Two new species of Cephalogonimidae Looss, 1899 (Digenea: Plagiorchioidea) from Africa (Mozambique and Guinea), including a new phylogenetic hypothesis for related plagiorchioids.
Two new species of Cephalogonimidae Looss, 1899 (from Emoleptalea Looss, 1900 and Masenia Chatterji, 1933) are described from African freshwater fishes. Emoleptalea mozambiquensis n. sp. infected the turquoise killifish, Nothobranchius furzeri Jubb, in Mozambique and differs from its nine congeners by the combination of differences in body shape and size, oral sucker shape, sucker width ratio, configuration of the digestive tract and gonads, vitelline follicle shape and vitellarium configuration. Emoleptalea dollfusi Srivastava, 1960 is a synonym of Emoleptalea loossi Srivastava, 1960, thus there are still nine accepted species. Masenia baroensis n. sp. infected the globe fish, Tetraodon lineatus L., in the Republic of Guinea and differs from its five African congeners and 15 Asian congeners by the combination of circumoral spine count, oral sucker shape, caecal extent, ovary shape, genital pore position, and configuration of the vitellarium. Masenia dayali (Gupta & Puri, 1984) Chandra & Saxena, 2016 and Masenia pushpanjalii are nomina dubia. We propose Masenia ritai (Agrawal, 1964) n. comb., with M. ritai Sircar & Sinha, 1970 its junior synonym. Heterorchis cf. crumenifer (identified tentatively due to egg size) is reported from the West African lungfish, Protopterus annectens (Owen), in Mozambique (new geographical record). Heterorchis protopteri Thomas, 1958 and Heterorchis ghanensis Thomas, 1968 are species inquirendae. Sequences (28S rDNA) from these parasites were included in a Bayesian phylogenetic analysis with 37 other ingroup taxa. Both new species formed a clade with Masenia nkomatiensis Dumbo, Dos Santos & Avenant-Oldewage, 2019 from Africa. These three species formed a sister relationship with the other available cephalogonimids: Cephalogonimus americanus Stafford, 1902 and Cephalogonimus retusus (Dujardin, 1845), both frog parasites from North America and Europe, respectively. Heterorchis cf. crumenifer represented a distinct lineage within the Plagiorchioidea but formed a polytomy with species from 10 plagiorchioid families.


Antarctic toothfish Dissostichus mawsoni as a bioindicator of trace and rare earth elements in the Southern Ocean.
The Antarctic toothfish Dissostichus mawsoni is a Southern Ocean long-lived top predator which is regularly captured on an annual fishery operating in the region. By its biological and ecological characteristics, it is a potential bioindicator for the concentrations of trace and rare earth elements in the Antarctic. As these elements are mainly transferred through the diet and a deficiency or excess of these elements can lead to diverse health problems, it is important to measure their concentrations on the organisms. This study provides, for the first time, the concentration of 27 trace (major essential, minor essential and non-essential) and rare earth elements in the muscle of D. mawsoni captured in three areas of the Amundsen and Dumont D'Urville Seas (Antarctica). Major essential elements had the highest concentrations, with potassium (K) as the most concentrated, and rare earth elements the lowest. Significant differences between areas were found for most of the studied elements. No bioaccumulation nor biomagnification potential was found for the studied elements, with several elements decreasing concentrations towards larger individuals. Decreasing trends are related with the different habitats occupied by D. mawsoni through their life, suggesting that elements' concentrations in the water is determinant for the concentrations in this top predator, and/or there is a dilution effect as the fish grows. Our results also support that Se presents a detoxification potential for Hg in D. mawsoni, but only when Hg concentrations are higher to unhealthy levels. This study supports D. mawsoni as a potential bioindicator for the concentrations of the different trace and rare earth elements in the Southern Ocean, though only when comparing individuals of similar size/age, but also to evaluate annual changes on their concentrations. Furthermore, D. mawsoni can be a good source of major essential elements to humans with concentrations of major essential elements above some of other marine fish worldwide.


Neuromyelitis optica with brain stem involvement in a middle-aged Ethiopian woman: a case report and review of literature.
Neuromyelitis optica is a demyelinating disease of the central nervous system that predominantly affects the optic nerves and spinal cord. In neuromyelitis optica, white blood cells and antibodies primarily attack the optic nerves and the spinal cord, but may also attack the brain. Brainstem manifestation has been described recently. So far, neuromyelitis optica is very rare in Ethiopia and there were only two case reports, but this is the first case report of neuromyelitis optica with brainstem involvement. A 47-year-old Addis Ababa woman presented to Saint Paul's Hospital Millennium Medical College with a history of visual loss of 7 years and bilateral lower limb weakness of 4 days duration. She had bilateral oculomotor nerve palsy. Her past medical history showed systemic hypertension for 18 years and dyslipidemia for 1 year. The objective evaluation of the patient revealed right optic nerve atrophy suggesting optic neuritis and flaccid paraplegia with sensory level at the fourth thoracic vertebra. Diagnostic work-up using electromyography and spinal magnetic resonance imaging revealed demyelinating anterior visual pathway dysfunction and signs of extensive cervicothoracic transverse myelitis from the third cervical to lower thoracic vertebrae, respectively. Then a diagnosis of neuromyelitis optica was established. After treatment with high-dose systemic steroid followed by azathioprine, the patient was stable for several months with significant improvement of vision and lower-extremity weakness with no relapse of symptoms. The case described here is a rare inflammatory demyelinating disorder of the central nervous system occurring in East Africa. It reminds clinicians to suspect neuromyelitis optica in a patient who presented with unexplained recurrent optic neuritis to make a timely diagnosis and prevention of permanent neuronal damage. Neuromyelitis optica can also be associated with oculomotor nerve involvement.


Typical ulcerative colitis treated by herbs-partitioned moxibustion: A case report.
Ulcerative colitis (UC), also known as chronic nonspecific UC, is an inflammatory bowel disease characterized by diffuse colonic mucosal inflammation. The incidence and prevalence of UC have risen markedly, and the disease seriously affects the quality of life of patients, and poses a great burden on the world health care infrastructure and economy. We present a 60-year-old man who had ulcerative colitis for more than 10 years, with recurrent abdominal pain, bloody diarrhea with mucopurulent stool. The treatments with sulfasalazine, mesalazine, and traditional Chinese medicine were not effective, and herbs-partitioned moxibustion (HPM) was then applied at "Zhongwan" (RN12), "Tianshu"(ST25), and "Qihai" (RN6) once a day for about 30 min, 3 times per week, for 6 mo.His main clinical symptoms of abdominal pain, bloody diarrhea with mucopurulent stool gradually improved, and the mucosa had nearly healed, as observed under endoscopy by the 6th mo. The patient's condition was alleviated without relapsing during the subsequent 3-mo follow-up period. HPM showed a significant effect in the treatment of ulcerative colitis in this case, and the effect would help the patient to maintain remission for at least 3 mo. A series of symptoms of this UC patient significantly improved with the treatment of HPM.


Molecular characterization of both transesterification reactions of the group II intron circularization pathway.
Group II introns can self-splice from RNA transcripts through branching, hydrolysis and circularization, being released as lariats, linear introns and circles, respectively. In contrast to branching, the circularization pathway is mostly based on assumptions and has been largely overlooked. Here, we address the molecular details of both transesterification reactions of the group II intron circularization pathway in vivo. We show that free E1 is recruited by the intron through base pairing interactions and that released intron circles can generate free E1 by the spliced exon reopening reaction. The first transesterification reaction was found to be induced inaccurately by the 3'OH of the terminal residue of free E1 at the 3' splice site, producing circularization intermediates with heterogeneous 3' ends. Nevertheless, specific terminal 3'OH, selected by a molecular ruler, was shown to precisely attack the 5' splice site and release intron circles with 3'-5' rather than 2'-5' bonds at their circularization junction. Our work supports a circularization model where the recruitment of free E1 and/or displacement of cis-E1 induce a conformational change of the intron active site from the pre-5' to the pre-3' splice site processing conformation, suggesting how circularization might initiate at the 3' instead of the 5' splice site.


Abdominal soft tissue sarcoma: a multicenter retrospective study.
Soft tissue sarcomas (STS) are rare mesenchymal neoplasms with a variety of histological subtypes. However, in Japan, data on the clinical characteristics and prognostic profiles of these tumors are lacking. The purpose of the present study was to clarify the clinical features and outcomes of Japanese patients with retroperitoneal and abdominal STS. We reviewed and analyzed retrospectively the data for 82 patients who underwent surgery for retroperitoneal and abdominal STS at Osaka University and affiliated hospitals from 2000 to 2007. The factors analyzed included patient demographics and clinical features. The histological subtypes included leiomyosarcoma in 32 patients (39.0%), liposarcoma in 30 (36.6%), malignant fibrous histiocytoma in 10 (12.2%), and other miscellaneous subtypes in 10 (12.2%). The overall survivals were 92, 69, and 62%, respectively, at 1, 3, and 5 years after primary surgery. The overall survival of patients with low-grade sarcoma was significantly better than that of patients with high-grade sarcoma. Complete resection was done in 63 patients (77%) and their recurrence-free survivals were 73, 34, and 23%, respectively, at 1, 3, and 5 years after the surgery. Subgroup analysis of differences between leiomyosarcoma and liposarcoma revealed that liposarcomas were mainly located in the retroperitoneum and leiomyosarcomas were located equally in the retroperitoneum and abdominal cavity. The tumor size of liposarcomas was larger than that of leiomyosarcomas; however, the recurrence-free survival was better in patients with liposarcoma than in those with leiomyosarcoma. Our results showed the clinical features and prognoses of retroperitoneal and abdominal STS in Japan. Further large-scale nationwide studies are required to clarify the detailed clinical behavior of retroperitoneal and abdominal STS in Japan.


[Oral paracoccidiodomycosis in an immunocompetent woman: a case report and literature review].
Paracoccidioidomycosis is a progressive, chronic, systemic disease which is the second most common form of mycosis in South America, affecting approximately 10million people in this region. It occurs most commonly in adult male farmers and mainly affects the lungs. Oral paracoccidioidomycosis is the second most frequent chronic presentation. We report the case of an immunocompetent female patient whose oral mucosae was infected with paracoccidium and discuss oral paracoccidium.


Detecting β-Galactosidase-Labeled Cells.
β-Galactosidase has been used extensively both as a label in enzyme immunoassays and for immunocytochemistry. One good substrate is 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal), which gives an intense blue product. The product is stable and insoluble in alcohol as well as H2O.


Low ferritin levels appear to be associated with worsened health in male repeat blood donors.
Frequent blood donation depletes iron stores of blood donors. Iron depletion may lead to anaemia, but the health effects of iron depletion without anaemia in healthy blood donors are not well understood. We studied in the FinDonor cohort whether worsening of self-rated health of blood donors during the study period was associated with biomarkers for iron levels or other self-reported changes in lifestyle. We included 1416 participants from the cohort who answered an 89-item questionnaire on their health and lifestyle during their enrolment visit and again at the end of the study. We performed multivariate logistic regression to test if blood donation-related factors affected the probability of reporting worsened health. To set these findings into a more holistic context of health, we subsequently analysed all other questionnaire items with a data-driven exploratory analysis. We found that donation frequency in men and post-menopausal women and ferritin level only in men was associated negatively with worsened health between questionnaires. In the exploratory analysis, stable physical condition was the only questionnaire item that was associated negatively with worsened health in both women and men. Our results suggest that low ferritin level is associated with worsened health even in non-anaemic repeat donors, although we find that when health is analysed more holistically, ferritin and other factors primarily related to blood donation lose their importance.


C-reactive protein polymorphisms and genetic susceptibility to ischemic stroke and hemorrhagic stroke in the Chinese Han population.
The inflammatory marker C-reactive protein (CRP) has been strongly correlated with the risk of cardiovascular disease. Some single-nucleotide polymorphisms (SNPs) have been reported to be associated with serum CRP levels. In this study, we assessed the genetic association between SNPs within the CRP gene and ischemic and hemorrhagic stroke in the Han Chinese population. This study comprises 564 ischemic stroke patients, 220 hemorrhagic stroke patients and 564 controls from the ethnic Han Chinese population in Wuhan. Four CRP SNPs, -757A>G (rs3093059), -717A>G (rs2794521), -286C>T>A (rs3091244) and +2147C>T (rs1205), were genotyped from patients using TaqMan assays. The A allele frequency for the -717A>G polymorphism was significant higher in controls than in ischemic stroke patients (P=0.037), after adjustment for traditional risk factors (odds ratio 0.28; 95% CI 0.12-0.65; P=0.003), suggesting a protective effect for this allele against ischemic stroke. Haplotype analysis showed that the H3 (G-C-C) haplotype conferred a significantly increased risk of ischemic stroke (odds ratio 1.052, 95% CI 1.001-1.106: P=0.047). Neither CRP genotypes nor haplotypes showed an association with hemorrhagic stroke. However, the frequency for haplotype H5 (A-T-C) was significantly higher in ischemic stroke than hemorrhagic stroke patients (P=0.0003). These data suggest that the CRP gene -717A allele confers a protective effect against ischemic stroke. Furthermore, the H3 haplotype (G-C-C) is an independent risk marker for ischemic stroke, whereas the H5 haplotype (A-T-C) can be used as a prognostic marker of hemorrhagic stroke.


Reduced-Intensity versus Myeloablative Conditioning in Cord Blood Transplantation for Acute Myeloid Leukemia (40-60 years) across Highly Mismatched HLA Barriers-On Behalf of Eurocord and the Cellular Therapy & Immunobiology Working Party (CTIWP) of EBMT.
The use of myeloablative conditioning (MAC) in umbilical cord blood transplantation (UCBT) has been associated with high nonrelapse mortality (NRM) in patients aged >40 years, especially those having a high HLA disparity, thus limiting wider applications. We hypothesized that the NRM advantage of reduced-intensity conditioning (RIC) and higher graft-versus-leukemia effect associated with greater HLA disparities would expand its use for patients (aged 40 to 60 years) without compromising efficacy and compared outcomes between RIC and MAC regimens. In total, 288 patients aged 40 to 60 years, with de novo acute myeloid leukemia, receiving UCBT with at least 2 HLA mismatches with RIC (n = 166) or MAC (n = 122) regimens were included. As compared to RIC, the MAC cohort included relatively younger patients, having received more single UCBT, with lower total nucleated cell counts and more in vivo T cell depletion. Median time to neutrophil engraftment, infections (bacterial, viral, and fungal), and grade II to IV acute and chronic graft-versus-host disease were similar in both groups. In the multivariate analysis, overall survival (hazard ratio [HR], 0.98; P = .9), NRM (HR, 0.68; P = .2), and relapse (HR, 1.24; P = .5) were not different between RIC and MAC. Refractory disease was associated with worse survival. Outcomes of UBCT for patients aged 40 to 60 years having ≥2 HLA mismatches are comparable after the RIC or MAC regimen.


Spray-drying encapsulation of microwave-assisted extracted polyphenols from Moringa oleifera: Influence of tragacanth, locust bean, and carboxymethyl-cellulose formulations.
In this work, polyphenols from Moringa oleifera (Mor) leaves were extracted by microwave-assisted extraction (MAE) and encapsulated by spray-drying (SD). Particularly, we explored the influence of tragacanth gum (TG), locust bean gum (LBG), and carboxymethyl-cellulose (CMC) as wall-materials on the physicochemical behavior of encapsulated Mor. Single or combined wall-material treatments (100:00 and 50:50 ratios, and total solid content 1%) were tested. The results showed the wall-material had a significant effect on the process yield (55.7-68.3%), encapsulation efficiency (24.28-35.74%), color (yellow or pale-yellow), total phenolic content (25.17-27.49 mg GAE g-1 of particles), total flavonoid content (23.20-26.87 mg QE g-1 of particles), antioxidant activity (DPPH• = 5.96-6.95 mg GAE g-1; ABTS•+ = 5.61-6.18 mg TE g-1 of particles), and particle size distribution (D50 = 112-1946 nm) of the encapsulated Mor. On the other hand, SEM analysis showed smooth and spherical particles, while TGA and DSC analyses confirmed the encapsulation of bioactive compounds based on the changes in thermal peaks. Finally, XRD analysis showed that the particles have an amorphous behavior. The encapsulated Mor produced with individual TG or CMC demonstrated better properties than those obtained from mixed gums. Thus, TG or CMC might be feasible wall materials for manufacturing encapsulated Mor that conserve the phenolic content and antioxidant activity.


Philosophers are doing something different now: quantitative data.
The philosophical study of mind in the twentieth century was dominated by a research program that used a priori methods to address foundational questions. Since that time, however, the philosophical study of mind has undergone a dramatic shift. To provide a more accurate picture of contemporary philosophical work, I compared a sample of highly cited philosophy papers from the past five years with a sample of highly cited philosophy papers from the twentieth century. In the twentieth century sample, the majority of papers used purely a priori methods, while only a minority cited results from empirical studies. In the sample from the past five years, the methodology is radically different. The majority of papers cite results from empirical studies, a sizable proportion report original experimental results, and only a small minority are purely a priori. Overall, the results of the review suggest that the philosophical study of mind has become considerably more integrated into the broader interdisciplinary field of cognitive science.


Highly sensitive and stable fructose self-powered biosensor based on a self-charging biosupercapacitor.
Herein, we present an alternative approach to obtain a highly sensitive and stable self-powered biosensor that was used to detect D-fructose as proof of concept.In this platform, we perform a two-step process, viz. self-charging the biosupercapacitor for a constant time by using D-fructose as fuel and using the stored charge to realize the detection of D-fructose by performing several polarization curves at different D-fructose concentrations. The proposed BSC shows an instantaneous power density release of 17.6 mW cm-2 and 3.8 mW cm-2 in pulse mode and at constant load, respectively. Moreover, the power density achieved for the self-charging BSC in pulse mode or under constant load allows for an enhancement of the sensitivity of the device up to 10 times (3.82 ± 0.01 mW cm-2 mM-1, charging time = 70 min) compared to the BSC in continuous operation mode and 100 times compared to the normal enzymatic fuel cell. The platform can potentially be employed as a self-powered biosensor in food or biomedical applications.


Might depression, psychosocial adversity, and limited social assets explain vulnerability to and resistance against violent radicalisation?
This study tests whether depression, psychosocial adversity, and limited social assets offer protection or suggest vulnerability to the process of radicalisation. A population sample of 608 men and women of Pakistani or Bangladeshi origin, of Muslim heritage, and aged 18-45 were recruited by quota sampling. Radicalisation was measured by 16 questions asking about sympathies for violent protest and terrorism. Cluster analysis of the 16 items generated three groups: most sympathetic (or most vulnerable), most condemning (most resistant), and a large intermediary group that acted as a reference group. Associations were calculated with depression (PHQ9), anxiety (GAD7), poor health, and psychosocial adversity (adverse life events, perceived discrimination, unemployment). We also investigated protective factors such as the number social contacts, social capital (trust, satisfaction, feeling safe), political engagement and religiosity. Those showing the most sympathy for violent protest and terrorism were more likely to report depression (PHQ9 score of 5 or more; RR = 5.43, 1.35 to 21.84) and to report religion to be important (less often said religion was fairly rather than very important; RR = 0.08, 0.01 to 0.48). Resistance to radicalisation measured by condemnation of violent protest and terrorism was associated with larger number of social contacts (per contact: RR = 1.52, 1.26 to 1.83), less social capital (RR = 0.63, 0.50 to 0.80), unavailability for work due to housekeeping or disability (RR = 8.81, 1.06 to 37.46), and not being born in the UK (RR = 0.22, 0.08 to 0.65). Vulnerability to radicalisation is characterised by depression but resistance to radicalisation shows a different profile of health and psychosocial variables. The paradoxical role of social capital warrants further investigation.


Butyrate kinase from Clostridium acetobutylicum.
Crude extracts of Clostridium acetobutylicum contain a butyrate kinase of high specific activity (5.2 mumol/min/mg of protein). The enzyme has been purified 77-fold in a six-step procedure to a specific activity of 402 mumol/min/mg of protein. The purified butyrate kinase showed a single band with a molecular weight of 85,000 on nondenaturing polyacrylamide gradient gel electrophoresis. Separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the enzyme is a dimer of two apparently identical subunits with molecular weights of 39,000. The pH optimum for the reaction in the butyryl phosphate-forming direction is 7.5, and the pI of the kinase is 5.6. The amino acid composition of the enzyme is also reported. It contains no tryptophan and is low in sulfur-containing amino acids. The kinase has a broad substrate specificity and exhibits its highest relative activities with butyrate and valerate. Butyrate kinase is rapidly inactivated at 50 degrees C in the absence of a fatty acid substrate. Although a reducing agent was required for maximum activity, treatment with several sulfhydryl-modifying agents failed to inhibit the enzyme.


Synthesis and evaluation of the antiviral activity of acyclic nucleosides carrying fluorine and sulfur substituents.
-2',3'-Seco nucleosides 5 carrying fluorine and sulfur substituents at C-3' and C-5', respectively, of acyclic sugar moiety were synthesized in enantiomerically and diastereoisomerically pure form. These products and some structurally similar 1',2'-seco-2'-nor-and 1',2'-seco-nucleosides 3 and 4 were tested in vitro for cytotoxicity and antiviral activity. At non-cytotoxic concentrations the compounds were inactive against human immunodeficiency virus and herpes simplex virus type-1.


Semiconducting polymer nano-radiopharmaceutical for combined radio-photothermal therapy of pancreatic tumor.
Pancreatic ductal adenocarcinoma (PDAC) is a devastatingly malignant tumor with a high mortality. However, current strategies to treat PDAC generally have low efficacy and high side-effects, therefore, effective treatment against PDAC remains an urgent need. We report a semiconducting polymer nano-radiopharmaceutical with intrinsic photothermal capability and labeling with therapeutic radioisotope 177Lu (177Lu-SPN-GIP) for combined radio- and photothermal therapy of pancreatic tumor. 177Lu-SPN-GIP endowed good stability at physiological conditions, high cell uptake, and long retention time in tumor site. By virtue of combined radiotherapy (RT) and photothermal therapy (PTT), 177Lu-SPN-GIP exhibited enhanced therapeutic capability to kill cancer cells and xenograft tumor in living mice compared with RT or PTT alone. More importantly, 177Lu-SPN-GIP could suppress the growth of the tumor stem cells and reverse epithelial mesenchymal transition (EMT), which may greatly reduce the occurrence of metastasis. Such strategy we developed could improve therapeutic outcomes over traditional RT as it is able to ablate tumor with relatively lower doses of radiopharmaceuticals to reduce its side effects.


Survival of patients with glioblastoma multiforme has not improved between 1993 and 2004: analysis of 625 cases.
Glioblastoma is the most common primary brain tumour. The aim of this study was to determine trends in survival over a 12-year period. Survival data were collected retrospectively for 625 patients who had surgery for histologically-confirmed glioblastoma between 1993 and 2004 in a single centre. Data including age, sex, preoperative Karnofsky performance score, tumour site, date of surgery, and type of surgical and adjuvant treatment were collected. Overall median survival was 189 days; there was no significant change in survival over 12 years. Multivariate analysis identified the following independent positive prognostic factors: age <60 years (p < 0.0005), Karnofsky score > or = 70 (p < 0.0001), tumour debulking, rather than biopsy (p < 0.001), right-sided lesion (p < 0.05), unilateral tumour (p < 0.05) and radiotherapy (p < 0.0001). Despite neurosurgical advances, the survival of patients with glioblastoma has not changed for more than a decade. Although, overall, glioblastoma has a short survival, our data show that individual patient survival is heterogeneous.


Source-level EEG and graph theory reveal widespread functional network alterations in focal epilepsy.
The hypersynchronous neuronal activity associated with epilepsy causes widespread functional network disruptions extending beyond the epileptogenic zone. This altered network topology is considered a mediator for non-seizure symptoms, such as cognitive impairment. The aim of this study was to investigate functional network alterations in focal epilepsy patients with good seizure control and high quality of life. We compared twenty-two focal epilepsy patients and sixteen healthy controls on graph metrics derived from functional connectivity of source-level resting-state EEG. Graph metrics were calculated over a range of network densities in five frequency bands. We observed a significantly increased small world index in patients relative to controls. On the local level, two left-hemisphere regions displayed a shift towards greater alpha band "hubness". The findings were not mediated by age, sex or education, nor by age of epilepsy onset, duration or focus lateralisation. Widespread functional network alterations are evident in focal epilepsy, even in a cohort characterised by successful anti-seizure medication therapy and high quality of life. These findings might support the position that functional network analysis could hold clinical relevance for epilepsy. Focal epilepsy is accompanied by global and local functional network aberrancies which might be implied in the sustenance of non-seizure symptoms.


Use of the Functioning Assessment Short Test (FAST) in defining functional recovery in bipolar I disorder. Post-hoc analyses of long-term studies of aripiprazole once monthly as maintenance treatment.
There is growing agreement that definitions of "recovery" in bipolar-I disorder (BP-I) should include functional outcomes beyond sustained symptomatic remission. In this post-hoc analysis, we assessed functional recovery rates according to the validated Functioning Assessment Short Test (FAST) in participants with BP-I after 52 weeks of maintenance treatment with aripiprazole once monthly (AOM). Rates of functional recovery with AOM 400 were investigated in two 52-week studies. NCT01567527 was a placebo-controlled, double-blind, randomized-withdrawal study and NCT01710709 was an open-label study. Functional recovery, assessed at the end of the respective maintenance phases, was defined as a total FAST score of ≤11 for 8 consecutive weeks. Post-hoc analyses included 229 patients from the randomized-withdrawal study (AOM 400 n=116; placebo n=113). The open-label study included 402 patients (including 321 de novo patients and 81 rollover patients who had completed the randomized-withdrawal study). In the randomized-withdrawal study, functional recovery was achieved by 30.2% (n=35) of the AOM 400 group compared with 24.8% (n=28) in the placebo group. The difference was not statistically significant (p=0.39). In the open-label study, 36% (n=116) of de novo patients and 43% (n=35) of rollover patients had functionally recovered after 52 weeks of AOM 400 treatment. These data highlight the utility of a sustained FAST total score of ≤11 as a definition of recovery and emphasize the possibility of achieving this ambitious treatment goal with effective long-term treatment.


The design, synthesis and anti-tumor mechanism study of new androgen receptor degrader.
Targeted protein degradation using small molecules is a novel strategy for drug development. In order to solve the problem of drug resistance in the treatment of prostate cancer, proteolysis-targeting chimeras (PROTAC) was introduced into the design of anti-prostate cancer derivatives. In this work, we synthesized two series of selective androgen receptor degraders (SARDs) containing the hydrophobic degrons with different linker, and then investigated the structure-activity relationships of these hybrid compounds. Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Among them, compound A9 displayed potent inhibitory activity against LNCaP prostate cancer cell line with IC50 values of 1.75 μM, as well as excellent AR degradation activity. Primary mechanism studies elucidated compound A9 arrested cell cycle at G0/G1 phase and induced a mild apoptotic response in LNCaP cells. Further study indicated that the degradation of AR was mediated through proteasome-mediated process. For all these reasons, compound A9 held promising potential as anti-proliferative agent for the development of highly efficient SARDs for drug-resistance prostate cancer therapies.


Hesperidin blunts streptozotocin-isoproternol induced myocardial toxicity in rats by altering of PPAR-γ receptor.
Hesperidin has been shown to possess cardioprotective and anti-diabetic potential. Hitherto, its molecular mechanism on isoproterenol (ISO)-induced myocardial dysfunction in diabetes is still not explored. Hence, for the first time we sought to investigate whether hesperidin exerts any beneficial effect on the pathophysiology of myocardial infarction (MI) in diabetes through the PPAR-γ pathway by assessing a variety of indices e.g., apoptosis, hemodynamic, biochemical and histoarchitectural changes. Diabetes was induced by a single dose of STZ (50 mg/kg IP). Diabetic rats received either hesperidin (100 mg/kg/day orally), the PPAR-γ antagonist GW9662 (1 mg/kg/day IP), or both for 14 days with concurrent administration of ISO (85 mg/kg SC) on days 13 and 14. ISO-STZ rats resulted in severe myocardial dysfunction (decreased ±LVdP/dt and increased LVEDP). In addition, augmented myocardial thiobarbituric acid-reactive substances and serum troponin-I with a concomitant decrease in level of glutathione and activities of catalase, superoxide dismutase antioxidants with cardiac injury biomarkers creatine kinase-MB isoenzyme, lactate dehydrogenase were seen. Morphological studies of the ISO-STZ challenged myocardium exhibited severe necrosis, edema and inflammatory changes. In Western blot analysis, Bcl-2 and PPAR-γ expression were decreased where as Bax expression was significantly increased, suggesting role of apoptosis in myocardial dysfunction. Interestingly, hesperidin treatment positively modulated these parameters as validated by improved hemodynamic and left ventricular functions, fortified endogenous anti-oxidant defence system and improved structural integrity of the myocardium. However, significant effects were lowered in animals treated with hesperidin plus GW9662. Moreover, down-regulated PPAR-γ and Bcl-2 expressions in myocardial infarcted diabetic hearts were increased by hesperidin treatment. Hence, for the first time the present study suggests that, hesperidin reduces oxidative stress, apoptosis and improves cardiac function via the PPAR-γ pathway.


Human papillomavirus testing in metastatic squamous cell carcinoma of the neck with unknown primary using PCR on fine-needle aspiration smears: a prospective clinical study.
Squamous cell carcinoma metastasis of the head and neck with unknown primary tumor (CUP) comprises a diagnostic challenge. Human papillomavirus (HPV) testing on cytologic specimens is gaining increasing focus as this may facilitate an early diagnosis of HPV-induced oropharyngeal carcinoma. This study aimed to prospectively assess PCR-based HPV-DNA testing on FNA smears in a clinical setting. Patients referred to a tertiary Head and Neck Cancer Center with suspected CUP were included from November 2016 to November 2018. Scraped cell material from FNA smears was analyzed for HPV-DNA with PCR using general primers (GP5 + /GP6 +) and correlated with the origin and histology of the primary tumor (oropharynx vs. outside oropharynx or benign tumor). The turn-around time reflecting the workflow for HPV-DNA testing by PCR was also calculated. A total of 93 patients were enrolled in the study. The sensitivity and specificity were 86.7% [95% CI 75.4-94.1%] and 92.0% [95% CI 74.0-99.0%], and the positive and negative predictive values were 96.3% [95% CI 87.3-99.0%] and 74.2% [95% CI 59.9-84.7%], respectively. The turn-around time for HPV testing was a mean four calendar days. HPV-DNA testing on FNA smears can be performed within a reasonable timeframe and can guide for the detection of an HPV-positive oropharyngeal primary tumor in the clinical setting for patients presenting with CUP of the head and neck.


Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Post Radiation Female Urethral Stricture - A Technical Appraisal With Outcomes.
Female urethral stricture following radiation has been reported sparsely in the literature with just a handful of case reports. Radiation to the pelvis affects the genitourinary tracts and afflicts damage by causing periurethral fibrosis, necrosis, and subsequent tissue contraction, posing as a hurdle to the reconstructive surgeon. We studied the technique and outcomes of dorsal onlay buccal mucosal graft (BMG) urethroplasty in patients of radiation-induced female urethral stricture disease (FUSD). Three cases of radiation-induced FUSD were reviewed. The preoperative and postoperative parameters like IPSS, Flow rate (Qmax), Postvoid residue (PVR), urethroscopy findings, and Videourodynamics study parameters were analyzed. All patients underwent dorsal onlay BMG urethroplasty. The salient steps of the operative procedure are demonstrated in this video presentation. The mean duration after the last radiation cycle was 2.33 years. Preoperatively mean IPSS, Qmax, and PVR were 27.33 ± 1.15, 6.46 ± 0.6 mL/s, and 56.67 ± 16.07 mL, respectively. After dorsal onlay BMG urethroplasty the mean IPSS, Qmax, and PVR were 3.33 ± 1.5, 23.33 ± 6.1 mL/s, 15.67 ± 8.14 mL, respectively. None of the patients reported bothersome lower urinary tract symptoms, and stricture recurrence in the 12-month follow-up. However, one patient had transient stress incontinence, which was managed conservatively. Dorsal onlay BMG urethroplasty achieves excellent outcomes in patients with postradiation FUSD. Adequate dorsal urethrotomy should be contemplated in previously irradiated strictures.


A Novel Coding Variant in SLC39A8 Is Associated With Adolescent Idiopathic Scoliosis in Chinese Han Population.
A genetic case-control association study. The aim of this study was to investigate the association of SLC39A8 with the susceptibility of adolescent idiopathic scoliosis (AIS) in Chinese Han population. A recent exome-wide association study identified a missense variant rs13107325 in SLC39A8 that was associated with AIS. However, there was a lack of study validating the association of this novel mutation with AIS in other populations. The variant rs13107325 was genotyped in 965 AIS patients and 976 healthy controls by allelic specific multiple ligase detection reactions. Variants located in the coding region of SLC39A8 were identified by exon sequencing for 192 AIS patients and 192 controls. Paraspinal muscles from 36 AIS patients and 36 age-matched congenital scoliosis patients were collected for the gene expression analysis. Comparison between the cases and controls was performed with the χ test for genotyping data or with Student t test for gene expression analysis. For the missense variant rs13107325, there was no case of mutation detected in the patients or the controls. All the subjects had homozygous genotype CC. Exon sequencing revealed that a coding variant rs11097773 of SLC39A8 had a significantly different distribution of minor allele frequency between patients and controls (7.81% vs. 14.8%, P = 0.002). The mRNA expression of SLC39A8 in the patients was remarkably lower than that in the controls (0.0015 ± 0.00026 vs. 0.0021 ± 0.00033, P < 0.001). The association of previously reported novel mutation (rs13107325 in SLC39A8) with AIS was not replicated in the Chinese population. Interestingly, a novel coding variant rs11097773 of SLC39A8 is found significantly associated with AIS. Moreover, the expression of SLC39A8 was obviously decreased in AIS patients. Further study is warranted to clarify the functional role of rs11097773 in the development of AIS. 3.


Strategy to reduce the number of patients perceiving impaired visual function after cataract surgery.
To reduce the number of patients who perceive more difficulties performing daily life activities 6 months after cataract extraction than before surgery. Surgeons at 4 surgical units participating in the yearly outcome studies organized by the Swedish National Cataract Register. This study comprised surgical outcomes data and completed Catquest results before and after surgery collected from consecutive patients during a 1-month period yearly since 1995. The reasons for a no-benefit outcome from 1995 to 1997 were identified. During the 1-month study period in 1999, a strategy was launched to reduce postoperative anisometropia and disturbances from cataract in the fellow eye through better surgical planning. The percentage of patients with a no-benefit outcome who had anisometropia or cataract in the fellow eye as a probable reason for the outcome decreased from 27.3% and 13.0%, respectively, in the 1995 to 1997 study to 10.5% and 10.5%, respectively, in the 1999 study. Other reasons for a no-benefit outcome such as ocular co-morbidity or few preoperative problems increased in frequency, presumably as a result of a change in case mix. A strategy to reduce the number of patients perceiving more difficulties in performing daily life activities after cataract extraction than before surgery was tested. The number of patients with reasons for a poor outcome that the study focused on was reduced. Patients who gave reasons for a poor outcome other than anisometropia or cataract in the fellow eye increased in frequency, probably as a result of a change in case mix.


Recombinant factor XIII prophylaxis is safe and effective in young children with congenital factor XIII-A deficiency: international phase 3b trial results.
Essentials Prophylaxis is the standard of care for congenital factor XIII-A (FXIII-A) deficiency. Six children with FXIII-A deficiency received once-monthly prophylaxis with recombinant FXIII-A. Prophylaxis was well tolerated and no anti-FXIII antibodies were detected. Prophylaxis was effective with an annualized bleeding rate of zero. Background Factor XIII deficiency is a rare, severe congenital bleeding disorder. Monthly prophylaxis with recombinant FXIII A-Subunit (rFXIII) has demonstrated favorable safety and efficacy in patients aged ≥ 6 years, and may similarly benefit younger children. Objective To evaluate the long-term safety and efficacy of rFXIII in children aged < 6 years with congenital FXIII A-subunit deficiency. Patients/methods Six children, who had previously completed a single-dose pharmacokinetic trial of rFXIII, received 35 IU kg-1 rFXIII every 28 days (± 2 days) for a minimum of 52 weeks, and were evaluated for bleeding and adverse events. The Berichrom FXIII activity assay was used to monitor FXIII activity. Results The children, three girls and three boys, had an average age of 3.0 years (range: 1-4 years) at enrollment. The total treatment duration was 1.8-3.5 years, giving a total of 16.6 patient-years. No antibody development, thromboembolic events or allergic reactions occurred. There were 93 mild and seven moderate adverse events. Two adverse events (lymphopenia and gastroenteritis) were reported as probably or possibly related to rFXIII in two children. Two serious adverse events, unrelated to rFXIII, were reported in a single child, each related to head injury, and neither resulting in intracranial hemorrhage. The geometric mean FXIII activity trough was 0.19 IU mL-1 . No bleeding episodes requiring treatment with an FXIII-containing hemostatic agent occurred during the trial; thus, the annualized bleeding rate was 0. Conclusions Consistent with data from older age groups, prophylaxis with rFXIII appears to be safe and effective in young children with congenital FXIII A-subunit deficiency.


2'-O-Methyl-8-methylguanosine as a Z-Form RNA Stabilizer for Structural and Functional Study of Z-RNA.
In contrast to Z-DNA that was stabilized and well-studied for its structure by chemical approaches, the stabilization and structural study of Z-RNA remains a challenge. In this study, we developed a Z-form RNA stabilizer m⁸Gm, and demonstrated that incorporation of m⁸Gm into RNA can markedly stabilize the Z-RNA at low salt conditions. Using the m⁸Gm-contained Z-RNA, we determined the structure of Z-RNA and investigated the interaction of protein and Z-RNA.


Giant axonal neuropathy: possibly secondary to vitamin b12 malabsorption.
A giant axonal neuropathy is described in an adult with no evidence of a childhood onset of his disease and no history of exposure to toxic hydrocarbons. A causal relation to vitamin B12 malabsorption is proposed. This case suggests the need to expand the spectrum of diagnoses that must be considered when giant axons are encountered in peripheral nerve biopsy specimens.


EST analysis of functional genes associated with cell wall biosynthesis and modification in the secondary xylem of the yellow poplar (Liriodendron tulipifera) stem during early stage of tension wood formation.
A cDNA library was constructed from secondary xylem in the stem of a 2-year-old yellow poplar after being bent for 6 h with a 45° configuration to isolate genes related to cell wall modification during the early stages of tension wood formation. A total of 6,141 ESTs were sequenced to generate a database of 5,982 high-quality expressed sequence tags (ESTs). These sequences were clustered into 1,733 unigenes, including 822 contigs and 911 singletons. Homologs of the genes regulate many aspects of secondary xylem development, including those for primary and secondary metabolism, plant growth hormones, transcription factors, cell wall biosynthesis and modification, and stress responses. Although there were only 1,733 annotated ESTs (28.9%), the annotated ESTs obtained in this study provided sequences for a broad array of transcripts expressed in the stem upon mechanical bending, and the majority of them were the first representatives of their respective gene families in Liriodendron tulipifera. In the case of lignin, xylem-specific COMTs were identified and their expressions were significantly downregulated in the tension wood-forming tissues. Additionally, the majority of the auxin- and BR-related genes were downregulated significantly in response to mechanical bending treatment. Despite the small number of ESTs sequenced in this study, many genes that are relevant to cell wall biosynthesis and modification have been isolated. Expression analysis of selected genes allow us to identify the regulatory genes that may perform essential functions during the early stages of tension wood formation and associated cell wall modification.


Feasibility first: developing public performance indicators on patient safety and clinical effectiveness for Dutch hospitals.
This paper describes the development and implementation of the first national, public and obligatory set of hospital performance indicators in the Netherlands. Focusing on effectiveness and safety, the set was developed by the Dutch Health Care Inspectorate to improve the effectiveness and efficiency of their task: monitoring the quality of the care delivered by providers. In addition, the set would enhance the transparency of the hospital sector, and stimulate individual hospitals to improve their scores. Bridging some of the classic distinctions between 'internal' and 'external' indicators, the Inspectorate's vision was to rapidly produce a feasible set of indicators that would fulfill these aims, while maximally preventing 'side effects' such as misinterpretations, defensive or perverse reactions. Explicitly avoiding the trap of searching for exhaustive validity of the indicators, the inspectorate's motto was 'feasability first'. This paper describes how this simultaneously philosophical, political and pragmatic strategy played out successfully, and how the indicator set was ultimately embraced by all parties involved.


Foot infections in swimming baths.
A 10% random sample of all bathers at a public swimming bath were examined for tinea pedis and verruca.The overall incidence of tinea pedis was 8.5% and of verruca 4.8%. The incidence of tinea pedis in 205 male adults was 21.5%, in 288 boys 6.3%, in 60 adult females 3.3%, and in 220 girls 0.9%. The incidence of verruca in juveniles ranged from 4.2% in boys to 10.5% in girls.It was clear that both infections spread within the baths, and since a relatively small proportion of users admitted to taking precautions to avoid contracting or developing infections it seems advisable that more publicity about recommendations on foot care should be provided.


The propensity to perceive meaningful coincidences is associated with increased posterior alpha power during retention of information in a modified Sternberg paradigm.
There are ample inter-individual differences in the frequency with which people perceive meaningful coincidences. Previous research has identified increased proactive interference, that is a reduced working memory capacity, as one possible mechanism associated with this phenomenon. The present study aimed at extending this finding into the domain of neuroscience, (1) by assessing EEG alpha oscillations during the retention of information, (2) by replicating the behavioral link between meaningful coincidences and proactive interference. In a sample of 52 participants, the behavioral replication was successful. Furthermore, participants who perceived more meaningful coincidences showed higher alpha power increases at parietal-occipital sites, and at the same time, displayed lower alpha power increases at frontal areas, during retention of information. This neurophysiological activation pattern further underlines the assumption that participants who perceive more meaningful coincidences show lower working memory capacities, since increased alpha power at parietal areas reflects a higher load on working memory demands.


Preparing Membrane Proteins for Simulation Using CHARMM-GUI.
Molecular dynamics simulations of membrane proteins have grown dramatically in the last 20 years. Running these simulations first requires embedding the protein's three-dimensional structure in a lipid bilayer of a suitable composition, one that resembles its native environment. This step is far from trivial, especially for modeling heterogeneous mixtures of lipids. CHARMM-GUI, a webserver for simulation system preparation greatly simplifies this step, allowing for the construction of complex heterogeneous and/or asymmetric membranes. Here, we demonstrate how to use CHARMM-GUI to build the membrane for the outer-membrane protein BamA.


In Silico Identification of the Full Complement of Subtilase-Encoding Genes and Characterization of the Role of TaSBT1.7 in Resistance Against Stripe Rust in Wheat.
Plant subtilases (SBTs) or subtilisin-like proteases comprise a very diverse family of serine peptidases that participates in a broad spectrum of biological functions. Despite increasing evidence for roles of SBTs in plant immunity in recent years, little is known about wheat (Triticum aestivum) SBTs (TaSBTs). Here, we identified 255 TaSBT genes from bread wheat using the latest version 2.0 of the reference genome sequence. The SBT family can be grouped into five clades, from TaSBT1 to TaSBT5, based on a phylogenetic tree constructed with deduced protein sequences. In silico protein-domain analysis revealed the existence of considerable sequence diversification of the TaSBT family which, together with the local clustered gene distribution, suggests that TaSBT genes have undergone extensive functional diversification. Among those TaSBT genes whose expression was altered by biotic factors, TaSBT1.7 was found to be induced in wheat leaves by chitin and flg22 elicitors, as well as six examined pathogens, implying a role for TaSBT1.7 in plant defense. Transient overexpression of TaSBT1.7 in Nicotiana benthamiana leaves resulted in necrotic cell death. Moreover, knocking down TaSBT1.7 in wheat using barley stripe mosaic virus-induced gene silencing compromised the hypersensitive response and resistance against Puccinia striiformis f. sp. tritici, the causal agent of wheat stripe rust. Taken together, this study defined the full complement of wheat SBT genes and provided evidence for a positive role of one particular member, TaSBT1.7, in the incompatible interaction between wheat and a stripe rust pathogen.


Characterization of a cDNA for human protein C inhibitor. A new member of the plasma serine protease inhibitor superfamily.
A cDNA library in lambda-phage lambda gt11 containing DNA inserts prepared from human liver mRNA was screened with monoclonal antibodies to human protein C inhibitor. Six positive clones were isolated from 6 X 10(6) phages and plaque purified. The cDNA in the phage containing the largest insert, which hybridized to a DNA probe prepared on the basis of the amino-terminal amino acid sequence of the mature inhibitor, was sequenced. This cDNA insert contained 2106 base pairs coding for a 5'-noncoding region, a 19-amino acid signal peptide, a 387-amino acid mature protein, a stop codon, and a long 3'-noncoding region of 839 base pairs. Based on the amino acid sequence of the carboxyl-terminal peptide released by cleavage of protein C inhibitor by activated protein C as well as by thrombin, the reactive site peptide bond of protein C inhibitor is Arg354-Ser355. Five potential carbohydrate-binding sites were found in the mature protein. The high homology of the amino acid sequence of protein C inhibitor to the other known inhibitors clearly demonstrates that protein C inhibitor is a member of the superfamily of serine protease inhibitors including alpha 1-antichymotrypsin, alpha 1-antitrypsin, antithrombin III, ovalbumin, and angiotensinogen. Based on the difference matrices for these proteins, we present possible phylogenetic trees for these proteins.


Biomarker-assisted assessment of aquatic health using the cosmopolitan common carp, Cyprinus carpio (L): a case study of bisphenol-A exposures.
Monitoring aquatic health from environmental pollutants is critical, none more so than bisphenol-A (BPA), a ubiquitous endocrine-disrupting chemical (EDC). The present study brings out the responses of selected transcripts, hormone levels, and tissue histomorphology in a widely distributed fish species Cyprinus carpio (Linn.), following exposure to environmentally relevant (10, 100 ng/L) and higher (1000 ng/L) concentration of BPA. The response of cyp19a1a, cyp19a1b, and c3 significantly decreased, while that of vtg increased in their respective tissue domains. The hematological parameters TEC, Hb, and Hct decreased significantly in contrast to TLC (p < 0.05) at all exposure concentrations, whereas none of the erythrocytic indices (MCV, MCH, and MCHC) was perturbed. The steroidogenic hormone levels, such as estradiol and progesterone, increased significantly with increasing BPA concentrations. In contrast, the testosterone and all the thyroid hormones (T3, T4, and TSH) were suppressed significantly (p < 0.05). At the histological level, the BPA induced chondrocyte proliferation, which was accompanied by hemorrhage of the gill lamellae, increased melanomacrophagic centers (MMCs), and degeneration of tubules and fluid accumulation in the kidney. In parallel, binucleated hepatocytes and inflammations were prominent in the liver. Collectively, the histomorphology confirmed induction of degenerative effects in all the tissues investigated, while the cyclic responses of biochemical markers suggest an ability to regulate the impacts. However, a chronic exposure could result in overriding the endemic reproductive pathways with potential population-level effects. In conclusion, the study identified multiple molecular, cellular, and physiological markers that could be employed to detect early signs of BPA and more broadly EDC exposures. These markers in combination with a wide distribution of C. carpio should allow comparative studies of pollutants at environmental concentrations.


Transesophageal echocardiography for diagnosis of inadvertant closure of inferior vena cava opening during minimally invasive atrial septal defect closure.
Transesophageal echocardiography (TEE) is widely used in cardiac surgery. TEE provides important diagnostic and functional information before and after cardiopulmonary bypass thereby having a very important impact on perioperative clinical outcomes. We describe a case in which intraoperative TEE was instrumental in the timely diagnosis of inadvertant closure of the inferior vena cava (IVC) opening during minimally invasive surgical closure of atrial septal defect.


A randomised controlled trial to test the effects of fish aggregating devices (FADs) and SBC activities promoting fish consumption in Timor-Leste: A study protocol.
Timor-Leste is one of the world's most malnourished nations where micronutrient-deficient diets are a contributing factor to the prevalence of child stunting, currently estimated to be 45.6% of children under five. Fish are an important source of nutrients and one that may assist the country's predominantly rural population of agriculturalists to exit poverty and malnutrition. However, a small national fishing fleet producing low catch volumes places fish out of reach of most inland and upland populations where it is needed most. Fish consumption is very low in rural, inland areas compared to coastal, regional, and global averages. This study is a one-year, partially masked, cluster-randomized controlled trial among families living in rural, inland Timor-Leste. We aim to test and compare the effects of two treatments, alone and in combination, on the frequency and volume of household fish consumption in rural, inland areas as a proxy for improved dietary diversity and micronutrient intake. Treatment 1 is the installation of nearshore, moored fish aggregating devices (FADs) to improve catch rates with existing fishing gears. Treatment 2 is a social and behaviour change (SBC) activity to promote fish consumption. Villages in inland communities will be randomized to receive treatment 1, treatment 2, both treatments, or neither treatment. Data will be collected at baseline (prior to the rollout of the treatments) and endline. Our study will determine the impact of an improved supply of fish, along with nutrition-oriented SBC activities, on the fish purchasing and consumption practices of rural, inland households. Findings from this study are urgently needed by Small Island Developing States to guide policy and investment decisions on how best to improve households' diets using locally available, nutrient-dense foods such as fish. Investments such as these are needed to break the cycle of malnutrition. This trial is registered at clinicaltrials.gov (NCT04729829). Trial registration: Trial registered at clinicaltrials.gov Identifier: NCT04729829.


Laryngotracheal separation through the cricoid ring for management of tracheobronchomegaly.
Tracheobronchomegaly is a rare condition characterized by diffuse dilation of the trachea and main bronchi. In ventilator-dependent neonates with tracheobronchomegaly, a tracheostomy may be hazardous due to the lack of an appropriate tracheostomy tube size that can fit the enlarged trachea. Here, we describe a modification of the laryngotracheal separation procedure to permit ventilation in a child with tracheobronchomegaly and severe bronchopulmonary dysplasia.


Nomogram Predicts Improvement of Ischemic Mitral Regurgitation After Coronary Artery Bypass Grafting.
Developing a nomogram to predict improvement in moderate ischemic mitral regurgitation (IMR) after coronary artery bypass grafting (CABG) is in need. We retrospectively collected data from 112 patients with prior myocardial infarction and moderate IMR undergoing CABG between 2010 and 2018. Patients were divided into 2 groups based on IMR degree 1 year after CABG as follows: Improved Group with no or mild IMR (n = 54) and Failure Group with moderate or severe IMR (n = 58). To determine the predictors of postoperative IMR improvement, preoperative clinical and echocardiographic data were compared, and a nomogram was formulated based on all independent predictors. Discriminative ability, calibration, and clinical usefulness of the prediction model were assessed. Independent predictors of IMR improvement after CABG constructing the nomogram included duration between infarction and operation, posterior-inferior to left ventricular volume ratio, maximum difference of the time to reach minimum systolic volume of 16 segments, P3 leaflet tethering angle, and annular nonplanar angle. The nomogram exhibited well-fitted calibration curves and excellent discriminative ability. The area under the receiver operating characteristic curve was 0.974. Patients with a score >236 demonstrated a high probability of IMR improvement (sensitivity, 90.7%; specificity, 93.1%). Patients in the Improved Group demonstrated greater actuarial survival rates than those in the Failure Group. The nomogram combining 5 preoperative clinical and echocardiographic predictors provides an accurate preoperative estimation of moderate IMR improvement after surgery, with excellent discriminative ability. Based on this nomogram, patients with a higher score have predicted higher probabilities of IMR improvement.


Endoprotease in Plasmodium yoelii nigeriensis.
1. P. yoelli nigeriensis has an acid endoprotease (cathepsin D) and an endoarylamidase. 2. The acid endoprotease is specific towards haemogloblin. It is found in 2 molecular forms, of molecular weight 100,000 and 50,000. It is inhibited by hematin and pepsatin. 3. In mouse normal red blood cells we find an acid protease having physico-chemical properties similar to those of the enzyme present in P. yoelii nigeriensis extracts, except as regards the pHi. 4. In parasite extracts there exists an enzyme active on the synthesis substrate N-acetyl alanine 4 nitro anilide. The main properties of this enzyme have been determined. 5. This enzyme must be also involved in the mechanism of haemoglobin degradation.


[Euthanasia: is this the law we need?]
The Spanish Euthanasia Law introduces a new right that is added to the portfolio of services provided by the Spanish health system and whose application is guaranteed within a period of 40 days. From the perspective of clinical experience, it is argued that without the effective right to quality palliative care and given the current shortcomings in dependant care, this law may send a threatening message to particularly fragile and dependant individuals that will lead to them feeling like a burden to their families and society. It is reasoned that basing the right to die on the dignity of the individual may have unexpected social repercussions. The text of the law presents the flaws of having been written hastily and without the support of advisory entities. There are issues that require clarification with regard to the application of euthanasia within the context of general practice. The conclusion is that this new law will pose more problems of the type it aims to resolve.


Local exercise based on voluntary contractions produces greater warm-up effects on balance control than electro-induced contractions.
On the one hand, while general (involving the whole body) warm-up exercises have been extensively used to optimize motor and postural performance, the effect of a local (involving a particular muscular group) warm-up has not yet been addressed. On the other hand, voluntary (VOL) and electro-induced (EI) contractions produce different physiological effects likely to differently affect motor and postural performance. The aim was to analyze and compare the effects of two local warm-up modalities, voluntary and electro-induced (VOL or EI warm-up) on balance control. Balance control was evaluated with a force platform (recording the displacement of the centre of foot pressure - COP) in 27 healthy young subjects before (PRE), immediately after (POST), 5 min after (POST5), and 10 min after (POST10) either warm-up. Each warm-up included 6 sets of 5 contractions at 10% of maximal voluntary contraction of the quadriceps femoris. The results showed that the VOL warm-up improved balance control at POST, POST5 and POST10 while the EI warm-up improved it only at POST10. In addition, balance control was significantly better after the VOL warm-up than after the EI warm-up at POST5 and POST10. A short and local VOL warm-up improved balance control immediately after its completion and for, at least, ten minutes, while the EI warm-up required some minutes of recovery before producing its improving effects.


Binding and diffusion kinetics of the interaction of a hydrophobic potential-sensitive dye with lipid vesicles.
The interaction of the dye oxonol V with unilamellar dioleoylphosphatidylcholine vesicles has previously been investigated using a fluorescence stopped-flow technique. It has been found that the most suitable mathematical description of the equilibrium and kinetic data is obtained by assuming the presence of saturable dye binding sites in both monolayers of the vesicle membrane and a potential-dependent diffusion across the membrane interior between these two classes of sites. A kinetic model is presented which takes into account the degree of saturation of the binding sites, the degree of fluorescence quenching within the membrane, and the production of an electrical potential gradient across the membrane interior by the binding of the negatively charged dye. The model successfully predicts the time course of the fluorescence change due to binding and diffusion over the complete range of dye and vesicle concentrations as well as the fluorescence response of the dye to changing membrane potential.


Improving contact lens compliance by explaining the benefits of compliant procedures.
To increase compliance with instructions for safe and successful contact lens wear by helping patients understand the advantages and consequences of compliant and non-compliant behavior respectively. A series of explanations which elucidate the practical and scientific basis for many of the instructions given at lens delivery and aftercare have been prepared as a means of extending patient education beyond simply being instructed on what to do. The summary versions of these explanations have been prepared at an easier level of readability (age 10-12 years) to assist young patients and adults with reading disabilities, including those for whom English is their second language. Patients may be non-compliant because they do not understand the practical and/or scientific basis for procedures and the potential consequences of aberrant behavior. Delay in the onset of symptoms associated with non-compliance may allow them to assume that compliance is not important. Explanations which describe why instructions given for lens use are consistent with sustained comfortable and safe lens wear, appear to have the potential to strengthen or change patient attitudes toward being compliant. Behavior modification which reduces the prevalence of non-compliance appears likely to also help sustain better contact lens performance and reduce the prevalence of contact lens failure. These explanations could be modified for use in different practices according to the preferences of individual practitioners and to include new research findings as they become available.


The role of c-erbB-2/HER2/neu in breast cancer progression and metastasis.
Gene amplification and/or overexpression of the c-erbB-2/HER2/neu tyrosine kinase are linked with poor prognosis in breast cancer. This is manifest in shorter disease-free intervals, increased risk of metastasis, and resistance to many types of therapy. The molecular mechanisms and signaling circuitry underlying these phenomena are now being elucidated. c-erbB-2, although having no known soluble ligand, is transactivated by heterodimerization with other family members (EGFR, c-erbB-3, c-erbB-4). Receptor activation potentiates tumor cell motility, protease secretion and invasion, and also modulates cell cycle checkpoint function, DNA repair, and apoptotic responses. Since it is expressed at low levels in normal adult tissues, c-erbB-2 is an ideal target for therapy. There is reason for optimism that agents targeting c-erbB-2 signaling will have profound and selective effects in breast cancer, either as single agents or more likely in combination with other therapeutic agents, to enhance their potency.


Colorectal cancer risk in association with colorectal cancer as a second malignancy in relatives: a nationwide cohort study.
Increasing number of individuals will have first-degree relatives (FDRs) diagnosed with colorectal cancer (CRC), as a second primary malignancy (CRCa-2) after a non-CRC cancer. We aimed to estimate whether and to what extent a family history of CRCa-2 is associated with an increased CRC risk. In this Swedish nationwide cohort study, rate ratio (RR) and cumulative incidence of CRC were estimated among 172,531 individuals with a family history of CRC as a first primary malignancy (CRCa-1) and 17,830 with a family history of CRCa-2, respectively, using individuals without cancer family history as the reference group. A cumulative incidence of CRC by age 80 was 6.3 and 5.6% for individuals with a parental and a sibling family history of CRCa-2, respectively. RRs of CRC for one FDR diagnosed with CRCa-1 and CRCa-2 were respectively 1.72 (95% CI, 1.65-1.79) and 1.50 (1.32-1.70); the latter RR was lower than the former (P = 0.0356), but no difference was observed after adjusting age of diagnosis of CRC in FDR and family relationship (P = 0.6898). Increased RRs were found to be associated with a CRCa-2 diagnosis in FDR that occured after cancers in upper aerodigestive tract, breast, prostate, kidney and nervous system. Individuals who have relatives with CRCa-2 have an increased risk of CRC, but the magnitude is lower than those having relatives with CRCa-1, which is related to different ages of diagnosis of CRC in FDR and family relationships.


Comparing nurse practitioners/physician assistants and physicians in diagnosing pediatric abdominal pain for ESI level 3 patients seen in the emergency department.
Accuracy of emergency department (ED) diagnosis affects care management including tests, discharges, and readmissions. This retrospective study compared nurse practitioners/physician assistants (NPs/PAs) with physicians (MDs/DOs) on accuracy of diagnosing Emergency Severity Index (ESI) level 3 pediatric abdominal pain (AP) in the ED. Abdominal pain unrelated to trauma is a common ED pediatric visit. Data acquired from four hospital sites of a multistate emergency group examined patients younger than 18 years who were initially admitted for AP ESI level 3. The accuracy of AP ESI level 3 diagnoses was 94.9%, 90.9%, and 96.5% by physicians, NPs/PAs, and a collaboration of NP/PA/physician, respectively (χ2 = 13.187, p < .001). Accuracy of AP ESI level 3 diagnoses was greater with general admissions, intensive care unit admissions, transfers, or left against medical advice (100%) than with those who were discharged (χ2 = 11.058, p = .001). Abdominal pain complaints were segmented into five areas (i.e., AP, back pain, chest pain, epigastric pain, and pelvic pain). Irrespective of provider, those with a final diagnosis of AP or epigastric pain were correctly triaged and those with a final diagnosis of chest or back pain were incorrectly triaged as AP ESI level 3. When comparing providers in this subset (n = 43), there was no significant difference in the accuracy of assigning AP ESI level 3 (χ2 = 0.467, p = .495). Only cases with a final diagnosis of pelvic/genitourinary pain saw disparity in the accuracy (27 correct, 16 incorrect, χ2 = 1,681.80, p < .001).


A new species of the rare buthid scorpion genus Lissothus Vachon, 1948 from Central Algeria (Scorpiones, Buthidae).
Taxonomic considerations are given for the genus Lissothus Vachon, 1948 (Scorpiones, Buthidae). Two species are currently known, Lissothus bernardi Vachon, 1948 from Libya and Lissothus occidentalis Vachon, 1950 from Mauritania. In this contribution, a new species, Lissothus chaambi sp. n., is described from the desert of Central Algeria. The new species is most closely related to L. bernardi. The geographical distribution of the genus is discussed.


CRISPR-based detection of Helicobacter pylori in stool samples.
Noninvasive detection of Helicobacter pylori plays an important role in clinical practice. However, few noninvasive methods have been applied in epidemiological studies due to the requirement for expensive equipment and complicated processes. The aim of this study was to establish a reliable, fast, and inexpensive noninvasive method based on CRISPR-Cas12a technology for the detection of Helicobacter pylori in stool specimens. A novel detection method based on CRISPR-Cas12a technology was established and validated with 41 stool specimens collected from Zhujiang Hospital and compared with reliable Helicobacter pylori detection assays, such as the rapid urease test and urea breath test. A CRISPR-Cas12a system-based method was established, and its sensitivity and specificity were evaluated. Utilizing a lateral flow biosensor, the limit of detection was 5 copies/μl, and our method could successfully distinguish Helicobacter pylori from other pathogens, suggesting no cross-reactivity with other pathogens. Furthermore, lateral flow biosensor strips were utilized to test stool specimens, which could display the detection results in an accessible way. Our CRISPR-Cas12a system-based method successfully detected Helicobacter pylori in stool specimens. It is a rapid, simple, and inexpensive method for the detection and screening of Helicobacter pylori, which makes it a very promising supplemental test. However, its sensitivity and specificity compared with those of the gold standard test still need to be examined.


Low blood pressure and blood glucose levels in Alzheimer's disease. Evidence for a hypometabolic disorder?
To test possible differences between patients with Alzheimer's disease (AD) and patients with other forms of dementia and the healthy population concerning body composition, blood pressure, metabolic data and leukoaraiosis (LA). Retrospective study on data collected according to a predefined protocol. A geriatric, neuropsychiatric diagnostic unit. Seventy-one consecutive patients with dementia. Body mass index, blood pressure, metabolism and LA in AD compared to other dementia forms. Mean blood pressure and fasting blood glucose levels were lower in patients with AD, 94 +/- 12 mmHg and 4.3 +/- 0.5 mmol l-1, compared to patients with unspecified dementia (NUD), 100 +/- 10 mmHg and 5.5 +/- 2.5 mmol l-1 (P < 0.05) and vascular dementia (VAD), 114 +/- 12 mmHg and 5.6 +/- 1.6 mmol l-1 (P < 0.001) and the age-matched healthy population. Body mass index, serum cholesterol and cortisol were similar in all groups of dementia patients whereas triglycerides were highest in the VAD group. No cases of diabetes or treatment for hypertension were found in the AD group while the prevalence was 21% and 36% for diabetes in the NUD and VAD groups and 8% in the population from the same region. There were 16% with antihypertensive treatment in dementia NUD, 50% in VAD, and 30% in the general population. Treated or newly detected hypothyreosis was present in 11% of the AD patients, none in the other dementia groups and 2% in the general population. Smoking was least common in AD. Degree of LA correlated with blood pressure and blood glucose levels. AD was clearly different to other dementia patients. They had lower blood pressure, blood glucose and higher prevalence of hypothyreosis than the healthy, age-matched population. These findings may indicate that AD could be a hypometabolic disorder.


Aggressive G-CSF-producing gastric cancer complicated by lung and brain abscesses, mimicking metastases.
A 57-year-old Japanese man had type II c gastric cancer with marked lymph node metastases associated with leukocytosis and elevated granulocyte colony-stimulating factor (G-CSF). Total gastrectomy and distal pancreatectomy with lymph node dissection were performed. Although the primary lesion was negative for G-CSF by histopathological immunostaining, a highly increased G-CSF m-RNA level, measured using reverse transcriptase-polymerase chain reaction in frozen sections, led to a diagnosis of G-CSF-producing gastric cancer. The leukocytes and G-CSF decreased immediately after surgery. He then had an intraabdominal recurrence, and was diagnosed with multiple tumors in his lung and brain, with abnormally elevated leukocytes and greatly increased G-CSF; he died 4 months after the surgery. Autopsy showed intraabdominal recurrence of cancer, with no metastases to the lung or brain, but with multiple brain and lung abscesses. We speculate that the excessively increased neutrophils induced by G-CSF infiltrated the lung and brain and formed abscesses, mimicking metastases.


[Studies on biological characterization of mammary tumours of the sprague-dawley-rat in the syngeneic tumour-host system. I. Spontaneous primary mammary tumours and tumours induced by oral and intravenous application of DMBA (author's transl)].
Spontaneous and DMBA-induced mammary tumours of a Sprague-Dawley inbred line reared in Berlin-Buch are described. The incidence of spontaneous tumours was 14.3%, of chemically induced tumours 43.6% of all the animals tested. 5 different schedules of application proved superior to the oral route with regard to dose, mortality and tumour incidence. 87.2% of the carcinomas and 12.8% of benign tumours following DMBA treatment developed in the region of the mammary glands.


Intermethod variation in bone histomorphometry: comparison between manual and computerized methods applied to iliac bone biopsies.
The intermethod variation in the measurement of basic bone histomorphometric parameters was evaluated on 100 undecalcified transiliac bone biopsies. Two contiguous samples were taken from 50 patients (33 females; 17 males; mean age: 52 +/- 19 years) for diagnostic purposes. The diagnoses were osteoporosis (n = 38), renal osteodystrophy (n = 18), primary hyperparathyroidism (n = 16), osteomalacia (n = 12), metastatic bone disease (n = 2), thyrotoxic bone (n = 2), fluorosis (n = 2), and 10 biopsies were considered as "normal" bone. Trabecular bone volume (TBV) was measured with both a manual integrating eyepiece and an automatic (QUANTIMET 720-Cambridge Instruments, Cambridge, England) method. Trabecular resorption surfaces (TRS), trabecular osteoid surfaces (TOS), and volume (TOV) were measured with both a manual and a semiautomatic (VIDEOPLAN-Kontron, Munich, West Germany) method. The calcification rate (CR) was measured with both a manual and a semiautomatic method in eight cases after double labeling with tetracycline. Inter- and intraobserver variations were always lower with the automatic and semiautomatic methods than with the manual method, except for TOV. For all the parameters there was a highly significant correlation between manual and computerized methods (0.98 greater than r greater than 0.90). For TBV and CR no significant difference was noted, but for TBV the QUANTIMET appeared more sensitive, that is, better able to detect low values of the structure to be measured. For TRS, the manual method underestimated low values and appeared less sensitive than the semiautomatic method. For the 100 biopsies, the VIDEOPLAN underestimated the osteoid parameters by 13% for TOS and 26% for TOV.(ABSTRACT TRUNCATED AT 250 WORDS)


miR-509-5p anti-infection response for mycoplasma pneumonia in sheep by targeting NF-κB pathway.
MicroRNAs play a key role in Mannan-binding lectin-mediated resistance to Mycoplasma ovipneumoniae pneumonia, by regulating the translation of mRNAs of target genes, thereby regulating the immune response. Additionally, TRAF6 is a key molecule in Toll-like receptor signal transduction, which mediates inflammation and apoptosis signaling pathways and is widely involved in inflammation and immune response. While the molecular regulation mechanism has not been reported. In this study, we screened differentially expressed miRNAs and genes of Anti-infection for M. pneumonia on Sheep, through relevant bioinformatics analysis. Further, the effect of differential expression of NF-κB signaling pathway related genes on the molecular mechanism of M. pneumonia was detected. We used miRNA-mRNA integrated analysed, the target gene TRAF6 of miR-509-5p was selected. TRAF6 dual luciferase reporter vector was co-transfected into HEK 293T cells and primary sheep respiratory mucosal epithelial cells to detect changes in luciferase activity. qRT-PCR was used to analyze the effect of miR-509-5p on the expression and regulation of TRAF6 and other genes related to the NF-κB signaling pathway. The result confirmed that TRAF6 was a target gene of miR-509-5p. Compared with miR-509-5p-NC group, the luciferase activity of miR-509-5p group was significantly down-regulated (P < 0.01). Further, in sheep respiratory mucosal epithelial cells, miR-509-5p mimic could significantly down-regulate the fold change value of TRAF6 (P < 0.01). On the contrary, miR-509-5p-inhibitor up-regulated the fold change value of TRAF6 (P < 0.05). Interestingly, the expression levels of other genes were different. Among them, miR-509-5p mimic significantly up-regulated TLR4 and IRAK4 (P < 0.05), significantly down-regulated TAK1 (P < 0.05) and NF-κB (P < 0.01). miR-509-5p-inhibitor significantly up-regulated NF-κB (P < 0.05) and TAK1 (P < 0.01). miR-509-5p targets TRAF6 to affect the expression of downstream genes, which negatively regulates the NF-κB pathway, thereby affecting the inflammatory response.


Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and neuromuscular disorders.
The skeletal muscle ryanodine receptor is an intracellular calcium release channel which plays a central role in excitation contraction coupling. At least 80 mutations have been identified in the gene encoding the skeletal muscle ryanodine receptor and linked to several neuromuscular disorders, whose common feature appears to be a dysregulation of calcium homeostasis. A decade of research into the functional consequences of how these mutations affect the functional properties of the ryanodine receptor and their impact on disease, have significantly advanced our understanding of Malignant Hyperthermia, Central Core Disease and Multiminicore Disease. This review gives an overview of the important findings in the field of calcium homeostasis in skeletal muscle and describes how mutations in the ryanodine receptor gene might affect the function of this intracellular calcium release channel and lead to neuromuscular disorders.


Influence of psychological stress on non-surgical periodontal treatment outcomes in patients with severe chronic periodontitis.
The aim of this study was to evaluate the influence of psychological stress on non-surgical periodontal treatment (SRP) outcomes in patients with severe chronic periodontitis (stage 3/4 generalized periodontitis) at 6 months in the French population. Patients diagnosed with severe generalized chronic periodontitis (periodontitis stage 3/4) were included in this study. At baseline, psychological status was evaluated by self-administered questionnaire (Depression Anxiety Stress Scale 42 [DASS-42] and Toulouse coping scale [TCS]). Plasma levels of cortisol and chromogranin-A were determined. Patients were then managed by oral hygiene instructions, scaling and root planing of sites with PD >3 mm and followed at 3 and 6 months. Quantitative and qualitative variables were described and interactions were determined by linear and logistic regressions. Seventy-one patients were included in this study and 54 were followed up to 6 months. An average probing depth (PD) reduction of 0.73 ± 0.11 mm and decrease of diseased sites (PD >3 mm) were measured at 6 months illustrating SRP efficacy. Multivariable analysis showed that increased DASS-stress score was associated to worsened SRP outcomes in terms of bleeding on probing (BOP) (OR = 1.02, P <0.05) and mean PD (P <0.05) reduction. An increase of DASS-depression score negatively influenced PD >5 mm (OR = 1.06, P <0.05), PD >7 mm (OR = 1.17, P <0.01), CAL >5 mm (OR = 1.03, P <0.05), and CAL >7 mm (OR = 1.07, P <0.05) reduction. Negative coping strategies were also associated with worsened SRP outcomes. Patients with increased stress, anxiety, and depression scores as well as those exhibiting negative coping strategies demonstrate worsened SRP outcomes. DASS-42 and TCS were useful to determine psychological status and their use could be incorporated to assess treatment prognosis.


Sulfur hexafluoride in owl monkey vitreous cavity.
Sulfur hexafluoride (SF6) gas, tested in the vitreous chamber of owl monkey eyes, remained in the vitreous cavity about twice as long as air (ten to 11 days vs. five to six days). Its volume expanded from the diffusion of other gases into the created gas pocket. Lens opacities developed when the lens was in continuous contact with SF6 or air. Sulfur hexafluoride appeared to be no more toxic to the retina than air, using electroretinographic, histologic, and electron microscopic criteria.


Removal of biological effects of organic pollutants in municipal wastewater by a novel advanced oxidation system.
The Advanced Oxidation System (AOS) is a novel electrochemical advanced oxidation process that effectively removes bacterial and organic contaminants from wastewater. However, potential formation of secondary oxidative species may pose additional hazards to aquatic organisms living in the receiving water affected by the post-treatment effluent. The effect of exposure to AOS treated water, especially the potential long-term effects on aquatic organisms, requires further investigation to demonstrate both efficacy and safety of this process. To examine the potential adverse effects of AOS treated water, three aquatic species, including daphnia, zebrafish, and rainbow trout, were exposed to treated and untreated municipal wastewater effluent (MWE) spiked with one of two model organic contaminants, benzo[a]pyrene (BaP) and 17β-estradiol (E2). The results indicated AOS treatment significantly reduced the adverse effects caused by exposure to MWE and model organic contaminants to baseline levels in daphnia (reduced fecundity), zebrafish embryo (elevated EROD activity), and rainbow trout (elevated plasma vitellogenin). The Ames test was also conducted to confirm the removal efficacy of carcinogenicity of BaP spiked in MWE. Overall, this study demonstrated that AOS treatment is a promising and environmentally friendly technology for wastewater treatment, remediation, and management.


The unilateral frontotemporal approach for large and giant olfactory groove meningioma: Experience with 18 consecutive patients.
Although the bifrontal approach used to be recommended for large olfactory groove meningioma (OGM), recent studies showed that large OGMs can also be resected safely via unilateral approaches. The present study aimed to discuss reasons for preferring a unilateral frontotemporal approach (UFTA), and the technical nuances and results of the UFTA, based on 18 cases. The clinical and surgical data of patients who had been operated on for large (4-6cm) or giant (>6cm) OGM via a UFTA between 2011 and 2018 were retrospectively collected. In all, 18 patients were included. All tumors were compatible with a diagnosis of OGM in the light of peri-operative examinations. 11 cases (61%) were large and 7 (39%) giant OGM; mean diameter was 6.1cm (range, 4-10cm). Resection extent was Simpson grade II in 14 cases (78%), grade III in 1 (5%), and grade IV in 3 (17%). Sixteen cases (89%) had no peri-operative complications, while 2 patients (11%) showed cerebrospinal fluid leakage and hemorrhagic deposition in the surgical area. There were no new neurological deficits nor deaths. The UFTA for OGM is a relatively safe and effective approach, ensuring a high total removal rate with low mortality and morbidity. This study, with a reasonable number of patients, is one of the few in the literature on the outcome of this approach.


The mechanism of base excision repair in Chlamydiophila pneumoniae.
Repair of damaged DNA is of great importance in maintaining genome integrity, and there are several pathways for repair of damaged DNA in almost all organisms. Base excision repair (BER) is a main process for repairing DNA carrying slightly damaged bases. Several proteins are required for BER; these include DNA glycosylases, AP endonuclease, DNA polymerase, and DNA ligase. In some bacteria the single-stranded specific exonuclease, RecJ, is also involved in BER. In this research, six Chlamydiophila pneumoniae (C. pneumoniae) genes, encoding uracil DNA glycosylase (CpUDG), endonuclease IV (CpEndoIV), DNA polymerase I (CpDNApolI), endonuclease III (CpEndoIII), single-stranded specific exonuclease RecJ (CpRecJ), and DNA ligase (CpDNALig), were inserted into the expression vector pET28a. All proteins, except for CpDNALig, were successfully expressed in E. coli, and purified proteins were characterized in vitro. C. pneumoniae BER was reconstituted in vitro with CpUDG, CpEndoIV, CpDNApolI and E. coli DNA ligase (EcDNALig). After uracil removal by CpUDG, the AP site could be repaired by two BER pathways that involved in the replacement of either one (short patch BER) or multiple nucleotides (long patch BER) at the lesion site. CpEndoIII promoted short patch BER via its 5'-deoxyribophosphodiesterase (5'-dRPase) activity, while CpRecJ had little effect on short patch BER. The flap structure generated during DNA extension could be removed by the 5'-exonuclease activity of CpDNApolI. Based on these observations, we propose a probable mechanism for BER in C. pneumoniae.


Heat-induced changes to lipid molecular structure in Vimy flaxseed: spectral intensity and molecular clustering.
Autoclaving was used to manipulate nutrient utilization and availability. The objectives of this study were to characterize any changes of the functional groups mainly associated with lipid structure in flaxseed (Linum usitatissimum, cv. Vimy), that occurred on a molecular level during the treatment process using infrared Fourier transform molecular spectroscopy. The parameters included lipid CH(3) asymmetric (ca. 2959 cm(-1)), CH(2) asymmetric (ca. 2928 cm(-1)), CH(3) symmetric (ca. 2871 cm(-1)) and CH(2) symmetric (ca. 2954 cm(-1)) functional groups, lipid carbonyl CO ester group (ca. 1745 cm(-1)), lipid unsaturation group (CH attached to CC) (ca. 3010 cm(-1)) as well as their ratios. Hierarchical cluster analysis (CLA) and principal components analysis (PCA) were conducted to identify molecular spectral differences. Flaxseed samples were kept raw for the control or autoclaved in batches at 120°C for 20, 40 or 60 min for treatments 1, 2 and 3, respectively. Molecular spectral analysis of lipid functional group ratios showed a significant decrease (P<0.05) in the CH(2) asymmetric to CH(3) asymmetric stretching band peak intensity ratios for the flaxseed. There were linear and quadratic effects (P<0.05) of the treatment time from 0, 20, 40 and 60 min on the ratios of the CH(2) asymmetric to CH(3) asymmetric stretching vibration intensity. Autoclaving had no significant effect (P>0.05) on lipid carbonyl CO ester group and lipid unsaturation group (CH attached to CC) (with average spectral peak area intensities of 138.3 and 68.8 IR intensity units, respectively). Multivariate molecular spectral analyses, CLA and PCA, were unable to make distinctions between the different treatment original spectra at the CH(3) and CH(2) asymmetric and symmetric region (ca. 2988-2790 cm(-1)). The results indicated that autoclaving had an impact to the mid-infrared molecular spectrum of flaxseed to identify heat-induced changes in lipid conformation. A future study is needed to quantify the relationship between lipid molecular structure changes and functionality/availability.


Fluorescence in-situ hybridisation and molecular studies used in the characterisation of a Robertsonian translocation (13q15q) in Prader-Willi syndrome.
A patient with classical Prader-Willi syndrome was found to have a Robertsonian translocation 45,XY,t(13q15q)mat. On CBG banding, the translocation chromosome had a large centromere with one primary constriction. Using fluorescence in situ hybridisation, positive signals were obtained with chromosome 13 and chromosome 15 centromere probes, proving that the translocation was dicentric. NOR banding was negative in this chromosome, suggesting that the breakpoints were at 13p11 and 15p11. DNA studies showed that, while there was no deletion involving 15(q11-13), maternal uniparental disomy for chromosome 15 was present. We compare our findings with the five other cases of familial Robertsonian translocation PWS that have been reported.


Defining the proteomic landscape of rheumatoid arthritis: progress and prospective clinical applications.
The heterogeneity of Rheumatoid Arthritis (RA) and the absence of clinical tests accurate enough to identify the early stages of this disease have hampered its management. Therefore, proteomics research is increasingly focused on the discovery of novel biological markers, which would not only be able make an early diagnosis, but also to gain insight into the different pathological mechanisms underlying the heterogeneity of RA and also to stratify patients, which is critical to enabling effective treatments. Areas covered: The proteomic approaches that have been utilised to provide knowledge about RA pathogenesis, and to identify biomarkers for RA diagnosis, prognosis, disease monitoring and prediction of response to therapy, are summarized. Expert commentary: Although each proteomic study is unique in its design, all of them have contributed to the understanding of RA pathogenesis and the discovery of promising biomarkers for patient stratification, which would improve clinical care of RA patients. Still, efforts need to be made to validate these findings and translate them into clinical practice.


Effects of rapid maxillary expansion on anchorage alveolar bone meta-analysis.
Rapid maxillary expansion (RME) is a routine method for correcting transverse maxillary deficiency. This paper investigated the effect of RME on anchorage alveolar bone and examined the differences between micro-implant-assisted RME and conventional RME. Relevant articles were selected from the PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases. Review Manager software (v.5.3) was used for the pooled analysis and Cochran Q and I2 statistic tests were used to assess the heterogeneity. Following conventional RME, the distal buccal alveolar bone thickness and the mesiobuccal alveolar thickness of the maxillary first molars were significantly reduced. Hyrax (standard mean difference [SMD]: -0.93, 95% confidence interval [CI]: -1.20-0.66) and Haas procedures (SMD: -0.88, 95% CI: -1.40-0.36) significantly reduced the buccal vertical alveolar height of the maxillary first molars. Similar results were obtained for the maxillary first premolars following RME. The thickness of the buccal alveolar bone decreased with conventional RME compared to when using the method assisted by micro-implants. Conventional RME can reduce the thickness and vertical height of maxillary alveolar bone, and there is less loss of alveolar bone when using micro-implant-assisted RME. Further research is needed to validate the findings.


Investigational drugs for the treatment of thymic cancer: a focus on phase 1 and 2 clinical trials.
Thymic epithelial tumors (TETs) are rare tumors of thymic epithelial cells. Treatment options for advanced disease patients who failed standard platinum-based chemotherapy are limited. Phase I and II trials published in the last five years testing new systemic treatments for advanced TET patients are discussed, as well as ongoing trials. A PubMed database literature review was conducted for articles published between January 2016 and December 2021, and ongoing clinical trials were retrieved from ClinicalTrials.gov database. The most promising classes of new drugs in TET patients are angiogenesis inhibitors and immune checkpoint antibodies (ICIs). Sunitinib and Lenvatinib showed response rates of 26% and 38%, respectively, and ICIs showed durable responses in 20-25% in thymic carcinoma (TCs). Both approaches are mainly active in TCs, therefore new treatment options for thymomas are an unmet medical need.Two major new therapeutic strategies are ICI combinations with other drugs and drugs that target pathways that are dysregulated in TETs.Future challenges include the development of preclinical models to help identify novel targets and test new treatment strategies, and randomized clinical trials to provide reliable evidence based on survival endpoints.


Laparoscopic management of juvenile cystic adenomyoma: four cases.
To highlight a recently identified rare cause of severe dysmenorrhea in young patients with poor response to medical management. Evidence obtained from several timed series with or without intervention (Canadian Task Force classification II-3). Tertiary care referral hospital. Four young (age, 16-24 years) nulliparous patients with juvenile cystic adenoma with severe secondary dysmenorrhea with poor response to medical management. Laparoscopic resection of the cystic adenomyoma. Complete resection of the cystic adenomyoma was performed laparoscopically in all patients. The lesion was uncapsulated (unlike myoma) and locally defined to the uterine myometrium (unlike diffuse adenomyosis), and there was chocolate-colored blood in the cavity. No other müllerian anomaly was observed in any patient. Histopathologic analysis revealed features suggestive of adenomyosis in all cases. After surgery, dysmenorrhea resolved completely in all patients. Compared with preoperative visual analog scores, significant improvement was observed at the first menstrual cycle after surgery. Patients are being followed up every 3 months for a minimum of 12 months to detect development of dysmenorrhea or any other menstrual disorder. Juvenile cystic adenomyosis is a rare cause of severe dysmenorrhea. However, it should be included in the differential diagnosis in patients with dysmenorrhea with poor response to medical treatment. All patients reported in the literature and in our series were younger than 30 years, which can be considered as an arbitrary cutoff point to differentiate juvenile from adult cystic adenomyosis. It can be considered a new type of müllerian anomaly that manifests as a noncommunicating accessory uterine cavity lined with endometrium and with an otherwise normal uterus. Surgery is the only therapeutic option for these patients. Minimally invasive surgery in expert hands is advisable to preserve fertility.