Risk factors for locoregional recurrence after postmastectomy radiotherapy in breast cancer patients with four or more positive axillary lymph nodes.
We investigated risk factors for locoregional recurrence (lrr) in breast cancer patients with 4 or more positive axillary lymph nodes receiving postmastectomy radiotherapy (pmrt). Medical records (1998-2007) were retrospectively reviewed for the population of interest. The Kaplan-Meier method was used to calculate the survival rate; Cox regression models were used for univariate and multivariate analysis of predictors of breast cancer lrr. The study enrolled 439 patients. Median duration of follow-up was 54 months. The 5-year rates of locoregional recurrence-free survival (lrrfs), distant metastasis-free survival (dmfs), and breast cancer-specific survival (bcss) were 87.8%, 59.5%, and 70.7% respectively. In patients with lrr and no concomitant metastasis, and in those without lrr, the 5-year rates of dmfs were 21.1% and 65.7% respectively (p < 0.001), and the 5-year rates of bcss were 34.5% and 76.4% respectively (p < 0.001). Univariate analysis showed that menopausal status (p = 0.041), pN stage (p = 0.006), and positivity for her2 [human epidermal growth factor receptor 2 (p = 0.003)] or the triple-negative disease subtype (p < 0.001) were determinants of lrrfs. Multivariate analysis showed that pN3 stage [hazard ratio (hr): 2.241; 95% confidence interval (ci): 1.270 to 3.957; p = 0.005], her2 positivity (hr: 2.705; 95% ci: 1.371 to 5.335; p = 0.004), and triple-negative disease subtype (hr: 4.617; 95% ci: 2.192 to 9.723; p < 0.001) were independent prognostic factors of lrrfs. In breast cancer patients with 4 or more positive axillary lymph nodes who undergo pmrt for breast cancer, lrr significantly influences survival. Patients who developed lrr carried a high risk for distant metastasis and death. Pathologic stage (pN3), her2 positivity, and the triple-negative disease subtype are risk factors that significantly influence lrrfs.


Missing atom as a source of carbon magnetism.
Atomic vacancies have a strong impact in the mechanical, electronic, and magnetic properties of graphenelike materials. By artificially generating isolated vacancies on a graphite surface and measuring their local density of states on the atomic scale, we have shown how single vacancies modify the electronic properties of this graphenelike system. Our scanning tunneling microscopy experiments, complemented by tight-binding calculations, reveal the presence of a sharp electronic resonance at the Fermi energy around each single graphite vacancy, which can be associated with the formation of local magnetic moments and implies a dramatic reduction of the charge carriers' mobility. While vacancies in single layer graphene lead to magnetic couplings of arbitrary sign, our results show the possibility of inducing a macroscopic ferrimagnetic state in multilayered graphene just by randomly removing single C atoms.


Lipid digestion in cystic fibrosis: comparison of conventional and high-lipase enzyme therapy using the mixed-triglyceride breath test.
Fat maldigestion occurs in most patients with cystic fibrosis. Conventional pancreatic enzyme replacement therapy partially corrects this defect. In this study, the mixed-triglyceride breath test was used to evaluate whether high-lipase enzymes are equivalent to conventional enzymes in improving fat maldigestion in children with cystic fibrosis. Fat digestion was studied in 11 patients with a mean age of 10.5 years. The mean intake of conventional enzyme capsules a day was 19. Four 13C mixed-triglyceride tests were performed on separate days and in random order. One test was taken without enzyme substitution, one with three capsules of 8,000 FIP units Creon (pancreatinum, Kali-chemie Pharma, Hannover, Germany) and one with one capsule of 25,000 FIP units. The fourth test was made with 13C octanoic acid to study gastric emptying time. Without enzyme intake, the mean cumulative percentage of 13C dose exhaled after 6 hours was 7.2+/-3.7%. This increased to 14.4+/-4% with intake of conventional pancreatinum and to 14.3+/-5.1% with intake of high-lipase pancreatinum (p = 0.0008 for both; paired t-test). There was no difference between both treatments. Also, the time course of 13C exhalation measured by percentage of 13CO2 exhaled per hour did not differ between enzyme treatments. The 13C mixed-triglyceride test is noninvasive and documents improved lipid digestion with pancreatic enzyme replacement therapy. If the lipase dose is kept constant, results obtained with high-lipase preparations are equivalent to those obtained with conventional preparations.


Obesity and patient-reported sexual health outcomes in gynecologic cancer survivors: A systematic review.
As obesity prevalence among gynecologic cancer (GC) survivors is expected to increase, the role of obesity in sexual health needs to be understood. This systematic review examined the impact of obesity on patient-reported sexual health outcomes (SHOs) in this population. PubMed, Embase, Web of Science, CINAHL, and PsycINFO were searched for original studies published between 2015 and 2020 following the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. We performed a narrative synthesis of findings via cancer type, cancer treatment, sexual health measures, and countries. Eleven observational studies were included. Most were conducted in European countries (n = 7), reported on endometrial cancer survivors (n = 7), and defined obesity as body mass index ≥30 kg/m2 (n = 10). Studies about cervical cancer survivors reported negative effects of obesity on sexual activity and body image while studies about endometrial cancer survivors reported positive effects of obesity on vaginal/sexual symptoms. Findings suggested interaction effects of radiotherapy and obesity on SHOs. Sexual functioning measured by the Female Sexual Function Index was less likely to be associated with obesity than other SHOs. A positive effect of obesity on SHOs was only found in studies conducted in European countries. Current evidence on the association between obesity and sexual health in GC survivors lacks in both quantity and quality. To better understand the effect of obesity on SHOs in the population, more studies are needed with critical evaluations of obesity and sexual health measures, careful considerations of cancer type and treatment, and a focus on the cultural context of obesity.


Non-traditional therapies for diabetes: fact or fiction.
The number of medications now available to treat Type 2 Diabetes has been expanding quickly over the past two decades. At the same time, the use of complementary and alternative medicine (CAM) has also been rising. Individuals with diabetes are 1.6 times more likely than those without diabetes to use modalities that are not considered part of conventional medicine. Numerous dietary supplements are available over the counter and are being advertized to treat diabetes and its co morbidities. No conclusive data on their clinical benefit, potential harms, dosing or interaction with other medications is yet available. But for clinicians to maintain a trusting relationship with their patient, a respectful non-confrontational attitude is needed to encourage open dialogue, provide accurate information, and facilitate changes to the medical regimen. It is essential that clinicians stay informed and advise their patient with the available scientific data accordingly. In this review, we focus on current data on six supplements commonly encountered in community practice for treating diabetes, including cinnamon, fenugreek, vinegar, ginseng, bitter melon, gymnema, chromium, and vanadium.


Methylarsonic and dimethylarsinic acids toxicity and total arsenic accumulation in edible bush beans, Phaseolus vulgaris.
The main objective was to evaluate whether arsenic accumulated in the edible pods and seeds of Phaseolus vulgaris, cv. F15 above the Spanish maximum recommended concentration for food crops, 1 mg kg(-1) on a fresh weight basis. Only organic arsenicals, methylarsonic and dimethylarsinic acids were used because they were: (1) the only arsenic species allowed for agricultural applications and (2) more mobile than inorganic species. Selection of French beans, a sensitive plant to arsenic, was based on the fact that arsenic-upward translocation is higher in sensitive than in tolerant plants. A 2 x 3 factorial experiment was conducted with two organic arsenic species (methylarsonic acid, dimethylarsinic acid) and three arsenic concentrations (0.2, 0.5, 1.0 mg l(-1)). Experimental results showed that the low bean plant tolerance to arsenic was possibly due to the high arsenic-upward transport to shoots, which could result in profound negative metabolic consequences. Even under extreme adverse conditions, arsenic residues in edible beans were below the maximum statutory limit set by the Spanish legislation. It is concluded that the major drawback of organic arsenical herbicides is that of decreased productivity rather than high arsenic intake by consumers of edible products from sensitive plant species.


IRF-1 is an essential mediator in IFN-gamma-induced cell cycle arrest and apoptosis of primary cultured hepatocytes.
IFN-gamma induces cell cycle arrest and p53-independent apoptosis in primary cultured hepatocytes. However, it is not yet understood what molecules regulate the mechanism. We report here that interferon regulatory factor 1 (IRF-1) is an essential molecule in these phenomena. Hepatocytes from IRF-1-deficient mice were completely resistant to IFN-gamma in apoptosis indicated by three different hallmarks such as LDH release, DNA fragmentation and the activation of caspase-3 family. Caspase-1 expression was little detected in hepatocytes, and constitutive and IFN-gamma-induced mRNA expression of Fas or caspase-3 did not change in between wild type and IRF-1-deficient hepatocytes. Expression of IFN-gamma-inducible caspase, caspase-11, did not change either. Thus, it is unlikely that these molecules directly regulate the mechanisms. Interestingly, IRF-1-deficient hepatocytes were also resistant to IFN-gamma-induced cell cycle arrest despite IFN-gamma-induced cell cycle arrest and apoptosis are regulated by independent pathways. Results by Northern blot analysis showed that IFN-gamma-induced but not constitutive p53 mRNA expression was regulated by IRF-1. In fact, IFN-gamma did not induce cell cycle arrest in p53-deficient hepatocytes. Taken together, IRF-1 mediates IFN-gamma signaling into primary hepatocytes for cell cycle arrest via p53 expression and for apoptosis.


Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management.
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with rising incidence. Globally, there has been substantial variation in prevalence of risk factors for HCC over years, like control of viral hepatitis in developing countries but growing epidemic of fatty liver disease in developed world. Changing epidemiology of HCC is related to trends in these risk factors. HCC remains asymptomatic until it is very advanced which makes early detection by surveillance important in reducing HCC related mortality. Management of HCC. depends on stage of the tumor and severity of underlying liver disease. At present, resection and transplant are still the best curative options for small HCC, but recent advances in locoregional therapy and molecular targeted systemic therapy has changed the management for HCC at intermediate and advanced stages. This review is overview of global epidemiology, prevention, surveillance and emerging therapies for hepatocellular carcinoma.


[A case of pelvic recurrence of rectal cancer successfully treated by surgical resection using the extraperitoneal approach].
Here, we report a case of recurrent rectal cancer successfully treated with resective surgery using the extraperitoneal approach. A 73-year-old man underwent the Miles operation for advanced rectal cancer (Rb-P, tub1, pMP, pN0, Stage I). At 20 months after the initial operation, computed tomography( CT) and magnetic resonance imaging( MRI) scans and 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) images showed a recurrent pelvic tumor( 20 mm in diameter) located in the lower presacral region. The tumor was surgically excised. The presacral space was easily exposed by the surgical procedure using the extraperitoneal approach, and the tumor was easily dissected and resected. We conclude that a surgical procedure using the extraperitoneal approach might be effective for the treatment of pelvic recurrence of rectal cancer.


F-spondin interaction with the apolipoprotein E receptor ApoEr2 affects processing of amyloid precursor protein.
A recent study showed that F-spondin, a protein associated with the extracellular matrix, interacted with amyloid precursor protein (APP) and inhibited beta-secretase cleavage. F-spondin contains a thrombospondin domain that we hypothesized could interact with the family of receptors for apolipoprotein E (apoE). Through coimmunoprecipitation experiments, we demonstrated that F-spondin interacts with an apoE receptor (apoE receptor 2 [ApoEr2]) through the thrombospondin domain of F-spondin and the ligand binding domain of ApoEr2. Full-length F-spondin increased coimmunoprecipitation of ApoEr2 and APP in transfected cells and primary neurons and increased surface expression of APP and ApoEr2. Full-length F-spondin, but none of the individual F-spondin domains, increased cleavage of APP and ApoEr2, resulting in more secreted forms of APP and ApoEr2 and more C-terminal fragments (CTF) of these proteins. In addition, full-length F-spondin, but not the individual domains, decreased production of the beta-CTF of APP and Abeta in transfected cells and primary neurons. The reduction in APP beta-CTF was blocked by receptor-associated protein (RAP), an inhibitor of lipoprotein receptors, implicating ApoEr2 in the altered proteolysis of APP. ApoEr2 coprecipitated with APP alpha- and beta-CTF, and F-spondin reduced the levels of APP intracellular domain signaling, suggesting that there are also intracellular interactions between APP and ApoEr2, perhaps involving adaptor proteins. These studies suggest that the extracellular matrix molecule F-spondin can cluster APP and ApoEr2 together on the cell surface and affect the processing of each, resulting in decreased production of Abeta.


Capillarity-Enhanced Organ-Attachable Adhesive with Highly Drainable Wrinkled Octopus-Inspired Architectures.
Mimicking the attachment of octopus suction cups has become appealing for the development of skin/organ adhesive patches capable of strong, reversible adhesion in dry and wet conditions. However, achieving high conformity against the three-dimensionally (3D) rough and curved surfaces of the human body remains an enduring challenge for further medical applications of wound protection, diagnosis, or therapeutics. Here, an adhesive patch inspired by the soft wrinkles of miniaturized 3D octopus suction cups is presented for high drainability and robust attachment against dry and wet human organs. Investigating the structural aspects of the wrinkles, a simple model is developed to maximize capillary interactions of the wrinkles against wet substrates. A layer of soft siloxane derivative is then transferred onto the wrinkles to enhance fixation against dry and sweaty skin as well as various wet organ surfaces. Our bioinspired patch offers opportunities for enhancing the versatility of adhesives for developing skin- and/or organ-attachable devices.


Simulation of conformational preconditioning strategies for electrophoretic stretching of DNA in a microcontraction.
We have used Brownian dynamics-finite element method to examine two conformational preconditioning approaches for improving DNA stretching in a microcontraction for the purpose of direct gene analysis. The newly proposed "pre-stretching" strategy is found to significantly improve the degree of DNA extension at the exit of the contraction. On the other hand, applying an oscillating extensional field to DNA yields no preconditioning effect. Detailed analysis of the evolution of DNA extension and conformation reveals that the success of our "pre-stretching" strategy relies on the "non-local" effect that cannot be predicted using simple kinematics analysis. In other words, accurate prediction can only be obtained using detailed simulations. Comparing to the existing preconditioning strategies, our "pre-stretching" method is easy to implement while still providing a very good performance. We hope that the insight gained from this study can be useful for future design of biomicrofluidic devices for DNA manipulation.


Enzymatic degradation of uric acid by uricase-loaded human erythrocytes.
Erythrocytes containing pig liver uricase have been prepared by hypotonic hemolysis in the presence of the enzyme. Uricase is shown to be active within the erythrocytes and to degrade uric acid as rapidly as it enters the cells when high intracellular enzyme concentrations are employed. The kinetics and characteristics of uric acid entry are shown to be the same for hemolysed and normal erythrocytes. At physiological concentrations of uric acid, loaded erythrocytes can degrade a maximum of about 21 mumol uric acid/liter erythrocytes per min. The possible application of enzyme-loaded erythrocytes to medicine is discussed.


Increased environmental sample area and recovery of Clostridium difficile spores from hospital surfaces by quantitative PCR and enrichment culture.
Clostridium difficile spores play an important role in transmission and can survive in the environment for several months. Optimal methods for measuring environmental C. difficile are unknown. We sought to determine whether increased sample surface area improved detection of C. difficile from environmental samples. Samples were collected from 12 patient rooms in a tertiary-care hospital in Toronto, Canada. Samples represented small surface-area and large surface-area floor and bedrail pairs from single-bed rooms of patients with low (without prior antibiotics), medium (with prior antibiotics), and high (C. difficile infected) shedding risk. Presence of C. difficile in samples was measured using quantitative polymerase chain reaction (qPCR) with targets on the 16S rRNA and toxin B genes and using enrichment culture. Of the 48 samples, 64·6% were positive by 16S qPCR (geometric mean, 13·8 spores); 39·6% were positive by toxin B qPCR (geometric mean, 1·9 spores); and 43·8% were positive by enrichment culture. By 16S qPCR, each 10-fold increase in sample surface area yielded 6·6 times (95% CI, 3·2-13) more spores. Floor surfaces yielded 27 times (95% CI, 4·9-181) more spores than bedrails, and rooms of C. difficile-positive patients yielded 11 times (95% CI, 0·55-164) more spores than those of patients without prior antibiotics. Toxin B qPCR and enrichment culture returned analogous findings. Clostridium difficile spores were identified in most floor and bedrail samples, and increased surface area improved detection. Future research aiming to understand the role of environmental C. difficile in transmission should prefer samples with large surface areas.


Clinical features of bipolar disorder with idiopathic basal ganglia calcification: a review of case reports in the literature.
Although idiopathic basal ganglia calcification (IBGC) is associated with various neuropsychiatric disturbances including several cases of bipolar disorder (BD), there has been no systematic review of clinical features of patients with BD and comorbid IBGC. We undertook a literature search to identify case reports of these patients. Most cases showed complex syndromes comprising not only mood disturbance but also cognitive disability and motor symptoms limited to depressive state and had favorable treatment response. These patients should have a careful and repeated psychiatric, neurological, and cognitive assessment to determine an optimal diagnostic and treatment approaches at each clinical stage.


Repetitive rapid increases in desflurane concentration blunt transient cardiovascular stimulation in humans.
Rapid increases in desflurane concentrations above minimum alveolar concentration (MAC) can cause transient (2-4-min) circulatory changes, possibly from stimulation of rapidly-adapting airway receptors. We hypothesized that the initial increase in concentration would produce greater changes than subsequent increases. Anesthesia was induced with propofol in nine volunteers (25 +/- 1 yr old, mean +/- SE) and maintained with 4% end-tidal desflurane for 32 min. We increased the desflurane to 8% (1.1 MAC) in 1 min, maintained this concentration for 10 min, and then decreased it to 4% for 32 min. We repeated this process twice. After 1 week, 5 subjects were treated similarly except that the second increase in concentration occurred 10 min and (on a separate occasion) 75 min after the initial increase. Four subjects received the initial increase after 75 rather than 32 min of anesthesia. In four we applied the repeated sequences in a background of 60% nitrous oxide. When a minimal cardiovascular response followed an increase of anesthetic concentration, a 60-s supramaximal 100-Hz tetanic stimulus was applied to an ulnar nerve percutaneously to test for sympathetic responsiveness. The initial increase in concentration increased heart rate (HR) from 57 +/- 2 to a peak of 119 +/- 7 beats/min (P < 0.05); mean arterial blood pressure (MAP) from 66 +/- 3 to 119 +/- 5 mmHg (P < 0.05); and plasma epinephrine by > 10-fold (P < 0.05). The second and third increases in desflurane concentration increased HR and MAP by less than 20% of the initial increases, regardless of the timing of the later concentration increases. Responses to initial concentration increases after 75 min of anesthesia did not differ from those after 32 min. Increases in plasma epinephrine with the second and third increases in desflurane concentration were attenuated. Subjects who did not responded to the second or third increase in desflurane always responded to tetanic electrical stimulation with substantial increases in HR and MAP (P < 0.05). Addition of nitrous oxide did not change results except for a smaller increase in MAP (P < 0.05). Ulnar nerve stimulation increased HR and MAP but not epinephrine or norepinephrine concentrations. An initial rapid increase in desflurane to 1.1 MAC produces much more stimulation than do subsequent increases, regardless of the presence of nitrous oxide. The decreased response is consistent with the hypothesis that stimulation of rapidly-adapting airway receptors produce the initial response.


Sensory nerve conduction in chronic uremic patients during the first six months of hemodialysis.
In an attempt to find the best electrophysiological indicator of improvement for the neuropathy present in patients with chronic renal failure undergoing hemodialysis, several types of nerve conduction were studied at the beginning of dialysis and six months later. Sural nerve conduction and late response latencies were recorded in addition to conventional motor and sensory nerve conductions. After six months of hemodialysis, sensory nerve conduction velocities in the median, ulnar and sural nerves were improved. These values appear to be the most sensitive indices of the beneficial effect of hemodialysis on the neuropathy.


Isolation, crystallization and preliminary crystallographic analysis of Salmonella typhimurium uridine phosphorylase crystallized with 2,2'-anhydrouridine.
Uridine phosphorylase (UPh; EC 22.214.171.124) is a member of the pyrimidine nucleoside phosphorylase family of enzymes which catalyzes the phosphorolytic cleavage of the C-N glycoside bond of uridine, with the formation of ribose 1-phosphate and uracil. This enzyme has been shown to be important in the activation and catabolism of fluoropyrimidines. Modulation of its enzymatic activity may affect the therapeutic efficacy of chemotherapeutic agents. The structural investigation of the bacterial uridine phosphorylases, both unliganded and complexed with substrate/product analogues and inhibitors, may help in understanding the catalytic mechanism of the phosphorolytic cleavage of uridine. Salmonella typhimurium uridine phosphorylase has been crystallized with 2,2'-anhydrouridine. X-ray diffraction data were collected to 2.15 A. Preliminary analysis of the diffraction data indicates that the crystal belongs to space group P2(1)2(1)2(1), with unit-cell parameters a = 88.52, b = 123.98, c = 133.52 A. The solvent content is 45.51%, assuming the presence of one hexamer molecule per asymmetric unit.


Detection of human papilloma virus infection in routine Papanicolaou-stained cervical smears.
Women at reproductive age were investigated cytologically for the presence of koilocytes in cervical scrapings to study the frequency of Human Papilloma Virus infections. Out of 2275 cervical smears, 51 (2.24%) revealed koilocytes. Koilocytes were more frequently associated with dysplasia and neoplasia than inflammation and negative smears. Higher frequency of HPV infection was observed in Hindu women as compared to Muslims. Blood stained or white discharge per vaginum is the commonest presenting symptom of the patients with HPV cervical lesions. The data observed in this study provide useful baseline information.


Sharing of worldwide distributed carbohydrate-related digital resources: online connection of the Bacterial Carbohydrate Structure DataBase and GLYCOSCIENCES.de.
Functional glycomics, the scientific attempt to identify and assign functions to all glycan molecules synthesized by an organism, is an emerging field of science. In recent years, several databases have been started, all aiming to support deciphering the biological function of carbohydrates. However, diverse encoding and storage schemes are in use amongst these databases, significantly hampering the interchange of data. The mutual online access between the Bacterial Carbohydrate Structure DataBase (BCSDB) and the GLYCOSCIENCES.de portal, as a first reported attempt of a structure-based direct interconnection of two glyco-related databases is described. In this approach, users have to learn only one interface, will always have access to the latest data of both services, and will have the results of both searches presented in a consistent way. The establishment of this connection helped to find shortcomings and inconsistencies in the database design and functionality related to underlying data concepts and structural representations. For the maintenance of the databases, duplication of work can be easily avoided, and will hopefully lead to a better worldwide acceptance of both services within the community of glycoscienists. BCSDB is available at http://www.glyco.ac.ru/bcsdb/ and the GLYCOSCIENCES.de portal at http://www.glycosciences.de/.


Putative neurotrophic factors and functional recovery from peripheral nerve damage in the rat.
1. In rats, recovery of sensory-motor function following a crush lesion of the sciatic or tibial nerve was monitored by measuring foot reflex withdrawal from a local noxious stimulation of the foot sole. 2. Putative neurotrophic compounds were tested on this functional recovery model: melanocortins (peptides derived from ACTH (corticotropin) and alpha-MSH (melanotropin], gangliosides and nimodipine were effective whereas isaxonine and TRH (thyrotropin releasing hormone) were not. 3. Structure-activity studies with melanocortins revealed a similar effectiveness of alpha-MSH, [N-Leu4, D-Phe7]-alpha-MSH, desacetyl-alpha-MSH and the ACTH analogue ORG 2766, questioning the validity of the previously suggested notion that the melanotrophic properties of these peptides are responsible for their neurotrophic effect. 4. As recovery of function after peripheral nerve damage follows a similar time course in hypophysectomized (five days post operation) and sham-operated rats, effective melanocortin therapy does not mimic an endogenous peptide signal in the repair process from pituitary origin. 5. Subcutaneous treatment with ORG 2766 (7.5 micrograms kg-1 48 h-1) facilitates recovery of function following peripheral nerve damage in young (6-7 weeks old), mature (5 month old) and old (20 month old) rats. 6. In view of the diversity in structure of the effective neurotrophic factors and the complexity of nerve repair, the present data support the notion that peripheral nerve repair may be facilitated by different humoral factors likely to be active on different aspects of the recovery process.


Are IVS4 SNPs of OLR1 gene associated with coronary artery disease: Is there a linkage between IVS4 SNPs?
The OLR1 gene has been identified as a candidate gene for coronary artery disease (CAD). Six single-nucleotide polymorphisms (SNPs) of the OLR1 gene located within intron 4 (IVS4-27G>C, IVS4-73C>T, IVS4-14A>G), intron 5 (IVS5-70A>G, IVS5-27G>T) and 3'UTR (188C>T) comprise a linkage disequilibrium (LD) block, which is strongly associated with the elevated risk of CAD. We aimed to investigate the effects of the OLR1 IVS4-14A>G and -73C>T SNPs on metabolic parameters in Turkish CAD patients, and the linkage between these 2 genetic variants. The present study was carried out in 97 CAD patients and 78 healthy individuals. The OLR1 IVS4 genotypings were performed by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. Serum high-density lipoprotein (HDL) cholesterol levels and body mass index (BMI) were higher in control subjects with IVS4-73CC genotype than in T allele carriers (CT+TT) (respectively, p = 0.002 and p = 0.024), while BMI values were lower in patients with CC genotype (p = 0.046). Patients with IVS4-14G allele (AG+GG) had a statistically higher low-density lipoprotein (LDL) cholesterol level (p = 0.027) than patients with -14AA genotype. Also the systolic blood pressure (SBP) levels were statistically higher in IVS4- 73C allele carriers (CT+CC) than in non-carriers (TT) (p = 0.045). A strong linkage between IVS4-14A>G and -73C>T SNPs of the OLR1 gene was detected in patients (D > 0.76). Our results indicated that the intron 4-14A>G and -73C>T SNPs of the OLR1 gene can be inherited together. The present data also suggests that the OLR1 gene may contribute to the development of hypercholesterolemia in patients with CAD.


Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin.
Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation. We identified Ccl20 as a HF-derived, microbiota-dependent chemokine and found its receptor, Ccr6, to be preferentially expressed by Tregs in neonatal skin. The Ccl20-Ccr6 pathway mediated Treg migration in vitro and in vivo. Thus, HF morphogenesis, commensal microbe colonization, and local chemokine production work in concert to recruit Tregs into neonatal skin, thereby establishing this tissue Treg niche early in life.


Combined pulmonary fibrosis and emphysema in a welder.
Combined pulmonary fibrosis and emphysema (CPFE) syndrome is an uncommon entity characterised by emphysema of the upper lobes and diffuse fibrosis of the lower lobes and carries a bad prognosis with the onset of pulmonary hypertension. Lung involvement due to exposures suffered by welders is generally considered benign though, rarely, a diffuse interstitial fibrotic disease has been reported. CPFE syndrome has however never been reported in welders. A 65-year-old man, welder by occupation and an ex-smoker, presented with progressive exertional dyspnoea associated with dry cough noticed for the last four months. On examination, there was mild tachypnea, clubbing and bilateral basal velcro crepitations on chest auscultation. Lung function test revealed mild mixed ventilatory impairment with severe diffusion defect. HRCT chest showed bilateral upper lobe emphysema and diffuse interstitial fibrosis in the lower lobes. Transbronchial lung biopsy revealed interstitial fibrosis, chronic inflammation and iron deposits. A diagnosis of combined pulmonary fibrosis with emphysema (CPFE) with interstitial pulmonary siderofibrosis (IPS) was established. A review of literature did not show any other report of a similar nature.


Cavity-tailored, self-sorting supramolecular catalytic boxes for selective oxidation.
Using a steric self-sorting strategy, the assembly of highly ordered and rigid supramolecular boxes possessing catalytic properties has been achieved in one step. The formation of these assemblies, comprising up to 18 porphyrin centers, was readily confirmed by solution X-ray scattering in conjunction with fluorescent spectroscopy. Size-selective and enantioselective oxidation catalysis were both demonstrated.


Carcinosarcoma of the adrenal cortex presenting with mineralocorticoid excess.
An adrenal carcinosarcoma is reported in a 79-year-old woman presenting with clinical signs of hyperaldosteronism. The tumor weighed 199 g and consisted of areas typical of adrenal carcinoma and areas of sarcoma. The sarcomatous component of the tumor showed osteogenic and chondroid differentiation. Vimentin stained both the carcinomatous and sarcomatous regions. Four months after resection, the patient developed metastases. This is the third reported case of adrenal carcinosarcoma and the only case in which hyperaldosteronism or bony differentiation was observed.


Chemical composition, silage fermentation characteristics, and in vitro ruminal fermentation parameters of potato-wheat straw silage treated with molasses and lactic acid bacteria and corn silage.
The aim of this study was to determine the effect of molasses and lactic acid bacteria (LAB) on the chemical composition, silage fermentation characteristics, and in vitro ruminal fermentation parameters of an ensiled potato-wheat straw mixture in a completely randomized design with 4 replicates. Wheat straw was harvested at full maturity and potato tuber when the leaves turned yellowish. The potato-wheat straw (57:43 ratio, DM basis) mixture was treated with molasses, LAB, or a combination. Lalsil Fresh LB (Lallemand, France; containing NCIMB 40788) or Lalsil MS01 (Lallemand, France; containing MA18/5U and MA126/4U) were each applied at a rate of 3 × 10 cfu/g of fresh material. Treatments were mixed potato-wheat straw silage (PWSS) without additive, PWSS inoculated with Lalsil Fresh LB, PWSS inoculated with Lalsil MS01, PWSS + 5% molasses, PWSS inoculated with Lalsil Fresh LB + 5% molasses, PWSS inoculated with Lalsil MS01 + 5% molasses, and corn silage (CS). The compaction densities of PWSS treatments and CS were approximately 850 and 980 kg wet matter/m, respectively. After anaerobic storage for 90 d, chemical composition, silage fermentation characteristics, in vitro gas production (GP), estimated OM disappearance (OMD), ammonia-N, VFA, microbial CP (MCP) production, and cellulolytic bacteria count were determined. Compared to CS, PWSS had greater ( < 0.001) values of DM, ADL, water-soluble carbohydrates, pH, and ammonia-N but lower ( < 0.05) values of CP, ash free-NDF (NDFom), ash, nitrate, and lactic, acetic, propionic, and butyric acids concentrations. When PWSS was treated with molasses, LAB, or both, the contents of CP and lactic and acetic acids increased, whereas NDFom, ammonia-N, and butyric acid decreased ( < 0.05). Based on in vitro ruminal experiments, PWSS had greater ( < 0.05) values of GP, OMD, and MCP but lower ( < 0.05) VFA and acetic acid compared to CS. With adding molasses alone or in combination with LAB inoculants to PWSS, the values of GP, OMD, MCP, cellulolytic bacteria population, VFA, and propionic acid increased ( < 0.05), whereas the acetic acid to propionic acid ratio decreased ( < 0.05). Overall, ensiling potato with wheat straw at a 57:43 ratio DM basis was possible; nevertheless, the fermentation quality of PWSS was lesser than that of CS. However, addition of molasses and molasses + LAB improved fermentation quality of PWSS.


The road to hell is paved with good intentions: the experience of applying for national data for linkage and suggestions for improvement.
We can improve healthcare services by better understanding current provision. One way to understand this is by linking data sets from clinical and national audits, national registries and other National Health Service (NHS) encounter data. However, getting to the point of having linked national data sets is challenging. We describe our experience of the data application and linkage process for our study 'LAUNCHES QI', and the time, processes and resource requirements involved. To help others planning similar projects, we highlight challenges encountered and advice for applications in the current system as well as suggestions for system improvements. The study set up for LAUNCHES QI began in March 2018, and the process through to data acquisition took 2.5 years. Several challenges were encountered, including the amount of information required (often duplicate information in different formats across applications), lack of clarity on processes, resource constraints that limit an audit's capacity to fulfil requests and the unexpected amount of time required from the study team. It is incredibly difficult to estimate the resources needed ahead of time, and yet necessary to do so as early on as funding applications. Early decisions can have a significant impact during latter stages and be hard to change, yet it is difficult to get specific information at the beginning of the process. The current system is incredibly complex, arduous and slow, stifling innovation and delaying scientific progress. NHS data can inform and improve health services and we believe there is an ethical responsibility to use it to do so. Streamlining the number of applications required for accessing data for health services research and providing clarity to data controllers could facilitate the maintenance of stringent governance, while accelerating scientific studies and progress, leading to swifter application of findings and improvements in healthcare.


Neural correlates of the chronic fatigue syndrome--an fMRI study.
Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS. We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups. Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error. Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.


Characterization of a defensin gene expressed in oil palm inflorescences: induction during tissue culture and possible association with epigenetic somaclonal variation events.
From differential display studies performed on oil palm (Elaeis guineensis Jacq.) tissue cultures bearing or lacking an epigenetic homeotic flowering abnormality, known as mantled, EGAD1, a gene coding for a putative plant defensin, has been identified and characterized. In whole plants, transcripts of the EGAD1 gene were detected only in inflorescences. The closest characterized relative of the oil palm EGAD1 gene is the Petunia PPT gene, which is expressed principally in the pistil of the flower. The 77 amino acid polypeptide encoded by the EGAD1 gene displays strong similarities with a number of plant defensin proteins, which are thought to play a protective role and which have been shown in some cases to possess antifungal properties. Oil palm tissue cultures exhibit a generally strong induction of accumulation of EGAD1 transcripts, which were detected to differing extents at all stages of the tissue culture regeneration process. The 5' flanking region of the EGAD1 gene was found to contain two different types of potential cis-acting DNA element previously identified in the promoters of plant defence-related genes, which may explain the observed expression in tissue cultures. At the callus stage of the in vitro regeneration procedure, a differential accumulation of EGAD1 transcripts was observed which correlated with the presence or absence of the mantled flowering abnormality. EGAD1 gene expression may therefore be a marker of epigenetic somaclonal variation events.


Diradylglycerols alter fatty acid inhibition of monoacylglycerol acyltransferase activity in Triton X-100 mixed micelles.
The activity of hepatic monoacylglycerol acyltransferase (MGAT) (EC 184.108.40.206), a developmentally expressed microsomal enzyme, is inhibited by long-chain fatty acids, and stimulated by its product 1, 2-diacyl-sn-glycerol. Because the quantities of fatty acids and diacylglycerols are likely to vary in membranes during different physiological conditions and could thereby alter MGAT activity, we examined their combined effects on MGAT in Triton X-100/phospholipid mixed micelles. MGAT's product, 1,2-diC18:1-sn-glycerol, which is also normally a cooperative activator of the activity, reversed the 50% inhibition caused by 10 mol % oleic acid. The presence of oleic acid also allowed low concentrations (<10 mol %) of 1, 2-diC18:1-sn-glycerol to stimulate MGAT activity without the lag that is observed in the absence of fatty acid. At 12.6 mol %, 1, 2-monoC18:1-sn-glycerol ether, which alone has no effect on MGAT activity, became an activator in the presence of 10 mol % oleic acid. Kinetic studies revealed that in the presence of 15 mol % oleic acid, 1,2-diC18:1-sn-glycerol ether increased the apparent Vmax by 3. 8-fold while minimally altering the apparent Km for palmitoyl-CoA. Other neutral lipids including tri-C18:1-glycerol, ceramide, and cholesterol oleate did not stimulate MGAT in either the presence or the absence of fatty acid. Assay conditions altered MGAT's apparent relative preferences for potential monoradylglycerol substrates. The presence of phospholipids and of MGAT's 1,2-diacyl-sn-glycerol product increased the enzyme's apparent preference for its 2-monoacyl-sn-glycerol substrate by selectively increasing the apparent Vmax 2.7-fold only when 2-monoC18:1-sn-glycerol was the substrate. Thus, in addition to previously reported regulation of MGAT by phospholipids and intracellular lipid second messengers, these studies lend additional support to the hypothesis that changes in other membrane-associated lipids, such as long-chain fatty acids and diradylglycerols, may also profoundly alter the activity of MGAT.


Asthma-Targeted MURs: How Confident are Community Pharmacists in Delivering Different Interventions?
This study aimed to identify and determine the confidence level of community pharmacists in providing different interventions during asthma-targeted medicine use reviews (MURs). A self-administered questionnaire was posted to 487 pharmacies accredited to provide the service, across Greater London, Southampton, Cornwall, Sheffield and Norwich. A total of 122 responses were obtained, giving a response rate of 25% (122/487). Around half of the community pharmacists (51.6%) were providing more than 60 asthma-targeted MURs annually with inhaler technique being the most offered intervention and stepping up/down therapy being the least. The majority of community pharmacists (94.3%) were confident in providing inhaler technique advice, followed by smoking cessation (91%). However, confidence was less with relevant vaccination (61.5%) and stepping up/down patients' therapy (56.6%). Confidence level can vary between community pharmacists regarding different interventions provided during respiratory MURs. The results stress the need to promote community pharmacists' confidence in providing interventions such as stepping up/down therapy during asthma-targeted MURs. Additional research in this field is highly recommended in order to evaluate community pharmacists' confidence level on a national scale and to determine the factors influencing it. The study also suggests that provision of different interventions during respiratory MURs can be related to how community pharmacists perceive their role.


Immunoglobulin level in donor blood reactive for antibodies to human immunodeficiency virus.
Blood samples from 98 asymptomatic volunteer blood donors, including 55 that were reactive for antibodies to human immunodeficiency virus (HIV) in Western blot (WB) assay, were tested for levels of immunoglobulin G (IgG), IgM, and titer of antibodies to HIV, cytomegalovirus, and herpes simplex virus. Levels of IgG were significantly elevated (P less than or equal to 0.001) in donors with specific anti-HIV reactivity. A total of 69% of donors with anti-HIV had IgG levels of greater than or equal to 12 mg/ml, and 44% had IgG levels of greater than or equal to 14.5 mg/ml. Levels of IgM were not significantly different among WB-reactive and nonreactive donors. The titer of anti-HIV was significantly (P less than 0.02) correlated with IgG levels among donors reactive in the WB assay. Elevation of IgG, however, was not significantly associated with the presence of anticytomegalovirus or anti-herpes simplex virus antibodies. The data show that elevation of IgG may represent an early manifestation of HIV infection before the development of clinical symptoms of acquired immunodeficiency syndrome.


A unique stylopod patterning mechanism by Shox2-controlled osteogenesis.
Vertebrate appendage patterning is programmed by Hox-TALE factor-bound regulatory elements. However, it remains unclear which cell lineages are commissioned by Hox-TALE factors to generate regional specific patterns and whether other Hox-TALE co-factors exist. In this study, we investigated the transcriptional mechanisms controlled by the Shox2 transcriptional regulator in limb patterning. Harnessing an osteogenic lineage-specific Shox2 inactivation approach we show that despite widespread Shox2 expression in multiple cell lineages, lack of the stylopod observed upon Shox2 deficiency is a specific result of Shox2 loss of function in the osteogenic lineage. ChIP-Seq revealed robust interaction of Shox2 with cis-regulatory enhancers clustering around skeletogenic genes that are also bound by Hox-TALE factors, supporting a lineage autonomous function of Shox2 in osteogenic lineage fate determination and skeleton patterning. Pbx ChIP-Seq further allowed the genome-wide identification of cis-regulatory modules exhibiting co-occupancy of Pbx, Meis and Shox2 transcriptional regulators. Integrative analysis of ChIP-Seq and RNA-Seq data and transgenic enhancer assays indicate that Shox2 patterns the stylopod as a repressor via interaction with enhancers active in the proximal limb mesenchyme and antagonizes the repressive function of TALE factors in osteogenesis.


Use of esters of N-hydroxysuccinimide in the synthesis of N-acylamino acids.
Several crystalline N-hydroxysuccinimide esters of short- and long-chain fatty acids have been synthesized. These compounds react with free amino acids to form preferentially N-acylamino acids. The reaction of the N-hydroxysuccinimide esters with hydroxylamine and the behavior of the N-acylamino acids on thin-layer chromatography are described.


New automatic optical design method based on combination of particle swarm optimization and least squares.
Damped least square method is one of the popular methods for automatic lens design. Various improvements in this automatic optical design are mainly due to the optimization of the damping factor and the weight factor. Especially in the four stages of lens design, designers pay more attention to the "correction" stage, and recognized the importance of human experience in "correction". The introduction of computer brought the feeling of indescribable about the balance aberration of computer. In fact, the function of computer has not gone beyond the range of balance aberration. In this paper, we discussed how to make the whole process of lens design completely automatic by computer, including the selection, correction and evaluation of the system. To achieve this process, the key step is how to make the computer think like a designer and select the type of lens. The success of lens design depends largely on the type selection. Designers who have a profound understanding of optical design theory and rich practical experience can select the simplest and most suitable one from a wide range of types, therefore, this method can also express a new global search method for optical design. Least squares is added to Particle Swarm Optimization (PSO) algorithm to optimize glass selection in optical system. After comparing and analysing the optimized design solutions, the system performance is well achieved. This method can be conveniently implemented and expands the solution space of the optical system.


An evaluation of completeness of tuberculosis notification in the United Kingdom.
There has been a resurgence of tuberculosis worldwide, mainly in developing countries but also affecting the United Kingdom (UK), and other Western countries. The control of tuberculosis is dependent on early identification of cases and timely notification to public health departments to ensure appropriate treatment of cases and screening of contacts. Tuberculosis is compulsorily notifiable in the UK, and the doctor making or suspecting the diagnosis is legally responsible for notification. There is evidence of under-reporting of tuberculosis. This has implications for the control of tuberculosis as a disproportionate number of people who become infected are the most vulnerable in society, and are less likely to be identified and notified to the public health system. These include the poor, the homeless, refugees and ethnic minorities. This study was a critical literature review on completeness of tuberculosis notification within the UK National Health Service (NHS) context. The review also identified data sources associated with reporting completeness and assessed whether studies corrected for undercount using capture-recapture (CR) methodology. Studies were included if they assessed completeness of tuberculosis notification quantitatively. The outcome measure used was notification completeness expressed between 0% and 100% of a defined denominator, or in numbers not notified where the denominator was unknown. Seven studies that met the inclusion and exclusion criteria were identified through electronic and manual search of published and unpublished literature. One study used CR methodology. Analysis of the seven studies showed that undernotification varied from 7% to 27% in studies that had a denominator; and 38%-49% extra cases were identified in studies which examined specific data sources like pathology reports or prescriptions for anti-tuberculosis drugs. Cases notified were more likely to have positive microbiology than cases not notified which were more likely to have positive histopathology or be surgical in-patients. Collation of prescription data of two or more anti-tuberculosis drugs increases case ascertainment of tuberculosis. The reporting of tuberculosis is incomplete in the UK, although notification is a statutory requirement. Undernotification leads to an underestimation of the disease burden and hinders implementation of appropriate prevention and control strategies. The notification system needs to be strengthened to include education and training of all sub-specialities involved in diagnosis and treatment of tuberculosis.


Seminoma in hybrid catfish [Clarias batrachus (Linnaeus) female x Clarias gariepinus (Burchell) male].
Spontaneous testicular tumors, seminoma, were noticed in four male hybrid catfish (C. batrachus female x C. gariepinus male) after the age of two years. The hybrids showed massive abdominal swelling with catchectic body and free lobulated, encapsulated tumors (> 325 g) within the serosanguinous fluid-filled peritoneal cavities. The tumor cells were large and polyhedral with prominent centrally located nuclei. Other vital organs appeared normal. It seems to be the first report of seminoma in hybrid catfish and possibly of genetic cause.


Dendrimer-activated surfaces for high density and high activity protein chip applications.
Highly functional Si and glass surfaces for protein immobilization have been prepared by a facile activation of native surface silanol groups. Poly(propyleneimine) dendrimers of generations 1-5 were immobilized onto the surface using a facile room-temperature coupling procedure that involved activation of native silanol groups of glass using 1,1'-carbonyldiimidazole under anhydrous conditions. The dendrimer-coated surfaces were used to immobilize proteins and were characterized with respect to surface loading and activity. A number of different chemical, physical, and biochemical techniques including contact angle measurement, ellipsometry, and fluorescence microscopy were used to characterize the resulting surfaces. Increasing the dendrimer generation past G-3 led to increased surface amine content, immobilized protein concentration, and the activity of immobilized alkaline phosphatase (used as a test system). Very high activity of the immobilized proteins in the case of higher generation (G-4 and G-5) dendrimers led us to conclude that such an approach has true potential for creating highly functional surfaces for protein chip applications.


Microswitch-aided programs with contingent stimulation versus general stimulation programs for post-coma persons with multiple disabilities.
Assessing the impact of microswitch-aided programs with contingent stimulation on response engagement (Study I) and post-session alertness (Study II) of post-coma participants with multiple disabilities. Study I included three participants whose scores on the Coma Recovery Scale-Revised (CRS-R) were 11 or 13. Study II included three participants whose CRS-R scores were 19, 13, and 14. In both studies, the participants received sessions with contingent stimulation (i.e., sessions in which activation of a microswitch with an eyelid or hand response produced 15 s of preferred stimulation) and sessions with general, non-contingent stimulation (i.e., stimulation lasted throughout the sessions). Study I showed an increase in response engagement/frequencies only during the contingent stimulation sessions. Study II showed that the participants' level of vigilance after those sessions was higher than after non-contingent stimulation sessions. Microswitch-aided programs with contingent stimulation would be more beneficial than programs with general/non-contingent stimulation.


[Outcomes of laryngotracheal reconstruction with anterior and posterior costal cartilage grafts in severe pediatric subglottic stenosis or laryngeal web].
Objective: To investigate outcomes of laryngotracheal reconstruction (LTR)with anterior and posterior costal cartilage grafts in severe pediatric subglottic stenosis (SGS) or laryngeal web (LW). Methods: A review of patients with severe subglottic stenosis or laryngeal web between January 2020 and January 2022 was performed. Demographic features including gender, age at diagnosis, age at surgery, etiology, airway support, and other comorbidities were collected preoperatively. Patients were evaluated in surgical site, breathing, swallowing, phonation and complications postoperatively.Descriptive analysis was used in this research. Results: Eight patients were included: six with grade Ⅲ SGS following Cotton-Myer grading scale, and two with type Ⅲ LW following Cohen's classification. All patients underwent LTR with anterior and posterior costal cartilage grafts. Five patients underwent single-stage LTR (ssLTR), and three patients underwent double-stage LTR (dsLTR). Seven out of eight patients were able to successfully extubate or decannulate with normal swallowing function; four patients had mild hoarseness, and three had moderate hoarseness. One patient failed in extubation, and underwent tracheotomy. Conclusions: LTR with anterior and posterior costal cartilage grafts is an effective and safe treatment for severe SGS or LW. Careful preoperative assessment of disease severity and overall medical status will help selection between ssLTR and dsLTR, thereby maximizing patient outcomes for both modalities.


Endovascular Coiling of Fenestrated Vertebrobasilar Cerebral Aneurysms.
Fenestrated vertebrobasilar junction aneurysms are uncommon vascular lesions. Surgical intervention remains extremely challenging due to the deep location and complex anatomy with adjacent cranial nerves and perforator vessels. Endovascular approach is safer and generally accepted as the primary treatment method. Optimal angiographic projections with three-dimensional reconstructions to guide microcatheter selection remain vital to successfully treating aneurysms with challenging fenestration anatomy. This report details the endovascular methods in two cases of fenestrated vertebrobasilar junction aneurysms with different coiling techniques.


Role for a Lytic Polysaccharide Monooxygenase in Cell Wall Remodeling in Streptomyces coelicolor.
Peptidoglycan is a major constituent of the bacterial cell wall and an important determinant for providing protection to cells. In addition to peptidoglycan, many bacteria synthesize other glycans that become part of the cell wall. Streptomycetes grow apically, where they synthesize a glycan that is exposed at the outer surface, but how it gets there is unknown. Here, we show that deposition of the apical glycan at the cell surface of Streptomyces coelicolor depends on two key enzymes, the glucanase CslZ and the lytic polysaccharide monooxygenase LpmP. Activity of these enzymes allows localized remodeling and degradation of the peptidoglycan, and we propose that this facilitates passage of the glycan. The absence of both enzymes not only prevents morphological development but also sensitizes strains to lysozyme. Given that lytic polysaccharide monooxygenases are commonly found in microbes, this newly identified biological role in cell wall remodeling may be widespread. IMPORTANCE Lytic polysaccharide monooxygenases are used in industry for the efficient degradation of recalcitrant polysaccharide substrates. Only recently, we have begun to appreciate some of their important biological roles. In this article, we provide evidence that these enzymes are involved in remodeling peptidoglycan, which is a conserved component of the bacterial cell wall. Given that lytic polysaccharide monooxygenases are commonly found in microbes, this newly identified biological role in cell wall remodeling may be widespread.


[System analysis of social motivation III: An estimation study of security and arousal regulation in adolescence].
An experiment using a simulated spaceflight scenario was applied to 32 adolescent subjects of both sexes in order to investigate human security and arousal regulation. In adolescence, these motivational systems play a key role in achieving two reorientations: the detachment from primary caregivers and the upcoming interest in strangers, which eventually establishes a new and mature form of attachment. Based on a control model proposed in an earlier article of this series, a parameter estimation was performed which allowed for a satisfactory simulation of the actual flight behavior of most subjects. A psychologically plausible interpretation of the parameters was possible. In particular, the results obtained indicate a gender specific differentiation in the development of both motivational systems during adolescence.


EEG Abnormalities in Children with Speech and Language Impairment.
Epilepsy, a chronic condition of recurrent seizures, affects language, but the extent and nature of the language disturbance varies widely according to the type, severity, and cause of the epilepsy. There is paucity of literature on the electroencephalographic abnormalities in children with speech and language impairment. The present study was therefore planned to find the association of epileptiform EEG abnormalities in children with speech and language impairment and if present, their localization and lateralization to the language areas of the brain that are present predominantly in the left hemisphere. The study was conducted on Paediatric patients having speech and language impairment (n=94, age-2 to 8 years) selected on the basis of detailed history and neurologic examination. Video Electroencephalography (EEG) was performed as per American Clinical Neurophysiology Society guidelines using 16 channel RMS computerized EEG machine for a minimum of 40 minutes to capture both wakefulness and sleep along with activation procedures like hyperventilation (if feasible) and photic stimulation. EEG was reviewed for any abnormal EEG background, benign variants, interictal epileptiform discharges and ictal discharges. In our cohort, 19.7% boys and 22.2% girls presented with seizures in their infancy and this gender difference was found to be statistically significant (p<0.05). EEG was abnormal in 47.9% children (45 out of 94) with no significant gender difference. Epileptiform EEG was seen in 73.6% of children with history of seizures and 41.3% of children without history of seizures (p<0.05). The EEG abnormities included: abnormal background (64.5%), presence of generalized interictal epileptiform discharges (57.8%), focal epileptiform discharges (20%) exclusively from left hemisphere and multifocal interictal epileptiform discharges (33.3%), each occurring in isolation or associated with other abnormities. In the current study, it is definite that presence of generalized abnormalities in EEG are seen in higher frequency and focal interictal epileptiform discharges are solely seen in left hemisphere in children with speech and language impairment. Although, there is no distinct pattern of EEG abnormalities in such patients, we recommend a routine EEG in them and also brain imaging to complement the EEG findings.


TAL-1 protein expression in vascular lesions.
The distribution of TAL-1 protein, an important vascular promoter in mice, has been examined immunohistochemically in a range of human vascular lesions and normal tissues. Formalin-fixed, paraffin-embedded vascular lesions including granulation tissue, haemangiomas, Kaposi's sarcomas, spindle cell haemangioendotheliomas, and angiosarcomas, were examined using a monoclonal antibody to recombinant TAL-1. Endothelial cells in all lesions gave positive immunostaining of variable intensity. Granulation tissue and spindle cell areas of the vascular tumours gave the strongest staining (nuclear and cytoplasmic). The better-differentiated endothelial cells within the tumours and resident well-formed vessels were less positive and some cells were in fact negative. The malignant endothelial cells in angiosarcomas showed less intense positive staining than KS cells. This study has shown TAL-1 protein expression in a range of reactive, benign, and malignant vascular lesions. Protein expression appears to be stronger in the spindle cell areas, perhaps reflecting greater expression in less-differentiated endothelial cells.


Oxidative DNA cleavage by free and oligonucleotide-conjugated O-bromobenzoic acid in the presence of copper(II) ions.
o-Bromobenzoic acid was found to promote copper-dependent reactive oxygen species formation from molecular oxygen, resulting in DNA base modification and backbone cleavage. The oligonucleotide conjugate bearing 5-(4'-aminopropyl-sulfomoyl)-2-bromobenzoic acid as a reactive group was synthesized and DNA cleavage activity of this oligonucleotide conjugate was tested on a model deoxyoligonucleotide.


[A case of rectal carcinoid tumor with lymph node and liver metastasis 5 years after curative resection].
A 65-year-old man was diagnosed with a rectal carcinoid tumor (10 mm in diameter) in July 2007. We performed low anterior resection with lymph node dissection. Histological depth of penetration of the rectal wall by the primary tumor was up to the submucosa, and lymph node metastasis was observed at station 251 (Japanese Classification of Colorectal Carcinoma, seventh Edition). Five years later, abdominal enhanced computed tomography (CT) revealed multiple liver tumors and swelling of the right obturator lymph nodes. During surgery, ultrasonography revealed 10 hypoechoic masses in both hepatic lobes. We performed right pelvic lymph node dissection, partial hepatectomy (S5/6, S7, and S8), and microwave coagulation therapy. After surgery, the patient was treated with octreotide long-acting repeatable( LAR). The patient remained disease-free for 10 months after surgery. Our findings suggest that careful monitoring is necessary for metachronous lymph node and liver metastasis during follow-up treatment for rectal carcinoid tumors.


Perfusion of the rat ovary in vitro: methodology, induction of ovulation, and pattern of steroidogenesis.
A method for perfusion of the rat ovary in vitro for the study of ovulation was developed and characterized. Immature rats (27-29 days old) were primed with 20 IU of pregnant mare's serum gonadotropin (PMSG). Two days later a laparotomy was performed, the aorta and vena cava were cannulated, the right ovary was isolated, and all vessels connecting with the aorta and vena cava except for the right ovarian artery and vein were ligated. The preparation was placed in the perfusion apparatus and perfused for up to 20 h with oxygenated Medium 199 containing 4% bovine serum albumin (37 degrees C, pH 7.4). The perfusion pressure was 70-90 mm Hg and the average flow was 1 ml . min . ovary. Ovulation was confirmed by oocyte recovery from the apparatus. Nine ovaries were perfused without further treatment (controls); only 1 ovulation occurred in this group. Nine ovaries received luteinizing hormone (LH; 0.1 microgram/ml) 1 h after the start of perfusion; 71 ovulations resulted (range, 3-13/ovary). Ovulations did not begin before 9 h after LH administration. Samples of medium were taken frequently for measurement of progesterone, estradiol and androstenedione. Levels of all three steroids rose rapidly and markedly in response to LH but increased only slightly in control perfusions. This study demonstrates that ovulation in the rat ovary can be induced in vitro and provides a basis for further studies on the mechanism of ovulation.


A Recurrent Platinum Refractory Ovarian Cancer Patient With a Partial Response After RRx-001 Resensitization to Platinum Doublet.
This case report describes the clinical course of a heavily pretreated patient enrolled on the Phase II QUADRUPLE THREAT clinical trial (NCT02489903) with recurrent metastatic epithelial ovarian cancer that was previously treated with a platinum doublet and that benefited from another reintroduction of a platinum doublet after a brief priming period with RRx-001. Platinum-taxane combination is the initial treatment of choice in ovarian cancer and the "go-to regimen" for patients with recurrent, platinum-sensitive disease. However, platinum resistance is an inevitable and uniformly fatal development. One of the "Holy Grails" in ovarian cancer, besides early detection, is to reverse this resistance and retreat with a platinum doublet regimen. Because of the correlation between therapeutic resistance and poor clinical outcomes, this case, which potentially demonstrates a new avenue of anticancer development in epithelial ovarian cancer provided it is repeatable with other ovarian patients, was felt to merit a report.


The history of confidentiality in medicine: the physician-patient relationship.
The author of this article reviews the history of the confidentiality of medical information relating to patients from its roots in the Hippocratic Oath to the current codes of medical ethics. There has been an important shift in the basis for the demand for confidentiality, from a physician-based commitment to a professional ideal that will improve the physician-patient relationship and thus the physician's therapeutic effectiveness, and replace it with a patientbased right arising from individual autonomy instead of a Hippocratic paternalistic privilege.


[The consideration and execution of the principles of no restraint and open door strategies in Hungarian psychiatry].
In order to understand the problems and dilemmas of Hungarian psychiatry regarding no-restraint, and open-door strategy, it is indispensable to comprehend the 18th century beginnings, the original principles and objectives of this healing approach. The first representatives of this method appeared between the second half of the 18th century, (V. Chiaruggi, Ph. Pinel, W. Tuke), and the first half of the 19th century (E.D. Esquirol, B.A. Morel, V. Magnan, J. Conolly), during the times when the main principles of keeping the mentally ill in asylums were those of security, guarding and separation. There were four reasons which led to the elaboration of restraint itself: (a) overcrowded institutes; (b) high proportion of restless and agitated patients among the sick-population; (c) outnumbered and undereducated medical staff; (d) and that the typical method of contemporary psychiatry preferred to apply sudden, unexpected and drastic effects assuming their healing power. As a result mechanical restraint was developed with a wide variety of means, regarding always as a principal objective to keep the patient isolated from the rest of society, and to obstruct him or her to make any harm either to himself or herself, or to the others. Thus restraint consisted of all forms of coercive and restrictive measures, such as mere physical limitation of motion, meals, relaxation, sleep, intellectual activities, and any other forms of personal liberty there might be. Consequently, the program of no-restraint intended to get rid of all of these measures and to guarantee the greatest possible level of liberty for the patients. This guiding principle of no-restraint appeared in the methods of psychiatric therapy, the objectives for the reorganization of psychiatric institutes, and in the legal actions taken to secure the civil rights of the mentally ill through parliamentary enactment. The realization of open door strategy belongs to the development of no-restraint in a wider sense. Just like in other countries the elaboration of this method--with more or less success--has been started in Hungary at the end of the last century as well, and is still in progress. The cardinal principle of this method is not to keep the doors of mental hospitals or wards by all means open, but to create a social milieu, an atmosphere in which any further harm for the patients that may occur as a result of their residence, are likely to be avoided. The open door strategy stands not for an unlimited but the greatest possible level of liberty for the mentally ill ... To sum up, we can conclude that the introduction of no-restraint systems was beneficial in the history of Hungarian psychiatry for the mentally insane, but only in those cases, when the cardinal principles of this method were adequately understood, and when it had been realized that for whom, when, and in what extent it could be applied. In other words, when the barriers of no-restraint were recognized.


Demonstration of glutamate dehydrogenase isozymes in beef heart mitochondria.
Glutamate dehydrogenase (GDH) has been purified from beef heart mitochondria and compared with crystalline beef liver GDH. The specific activity of heart GDH was 127 units and of liver GDH 80 units. Heart GDH subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis had a protein corresponding to liver GDH and a smaller molecular weight protein. On agarose gel electrophoresis heart GDH activity was resolved into two fractions (with or without protease inhibitors) while liver had only one fraction. One of the heart fractions moved with liver GDH on electrophoresis. Thermal stability studies showed heart and liver GDH activity differed. Mouse antibodies to liver GDH precipitated both liver and heart GDH on double immunodiffusion. Mouse antibodies to liver GDH identified on nitrocellulose paper the polypeptide band of liver and heart GDH that were the same molecular weight but did not cross-react with the smaller molecular weight polypeptide present in heart GDH. Trypsin digestion of the two major protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified GDH from beef heart mitochondria did not show any overlapping peptides. We conclude beef heart GDH activity is composed of two isozymes. One is the same as beef liver GDH, and the other is a smaller molecular weight protein. We propose the terms GDH-LM for the liver GDH isozyme and GDH-HM for the smaller molecular weight isozyme present in heart mitochondria but not liver.


Intra-abdominal pulmonary sequestration exhibiting congenital cystic adenomatoid malformation. Report of a case and review of the literature.
We describe the fifth case, to our knowledge, of an intra-abdominal pulmonary sequestration that histologically displayed the features of congenital cystic adenomatoid malformation (CCAM) type 2. This mass was found during routine prenatal ultrasound in an infant with no other congenital malformations. A literature search found 13 previously reported cases of CCAM in extralobar pulmonary sequestration (EPS), nine of which were thoracic and only four were intra-abdominal. An analysis of our case and the 13 previously reported cases shows that the clinical features of EPS containing CCAM type 2 do not differ significantly from those of EPS occurring alone. The presence of CCAM type 2 in our patient is consistent with previously reported cases. Extralobar pulmonary sequestrations located in the abdomen are rarely diagnosed prior to excision, and the presence of CCAM type 2 in this situation may further compound diagnostic difficulties. The morphologic features separating CCAM into three distinct types and the exclusive association of CCAM type 2 occurring in EPS are also discussed.


A review of neuromuscular blockade in the critically ill patient.
The continuous administration of neuromuscular blocking agents is thought to be associated with a number of adverse effects and complications, including post-paralytic syndrome (characterized by persistent paralysis), muscle weakness, and the inability to wean from the ventilator despite discontinuation of the therapy. Consequently, clinical objectives emphasize administering only the dose necessary to optimize the effect of the drug and for the shortest possible time. This article provides an overview of the administration of neuromuscular blocking agents, from the perspective of a critical care pharmacist and critical care nurses. The complexities associated with pharmacological paralysis in critically ill patients warrants the comprehensive approach to care that multidisciplinary team members can provide.


Status of oxidative stress in rheumatoid arthritis.
To assess the oxidative stress status in rheumatoid arthritis by measuring markers of free radical production, systemic activity of disease, free radical mediated tissue destruction and levels of antioxidant. Peripheral blood samples were used for all the assays. Total nitric oxide (NO) was quantitatively measured using immunoassay kit. Malondialdehyde (MDA) and vitamin E were measured by spectrophotometric methods. Statistically significant changes were observed in the levels of MDA, vitamin E, total NO and erythrocyte sedimentation rate (ESR) in the patient group. Significant differences were also observed in ESR and vitamin E levels in patients with active disease. Increased oxidative stress status exists, which may lead to connective tissue degradation leading to joint and periarticular deformities in rheumatoid arthritis.


Usefulness of rectal dialysis to determine intrarectal eicosanoids release in ulcerative colitis.
The quantification of the local production of eicosanoids is of interest because it has been implicated in the mucosal damage of ulcerative colitis. In situ production of eicosanoids is not reflected by its urinary or seric levels, requiring invasive examinations. Thus, new non-invasive techniques such as rectal dialysis have been investigated. The purpose of this study was to assess whether the determination of the intrarectal eicosanoid levels measured by rectal dialysis is useful in detecting the presence of rectal inflammation in patients with ulcerative colitis. Thirty one patients with clinically active colitis and 7 controls with irritable bowel syndrome have been studied. A 10 cm long dialysis bag was placed in the rectum for 1 hour. To determine the variability of the technique, the dialysis was repeated the next day in 6 controls. To detect intrarectal eicosanoids release in inactive colitis, rectal dialysis was performed in another group of 15 patients with clinical and endoscopically inactive colitis and compared with 9 patients with active colitis. PGE2, TXB2, and LTB4 were measured in rectal dialysates by immunospecific RIA. Dialysis was well tolerated by all participants. Intrarectal level of every eicosanoid was much higher in active colitis than in controls (p < 0.05) and in inactive colitis (p < 0.001). The mean coefficient of variation of duplicated dialysis ranged from 15 to 28%. In conclusion, rectal dialysis is a non-invasive technique that allows to prove the presence of active inflammation in ulcerative colitis patients.


Screening of breast cancer stem cell inhibitors using a protein kinase inhibitor library.
Cancer stem cells (CSCs), a subpopulation in tumors, are known to cause drug resistance, tumor recurrence and metastasis. Based on the characteristic formation of mammospheres in in vitro conditions, the mammosphere formation assay has become an essential tool for quantifying CSC activity in breast cancer research. However, manual counting of mammospheres is a time-consuming process that is not amenable to high-throughput screening, and there are occasional inaccuracies in the process of determining the mammosphere diameter. In this study, we proposed a novel automated counting method of mammosphere using the National Institute of Standards and Technology (NIST)'s Integrated Colony Enumerator (NICE) with a screening of protein kinase library. Human breast cancer cell line MCF-7 was used for evaluation of tumor sphere efficiency, migration, and phenotype transition. Cell viability was assessed using MTT assay, and CSCs were identified by an analysis of CD44 expression and ALDEFLUOR assay using flow cytometry. Automated counting of mammosphere using NICE program was performed with a comparison to the result of manual counting. After identification of inhibitors to ameliorate CSC formation by screening a library of 79 protein kinase inhibitors using automated counting in primary, secondary and tertiary mammosphere assay, the effect of selected kinase inhibitors on migration, colony formation and epithelial-to-mesenchymal transition (EMT) of MCF-7 cells was investigated. Automated counting of mammosphere using NICE program was an easy and less time-consuming process (<1 min for reading 6-well plate) which provided a comparable result with manual counting. Inhibition of calcium/calmodulin-dependent protein kinase II (CaMKII), Janus kinase-3 (JAK-3), and IκB kinase (IKK) were identified to decrease the formation of MCF-7-derived CSCs in primary, secondary and tertiary mammosphere assay. These protein kinase inhibitors alleviated TGF-β1-induced migration, colony formation and EMT of MCF-7 cells. We have developed a novel automated cell-based screening method which provided an easy, accurate and reproducible way for mammosphere quantification. This study is the first to show the efficacy of an automated medium-throughput mammosphere-counting method in CSC-related research with an identification of protein kinase inhibitors to ameliorate CSC formation.


The role of transposable elements in human evolution and methods for their functional analysis: current status and future perspectives.
Transposable elements (TEs) are mobile DNA sequences that can insert themselves into various locations within the genome, causing mutations that may provide advantages or disadvantages to individuals and species. The insertion of TEs can result in genetic variation that may affect a wide range of human traits including genetic disorders. Understanding the role of TEs in human biology is crucial for both evolutionary and medical research. This review discusses the involvement of TEs in human traits and disease susceptibility, as well as methods for functional analysis of TEs.


Restricted and repetitive behaviors and their developmental and demographic correlates in 4-8-year-old children: A transdiagnostic approach.
Background: Restricted and repetitive behaviors (RRBs) are a broad class of behaviors characterized by frequent action repetition and intense preference for sameness. Research has predominantly focused on RRBs in diagnosed clinical groups, particularly in autism spectrum disorder and genetic disorders. Using a transdiagnostic approach, the current study examined RRBs in a diverse sample of children in relation to developmental and demographic correlates (age, language, non-verbal ability, child anxiety, sex, and socioeconomic status). Separate analyses examined two RRB subtypes; repetitive sensory and motor behaviors (RSMB) and insistence on sameness (IS). Method: Children (N = 260, age 4-8 years, 174 male, 86 female) in mainstream schools identified by teachers as having behavioral, emotional, and/or cognitive difficulties, were assessed using the Repetitive Behavior Questionnaire-2 (RBQ-2), the British Picture Vocabulary Scale (BPVS), Lucid Ability Scale, the Welsh Index of Multiple Deprivation (WIMD) and the Screen for Child Anxiety Related Emotional Disorders (SCARED). Recruitment excluded diagnosed clinical conditions. The Strengths and Difficulties Questionnaire (SDQ) was used to assess children's difficulties. Results: RRB scores were of high frequency and the scores for the IS were higher than for RSMB. The severity of anxiety symptoms and male sex were significantly associated with both RRB subtypes, and younger age and SES scores were associated with IS. Elevated RRB total and subtype scores were significantly related to SDQ scores for emotion, conduct, hyperactivity, and peer-relations. Discussion: The study provides the first evidence of RRBs in a diverse sample of young children with emerging difficulties in behavior, cognition, and/or emotion. The results contribute to proposals about psychological development in RRB and indicate that RRBs are best represented on a continuum of severity found across children in the early school years. The results support previous findings of a relation between RRB and anxiety reported in clinical samples and importantly, they indicate that it is time to move beyond the study of categorically defined groups and consider correlates of RRBs that include broad indices of mental health and well-being.


ClonoCalc and ClonoPlot: immune repertoire analysis from raw files to publication figures with graphical user interface.
Next generation sequencing (NGS) technologies enable studies and analyses of the diversity of both T and B cell receptors (TCR and BCR) in human and animal systems to elucidate immune functions in health and disease. Over the last few years, several algorithms and tools have been developed to support respective analyses of raw sequencing data of the immune repertoire. These tools focus on distinct aspects of the data processing and require a strong bioinformatics background. To facilitate the analysis of T and B cell repertoires by less experienced users, software is needed that combines the most common tools for repertoire analysis. We introduce a graphical user interface (GUI) providing a complete analysis pipeline for processing raw NGS data for human and animal TCR and BCR clonotype determination and advanced differential repertoire studies. It provides two applications. ClonoCalc prepares the raw data for downstream analyses. It combines a demultiplexer for barcode splitting and employs MiXCR for paired-end read merging and the extraction of human and animal TCR/BCR sequences. ClonoPlot wraps the R package tcR and further contributes self-developed plots for the descriptive comparative investigation of immune repertoires. This workflow reduces the amount of programming required to perform the respective analyses and supports both communication and training between scientists and technicians, and across scientific disciplines. The Open Source development in Java and R is modular and invites advanced users to extend its functionality. Software and documentation are freely available at https://bitbucket.org/ClonoSuite/clonocalc-plot .


Growth and development of competence in the group H streptococci.
The growth and development of competence by group H streptococci, strain Challis, were compared in synthetic, semisynthetic, and complex media with respect to the cultural conditions required, time of onset and persistence of competence and transformation efficiency. Provided that cultural conditions were strictly controlled in the synthetic system, transformation frequencies of 1% or above were routinely observed. The initial pH must be between 7.3 and 7.6, and the addition of freshly prepared bicarbonate ion was required. Furthermore, competence was sensitive to the degree of initial agitation of the culture. There was no evidence that "step-down" or "unbalanced" growth conditions were required. Competence could be provoked in the incompetent strain Wicky, growing in complex or semisynthetic media, by the addition of heat-killed or filtered cultures of strain Challis prepared during the competent period of growth in synthetic medium.


Chiral Recognition and Resolution of Phosphoric Acids Using Octahedral Cobalt Complexes.
Determining the chirality of phosphoric acids can be a challenging task. In this study, we present a novel approach for the chiral recognition of phosphates using cationic octahedral cobalt complexes. By utilizing 31P NMR spectroscopy, we are able to accurately measure the enantiopurities of chiral phosphoric acids after forming ion pairs with the cobalt complexes. We have successfully applied this method to a variety of chiral phosphoric acids derived from BINOL, H8-BINOL, SPINOL, VAPOL, and VANOL compounds, as well as ATP, and were able to efficiently resolve them in 31P{1H} NMR spectra. Furthermore, we were able to achieve an optical resolution of a phosphoric acid with an enantiomeric excess of greater than 99%.


Solubility of lead and copper in biochar-amended small arms range soils: influence of soil organic carbon and pH.
Biochar is often considered a strong heavy metal stabilizing agent. However, biochar in some cases had no effects on, or increased the soluble concentrations of, heavy metals in soil. The objective of this study was to determine the factors causing some biochars to stabilize and others to dissolve heavy metals in soil. Seven small arms range soils with known total organic carbon (TOC), cation exchange capacity, pH, and total Pb and Cu contents were first screened for soluble Pb and Cu concentrations. Over 2 weeks successive equilibrations using weak acid (pH 4.5 sulfuric acid) and acetate buffer (0.1 M at pH 4.9), Alaska soil containing disproportionately high (31.6%) TOC had nearly 100% residual (insoluble) Pb and Cu. This soil was then compared with sandy soils from Maryland containing significantly lower (0.5-2.0%) TOC in the presence of 10 wt % (i) plant biochar activated to increase the surface-bound carboxyl and phosphate ligands (PS450A), (ii) manure biochar enriched with soluble P (BL700), and (iii) unactivated plant biochars produced at 350 °C (CH350) and 700 °C (CH500) and by flash carbonization (corn). In weak acid, the pH was set by soil and biochar, and the biochars increasingly stabilized Pb with repeated extractions. In pH 4.9 acetate buffer, PS450A and BL700 stabilized Pb, and only PS450A stabilized Cu. Surface ligands of PS450A likely complexed and stabilized Pb and Cu even under acidic pH in the presence of competing acetate ligand. Oppositely, unactivated plant biochars (CH350, CH500, and corn) mobilized Pb and Cu in sandy soils; the putative mechanism is the formation of soluble complexes with biochar-borne dissolved organic carbon. In summary, unactivated plant biochars can inadvertently increase dissolved Pb and Cu concentrations of sandy, low TOC soils when used to stabilize other contaminants.


[Epigenetic modifications in children associated with maternal emotional stress during pregnancy].
Besides typical physical and hormonal changes during pregnancy, this life period is often associated with an increased emotional and mental stress for women. For the child, the time in utero is regarded as a critical developmental period since adverse stimuli during pregnancy can have lasting consequences for the fetal and postnatal health and development. Thus, prenatal depression, anxiety and stress are considered as risk factors for developmental delay, emotional and behavioral problems. Epigenetic modifications, especially modifications in DNA methylation, are discussed as a possible biological mechanism that could explain the association between prenatal emotional stress and altered developmental and health outcomes of the child. This review summarizes evidence for DNA methylation changes related to prenatal emotional stress from studies with a candidate-gene approach as well as epigenome-wide association studies. Problematic issues are discussed and recommendations for future research are presented.


Observation on the Clinical Efficacy of Traditional Chinese Medicine Non-Drug Therapy in the Treatment of Insomnia: A Systematic Review and Meta-Analysis Based on Computer Artificial Intelligence System.
Insomnia is a common and frequently occurring disease affecting the health of the population, which can seriously affect the work and life of patients. Drug treatment of insomnia has a rapid onset of action but has a large adverse reaction incidence rate. Traditional external treatment of traditional Chinese medicine (TCM) belongs to a type of non-drug therapy, the treatment of insomnia has a long history, but the methods of non-drug treatment of TCM are diverse, and the efficacy is also different. This study investigated the efficacy of TCM non-drug therapy in the treatment of insomnia by means of literature search and meta-analysis. We searched Embase, Pubmed, OVid, WOS, CNKI, and CBM for randomized controlled trials (RCTs) on the use of TCM as a non-drug treatment for primary insomnia. After doing a literature search according to the inclusion and exclusion criteria, we used Cochrane rob v2.0 to assess the potential for bias in the studies that were included, and we did a combined analysis and assessment of the effectiveness of the therapy. 16 articles were included in this study for quantitative analysis, and a total of 1285 patients participated in the study, including 643 patients in the intervention group and 642 patients in the control group. Meta-analysis showed that non-drug therapy of TCM could improve the treatment response rate of insomnia patients [OR = 6.88, 95%CI (4.40,10.74), Z = 8.48, P < 0.0001], reduce post-treatment PSQI total score [MD = -3.42, 95%CI (-4.62, -2.22), Z = -5.60, P < 0.0001], and improved patient anxiety [SMD = -1.25, 95%CI (-2.13, -0.37), Z = -2.78, P=0.01] and degree of depression [SMD = -1.53, 95%CI (-2.84, -0.21), Z = -2.28, P=0.02]. The heterogeneity survey showed that treatment time was one of the sources of heterogeneity. Meta-regression analysis revealed that publication year, patient age, sample size, and intervention characteristics were not specific factors affecting the combined results. Discussion. TCM non-drug therapy (acupuncture, moxibustion, massage, and auricular point pressing beans) can significantly improve the PSQI score of patients after treatment and improve the degree of anxiety and depression of patients, with significant effect, which is worthy of clinical promotion.


New drug target in protozoan parasites: the role of thioredoxin reductase.
Amebiasis causes approximately 70,000 deaths annually and is the third cause of death due to parasites worldwide. It is treated primarily with metronidazole, which has adverse side effects, is mutagenic and carcinogenic, and emergence of resistance is an increasing concern. Unfortunately, better therapeutic alternatives are lacking. Re-purposing of older FDA approved drugs is advantageous to drug discovery since safety and pharmacokinetic effects in humans are already known. In high throughput screening studies, we recently demonstrated that auranofin, a gold containing compound originally approved to treat rheumatoid arthritis, has activity against trophozoites of E. histolytica, the causative agent of amebiasis. Auranofin's anti-parasitic activity is attributed to its monovalent gold molecule that readily inhibits E. histolytica thioredoxin reductase. This anti-oxidant enzyme is the only thiol-dependent flavo-reductase present in E. histolytica. Auranofin has also shown promising activity against other protozoans of significant public health importance. Altogether, this evidence suggests that auranofin has the potential to become a broad spectrum alternative therapeutic agent for diseases with a large global burden.


Recognition Without Words: Using Taste to Explore Survival Processing.
Many educational demonstrations of memory and recall employ word lists and number strings; items that lend themselves to semantic organization and "chunking." By applying taste recall to the adaptive memory paradigm, which evaluates memory from a survival-based evolutionary perspective, we have developed a simple, inexpensive exercise that defies mnemonic strategies. Most adaptive memory studies have evaluated recall of words encountered while imagining survival and non-survival scenarios. Here, we've left the lexical domain and hypothesized that taste memory, as measured by recognition, would be best when acquisition occurs under imagined threat of personal harm, namely poisoning. We tested participants individually while they evaluated eight teas in one of three conditions: in one, they evaluated the toxicity of the tea (survival condition), in a second, they considered the marketability of the tea and, in the third, they evaluated the bitterness of the tea. After a filler task, a surprise recognition task required the participants to taste and identify the eight original teas from a group of 16 that included eight novel teas. The survival condition led to better recognition than the bitterness condition but, surprisingly, it did not yield better recognition than the marketing condition. A second experiment employed a streamlined design more appropriate for classroom settings and failed to support the hypothesis that planning enhanced recognition in survival scenarios. This simple technique has, at least, revealed a robust levels-of-processing effect for taste recognition and invites students to consider the adaptive advantages of all forms of memory.


XNEOr: development and evaluation of an expert system to improve the quality and cost of decision-making in neuro-oncology.
The treatment of brain tumors requires a large team of medical experts. However, the process of medical decision-making for these patients is hampered by the frequent inaccessibility of the experts because of conflicting scheduling, inconsistencies in the management of different patients, and the fact that multiple experts often yield multiple opinions. The goals of this work were (1) to develop and validate an expert system to assist the medical team deliver efficient, quality care to children with recurrent medulloblastoma, a common type of pediatric brain tumor, and (2) to determine if the expert system can be used as an educational tool. The results of our study indicate that residents enjoy learning by using XNEOr, the brain tumor expert system. XNEOr enabled residents to order appropriate ancillary tests for patients and to make fewer incorrect treatment decisions. The potential net effect of residents using XNEOr may be increased patient and family satisfaction and decreased probability of medical liability. At a time of important changes in our health care system, novel expert systems hold promise as tools to reduce medical costs, improve the quality of multi-expert medical care, and advance health care education.