgNPs were carried out against R. (B.) microplus and the results showed the LC(50) values of 16.72 and 3.44 mg/L; r(2)=0.856 and 0.783), respectively.


Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit?
Hepatic artery chemoembolization was introduced in the treatment of patients with unresectable hepatocellular carcinoma waiting for liver transplantation. The rationale for this preoperative treatment was to control tumor growth during the waiting period and to improve long-term survival. This study aimed to investigate whether preoperative chemoembolization not only induces marked tumor necrosis but also has a survival benefit. In this study 21 patients with hepatocellular carcinoma who underwent pretransplant chemoembolization (group I) were compared with 21 historical control patients (group II) without preoperative chemoembolization in a case-control study. The number of pretransplant chemoembolizations in each patient in group I varied between 1 and 5 with a mean of 2.44+/-1.15. In addition, six patients of this group received preoperative systemic chemotherapy. Overall, there were no differences in survival between the groups with and without pretransplant chemoembolization at 1 year (60.8% vs 61.5%) and at 3 years (48.4% vs 53.9%). In group I, three patients developed unexplained severe pneumonia, leading to death very early after liver transplantation. Marked tumor necrosis (>50%) was found in 14 cases in group I. In 6 out of these 14 patients, total tumor necrosis was observed. Although preoperative chemoembolization or chemotherapy induced marked tumor necrosis, these patients showed no benefit in survival compared to historical controls, and appeared to be at higher risk of developing immediate postoperative infective complications.


Chronic HPA activity in mothers with preterm delivery: A pilot nested case-control study.
Chronic hypothalamic-pituitary-adrenal (HPA) axis activity role in the pathogenesis of preterm birth (PTB) remains unclear due to inconsistent measures with limited ability to monitor long-term cortisol concentrations. We explored this relationship using the novel method of assessing cortisol in hair, which is a valid and reliable measure of chronic HPA axis activity. 137 participants (40 PTB cases and 97 controls from a birth cohort of pregnant women in Peru) were interviewed and invited to provide a 9-cm hair sample from the posterior vertex position of the scalp (mean = 13 weeks gestation). Hair cortisol concentration (HCC) was determined using luminescence immunoassay and values were natural-log transformed. PTB cases were defined as women who delivered before 37 gestational weeks. Case-control differences were assessed using multivariable linear and logistic regressions. Overall, combined pre-conception and first-trimester HCC was 13% lower among cases as compared with controls (p-value = 0.01). Compared with controls, maternal HCC among PTB cases were 14% (p = 0.11), 10% (p = 0.22) and 14% (p = 0.08) lower for 3-6 months pre-conception, 0-3 months pre-conception, and first trimester, respectively. After adjusting for putative confounders, a 1-unit increase in HCC was associated with 55% reduced odds of PTB (aOR = 0.45; 95% CI: 0.17-1.17). For a 1-unit increase in HCC in the scalp-intermediate and scalp-distal segments (representing HCC concentrations in 0-3 months pre-conception and first trimester), the corresponding odds for PTB were 0.53 (95% CI: 0.19-1.48) and 0.39 (95% CI: 0.13-1.13), respectively. Women who deliver preterm, as compared with those who deliver at term, have lower preconception and first trimester HCC. Our findings suggest that HPA axis activation, integral to the adaptive stress-response system, may be chronically dysregulated in women at increased risk of PTB.


[Tumor cytogenetics].
Cytogenetic analysis by classical chromosome banding, in combination with different fluorescence in situ hybridization (FISH) based methods, including comparative genomic hybridization and multicolour FISH, provides important information concerning the diagnosis, staging and prognosis of, as well as the planning of therapeutic intervention against, leukemias, malignant lymphomas and solid tumors, and may be helpful in monitoring the course of the disease. Cytogenetic methods identify primary chromosome anomalies that are causally involved in the emergence of the disease and its histopathological subtype, as well as secondary anomalies which have an effect upon the course of the disease and the responsiveness to therapy. Tumor cytogenetics is an independent discipline, and by no means only a diagnostic service for, or subdiscipline of, haematological, oncological and pathological fields. It is important, however, to point out that tumor cytogenetics is a cooperation-orientated and interdisciplinary science that deals with its own original questions in collaboration with clinicians, pathologists and molecular geneticists.


Estrogen formation in the mammalian brain: possible role of aromatase in sexual differentiation of the hippocampus and neocortex.
Recent studies suggest that sex differences in cognitive function may involve effects of circulating androgens on the developing cerebral cortex and hippocampus. The mechanism of these effects is not understood. In rhesus monkeys, aromatase activity is present in the hippocampus and several areas of the cerebral cortex during late fetal and early postnatal life. Similarly, work in rats and mice indicates that the hippocampus and cerebral cortex may be capable of estrogen biosynthesis during early development. These results are consistent with the hypothesis that the actions of androgens on the developing cerebral cortex and hippocampus may involve local estrogen-mediated effects similar to those responsible for differentiation of the hypothalamic mechanisms controlling reproductive function.


Dermatofibrosarcoma protuberans and the Bednar tumor: treatment in the pediatric population.
Dermatofibrosarcoma protuberans (DFSP) is a low-intermediate-grade cutaneous sarcoma that has a marked propensity for local recurrence after excision. The Bednar variant of this tumor is even less common and is distinguished histologically by the dispersal of melanin containing cells in an otherwise typical DFSP. Both are considered to be tumors of the third and forth decades of life, but both DFSP and the Bednar variant have been described in children. Until this report of a congenital Bednar tumor, only the DFSP has also been described in the neonate. The histopathology and surgical management of DFSP and Bednar tumors are outlined with emphasis on reported experience in the pediatric population. The surgical management of these lesions in children is based on numerous series in adults and the limited pediatric experience. The recommended treatment is wide excision with 3-cm margins of visibly uninvolved tissue and inclusion of superficial fascia.


Should renal ultrasound be performed in the patient with microscopic hematuria and a normal excretory urogram?
We determine what additional information would be detected by renal ultrasonography that was not identified by a normal excretory urogram (IVP) performed for the evaluation of microscopic hematuria. A retrospective review was done of 101 patients with microscopic hematuria and a normal IVP who underwent renal ultrasonography. Of the 101 patients with microscopic hematuria and a normal IVP, renal ultrasonography was abnormal in 20%. All findings were ultimately proved to be of no clinical significance, although 6 of 21 patients required a total of 10 additional studies, including 9 computerized tomography scans and 1 renal arteriogram. These data demonstrate that renal ultrasonography is unnecessary in a patient with microscopic hematuria and a normal IVP.


Intracardiac echocardiography techniques to identify ventricular arrhythmia substrate.
Intracardiac echocardiography (ICE) is increasingly used to facilitate catheter ablation of ventricular arrhythmias (VA). It allows intraprocedural recognition of myocardial substrate, optimization of catheter-tissue contact, identification of anatomical barriers to ablation, and early recognition of complications. In the era where the 3-dimensionality of substrate for VA is increasingly recognized, ICE is invaluable in identifying scar topography in the endocardial, midmyocardial, and epicardial layers. ICE assists in identifying endocavitary structures that are a common source of VA in idiopathic and structural heart disease. Furthermore, as substrate imaging of the right ventricle has not been optimized with other imaging modalities, ICE offers a unique opportunity to visualize substrate in this chamber. Real-time substrate identification can be particularly useful where there are contraindications to use of other imaging modalities or the images are obscured by artefact in the presence of cardiac device leads. In this review we provide a step-by-step guide in the techniques used to image ventricular arrhythmia substrate with ICE. We also discuss the benefits and limitations of this technique in comparison to other imaging modalities.


Computer versus cardiologist: Is a machine learning algorithm able to outperform an expert in diagnosing a phospholamban p.Arg14del mutation on the electrocardiogram?
Phospholamban (PLN) p.Arg14del mutation carriers are known to develop dilated and/or arrhythmogenic cardiomyopathy, and typical electrocardiographic (ECG) features have been identified for diagnosis. Machine learning is a powerful tool used in ECG analysis and has shown to outperform cardiologists. We aimed to develop machine learning and deep learning models to diagnose PLN p.Arg14del cardiomyopathy using ECGs and evaluate their accuracy compared to an expert cardiologist. We included 155 adult PLN mutation carriers and 155 age- and sex-matched control subjects. Twenty-one PLN mutation carriers (13.4%) were classified as symptomatic (symptoms of heart failure or malignant ventricular arrhythmias). The data set was split into training and testing sets using 4-fold cross-validation. Multiple models were developed to discriminate between PLN mutation carriers and control subjects. For comparison, expert cardiologists classified the same data set. The best performing models were validated using an external PLN p.Arg14del mutation carrier data set from Murcia, Spain (n = 50). We applied occlusion maps to visualize the most contributing ECG regions. In terms of specificity, expert cardiologists (0.99) outperformed all models (range 0.53-0.81). In terms of accuracy and sensitivity, experts (0.28 and 0.64) were outperformed by all models (sensitivity range 0.65-0.81). T-wave morphology was most important for classification of PLN p.Arg14del carriers. External validation showed comparable results, with the best model outperforming experts. This study shows that machine learning can outperform experienced cardiologists in the diagnosis of PLN p.Arg14del cardiomyopathy and suggests that the shape of the T wave is of added importance to this diagnosis.


Strategic management as adaptation to changes in the ecosystems of public hospitals in Israel.
Health systems worldwide function in constantly changing local and global ecosystems. This is the result of economic, demographic, and technological changes, among others. In recent decades Israel has started implementing reforms in the public health services that have led to far-reaching changes in the health system, and consequently, increased competition within it. The impact of these changes has been exacerbated by pressure to reduce per capita public health costs, coupled with increased demand and greater health awareness. All these changes have created a turbulent environment for healthcare organizations in Israel. To cope with this dynamic environment, various parts of the system have had to adopt appropriate management behaviors and business styles. This study, carried out in six public hospitals in Israel, evaluates the nature and degree of adaptation, implementation, and inculcation of management strategies in public hospitals in Israel, using the Ginter model of strategic management of health organizations. The study used semi-structured in-depth interviews of key figures in the health system and managers at various levels in the hospitals and HMOs included in the sample. The 55 interviews, conducted in two time periods, were analyzed in accordance with an established theory of qualitative methodological analysis. The main findings are that the health market and hospitals in Israel are increasingly adopting competitive business behaviors. But strategic managerial behavior has been adopted only in part, and there is a lack of collaboration between staff and management in defining goals and strategic activity. These are obstacles to change and inculcation of the strategy in hospitals. This study affords an important view over time and a better understanding of the behavior and adaptation of hospitals in Israel to their constantly changing surroundings. Adapting and inculcating appropriate managerial strategies in hospitals requires close collaboration between staff and management; its absence is an obstacle that contributes to partial, and possibly counter-productive, strategic behavior. The solution may lie in a combination of changes: providing hospital management with the necessary tools and broad professional support by the Ministry of Health; organizational changes in hospital management and departments; the creation of a clinical leadership role; and a self-supervised planning system . These recommendations regarding training and the direction and organization of the change, coupled with systemic oversight of them by the Ministry of Health, will enable the system to become more efficient. They are particularly relevant today because the Covid-19 pandemic has exacerbated and highlighted Israeli public hospitals' financial and organizational problems. Hospitals that already faced many challenges have had to cope with an unfamiliar medical crisis and a reduction of elective medical activity, causing them various types of damage, especially in term of economic stability. The hospitals' fragile situation must become a top government priority because it can no longer be ignored. To achieve a strong healthcare system with stable hospitals, able to respond both to everyday challenges and to crises like the current pandemic, policymakers must provide financial and organizational support alongside managerial training, while maintaining an overall systemic plan.


Alpha-herpesvirus glycoprotein D interaction with sensory neurons triggers formation of varicosities that serve as virus exit sites.
Alpha-herpesviruses constitute closely related neurotropic viruses, including herpes simplex virus in man and pseudorabies virus (PRV) in pigs. Peripheral sensory neurons, such as trigeminal ganglion (TG) neurons, are predominant target cells for virus spread and lifelong latent infections. We report that in vitro infection of swine TG neurons with the homologous swine alpha-herpesvirus PRV results in the appearance of numerous synaptophysin-positive synaptic boutons (varicosities) along the axons. Nonneuronal cells that were juxtaposed to these varicosities became preferentially infected with PRV, suggesting that varicosities serve as axonal exit sites for the virus. Viral envelope glycoprotein D (gD) was found to be necessary and sufficient for the induction of varicosities. Inhibition of Cdc42 Rho GTPase and p38 mitogen-activated protein kinase signaling pathways strongly suppressed gD-induced varicosity formation. These data represent a novel aspect of the cell biology of alpha-herpesvirus infections of sensory neurons, demonstrating that virus attachment/entry is associated with signaling events and neuronal changes that may prepare efficient egress of progeny virus.


Synthesis and antioxidant activity of a new class of mono- and bis-heterocycles.
A new class of mono- and bis-heterocycles, 2-arylsulfonylaminosulfonylmethyl-5-styrylsulfonylmethyloxadiazoles, pyrazolyl oxadiazoles, and isoxazolyl oxadiazoles, were synthesized and tested for their antioxidant activity. The styrylsulfonylmethyloxadiazole 5b showed good antioxidant activity when compared with the standard ascorbic acid.


TNF, IL-6, and IL-10 cytokines levels and their polymorphisms in renal function and time after transplantation.
Cytokine polymorphisms can influence their plasma levels and thus affect the immune response in renal transplantation. A total of 146 renal transplant recipients (RTR) were classified into groups according to the estimated glomerular filtration rate (R1: < 60 and R2: ≥ 60 mL/min/1.73 m2) and time after transplantation (T1: 1 to 24, T2: 25 to 60, T3: 61 to 120, and T4: > 120 months after transplantation). The polymorphisms were genotyped by single specific primer-polymerase chain reaction. IL-10 was measured by ELISA and IL-6, and TNF levels were determined using Miliplex®. A higher frequency of the - 308G allele and the - 308G/G genotype, low-producer, was observed in the R1 group compared with R2. In addition, a higher frequency of the - 308A carriers, high-producer, was found in the R2 group. However, no significant difference was observed in cytokine levels when both groups were compared. Higher levels of IL-6 were observed in T1 compared with T2 and T4 groups. Lower IL-6 levels were found in T2 compared with T3 group. Lower levels of IL-10 were also found in T1 group in relation to T2, while higher levels of this cytokine were observed in T2 group compared with T3. The results suggest that the - 308G > A polymorphism in the TNF gene is associated with filtration function after renal transplantation, and IL-6 and IL-10 levels change according to the time after transplantation. Thus, the joint evaluation of - 308G > A polymorphism in TNF gene and IL-6 and IL-10 levels would provide a broader and effective view on the clinical monitoring of RTR.


Substantial regional differences in the biomechanical behavior of molar treated with selective caries tissue removal technique: a finite element study.
Selective caries removal (SCR) is recommended over non-selective removal for managing deep carious lesions to avoid pulp exposure and maintain pulp vitality. During SCR, residual carious dentin is left behind and sealed beneath the restoration. The biomechanical effects of such residual lesions on the restored tooth remain unclear and were assessed using finite element modeling (FEM). Based on μ-CT images of a healthy permanent human third molar, we developed five finite element models. Generic class I and II cavity restorations were modeled where residual lesions of variable sizes were either left or fully removed on occlusal and proximal surfaces. The cavities were restored with adhesive composite. All 3D-FE models were compared with a model of a healthy, non-treated molar. A vertical load of 100 N was applied onto the occlusal surface. Regardless of the lesion size, in molars with occlusal lesions higher mean stresses were predicted along the filling-lesion interface than in all other models. The smallest occlusal lesion (Ø1 = 1 mm) resulted in the highest maximum stresses at the filling-lesion interface with large stress concentrations at the filling walls indicating failure risk. In conclusion, lesion site and extent are influencing parameters affecting the filling-lesion interactions and thus the biomechanical behavior of the tooth after SCR. Retaining carious lesions around the pulpal floor affects the deformation and stress states in tooth-filling complexes. The higher stresses observed in molars with occlusal lesions may affect restoration stability and longevity. Suprisingly, more extended occlusal lesions may provide a more favorable tooth performance than less extended ones. In contrast, in molars with proximal lesions the residual lesion had only limited effect on the tooth's biomechanical condition.


Variation, selection and evolution of function-valued traits.
We describe an emerging framework for understanding variation, selection and evolution of phenotypic traits that are mathematical functions. We use one specific empirical example--thermal performance curves (TPCs) for growth rates of caterpillars - to demonstrate how models for function-valued traits are natural extensions of more familiar, multivariate models for correlated, quantitative traits. We emphasize three main points. First, because function-valued traits are continuous functions, there are important constraints on their patterns of variation that are not captured by multivariate models. Phenotypic and genetic variation in function-valued traits can be quantified in terms of variance-covariance functions and their associated eigenfunctions: we illustrate how these are estimated as well as their biological interpretations for TPCs. Second, selection on a function-valued trait is itself a function, defined in terms of selection gradient functions. For TPCs, the selection gradient describes how the relationship between an organism's performance and its fitness varies as a function of its temperature. We show how the form of the selection gradient function for TPCs relates to the frequency distribution of environmental states (caterpillar temperatures) during selection. Third, we can predict evolutionary responses of function-valued traits in terms of the genetic variance-covariance and the selection gradient functions. We illustrate how non-linear evolutionary responses of TPCs may occur even when the mean phenotype and the selection gradient are themselves linear functions of temperature. Finally, we discuss some of the methodological and empirical challenges for future studies of the evolution of function-valued traits.


Novel SOD1 mutation p.V31A identified with a slowly progressive form of amyotrophic lateral sclerosis.
The SOD1 gene encoding the superoxide dismutase 1 (SOD1) protein is mutated in approximately 15% of familial amyotrophic lateral sclerosis (ALS) and 3% of sporadic ALS. We identified a novel mutation in SOD1 in a man who presented at age 49 with lower limb stiffness, and at age 53, a spastic paraparesia with distal muscular atrophy in the lower limbs and fasciculations in the quadriceps. A diagnosis of ALS was established. Eleven years after disease onset his condition continues gradually and slowly to deteriorate. The heterozygous mutation observed in exon 2 resulted in a valine to alanine substitution at position 31 in the β-barrel domain of the SOD1 protein. Functional analysis in NSC34 cells showed that the overexpression of the mutant form of SOD1(V31A) induced aggregates and decreased cell viability. This mutation is located outside of the regions carrying most of the ALS-related mutations (i.e., the catalytic center, the region of dimerization, and the loops between the β-strands of the β-barrel). In conclusion, we identified a novel SOD1 mutation in a patient with slow disease progression and supported the idea that different SOD1 mutations can lead to distinct ALS phenotypes.


Brown Adipose Tissue Development and Metabolism.
Brown adipose tissue is well known to be a thermoregulatory organ particularly important in small rodents and human infants, but it was only recently that its existence and significance to metabolic fitness in adult humans have been widely realized. The ability of active brown fat to expend high amounts of energy has raised interest in stimulating thermogenesis therapeutically to treat metabolic diseases related to obesity and type 2 diabetes. In parallel, there has been a surge of research aimed at understanding the biology of rodent and human brown fat development, its remarkable metabolic properties, and the phenomenon of white fat browning, in which white adipocytes can be converted into brown like adipocytes with similar thermogenic properties. Here, we review the current understanding of the developmental and metabolic pathways involved in forming thermogenic adipocytes, and highlight some of the many unknown functions of brown fat that make its study a rich and exciting area for future research.


The secondary structure of human amyloid deposits as determined by circular dichroism spectroscopy.
The deposition of amyloid fibrils has been associated with a diversity of pathologies including plasma cell dyscrasias, chronic inflammatory diseases, and several types of neurological diseases including Alzheimer's disease. Using circular dichroism spectroscopy, the secondary structure of a human amyloid protein deposit from a patient with plasma cell (light chain)-associated amyloidosis (amyloidosis AL) has been determined. The protein contains 52% beta structure, which is consistent with these depositions arising from the aberrant catabolism of immunoglobulin light chains, which are rich in beta sheets. The protein was also found to contain 20% alpha-helix, suggesting that partial refolding may occur during amyloidogenesis.


Correlation between the triglyceride-to-high-density lipoprotein cholesterol ratio and other unconventional lipid parameters with the risk of prediabetes and Type 2 diabetes in patients with coronary heart disease: a RCSCD-TCM study in China.
Type 2 diabetes mellitus (T2DM) is often accompanied by undiagnosed dyslipidemia. Research on the association of unconventional lipid markers with prediabetes (pre-DM) and T2DM simultaneously is limited in coronary heart disease (CHD) patients. This study included 28,476 patients diagnosed with CHD. Their lipid levels, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were measured, and non-traditional lipid parameters were calculated. The patients were divided into three groups based on the diabetic status including normoglycemic (NG), pre-DM, and T2DM. Multiple logistic regression was used to compare the association of TG/HDL-C and other non-traditional lipid parameters with pre-DM and T2DM. The tertiles of TG/HDL-C included T1 (TG/HDL-C < 1.10), T2 (1.10 ≤ TG/HDL-C ≤ 1.89) and T3 (TG/HDL-C > 1.89). Low and high TG/HDL-C was defined with sex-specific cutoff points. Multiple logistic regression results showed that the non-traditional lipid parameters, including non-HDL-C, LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C and TG/HDL-C, were all correlated with the risk of pre-DM and T2DM. Meanwhile TG/HDL-C showed the strongest correlation (odds ratio [OR]: 1.19; 95% confidence interval [CI] 1.16-1.23), (OR: 1.36; 95% CI 1.33-1.39). When dividing TG/HDL-C into tertiles, using T1 as a reference, T3 was observed to have the highest association with both pre-DM and T2DM (OR: 1.60; 95% CI 1.48-1.74), (OR: 2.79; 95% CI 2.60-3.00). High TG/HDL-C was significantly associated with pre-DM and T2DM (OR: 1.69; 95% CI 1.52-1.88), (OR: 2.85; 95% CI 2.60-3.12). The association of TG/HDL-C with T2DM and pre-DM existed across different sex, age, smoking, and drinking statuses. Elevated non-traditional lipid parameters were significantly associated with pre-DM and T2DM in CHD patients, especially TG/HDL-C. High TG/HDL-C was the risk factor with a strong correlation with the risk of pre-DM and T2DM.


Metabolic, neuroendocrine and behavioral effects of social defeat in male and female mice using the chronic non-discriminatory social defeat stress model.
Stress-related disorders predominately affect females, yet preclinical models of chronic stress exclusively use males especially in models where social stressors are studied. Here, we implemented a 21-day novel social defeat paradigm in which a female and male C57 intruder are simultaneously placed in the cage of a territorial, resident CD-1 male mouse, and the resident proceeds to attack both intruders. Mice were given access to a regular laboratory diet, high in carbohydrates, and a palatable diet, high in fat. Chronic social defeat stress using this paradigm resulted in increased caloric intake in male and female mice, with the effects being more pronounced in females. We observed sex differences in high fat diet intake in response to stress, which was correlated with higher levels of plasma ghrelin observed in female mice but not male mice. Furthermore, females exposed to chronic stress displayed changes in growth hormone secretatogue receptor (ghsr) and neuropeptide-y (npy) expression in the arcuate nucleus of the hypothalamus, potentially increasing ghrelin sensitivity and inducing changes in diet choice and caloric intake. Behavioral results show that females tended to spend more time interacting during the social interaction test, compared to males who displayed higher vigilance towards the stranger mouse. Overall, our results highlight unique neurometabolic alterations in female mice in response to stress that is not present in male mice and may be important for coping with chronic stress and sustaining reproductive function.


Rituximab improves not only back stiffness but also "stiff eyes" in stiff person syndrome: Implications for immune-mediated treatment.
Stiff person syndrome (SPS) is usually characterized by truncal muscle rigidity and episodic painful spasms, but it sometimes appears with ocular symptoms called "stiff eyes". We recorded saccade movements in an SPS patient manifesting with "stiff eyes" conditions with slow saccade velocity and evaluated the effect of immunotherapy including rituximab on saccade parameters. We repeatedly conducted saccade eye recordings using video-based eye tracking system on a 42-year-old male SPS patient with slow saccade. The velocity and onset latency of visual guided saccades (VGS) were measured at each recording. Because VGS velocity is affected by saccade amplitude, estimated peak velocity (Vmax) was also calculated by taking the relationship between the velocity and the amplitude of saccade into account. The mean VGS velocity improved significantly after two courses of rituximab administration compared with its lowest value. The estimated Vmax decreased as the clinical manifestations worsened, but it increased after rituximab administration. Other neurological symptoms in this patient such as muscle rigidity and gait instability also improved after the treatment. Slow saccade in a "stiff eyes" patient improved after rituximab administration. Our study also indicated that the saccade eye recording is useful for evaluating the clinical condition of SPS when it is complicated with ocular symptoms.


Seroprevalence of hepatitis B and C virus infection among patients attending serology laboratory of Gondar University Hospital.
Hepatitis B virus (HBV) and hepatitis C virus (HBV) infections accounts for substantial proportions of the world wide liver disease. The two hepatotropic virus share common modes of transmission and their co-infection are common. Patients with dual HBV and HCV infection have more severe liver disease and are at increased risk of progression to hepatic cell carcinoma. This study was aimed to assess the prevalence of HBV and HCV among patients attending serology laboratory of Gondar University Teaching Hospital. A retrospective study was conducted from January 2007 to December 2011 at serology laboratory of Gondar University Teaching Hospital. Data were cross checked for completeness, entered and analyzed using SPSS version 16 statistical package. From the total of 2,684 clinicaly suspected hepatitis patients, 563 (20.98%) were positive for HBsAg and anti-HCV test. Of all, 14.4% were seropositive for HBV (male= 7.89% female=6.27%) (p-value=0.011) while 12.4% were seropositive for HCV (male =7.6% and female=4.13%) (p-value<0.001). The co-incidence of HBV and HCV were found to be 36 (6.39%) (male=3.9% and female=2.4%) (p-value <0.001). Majority of HBV (30.2%) and HCV (30.7%) infections were detected among age group of 25-34 years old (p-value=0.36) and 15-24 years old (p-value<0.001) respectively. The overall prevalence of HBV and HCV is high. Males and younger age groups were more affected. Community awareness about the transmission and prevention of viral hepatitis infection should be strengthened by giving health education and herd immunization.


Introducing the "Bone-Screw-Fastener" for improved screw fixation in orthopedic surgery: a revolutionary paradigm shift?
Conventional screws used for fracture fixation in orthopedic surgery continue to rely on the historic buttress thread design. While buttress screws generally provide solid resistance against unidirectional axial loading forces, their design suffers from several limitations, as the buttress thread does not adequately resist multiaxial forces. Furthermore, the buttress screw is prone to stripping at the bone-screw interface and can cause microfracturing of the surrounding bone due to its thread design. Standard buttress screws are therefore at risk of adverse postoperative outcomes secondary to failure of bone fixation. A new patented Bone-Screw-Fastener was recently designed that is based on an interlocking thread technology. This new fastener provides distributive forces from the threads onto the bone and therefore resists loads in multiple directions. The underlying concept is represented by a "female thread" bone cutting technology designed to maximize bone volume, preserve bone architecture, and create a circumferential interlocking interface between the implant and bone that protects the thread from stripping and from failing to multiaxial forces. We hypothesize that the new Bone-Screw-Fastener overcomes the classic shortcomings of conventional orthopedic screws with buttress threads by ease of insertion, improved bone preservation, increased resistance to off-axis multidirectional loading forces and to stripping of the threads. These advanced biomechanical and biological properties can potentially mitigate the classic limitations of conventional buttress screws by providing better resistance to implant failure under physiological loads, preserving bone biology, and thus potentially improving patient outcomes in the future. The presumed superiority of the new fastener will require testing and validation in well-designed prospective multicenter randomized controlled trials (RCTs), using the conventional buttress screw as control. Once validated in multicenter RCTs, the new Bone-Screw-Fastener may drive a change in paradigm with regard to its innovative biomechanical principles and biologic bone preservation for surgical applications requiring screw fixation.


Maternal morbidity rates in a managed care population.
To identify and estimate prevalence rates of maternal morbidities by pregnancy outcome and selected covariates during the antepartum, intrapartum, and postpartum periods in a defined population of pregnant women. We used electronic data systems of a large, vertically integrated, group-model health maintenance organization (HMO) to develop an algorithm that searched International Classification of Diseases, 9th Revision, Clinical Modification, codes for 38 predetermined groups of pregnancy-related complications among women enrollees of this HMO between January 1, 1998, and December 31, 2001. We identified 24,481 pregnancies among 21,011 women. Although prevalence and type of morbidity varied by pregnancy outcome, overall, 50% of women had at least one complication. The most common complications were anemia (9.3%), urinary tract infections (9.0%), mental health conditions (9.0%), hypertensive disorders (8.5%), and pelvic and perineal trauma (7.0%). A range of mild-to-severe pregnancy complications were identified using linked inpatient and outpatient databases. The most common complications we found usually do not require hospitalization so would be missed in studies that use only hospitalization data. Our data allowed examination of a broad scope of conditions and severity. These findings increase our understanding of the extent of maternal morbidity. II.


Hematopoietic Stem Cell Transplant for Immune Deficiency and Immune Dysregulation Disorders.
Primary immunodeficiency disorders were among the first diseases in which hematopoietic stem cell transplant (HSCT) was attempted. Initial attempts at HSCT were discouraging and fraught with complications, but with increased knowledge and sophistication of HLA typing and donor matching, development of improved transplant conditioning regimens, and advances in prophylaxis and treatment of graft-versus-host disease, there has been a marked improvement in outcomes. This improvement has allowed an ever-growing number of different immunodeficiency and immune dysregulation disorders to be treated by HSCT. This article provides an overview of the approach to HSCT in these disorders.


Complement system activation by contrast media in neuroradiology.
Complement system activation was studied in six series of 12 patients undergoing routine contrast study following IV injection of five recently developed contrast media. The decreasing order of effectiveness on the complement system was as follows: ioxaglic acid, metrizamide, iodamidol. Metrizoic and ioxithalamic acids did not provoke any complement depletion at the doses used in this study. Both pathways of activating the complement system were involved. We could not find any definite correlation with osmolarity, ionic or nonionic formulation, protein binding, or hydrophobicity.


Design and synthesis of thiol-reactive lipopeptides.
Lipopeptides are potent adjuvants that trigger an immune response against covalently conjugated low molecular mass antigens. We report here the design and synthesis of thiol-reactive lipopeptides (6, 7) which can be incorporated into liposomes and react, under mild conditions, with synthetic peptides carrying a thiol function.


Evaluation of the SMARTCHEK Genesystem RT-qPCR assay for the detection of SARS-CoV-2 in clinical samples.
The COVID-19 pandemic remains the main public health problem, due to the quick and easy dissemination of the causal agent, SARS-CoV-2 virus, around the world. Since the beginning of the pandemic, an opportune laboratory diagnosis has been critical to respond this emergency, and RT-qPCR has been used as reference molecular tests for detection of SARS-CoV-2. In this study, we performed the evaluation of a RT-qPCR SMARTCHEK platform (SMARTCHEK, Genesystem) for SARS-CoV-2 detection based on the amplification of RdRp and N gene markers. The platform was evaluated with nasopharyngeal swab samples corresponding to 360 suspected cases of COVID-19 which were remitted to Instituto Nacional de Salud in Peru. This quick method was compared with conventional RT-qPCR as gold standard. The RT-qPCR SMARTCHEK showed a 98.1% sensitivity (CI: 93.3-99.8%), a 98.8% specificity (CI: 96.6-99.8%), a 97.2% positive predictive value (CI: 92-99.4%) and a 99.2% negative predictive value (CI: 97.2-99.9%). The assay demonstrated a strong agreement between the RT-qPCR SMARTCHEK and conventional RT-qPCR (kappa value ≥ 0.966). The RT-qPCR SMARTCHEK is a platform that gives reliable and fast results, with high sensitivity and specificity for the detection of SARS-CoV-2, and it will be considered a suitable alternative to COVID-19 diagnosis in low-resource settings.


Rupture of liver metastasis in high-volume metastatic prostate cancer patient on androgen deprivation therapy combined with upfront docetaxel chemotherapy.
Recent studies have indicated an improvement in the survival rate of patients using docetaxel in addition to androgen deprivation therapy for high-volume metastatic hormone-sensitive prostate cancer. Hepatorrhexis, characterized by the rupture of the liver, is a rare complication associated with chemotherapies. We report a case of hepatic metastases rupture during androgen deprivation therapy combined with upfront docetaxel chemotherapy. A 77-year-old man diagnosed with high-volume metastatic hormone-sensitive prostate cancer received an upfront docetaxel treatment combined with androgen deprivation therapy. Hepatic metastases rupture with substantial hemoperitoneum occurred on the 14th day of the fifth cycle of docetaxel chemotherapy. Transcatheter arterial embolization was performed; however, despite receiving optimal supportive care, the patient died. The addition of upfront docetaxel to androgen deprivation therapy may be effective in patients with high-volume metastatic hormone-sensitive prostate cancer; however, strict observation is required to monitor for the occurrence of rare complications, including hepatorrhexis.


Long-term effects of a community intervention for early identification of first-episode psychosis.
To assess whether an Early Case Identification Program (ECIP) for first-episode psychosis (FEP), which showed no significant short-term effects, has a delayed impact on duration of untreated psychosis (DUP). Using a historical control design, FEP patients were assessed on clinical variables over three consecutive phases, 2 years prior, 2 years during and 3 years after implementation of the ECIP. Additional analyses were conducted on non-affective and schizophrenia spectrum psychoses cases only. There was no overall significant difference in DUP across the three phases. For cases treated within the first year of illness a nonsignificant reduction in DUP to less than 2 months observed during the active phase was sustained post-ECIP. In some jurisdictions community-wide early case detection may fail to have an immediate or delayed effect on DUP, especially for cases who normally present for treatment with DUP >1 year.


Idiopathic ulcerative colitis in Istanbul: clinical review of 204 cases.
A clinical review of 204 cases of idiopathic ulcerative colitis (IUC) seen in an insurance hospital in Istanbul during a period of nine years is presented. The criteria of diagnosis were based on history and results of rectosigmoidoscopic, biopsy, and barium-enema examinations. In the majority of cases (74 per cent), the disease manifested in the mild form, despite a history of one to five years' duration at the time of diagnosis. These patients usually had single attacks, with recovery in reponse to treatment. The mortality rate for the whole series was 3.9 per cent. Death occurred in eight cases of patients who had the severe form of the disease involving the entire colon, with fulminating courses. One additional death was due to an accident. Treatment consisted of a high-protein, low residue diet, vitamins, rest, sulfa drugs and steroids. Azathioprine, in addition, was used in fulminating cases. Surgery supplemented medical therapy in 19 cases. Indications for surgical treatment were resistance to medical management, cancer, and polyposis. Only two patients (1.0 per cent) were found to have cancer during the follow-up period. These two were operated upon. Idiopathic ulcerative colitis is not a rare entity; with awareness and use of appropriate diagnosis facilities, more cases are being discovered.


Consensus of multiple national guidelines: agreed strategies for initial stone management during COVID-19.
To review the existing available information regarding urolithiasis management and the impact of COVID-19 on this, and propose recommendations for management of emergency urolithiasis presentations in the COVID-19 era. Review of published guidelines produced by Urological Governing Bodies, followed by the literature review regarding urolithiasis management during the COVID-19 pandemic. Consistent recommendations across guidelines and literature were that urolithiasis with concurrent sepsis or renal failure remains a urological emergency warranting urgent intervention within the pandemic environment. Ureteric stenting and percutaneous nephrostomy are considered equivalent for decompression in this setting, with both ideally to be performed under local anaesthesia where possible to spare ventilators and reduce aerosol-generating procedures. Greater utilization of medical expulsive therapy and dissolution chemolysis may occur during the pandemic, and longer indwelling stent times may be accepted while definite stone clearance is deferred. Urolithiasis will continue to be a source of emergency presentations requiring urgent intervention during the COVID-19 pandemic. However, it is possible to limit these interventions to decompression of the collecting system in the setting of concurrent obstruction or infection, performed under local anaesthesia to limit use of resources and minimise aerosol-generating procedures, with deferral of definitive management.


Indicators of haemodynamic instability and left ventricular function in a porcine model of esmolol induced negative inotropy.
To investigate if the Hypotension Prediction Index was an early indicator of haemodynamic instability in a negative inotropy porcine model, and to assess the correlation of commonly measured indicators of left ventricular systolic function. Eight anaesthetised pigs were volume resuscitated and then underwent an incremental infusion of esmolol hydrochloride (0-3000 mg/hr), following which it was then reduced in a stepwise manner. Full haemodynamic measurements were taken at each stage and measurements of left ventricular systolic function including left ventricular stroke work index, ejection fraction and peripheral dP/dT were obtained. At an infusion rate of 500 mg/hr of esmolol there were no significant changes in any measured variables. At 1000 mg/hr MAP was on average 11 mmHg lower (95% CI 1 to 11 mmHg, p = 0.027) with a mean of 78 mmHg, HPI increased by 33 units (95% CI 4 to 62, p = 0.026) with a mean value of 63. No other parameters showed significant change from baseline values. Subsequent increases in esmolol showed changes in all parameters except SVV, SVR and PA mean. Correlation between dP/dt and LVSWI was 0.85 (95% CI 0.77 to 0.90, p < 0.001), between LVEF and dP/dt 0.39 (95% CI 0.18 to 0.57, p < 0.001), and between LSWI and LVEF 0.41 (95% CI 0.20 to 0.59, p < 0.001). In this model haemodynamic instability induced by negative inotropy was detected by the HPI algorithm prior to any clinically significant change in commonly measured variables. In addition, the peripheral measure of left ventricular contractility dP/dt correlates well with more established measurements of LV systolic function.


Maternal zinc supplementation improves spatial memory in rat pups.
A large body of evidence supports an opinion that adequate dietary zinc is essential for prenatal and postnatal brain development. Behavioural effects of maternal supplementation with ZnSO(4) were analysed in rat pups with the Morris water task performance, a hole board and a T-maze. Wistar females during pregnancy and lactation received a drinking water solution of ZnSO(4) at doses of 16 mg/kg (group Zn16) or 32 mg/kg (group Zn32). Behavioural tests were conducted on the 4-week-old male rat pups. Zinc concentration in the serum, hippocampus and prefrontal cortex of offsprings was determined by means of atomic absorption techniques. The Newman-Keuls multiple comparison test revealed an increase of climbing in the Zn16 group in comparison to the control group (Con) and the Zn32 group during the hole board test. ANOVA for repeated measures showed a significant memory improvement in both supplemented groups compared to the control in the probe trial on day 5 of the water maze test. ZnSO(4) treatment significantly elevated zinc levels in the rat serum. Follow-up data on brain content of zinc in the hippocampus revealed significant differences between the groups and in supplemented groups correlated with crossings above the original platform position. These findings suggest that pre- and postnatal zinc supplementation may improve cognitive development in rats.


Can microplastics from personal care products affect stream microbial decomposers in the presence of silver nanoparticles?
Microplastics (MPs) are emerging contaminants of great concern due to their abundance and persistence over time in aquatic environments. However, studies on their impacts on freshwater organisms are scarce. In resemblance, silver nanoparticles (Ag-NPs) are incorporated into textiles and personal care products and are also classified as emerging contaminants. We used the leaf litter decomposition model system to investigate the effects of MPs from a commercially used personal care product, alone or in mixture with Ag-NPs, on the diversity and activities of freshwater microbial decomposers. We exposed stream microbial communities associated with leaf litter to increasing concentrations of MPs (polyethylene extracted from a personal care product; 100 μg L-1 up to 1 g L-1 5 concentrations plus 1 control) for 27 days in the absence or presence of Ag-NPs (0.1 mg L-1 and 1 mg L-1). The exposure to MPs, alone or in mixture with Ag-NPs, negatively affected fungal diversity and sporulation, with a reduction in leaf litter decomposition (Cohen's d > 1.5; r> 0.8; Bonferroni, P < 0.01). Shifts in community structure of sporulating fungi were observed, and effects were more pronounced in mixtures with Ag-NPs at the highest concentration. Mixtures of MPs with Ag-NPs (at the higher concentration) had the strongest impacts on extracellular enzymatic (β-glucosidase, Cohen's d > 1; r > 0.5; phenol oxidase, Cohen's d > 1; r > 0.4) activities (ANOVAs, P < 0.05). Apart from sporulation rates, observed toxicity in mixtures was lower than that expected based on individual toxicity effects, mainly for higher concentrations (Bonferroni, P < 0.05). Our study provided evidence of the potential harmful effects of MPs, alone or in mixtures with Ag-NPs, on the activities of aquatic fungi and on a key ecosystem process, determinant to organic matter turnover in streams.


Budget Impact Analysis of Expanding Gliflozin Coverage in the CKD Population: A French Perspective.
Gliflozins have historically been indicated for type 2 diabetes in France. However, their efficacy has recently been demonstrated in heart failure and chronic kidney disease (CKD), with positive recommendations by Haute Autorité de Santé for gliflozin therapies in these indications. The study objective was to investigate the 5-year budget impact associated with the introduction of gliflozins in addition to standard therapy in people with CKD and elevated albuminuria, regardless of diabetes status, from the perspective of the French healthcare system. A budget impact model was developed to estimate the 5-year implications of incorporating gliflozins in the treatment of patients with CKD in France, using efficacy data from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial. Direct medical costs associated with drug acquisition and management, treatment-related adverse events, dialysis and kidney transplantation, and adverse clinical outcomes were considered. Market share forecasts were estimated from historical data and expert opinions. Event rates were derived from trial data, while cost data were sourced from published estimates. The introduction of gliflozins was estimated to be cost saving compared to the no gliflozins scenario, with an expected cumulative 5-year budget impact of -€650 million, driven by slowed disease progression in patients treated with gliflozins, with fewer patients cumulatively progressing to end-stage kidney disease (84,526 vs. 92,062). This, in addition to fewer hospitalisations for heart failure and deaths from any cause, led to substantial medical care cost offsets (kidney-related: - €894 million; hospitalisation for heart failure: - €14.3 million; end-of-life care: - €17.3 million) to the additional drug acquisition (€273 million) and treatment-related adverse events costs (€2.98 million). In concert with early diagnosis and proactive management of CKD, the expansion of the gliflozin indications into the French CKD population presents the opportunity to reduce the substantial burden associated with cardio-renal complications which outweighs the additional cost of the new treatment. INFOGRAPHIC.


[Retrograde partial hepatectomy: report of 11 patients].
To study a new approach to hepatectomy for liver tumors resected difficulty by typical method. The operative order is retrograde as compared with typical hepatectomy, namely, transection of the liver is performed first, isolating adhesions between the tumor and the diaphragm or partial invaded phrenectomy is performed second, and then after cutting corresponding ligaments, liver tumor is removed. If the surrounding organs were invaded or adhered by tumor too tightly to be separated. They were resected with the tumor. The approach was used in 11 patients with malignant tumors of liver from June 1994 to January 1996. Operation time was 192 min (150 - 250 min) and estimated blood loss during operation was 1460 ml (800 - 4, 200 ml). No operative mortality was found and all of the patients recovered uneventfully. The retrograde partial hepatectomy is a good method for resection of liver tumors resected difficulty by typical hepatectomy.


Mapping splice QTLs reveals distinct transcriptional and post-transcriptional regulatory variation of gene expression and identifies putative alternative splicing variation mediating complex trait variation in pigs.
Alternative splicing is an important step in gene expression, generating multiple isoforms for the same genes and greatly expanding the diversity of proteomes. Genetic variation in alternative splicing contributes to phenotypic diversity in natural populations. However, the genetic basis of variation in alternative splicing in livestock including pigs remains poorly understood. In this study, using a Duroc x Pietrain F2 pig population, we performed genome-wide analysis of alternative splicing estimated from stranded RNA-Seq data in skeletal muscle. We characterized the genetic architecture of alternative splicing and compared its basic features with those of overall gene expression. We detected a large number of novel alternative splicing events that were not previously annotated. We found heritability of quantitative alternative splicing scores (percent spliced in or PSI) to be lower than that of overall gene expression. In addition, heritabilities showed little correlation between alternative splicing and overall gene expression. We mapped expression QTLs (eQTLs) and splice QTLs (sQTLs) and found them to be largely non-overlapping. Finally, we integrated sQTL mapping with phenotype QTL (pQTL mapping to identify potential mediator of pQTL effect by alternative splicing. Our results suggest that regulatory variation exists at multiple levels and that their genetic controls are distinct, offering opportunities for genetic improvement.


Genotoxicity assessment of per- and polyfluoroalkyl substances mixtures in human liver cells (HepG2).
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, toxic, and persistent environmental chemicals of concern that have been widely detected in all environmental matrices including human biological fluids. Although humans are exposed to complex mixtures of PFAS, it remains uncertain whether the co-exposure to PFAS mixtures could induce genotoxic damage in humans. Hence, this study evaluated the combined genotoxicity of PFAS mixtures in a human cell line system. To assess the possible genotoxic damage caused by human exposure to PFAS and their mixtures, we investigated their potential to induce cytotoxicity (cell viability) and genotoxicity (DNA damage) in a human liver cell line (HepG2). The selected PFAS include perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS). The interaction toxicities of these PFAS in binary mixtures were also determined using the additive index approach. The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures induced a concentration-dependent decrease in cell viability. The additive index values indicated that the binary mixtures of PFOS + PFNA, PFOS + PFDA, and PFOS + PFOA displayed synergistic interaction, whereas the binary mixtures of PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS behaved additively. Using the alkaline Comet assay, the potential of PFAS and their mixtures to induce DNA damage was evaluated based on a 1:1 ratio of the concentration of respective compounds required to produce a 1/10th of effective concentrations causing 50 % inhibition in cell viability (EC50). The results revealed that exposure to PFNA, PFOS, PFDA, PFOA, and PFHxS singly and in binary mixtures (PFOS + PFNA, PFOS + PFDA, PFOS + PFOA, PFOS + PFHxS, PFOA + PFNA, PFOA + PFDA, and PFOA + PFHxS) caused a moderate increase in cellular DNA damage, but no dose-response relationship was observed. Overall, this study indicates that the tested PFAS causes a concentration-dependent decrease in cell viability and only a modest increase in cellular DNA damage under these conditions.


Direct measurements of mRNA translation kinetics in living cells.
Ribosome mediated mRNA translation is central to life. The cycle of translation, however, has been characterized mostly using reconstituted systems, with only few techniques applicable for studies in the living cell. Here we describe a live-cell ribosome-labeling method, which allows us to characterize the whole processes of finding and translating an mRNA, using single-molecule tracking techniques. We find that more than 90% of both bacterial ribosomal subunits are engaged in translation at any particular time, and that the 30S and 50S ribosomal subunits spend the same average time bound to an mRNA, revealing that 30S re-initiation on poly-cistronic mRNAs is not prevalent in E. coli. Instead, our results are best explained by substantial 70S re-initiation of translation of poly-cistronic mRNAs, which is further corroborated by experiments with translation initiation inhibitors. Finally, we find that a variety of previously described orthogonal ribosomes, with altered anti-Shine-Dalgarno sequences, show significant binding to endogenous mRNAs.


Periodic solutions in next generation neural field models.
We consider a next generation neural field model which describes the dynamics of a network of theta neurons on a ring. For some parameters the network supports stable time-periodic solutions. Using the fact that the dynamics at each spatial location are described by a complex-valued Riccati equation we derive a self-consistency equation that such periodic solutions must satisfy. We determine the stability of these solutions, and present numerical results to illustrate the usefulness of this technique. The generality of this approach is demonstrated through its application to several other systems involving delays, two-population architecture and networks of Winfree oscillators.


Microalgal secondary metabolite productions as a component of biorefinery: A review.
The interest in developing microalgae for industrial use has been increasing because of concerns about the depletion of petroleum resources and securing sustainable energy sources. Microalgae have high biomass productivity and short culture periods. However, despite these advantages, various barriers need to be overcome for industrial applications. Microalgal cultivation has a high unit price, thus rendering industrial application difficult. It is indispensably necessary to co-produce their primary and secondary metabolites to compensate for these shortcomings. In this regard, this article reviews the following aspects, (1) co-production of primary and secondary metabolites in microalgae, (2) induction methods for the promotion of the biosynthesis of secondary metabolites, and (3) perspectives on the co-production and co-extraction of primary and secondary metabolites. This paper presents various approaches for producing useful metabolites from microalgae and suggests strategies that can be utilized for the co-production of primary and secondary metabolites.


The pediatrician's guide to managing the difficult pediatric headache patient.
Pediatric headache is a common pain complaint in children and adolescents, and pediatricians are the first source of headache assessment and treatment. This article provides guidelines for pediatricians in managing difficult headache patients typically seen in our practice. The 3 categories we typically evaluates and treats include (a) "It's medical, not psychological"; (b) "You're the only doctor who can help me"; and (c) "My child is perfect." A brief case presentation illustrates each of these categories of patients. Specific recommendations for treatment, as well as guidelines for parents, are provided.


Laser speckle contrast analysis: a new method to evaluate peripheral blood perfusion in systemic sclerosis patients.
The aim of this pilot study was to assess peripheral blood perfusion (PBP) by a new technique, the laser speckle contrast analysis (LASCA), in systemic sclerosis (SSc) patients showing different patterns of nailfold microangiopathy. Correlations between LASCA and single laser Doppler flowmetry (LDF) analysis were also checked. Sixty-one SSc patients and 61 healthy subjects were enrolled. PBP was evaluated using LASCA and LDF. Scleroderma patterns and microangiopathy evolution score (MES) were assessed by nailfold videocapillaroscopy (NVC). As detected by LASCA and LDF, PBP was lower in SSc patients than in healthy subjects (p<0.0001), showing SSc patients with the 'Early', 'Active' or 'Late' NVC pattern a progressively lower PBP (p=0.04 and p=0.002, respectively). There was a negative correlation between PBP and MES values (p=0.006 and p=0.002 for LASCA and LDF, respectively). A positive correlation was detected between LASCA and LDF values, in all subjects (p<0.0001). However, LASCA evaluates larger skin areas, is significantly less time consuming, is more accepted by patients and shows lower intra-operator variability than LDF. LASCA detected lower PBP in SSc patients than in healthy subjects, and for the first time, LASCA perfusion values were found correlated with progression of NVC patterns of microangiopathy.


The glucocorticoid domain of response: measurement of pleiotropic cellular responses by two-dimensional gel electrophoresis.
In this article, we have provided two examples of pleiotropic regulation by specific effector molecules as assayed by two-dimensional gel electrophoresis. In one case, catabolite repression in the bacterium Escherichia coli was examined by measuring the response to cyclic cAMP. In the other, the effect of dexamethasone on the rate of synthesis of over a thousand cell proteins was analyzed in HTC cells. It was found that in E. coli, cAMP regulates the synthesis of about 10 percent of the cell's proteins; both inductions and repressions are observed, but inductions clearly predominate. In HTC cells, dexamethasone induces the synthesis of seven proteins, or about 0.7 percent of the total cellular proteins; repression was not consistently observed. In another rat hepatoma line (FAZA) a similar number but essentially different set of proteins was induced. These data are discussed in terms of the notion of domains of response originally proposed by TOMKINS [1].


MRI Based Preterm White Matter Injury Classification: The Importance of Sequential Imaging in Determining Severity of Injury.
The evolution of non-hemorrhagic white matter injury (WMI) based on sequential magnetic resonance imaging (MRI) has not been well studied. Our aim was to describe sequential MRI findings in preterm infants with non-hemorrhagic WMI and to develop an MRI classification system for preterm WMI based on these findings. Eighty-two preterm infants (gestation ≤35 weeks) were retrospectively included. WMI was diagnosed and classified based on sequential cranial ultrasound (cUS) and confirmed on MRI. 138 MRIs were obtained at three time-points: early (<2 weeks; n = 32), mid (2-6 weeks; n = 30) and term equivalent age (TEA; n = 76). 63 infants (77%) had 2 MRIs during the neonatal period. WMI was non-cystic in 35 and cystic in 47 infants. In infants with cystic-WMI early MRI showed extensive restricted diffusion abnormalities, cysts were already present in 3 infants; mid MRI showed focal or extensive cysts, without acute diffusion changes. A significant reduction in the size and/or extent of the cysts was observed in 32% of the infants between early/mid and TEA MRI. In 4/9 infants previously seen focal cysts were no longer identified at TEA. All infants with cystic WMI showed ≥2 additional findings at TEA: significant reduction in WM volume, mild-moderate irregular ventriculomegaly, several areas of increased signal intensity on T1-weighted-images, abnormal myelination of the PLIC, small thalami. In infants with extensive WM cysts at 2-6 weeks, cysts may be reduced in number or may even no longer be seen at TEA. A single MRI at TEA, without taking sequential cUS data and pre-TEA MRI findings into account, may underestimate the extent of WMI; based on these results we propose a new MRI classification for preterm non-hemorrhagic WMI.


Toxic hepatitis in black patients in natal.
The clinical and pathological features of toxic centrilobular zonal necrosis in Natal Blacks are described. It is suggested that this condition may be caused by the toxic action of Callilepis laureola (known to the Zulu as 'impila'). This plant and other herbs are used by many Blacks for self-medication or are prescribed by herbalists and witchdoctors.


Quantitative nuclear cystogram. Aid in determining spontaneous resolution of vesicoureteral reflux.
The quantatitative data derived from serial nuclear cystograms over a five-year period in 37 children were compared with the clinical course. A direct correlation (92 per cent) between an increasing bladder volume at which reflux occurs was observed in the clinically stable group. In the clinically unstable group, there was a 75-per cent correlation of an unchanged or decreasing bladder volume at which reflux occurs. The quantitative nuclear cystogram provides an objective as opposed to subjective data base for management of patients with vesicoureteral reflux.


Structural basis for high selectivity of a rice silicon channel Lsi1.
Silicon (Si), the most abundant mineral element in the earth's crust, is taken up by plant roots in the form of silicic acid through Low silicon rice 1 (Lsi1). Lsi1 belongs to the Nodulin 26-like intrinsic protein subfamily in aquaporin and shows high selectivity for silicic acid. To uncover the structural basis for this high selectivity, here we show the crystal structure of the rice Lsi1 at a resolution of 1.8 Å. The structure reveals transmembrane helical orientations different from other aquaporins, characterized by a unique, widely opened, and hydrophilic selectivity filter (SF) composed of five residues. Our structural, functional, and theoretical investigations provide a solid structural basis for the Si uptake mechanism in plants, which will contribute to secure and sustainable rice production by manipulating Lsi1 selectivity for different metalloids.


Effectiveness of dishwashing liquids in removing chlorothalonil and chlorpyrifos residues from cherry tomatoes.
Washing is the most practical way to remove pesticide residues in fruits and vegetables. Two commonly used kitchen dishwashing liquids (detergents) in Chinese market were tested for enhanced removal of chlorpyrifos (CHP) and chlorothalonil (CHT) in cherry tomatoes by soaking the cherry tomatoes in the detergent solutions. The critical micelle concentrations of detergent A and detergent B were about 250 mg L(-1) and 444 mg L(-1), respectively. Detergent A had a higher solubilizing ability for pesticides and hence washing effectiveness than detergent B. The apparent solubility of CHP increased with increasing detergent concentration, while that of CHT remained comparatively invariant independent of detergent concentration within the tested range. The apparent solubility of CHP was also consistently higher in solutions of both detergents as compared to CHT. Due probably to its lower logKow value, CHT was more readily washed off cherry tomatoes than CHP. In terms of washing, a duration of 10-20 min was sufficient for removal of pesticides on cherry tomatoes in distilled water and detergent solutions. The effectiveness of removing pesticides increased with increasing detergent concentration from 50 mg L(-1) to 5 g L(-1), with up to 80% CHT and 42% CHP removed. Multiple washing further increased pesticide removal. Adding 10% acetic acid to lower pH or increasing washing temperature favored pesticide removal, but 10% NaCl produced the shielding effect and substantially reduced the effectiveness of detergent A for pesticide removal.


Selenium Deficiency Caused Fibrosis as an Oxidative Stress-induced Inflammatory Injury in the Lungs of Mice.
Selenium (Se) is a vital trace element in the regulation of inflammation and antioxidant reactions in both animals and humans. Se deficiency is rapidly affecting lung function. The present study investigated the molecular mechanism of Se deficiency aggravates reactive oxygen species (ROS)-induced inflammation, leading to fibrosis in lung. Mice fed with different concentrations of Se to establish the model. In the Se-deficient group, the ROS and malondialdehyde (MDA) was increased, and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and catalase (CAT) reduced. The histopathological observation showed that Se deficiency lead to lung texture damage with varying degrees of degeneration, necrosis, shedding of some alveolar epithelial cells, and inflammatory cell infiltration. Immunohistochemistry showed that the expression of α-smooth muscle actin (α-SMA) increased. The fibrosis index was verified with Sirius red staining. The ELISA and qPCR results showed that the inflammatory cytokines (TNF-α and IL-1β) and ECM (collagen I, collagen IV, fibronectin, and laminin) were increased with ROS increasing, which was induced by Se deficiency. The results displayed that oxidative stress with Se deficiency led to an increase in tissue inhibitors of metalloproteinase (TIMPs), but a decrease in matrix metalloproteinases (MMPs). All the results indicated that Se deficiency induced excessive ROS accumulation to generate inflammation, which disrupted ECM homeostasis and aggravated fibrosis in the lung.


Analgesic efficacy of piroxicam in the treatment of postoperative pain.
Two randomized, double-blind, single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain. Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo. A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours, with a global assessment made at the completion of 24 hours. Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables, including the sum of the pain intensity differences (SPID), total pain relief (TOTAL), percent SPID, duration of effect, and time to remedication. Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures. Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication. Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo. Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication. Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference (PID) and relief scores, as well as for SPID and TOTAL. Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL. Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID, TOTAL, and hourly measures beginning with Hour 6 through Hour 12. Piroxicam 20 mg was significantly better than aspirin for a few hourly measures: Hours 7 to 9 for relief and Hour 7 for PID. In addition, effects of piroxicam 20 mg had a significantly longer duration than aspirin. Similarly, piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo. The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain.