Cryoglobulinemia-related vasculitis during effective anti-HCV treatment with PEG-interferon alfa-2b.
HCV infection may be related to many extrahepatic manifestations including mixed cryoglobulinemia (MC). Clinical manifestations commonly associated to MC include arthralgia, purpura, vasculitis, peripheral neuropathy and renal function abnormalities. Treatment with interferon often leads to remission, especially in virological responders, or to disappearance of MC-related clinical manifestations. We report on a patient with chronic hepatitis C, deficit of G6P-DH, type II MC, who developed a cryoglobulinemic vasculitis with purpura, renal impairment and arterial hypertension, during treatment with PEG-interferon a-2b plus amantadine. The occurrence of purpuric lesions and MC-related nephropathy with increased cryocrit despite negative viremia, in a patient previously asymptomatic, during interferon treatment, is unusual.


Effective extraction of fluoroquinolones from water using facile modified plant fibers.
In this study, ecofriendly and economic carboxy-terminated plant fibers (PFs) were used as adsorbents for the effective in-syringe solid phase extraction (IS-SPE) of fluoroquinolone (FQ) residues from water. Based on the thermal esterification and etherification reaction of cellulose hydroxy with citric acid (CA) and sodium chloroacetate in aqueous solutions, carboxy groups grafted onto cotton, cattail, and corncob fibers were fabricated. Compared with carboxy-terminated corncob and cotton, CA-modified cattail with more carboxy groups showed excellent adsorption capacity for FQs. The modified cattail fibers were reproducible and reusable with relative standard deviations of 3.2%-4.2% within 10 cycles of adsorption-desorption. A good extraction efficiency of 71.3%-80.9% was achieved after optimizing the extraction condition. Based on carboxylated cattail, IS-SPE coupled with ultra-performance liquid chromatography with a photodiode array detector was conducted to analyze FQs in environmental water samples. High sensitivity with limit of detections of 0.08-0.25 μg/L and good accuracy with recoveries of 83.8%-111.7% were obtained. Overall, the simple and environment-friendly modified waste PFs have potential applications in the effective extraction and detection of FQs in natural waters.


Theoretical investigation of multiferroic metal-organic framework magnet [CH3NH3][Co(HCOO)3]: Green's function method.
For the first presented magnetic ordering-induced multiferroics with a metal-organic framework (MOF) of formula [CH3NH3][Co(HCOO)3], we theoretically investigate its multiple ferroics. It is found that Dzyaloshinskii-Moriya interaction is a main cause that leads to non-zero magnetization, and electric polarization, and the induced electric polarization can be regulated by magnetic fields. As an assistant mechanism, magnon-magnon interaction and quantum fluctuation play an important role on ferroelectrics and magnetism. Our methods are based on the double-time Green's function and Holstein-Primakoff transformation. Theoretical results can be compared with experiments, though there are some discrepancies.


Natural killer cells and lung transplantation, roles in rejection, infection, and tolerance.
Despite improvements in surgical technique, organ preservation, immunosuppression, and management of infection, the long term survival following lung transplantation remains low, mainly due to immune mediated complications such as acute and chronic rejection. Almost all immunosuppressive agents used in the prophylaxis and treatment of rejection following lung transplantation are targets of T cell maturation, function or proliferation, which in theory should cause sufficient disruption of the adaptive immune system to prevent graft rejection. However the five year survival rate of only 50% suggests this is not the case. More recent evidence suggests that NK cells may play a significant role in immune processes following lung transplantation. This article reviews the literature on the potential function of NK cells in rejection, infection, malignancy and tolerance following lung transplantation.


Nanocarrier-based targeting of metabolic pathways for endometrial cancer: Status and future perspectives.
Cancer is the second-most lethal global disease, as per health reports, and is responsible for around 70% of deaths in low- and middle-income countries. Endometrial cancer is one of the emerging malignancies and has been predicted as a public health challenge for the future. Insulin resistance, obesity, and diabetes mellitus are the key metabolic factors that promote risks for the development of endometrial cancer. Various signaling pathways and associated genes are involved in the genesis of endometrial cancer, and any mutation or deletion in such related factors leads to the induction of endometrial cancer. The conventional way of drug delivery has been used for ages but is associated with poor management of cancer due to non-targeting of the endometrial cancer cells, low efficacy of the therapy, and toxicity issues as well. In this context, nanocarrier-based therapy for the management of endometrial cancer is an effective alternate choice that overcomes the problems associated with conventional therapy. In this review article, we highlighted the nanocarrier-based targeting of endometrial cancer, with a special focus on targeting various metabolic signaling pathways. Furthermore, the future perspectives of nanocarrier-based targeting of metabolic pathways in endometrial cancer were also underpinned. It is concluded that targeting metabolic signaling pathways in endometrial cancer via nanocarrier scaffolds is the future of pharmaceutical design for the significant management and treatment of endometrial cancer.


Formation of a molten globule like state in bovine serum albumin at alkaline pH.
Little work has been done to understand the folding profiles of multi-domain proteins at alkaline conditions. We have found the formation of a molten globule-like state in bovine serum albumin at pH 11.2 with the help of spectroscopic techniques; like far and near ultra-violet circular dichroism, intrinsic and extrinsic fluorescence spectroscopy. Interestingly, this state has features similar to the acid-denatured state of human serum albumin at pH 2.0 reported by Muzammil et al. (Eur J Biochem 266:26-32, 1999). This state has also shown significant increase in 8-anilino-1-naphthalene-sulfonate (ANS) binding in compare to the native state. At pH 13.0, the protein seems to acquire a state very close to 6 M guanidinium hydrochloride (GuHCl) denatured one. But, reversibility study shows it can regain nearly 40% of its native secondary structure. On the contrary, tertiary contacts have disrupted irreversibly. It seems, withdrawal of electrostatic repulsion leave room for local interactions, but disrupted tertiary contacts fail to regain their original states.


Systematic review of progesterone use by midlife and menopausal women.
Progesterone treatment for menopausal symptoms is still controversial. Progesterone levels fall during menopause transition, therefore some menopausal women may benefit from progesterone therapy. A systematic review was conducted of studies published from 2001 reporting on progesterone use to treat symptoms associated with menopause or postmenopausal women. Fourteen data bases were searched using the search terms progesterone, menopause, aged, female and human; exclusions were breast cancer, animal and contraception. Thirteen studies were selected for inclusion (11 clinical trials, 1 cohort study and 1 qualitative study), evaluating progesterone effects on menopausal symptoms, bone, sleep, skin, cognition, plasma lipids and plaque progression. Most studies were of low methodological quality (GRADE low or very low). Progesterone improved vasomotor symptoms and sleep quality, with minimal risk. Large studies designed to identify confounders, such as hormone levels, menopausal status and metabolism are required to understand the place of progesterone in clinical practice.


MicroRNA-613 inhibited ovarian cancer cell proliferation and invasion by regulating KRAS.
MicroRNAs (miRNAs) play several important roles in carcinogenesis, and the dysregulation of miRNAs is associated with cancer progression. Little is known about the role of miR-613 in ovarian cancer. In the present study, we demonstrate that miR-613 expression is downregulated in human ovarian cancer cell lines and tissues. Additionally, miR-613 overexpression suppressed ovarian cancer cell proliferation, colony formation, and invasion. Furthermore, KRAS was identified as a target of miR-613. Reintroducing KRAS rescued the inhibitory effects exerted by miR-613 on ovarian cancer cell proliferation and invasion. Taken together, our findings suggest that miR-613 functions as a candidate tumor suppressor miRNA in ovarian cancer by directly targeting KRAS. To the best of our knowledge, this is the first study to show that miR-613 affects the proliferation and invasion of ovarian cancer.


Preparation of hollow capsule-stabilized gold nanoparticles through the encapsulation of the dendrimer.
The narrow-dispersed dendrimer-encapsulated gold nanoparticles without agglomeration were prepared from the grafted-dendrimers on the surface of the silica microspheres, successively by complexation of the gold chloride anion with the nitrogen atom of the dendrimer and the reduction with sodium borohydride as reductant. The hollow capsule-stabilized gold nanoparticles were prepared through the encapsulation of dendrimer successively by LBL self-assembly process of polyelectrolytes with modified-silica as template and removal of the silica core by hydrofluoric acid. The size of gold nanoparticles was 2.3+/-0.8 nm. The catalytic activity of the capsule-stabilized gold nanoparticles was investigated in the reduction reaction of 4-nitrophenol to 4-aminophenol with sodium borohydride as reductant.


The Materials Science beamline upgrade at the Swiss Light Source.
The Materials Science beamline at the Swiss Light Source has been operational since 2001. In late 2010, the original wiggler source was replaced with a novel insertion device, which allows unprecedented access to high photon energies from an undulator installed in a medium-energy storage ring. In order to best exploit the increased brilliance of this new source, the entire front-end and optics had to be redesigned. In this work, the upgrade of the beamline is described in detail. The tone is didactic, from which it is hoped the reader can adapt the concepts and ideas to his or her needs.


Outcomes of inborn and transported extremely premature very-low-birthweight infants in Hawai'i.
Delivery of premature infants outside tertiary care centers is not always preventable. The aim of this study was to compare rates of survival and common morbidities in extremely premature babies transported to a level III facility versus those born at the level III center. Retrospective chart review was performed on all neonates born at ≤ 28 weeks of gestation with birthweight ≤ 1500 g who were admitted to the Newborn Intensive Care Unit at Kapi'olani Medical Center for Women and Children (KMCWC) between 1 January 2000 and 31 December 2005. Infants were divided into two groups, those born at KMCWC (Inborn) and those born at level I institutions and subsequently transported (Transport) to KMCWC. A total of 394 neonates met the study criteria; 349 were inborn while 45 were transported. Survival rates were identical for both groups. However, the Transport group survivors displayed a significantly longer mean length of stay and higher rate of severe retinopathy of prematurity than those in the Inborn group (P ≤ 0.01). Identical rates of survival in both groups suggest that community medical professionals are providing satisfactory care to stabilize critical neonates without reducing their chances of survival. However, increased length of stay and higher rate of retinopathy of prematurity in the Transport group suggest that differences in medical management during the first few hours of life may adversely affect outcomes.


Diagnosis and Management of an Intramyometrial Ectopic Pregnancy Within a Septate Uterus.
An intramyometrial pregnancy is a rare form of ectopic pregnancy, making up an estimated 1% of all ectopic pregnancies. Previously described management options have included surgical excision in the emergency setting. A 32-year-old woman, gravida 4 para 0, at 6 0/7 weeks of gestation by last menstrual period, was noted to have a gestational sac implanted entirely within the uterine myometrium. Ultrasonography and magnetic resonance imaging confirmed the presence of an intramyometrial ectopic pregnancy within a septate uterus. The patient's abnormal pregnancy was successfully treated with multidose methotrexate. Intramyometrial pregnancy is a rare entity that should be considered when it is suggested by ultrasonography or if an intrauterine pregnancy is surgically inaccessible from the endometrial cavity. In a stable patient, multidose systemic methotrexate may be a feasible management strategy.


Magnetic-resonance morphometry in patients with major depression.
Magnetic-resonance morphometry performed on 72 patients with major depression compared with 38 control subjects replicated previously reported, statistically significant reductions in the volumes of the caudate (P < 0.03) and putamen (P < 0.05) in depressed patients. Borderline statistical significance was observed for whole-brain (P < 0.07) and frontal volume (P < 0.10) in a subsample of 32 patients matched on age and sex with 32 control subjects, whereas statistical significance was observed for the full sample (P < 0.007 and P < 0.03, respectively). Chronological age was related to volume of the frontal lobes (P < 0.0002), caudate (P < 0.0001), putamen (P < 0.008), thalamus (P < 0.002), cerebellum (P < 0.007), lateral ventricles (P < 0.0001), and ratios of [whole brain]/[whole brain + cerebrospinal fluid (CSF)] (P < 0.0001) and [frontal]/[frontal + CSF] (P < 0.0001). Age of first depressive episode was related to putamen volume after accounting for chronological age (R2= 0.16, P < 0.005), and a correlation of 0.26 (P < 0.04) was observed between caudate volume and global mental status. Results are in accord with previous reports of basal-ganglia abnormalities in depressed patients and support the role of subcortical structures in mediating affective disorder.


Upregulation of long noncoding RNA RAB11B-AS1 promotes tumor metastasis and predicts poor prognosis in lung cancer.
Lung cancer (LC) is one of the leading causes of cancer-related mortality in China and worldwide. Despite the progress in diagnosis and treatment of LC, the prognosis of LC remains poor. Studies have demonstrated that long non-coding RNAs (lncRNAs) play a critical role in carcinogenesis and cancer development. Here we examined the expression and potential function of lnc-RAB11B-AS1 in LC both in vitro and in vivo. All experiments in this study were conducted using A549 and PC-9 cell lines according to protocols described in this paper. The clinic characteristics were analyzed using logistic regression, cox model, log rank test, biochemical analysis using qRT-PCR, transfections, nude mice model, and cell biological analysis using Transwell assay, CCK-8 assay, flow cytometry, and rescue experiments, and immunohistochemistry. The results showed that lnc-RAB11B-AS1 was significantly overexpressed in LC tissues compared to the corresponding non-tumor tissues. Patients with a higher level of lnc-RAB11B-AS1 expression showed a poorer overall survival rate. Functionally, overexpression of lnc-RAB11B-AS1 promotes cell proliferation, migration and invasion abilities of LC cell lines, which suggests lnc-RAB11B-AS1 may play an oncogenic role in LC. lnc-RAB11B-AS1 was located in physical contiguity with RAB11B gene and found positively regulates the RAB11B expression, and the protein levels of RAB11B in LC tissues also found to positively correlated with the level of lnc-RAB11B-AS1 expression. RAB11B silencing partially abrogated lnc-RAB11B-AS1-induced proliferation of the LC cell lines used in this study. This study provided a novel evidence into the function of lncRNA-driven carcinogenesis. Our findings highlighted the importance of lnc-RAB11B-AS1 and RAB11B in LC progression and indicated that lnc-RAB11B-AS1 may serve as a novel and valuable prognostic biomarker for LC.


Effects of global change factors and living roots on root litter decomposition in a Qinghai-Tibet alpine meadow.
Roots account for a major part of plant biomass in Tibetan alpine meadows. Understanding root decomposition with global change is key to predict carbon (C) and nutrient dynamics on the Qinghai-Tibet Plateau. Yet, few experiments have carefully examined root decomposition as influenced by global change. We conducted a field study to investigate the effects of nitrogen (N) addition, air warming, precipitation change, and the presence/absence of living roots on root decomposition in a Tibetan alpine meadow. Our results showed that N addition increased the mass and C remaining, and induced N accumulation in the litter. Increased precipitation significantly amplified the positive effect of N addition on litter mass remaining. The presence of alive roots in the litterbags decreased root litter C remaining but significantly increased N and phosphorus remaining of the litter. However, we did not find any significant effects of air warming on the litter decomposition. In the Qinghai-Tibet Plateau, N deposition is predicted to increase and precipitation regime is predicted to change. Our results suggest that the interaction between increased N and precipitation may reduce root decomposition in the Qinghai-Tibet Plateau in the future, and that the large stock of living roots exert a dominant impact on nutrient dynamics of root decomposition in the Tibetan alpine systems.


Post-Transplantation Cyclophosphamide-Based Graft- versus-Host Disease Prophylaxis with Nonmyeloablative Conditioning for Blood or Marrow Transplantation for Myelofibrosis.
We describe outcomes after post-transplantation cyclophosphamide and nonmyeloablative conditioning-based allogeneic blood or marrow transplantation for myelofibrosis using matched or mismatched related or unrelated donors. The conditioning regimen consisted of fludarabine, cyclophosphamide, and total body irradiation. Forty-two patients were included, with a median age of 63 years, of whom 19% had Dynamic International Prognostic Scoring System (DIPSS)-plus intermediate-1 risk, 60% had intermediate-2 risk, and 21% had high-risk disease, and 60% had at least 1 high-risk somatic mutation. More than 90% of patients engrafted neutrophils, at a median of 19.5 days, and 7% experienced graft failure. At 1 year and 3 years, respectively, overall survival was 65% and 60%, relapse-free survival was 65% and 31%, relapse was 5% and 40%, and nonrelapse mortality was 30% and 30%. Acute graft-versus-host disease grade 3-4 was seen in 17% of patients at 1 year, and chronic graft-versus-host disease requiring systemic therapy in occurred in 12% patients. Spleen size ≥17 cm or prior splenectomy was associated with inferior relapse-free survival (hazard ratio [HR], 3.50; 95% confidence interval [CI], 1.18 to 10.37; P = .02) and higher relapse rate (subdistribution HR [SDHR] not calculable; P = .01). Age >60 years (SDHR, 0.26; 95% CI, 0.08 to 0.80, P = .02) and receipt of peripheral blood grafts (SDHR, 0.34; 95% CI, 0.11 to 0.99; P = .05) were associated with a lower risk of relapse. In our limited sample, the presence of a high-risk mutation was not statistically significantly associated with an inferior outcome, although ASXL1 was suggestive of inferior survival (SDHR, 2.36; 95% CI, 0.85 to 6.6; P = .09). Overall, this approach shows outcomes comparable those of to previously reported approaches and underscores the importance of spleen size in the evaluation of transplantation candidates.


Molecular dissection of a specific nuclear domain: the chromatin region of the ribosomal gene cluster in Xenopus laevis.
Molecular dissection of the nuclear domain corresponding to the ribosomal chromatin cluster was investigated. The experimental scheme was based on the ability of restriction enzymes to digest the whole genome without affecting this region (several megabases in length). Such a strategy involved the judicious choice of restriction enzymes, which is possible in Xenopus laevis, where the rDNA sequence is known and the repeated units are organized into one unique cluster. SalI, XhoI, and EcoRV digestion produced frequent cutting of the genome leaving the ribosomal cluster intact. Isolation of the rDNA cluster was confirmed by separation of the digested DNA by pulsed-field electrophoresis. When applied to purified nuclei, this approach allowed the isolation of the ribosomal chromatin cluster under very mild conditions: no cleavages (either enzymatic or mechanical) were detectable. Since the purification scheme depends only on the DNA sequence outside of the rDNA cluster, it permits the obtention of this domain in different functional states. Electron microscopic analysis demonstrated that the domain organization is substantially preserved and maintains its looped organization (the size and the full number of loops were preserved). This purification scheme provides a powerful tool for studying the structure-function relationships within the ribosomal nuclear domain.


Ultra-processed foods and allergic symptoms among children and adults in the United States: A population-based analysis of NHANES 2005-2006.
There is a strong correlation between dietary intake and allergic diseases. Ultra-processed foods (UPFs) are gradually becoming dominant worldwide and causing health problems for children and adults. We hope to determine whether links exist between UPFs and allergic symptoms. We investigated data from 2,736 children (16-19 years) and 4,256 adults (≥20 years) from the National Health and Nutritional Examination Survey (NHANES) 2005-2006. The associations between the mean UPFs contribution to total energy intake and all allergic symptoms (IgE, current asthma, allergy, rash, sneeze, wheeze, eczema, and hay fever) were estimated by weighted multivariate logistic regression. Logistic regression analysis showed UFPs were negatively associated with IgE levels in children. Those with higher quartiles had a reduced risk from 16% (OR, 0.84, 95%CI, 0.55 to 1.28) to 34% (OR, 0.66, 95%CI, 0.49 to 0.89), p for trend = 0.006. UPFs were also positively related to current asthma in children with an increased risk of 11% (OR, 1.11, 95%CI, 0.79 to 1.56) to 76% (OR, 1.76, 95%CI, 1.10 to 2.82), p for trend = 0.0393. UPFs were also associated with eczema in girls. But there was no association observed between UPFs and allergic symptoms in adults. Our results suggested that UPFs assessed by the NOVA system were associated with IgE, current asthma in children, and eczema in girls. These results further support the need to test the association of modern dietary patterns with allergic symptoms.


Highly efficient conversion of CO2 to cyclic carbonates with a binary catalyst system in a microreactor: intensification of "electrophile-nucleophile" synergistic effect.
An intensification of the "electrophile-nucleophile" synergistic effect was achieved in a microreactor for the coupling reaction of CO2 and epoxides mediated by the binary Al complex/ternary ammonium salt catalyst system. The microreactor technology is proven to be a powerful tool for the preparation of cyclic carbonates with an improved reaction rate and a wide substrate scope.


Short article: Outcome of medical and surgical management for perforated jejunal diverticulitis.
Perforated jejunal diverticulitis (PJD) is rare, but it has high mortality rates. The role of nonsurgical management is debated. The aim of this study is to assess the outcomes of medical and surgical management of PJD. A single-centre study on a series of emergency patients diagnosed with PJD between 2010 and 2016 was conducted. Eleven patients with PJD were treated (seven women). Nine out of 11 were diagnosed by a computed tomography scan, and two were diagnosed at laparotomy. The initial approach was medical treatment in five patients, based on clinical and imaging findings. Four (80%) of these five patients were discharged without the need for surgical intervention. The median hospital stay was 7.5 days. Seven patients required surgery overall with a median length of hospital stay of 10.8 days. Surgical procedures consisted of segmental bowel resection and primary anastomosis in six patients and simple closure in one. There was no perioperative deaths. One patient required percutaneous drainage because of anastomotic leak, and one required reoperation owing to evisceration. Selected patients with PJD can be successfully managed with conservative approach, based on clinical and computed tomography findings.


Phytochemical profile, in vitro bioaccessibility, and anticancer potential of golden root (Rhodiola rosea L.) extracts.
The effects of water and ethanolic (40 %, 70 %, and 96 %) extraction on the Rhodiola rosea L. phytochemical profile (HPLC analysis), stability during extract drying, potential bioaccessibility in simulated gastric and intestinal conditions, and cytotoxic activity against human colorectal adenocarcinoma cells (Caco-2 and HT-29 cell lines) were investigated. The phytochemical profile, extractability, and stability during extract processing depend on the solvent type. In general, compounds derived from dry extracts were characterized by higher bioaccessibility than those extracted from powdered plant material. In the case of salidroside, tyrosol, and rosavins, one of the highest bioaccessibilities (often about 100 %) were found for the 70 % ethanolic extract after gastric digestion. Furthermore, the 70 % ethanolic extract most effectively reduced the viability of Caco-2 cells (IC50 85.8 µg∙mL-1). The results suggest that golden root extracts, in particular 70 % ethanolic extract, seem to be promising supplements for the food industry.


Treatment of mouse muscular dystrophy with the protease inhibitor pepstatin.
Dystrophic mice were treated for 5 weeks beginning at 3 weeks of age with 20 ugm per day of pepstatin, a potent inhibitor of cathepsin D. Mortality was less and weight gain greater in pepstatin treated mice than in controls. Muscle bulk was greater and hind lamb contractures were reduced in treated mice. Mean muscle fiber mass was significantly increased by pepstatin treatment. Inhibition of muscle protease may be the mechanism by which pepstatin slows the tempo of progression of mouse muscular dystrophy.


Synthesis and bioactivity of 3,5-dimethylpyrazole derivatives as potential PDE4 inhibitors.
A series of 3,5-dimethylpyrazole derivatives containing 5-phenyl-2-furan moiety were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. Bioassay results showed that the title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Among the designed compounds, compound If showed the best inhibitory activity against PDE4B with the IC50 value of 1.7 μM, which also showed good in vivo activity in animal models of asthma/COPD and sepsis induced by LPS. The primary structure-activity relationship (SAR) study and docking results suggested that introduction of the substituent groups to the phenyl ring at the para-position, especially methoxy group, was helpful to enhance inhibitory activity against PDE4B.


Simultaneous arthroscopic ACL and PCL reconstruction using allograft Achilles tendon.
Multi-ligamentous injuries to the anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL) are uncommon but debilitating injuries. They mostly lead in functional disabilities and further surgeries. The aim of the present study was to evaluate the outcomes of simultaneous arthroscopic reconstruction of ACL and PCL using allograft Achilles tendon. Case-series study. This study was performed on patients with combined ACL-PCL injuries which attended for treatment to a referral center from January 2010 to January 2014. All of them underwent simultaneous arthroscopic reconstruction of ACL and PCL using allograft Achilles tendon. Range of motion (flexion and extension loss), giving way, anterior and posterior knee stability, proximal tibia step off, subjective assessment of knee function and patients satisfaction were evaluated at 3, 6, 12, 24 months and final follow-up. Data were analyzed by SPSS version 21 with consideration of P < 0.05 as significant difference. Among 28 included patients, 21 patients (75%) were male. Mean age of patients was 30.86 ± 7.25 years (range: 18-49 years). The mean follow-up time was 35.7 ± 6.8 months (range: 26-50 months). Our results demonstrated that knee function, stability, and range of motion were improved along the follow-up periods. At final follow-up none of the patients had giving way and all of them were completely satisfied from the surgery. Simultaneous reconstruction of injured cruciate ligaments using allograft Achilles tendon resulted in appropriate functional outcomes and acceptable range of motion. IV.


Herminiimonas fonticola gen. nov., sp. nov., a Betaproteobacterium isolated from a source of bottled mineral water.
Several yellowish-pigmented bacteria with an optimum growth temperature of about 30 degrees C, were recovered from the source (borehole) of bottled mineral water in the Serra da Estrela in Eastern Portugal. Phylogenetic analyses of the 16S rRNA gene sequence of strains S-94T , S-97, S-99 and S-92 indicated that these organisms represent a new species of the Betaproteobacteria that is not closely related to any other known species. The major fatty acids of the strains are 16:1 omega7c and 16:0. Ubiquinone 8 is the major respiratory quinone. The new isolates are strictly organotrophic and aerobic. The new strains only assimilated organic acids, glycine and alanine. Casamino acids and a mixture of all natural amino acids are not used as sole carbon and nitrogen sources; these are used as nitrogen source in the presence of organic acids. On the basis of the phylogenetic analyses, physiological and biochemical characteristics, we are of the opinion that strains S-94T, S-97, S-99 and S-92 represent a new species of a novel genus for which we propose the name Herminiimonas fonticola gen. nov., sp. nov.


Corrigendum: Increased central auditory gain in 5xFAD Alzheimer's disease mice as an early biomarker candidate for Alzheimer's disease diagnosis.
[This corrects the article DOI: 10.3389/fnins.2023.1106570.].


The Transformative Power of Birth.
A mother recalls the home birth of her first child. Her story exemplifies the power of birth when a mother is supported to listen to her body and labor on her own terms, and she praises the comfort of home birth and the respect of midwifery care. She emerges from the other side of her birth empowered and transformed, ready to embrace motherhood.


Successful heart transplant in a child with congenital core myopathy and delayed-onset restrictive cardiomyopathy due to recessive mutations in the titin (TTN) gene.
Mutations in the TTN gene, encoding the muscle filament titin, are a major cause of inherited dilated cardiomyopathy. Early-onset skeletal muscle disorders due to recessive TTN mutations have recently been described, sometimes associated with cardiomyopathies. We report the case of a boy with congenital core myopathy due to compound heterozygosity for TTN variants. He presented in infancy with rapidly evolving restrictive cardiomyopathy, requiring heart transplantation at the age of 5 years with favorable long-term cardiac and neuromuscular outcome. Heart transplantation may have a role in selected patients with TTN-related congenital myopathy with disproportionally severe cardiac presentation compared to skeletal and respiratory muscle involvement.


Propofol: Milk of Amnesia.
This year's Lasker Clinical Research Award goes to James Baird Glen for the discovery and development of the anesthetic propofol. Patients benefit from its fast onset and rapid systemic clearance, eliminating the prolonged sedation effects experienced with earlier agents. In just 30 years, propofol has been adopted around the world for safe and controlled induction of anesthesia.


Prolonged cultured human hepatocytes as an in vitro experimental system for the evaluation of potency and duration of activity of RNA therapeutics: Demonstration of prolonged duration of gene silencing effects of a GalNAc-conjugated human hypoxanthine phosphoribosyl transferase (HPRT1) siRNA.
We report here the evaluation of a novel in vitro experimental model, prolonged cultured human hepatocytes (PCHC), as an experimental system to evaluate the potency and duration of effects of oligonucleotide therapeutics. A novel observation was made on the redifferentiation of PCHC upon prolonged culturing based on mRNA profiling of characteristic hepatic differentiation marker genes albumin, transferrin, and transthyretin. Consistent with the known de-differentiation of cultured human hepatocytes, decreases in marker gene expression were observed upon culturing of the hepatocytes for 2 days. A novel observation of re-differentiation was observed on day 7 as demonstrated by an increase in expression of the marker genes to levels similar to that observed on the first day of culture. The expression of the differentiation marker genes was highest on day 7, followed by a gradual decrease but remained higher than that on day 2 for up to the longest culture duration evaluated of 41 days. The redifferentiation phenomenon suggests that PCHC may be useful for the evaluation of the duration of effects of oligonucleotide therapeutics on gene expression in human hepatocytes. A proof of concept study was thereby conducted with PCHC with a GalNAc-conjugated siRNA targeting human hypoxanthine phosphoribosyl transferase1 (HPRT1). HPRT1 mRNA expression in siRNA-treated cultures decreased to 21% of that in untreated hepatocytes on day 1, <10% from days 2 to 12, <20% from days 16 to 33, and eventually recovered to 64% by day 41. Our results suggest that PCHC represent a clinically-relevant cost- and time-efficient experimental tool to aid in the evaluation of GalNAc-siRNA silencing activity, providing information on both efficacy and duration of efficacy. PCHC may be applicable in the drug development setting as a species- and cell type-relevant experimental tool to aid the development of oligonucleotide therapeutics.


Congenital proptosis secondary to orbital teratoma. Clinicopathological study.
A newborn male with right proptosis secondary to a retroocular mass. Ophthalmological examination also showed corneal ulcer and perforation, iris hernia, total ophthalmoplegia, chemosis and eyelid retraction. The histopathology diagnosis was mature teratoma. Teratomas are tumors composed of a mixture of mature tissues consisting of 3 germ layers. Congenital teratomas of the orbit are very rare and should be included as a possibility in cases with a primary tumor in the orbit.


Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero.
To study the neonatal outcome of infants exposed to buprenorphine in utero. We prospectively followed 54 buprenorphine-using pregnant women and their 58 infants. Urinary buprenorphine and norbuprenorphine concentrations in the mothers were measured prior to delivery, and in the infants during the first 3 days of life. The Finnegan score was used to evaluate neonatal abstinence syndrome. Other medical problems as well as social outcomes were recorded. All infants had buprenorphine in their urine. A total of 38 infants required 20 +/- 10 days (range 7-48 days) of morphine treatment for neonatal abstinence syndrome. The length of hospital stay for all infants was 25 +/- 19 days (range 3-125 days). The infants' highest urinary norbuprenorphine concentrations across their first 3 days of life correlated with the length of hospital stay and duration of morphine treatment (both p < 0.05). The mean birth weight and mean head circumference (n = 58) were below average (mean -0.7 standard deviation [SD] and mean -0.5 SD, respectively). Eleven infants were discharged home, 19 infants were placed in foster care and 28 infants were discharged with their mothers to Mother and Child homes or to other institutions. Maternal buprenorphine use at the time of birth may cause neonatal abstinence syndrome, requiring long-term hospitalization. Multiple social problems require a multidisciplinary team approach.


Empathy and ethical sensitivity among intensive and critical care nurses: A path analysis.
Intensive and critical care nurses need to demonstrate ethical sensitivity especially in recognizing and dealing with ethical dilemmas particularly as they often care for patients living with life-threatening conditions. Theories suggest that there is a convergence between nurses' empathy and ethical sensitivity. Evidence in the literature indicates that nurses' emotional, demographic, and work characteristics are associated with their level of empathy and ethical sensitivity. To investigate the relationship between nurses' empathy and ethical sensitivity, considering their emotional states (depression, anxiety, and stress), demographic and work characteristics, and test an empirical model describing potential predictors of empathy (as a mediator) and ethical sensitivity using path analysis. Using a cross-sectional design, the philosophical theory of care ethics and empathy was extended and adopted as a conceptual framework for this study and tested by path analysis. Data were collected from 347 intensive care nurses recruited by ten educational-medical hospitals in Iran using a questionnaire between February and March 2021. The study was reviewed by the Ethical Advisory Board in Iran and conducted according to the Declaration of Helsinki. Study participants demonstrated a mild level of stress, anxiety, and depression, alongside a relatively high level of empathy and ethical sensitivity. Nurses with good socioeconomic status had higher empathetic behavior with patients than those with weak status. Nurses aged over 40 who had received ethics training and had higher work experience were associated with higher ethical sensitivity compared to nurses under 20 years of age. Empathy directly affected ethical sensitivity; however, anxiety had an indirect effect on ethical sensitivity through empathy. Among demographic factors, age had a positive direct effect on ethical sensitivity. Less anxiety and a high level of empathy contribute to higher levels of ethical sensitivity among intensive and critical care nurses.


Interactive effect of flooding and grazing on the growth of Serengeti grasses.
Grazing and flooding may potentially interact in particular habitats of many grassland regions around the world. We tested the hypothesis that grazing and flooding induce different and largely opposed allocation responses in individual plants. As a result, their combined effect on plant growth would be negative. We studied the response of three grass species from the Serengeti ecosystem (Tanzania) to the effects of flooding and clipping. Plants under the combined effect of flooding and clipping had lower growth rates than plants growing under the effect of either of the two factors individually. Plants under flooding grew taller and allocated more resources to stem growth than controls; for two of the three species, flooded plants also generated a new root system above soil level. All these morphological and physiological responses conflict with the ability of a plant to respond to defoliation with minimum reduction in growth rates. The three species showed a response to flooding reflecting their distribution ranges in the field: the species from the most flood-prone habitat showed a positive effect of flooding on growth, whereas the species from dry uplands showed a strong negative effect of flooding. Flood-tolerant species were taller and less tolerant of clipping than flooding sensitive species. Our results suggest that, in ecological time, individuals subjected to both flooding and grazing have their growth reduced to a greater extent than by either of the two factors acting individually, whereas in evolutionary time, species adapted to flooding are poor grazing tolerators and species adapted to grazing are poor flooding tolerators.


[Non-pharmacological interventions for the treatment of erectile dysfunction in adult men: systematic review].
To review current evidence on the non-pharmacological (non-invasive) treatment of erectile dysfunction (ED). We performed a systematic review of research articles that included adult men diagnosed with ED who had undergone some type of non-pharmacological and non-surgical intervention for this disorder. Free-access, complete texts with an available summary published between 2000 and 2006 were sought. Studies not published in English were excluded. A total for 124 articles were found, and after critical analysis only 8 matched the inclusion criteria (of the 8 articles, 2 were classified as showing quality criterion 1-B and none met the criterion for 1-A). Four types of non-pharmacological, non-surgical therapy were found, which could reverse or improve ED in patients with organic, psychological or mixed impairment and could be applied by nurses. Among these therapies were lifestyle changes (losing weight, pelvic musculature strengthening, psychotherapy and/or psychoeducation and the use of Internet and/or other multimedia devices. Alternative therapies are available for men with ED. These therapies help to improve or reverse ED and guarantee satisfactory and lasting Results. Nevertheless, we stress that our aim is not to compete with invasive and non-invasive therapies but rather to provide a greater number of treatment alternatives. The low quality of studies could be attributed to the lack of economic resources and the fact that ED is still an emerging subject in current medicine.


Aconitase 2 sensitizes MCF-7 cells to cisplatin eliciting p53-mediated apoptosis in a ROS-dependent manner.
Aconitase 2 (ACO2) belongs to the tricarboxylic acid (TCA) cycle, which represents a key metabolic hub for cellular metabolism that is frequently altered in cancer for satisfying bioenergetic and biosynthetic requirements of proliferating cells. The promotion of ACO2 activity in breast cancer cell lines was shown to slow down proliferation imposing a switch from aerobic glycolysis to oxidative metabolism. The alteration of metabolic pathways in cancer also impinges on the sensitivity to chemotherapeutic interventions. In this work, we evidence that the presence of ACO2 sensitizes cells to the treatment with the genotoxic agents cisplatin (CDDP) and doxorubicin activating the apoptotic cell death mechanism. This response was driven by the accumulation of reactive oxygen species (ROS) following both ACO2 overexpression and CDDP exposure that permit the stabilization/activation of p53 in nuclear and mitochondrial compartments. Collectively, our results highlight that in ACO2 overexpressing cells the promotion of mitochondrial metabolism accounts for increased ROS production that was buffered by p53 mitochondrial recruitment and autophagy induction. However, these systems are not able to counteract the CDDP-mediated oxidative stress that becomes the Achilles heel for increasing susceptibility to apoptotic cell death.


Determinants of perioperative morbidity and mortality after pneumonectomy.
A total of 197 consecutive patients undergoing pneumonectomy at the M.D. Anderson Cancer Center from 1982 to 1987 were reviewed. Sixty-five variables were analyzed for the predictive value for perioperative risk. The operative mortality rate was 7% (14/197). Patients having a right pneumonectomy (n = 95) had a higher operative mortality rate (12%) than patients having a left pneumonectomy (1%, p less than 0.05). The extent of resection correlated with the operative mortality rate (chest wall resection or extrapleural pneumonectomy, n = 39, 15%; versus simple or intrapericardial pneumonectomy, n = 158, 5%; p less than 0.05). Patients whose predicted postoperative pulmonary function, by spirometry and xenon 133 regional pulmonary function studies, was a forced expiratory volume in 1 second greater than 1.65 L, forced expiratory volume in 1 second greater than 58% of the preoperative value, forced vital capacity greater than 2.5 L, or forced vital capacity greater than 60% of the preoperative value had a lower operative mortality rate (p less than 0.05). Atrial arrhythmia was the most common postoperative complication (23%). Xenon 133 regional pulmonary function studies are useful in predicting the risks of pneumonectomy.


A new clinical disorder of twisted and rolled body hairs with multiple, large knots.
We present a new hair disorder characterized by an unusual twisting and matting of body hairs. This disorder may occur as an acquired or, possibly, an inherited trait. Our purpose was to analyze the clinical features of three patients and report the changes revealed by light microscopy and scanning electron microscopy. We examined two unrelated adults with acquired multiple large knots of body hairs and a newborn infant with a familial history of the same entity. In the two adults the hairs were rolled and knotted together, and twisting of body hairs occurred in areas where rubbing was frequent. In the familial type, which was suggestive of an autosomal dominant inheritance pattern, no mechanical explanation could be found. Light microscopy confirmed the clinical impression of twisted and felted hairs, and scanning electron microscopy revealed sticking of at least 20 hairs. No underlying skin disease or deeper process was found. Multiple twisted and rolled body hairs that may develop into multiple, large knots may appear as a minor variant of hair matting or felting. Scanning electron microscopy shows multiple hairs that originate from different hair follicles and roll and stick together centrally.


Detection of central nervous system metastasis with cerebrospinal fluid beta-2-microglobulin.
Beta-2-microglobulin determinations in cerebrospinal fluid (CSF) of patients with leukemia, lymphoma, and oat cell carcinoma were performed to evaluate the utility of this test in early detection of metastasis to the central nervous system (CNS). In the presence of CNS disease, significantly higher levels (P less than 0.001) were found than in normals or patients without CNS disease. Serial measurements were performed on two patients, and in all cases beta-2-microglobulin became elevated coincident with CNS relapse, and returned to normal as remission was achieved. Serial testing of CSF beta-2-microglobulin, in patients with cancers known to invade the CNS, should facilitate prompt treatment of CNS metastasis.


Ferroptosis: a double-edged sword mediating immune tolerance of cancer.
The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type of necrosis and is distinguished from apoptosis and autophagy. Actuated by iron-dependent phospholipid peroxidation, ferroptosis is modulated by various cellular metabolic and signaling pathways, including amino acid, lipid, iron, and mitochondrial metabolism. Notably, ferroptosis is associated with numerous diseases and plays a double-edged sword role. Particularly, metastasis-prone or highly-mutated tumor cells are sensitive to ferroptosis. Hence, inducing or prohibiting ferroptosis in tumor cells has vastly promising potential in treating drug-resistant cancers. Immunotolerant cancer cells are not sensitive to the traditional cell death pathway such as apoptosis and necroptosis, while ferroptosis plays a crucial role in mediating tumor and immune cells to antagonize immune tolerance, which has broad prospects in the clinical setting. Herein, we summarized the mechanisms and delineated the regulatory network of ferroptosis, emphasized its dual role in mediating immune tolerance, proposed its significant clinical benefits in the tumor immune microenvironment, and ultimately presented some provocative doubts. This review aims to provide practical guidelines and research directions for the clinical practice of ferroptosis in treating immune-resistant tumors.


Studies in gnotobiotic piglets on non-O157:H7 Escherichia coli serotypes isolated from patients with hemorrhagic colitis.
A number of verotoxin-producing Escherichia coli strains isolated from sporadic cases of hemorrhagic colitis in the United States over the last 5 yr were shown to belong to serogroups other than O157:H7-the serotype originally implicated in this disease. Experimental infection of gnotobiotic piglets with five such strains (0111:NM, 0145:NM, 045:H2, 04:NM, and Ound:NM) caused diarrhea resulting from mucosal lesions in the cecum and colon that were indistinguishable from those previously described in piglets infected with E. coli O157:H7. This suggests that, as with other categories of pathogenic E. coli, several serotypes cause hemorrhagic colitis in humans. The five E. coli strains that were compared with one O157:H7 strain and with an enteropathogenic calf strain (serotype 05:NM) caused a spectrum of disease ranging from moderate diarrhea (O157:H7) to severe illness (including septicemia and death) (0111:NM). Characteristic lesions, which were identical for all seven pathogenic strains, included bacterial attachment, effacement of the microvillus border, and dissolution of the cell membranes of surface and glandular epithelium, resulting in complete cell destruction. Some piglets exhibited neurologic signs of convulsions and ataxia. It is concluded that a number of E. coli serotypes, in addition to O157:H7, fulfill the present limited criteria for enterohemorrhagic E. coli, which include association with hemorrhagic colitis, production of one or more verotoxins, possession of a large plasmid (50-70 megadaltons), and induction of distinct mucosal lesions in the large bowel of gnotobiotic piglets.


Polar Desolvation and Position 226 of Pancreatic and Neutrophil Elastases Are Crucial to their Affinity for the Kunitz-Type Inhibitors ShPI-1 and ShPI-1/K13L.
The Kunitz-type protease inhibitor ShPI-1 inhibits human neutrophil elastase (HNE, Ki = 2.35·10-8 M) but does not interact with the porcine pancreatic elastase (PPE); whereas its P1 site variant, ShPI-1/K13L, inhibits both HNE and PPE (Ki = 1.3·10-9 M, and Ki = 1.2·10-8 M, respectively). By employing a combination of molecular modeling tools, e.g., structural alignment, molecular dynamics simulations and Molecular Mechanics Generalized-Born/Poisson-Boltzmann Surface Area free energy calculations, we showed that D226 of HNE plays a critical role in the interaction of this enzyme with ShPI-1 through the formation of a strong salt bridge and hydrogen bonds with K13 at the inhibitor's P1 site, which compensate the unfavorable polar-desolvation penalty of the latter residue. Conversely, T226 of PPE is unable to establish strong interactions with K13, thereby precluding the insertion of K13 side-chain into the S1 subsite of this enzyme. An alternative conformation of K13 site-chain placed at the entrance of the S1 subsite of PPE, similar to that observed in the crystal structure of ShPI-1 in complex with chymotrypsin (PDB: 3T62), is also unfavorable due to the lack of stabilizing pair-wise interactions. In addition, our results suggest that the higher affinity of ShPI-1/K13L for both elastases mainly arises from the lower polar-desolvation penalty of L13 compared to that of K13, and not from stronger pair-wise interactions of the former residue with those of each enzyme. These results provide insights into the PPE and HNE inhibition and may contribute to the design of more potent and/or specific inhibitors toward one of these proteases.


Contrasting changes in snow cover and its sensitivity to aerosol optical properties in Hindukush-Karakoram-Himalaya region.
Snow cover plays a major role in the earth's climate system. The stability of the snow mass over Hindukush-Karakoram-Himalaya (HKH) in contrast to the worldwide retreat of mountainous glaciers and its relation to aerosol concentration remains poorly understood. The proposed study focused on the understanding of this relationship between various snow parameters and the optical properties of atmospheric aerosols over the HKH region of Northern Pakistan between March and June for a prolonged study period from 2005 to 2015. The aerosol's optical properties were retrieved from snow covered pixels in the study area to avoid the contamination of snow albedo (SA) by other features of land surfaces. The results revealed an increasing trend in the snow cover area (SCA) at the rate of 577.3, 1090.6 and 652.3 km2/year in March, May and June, respectively, with a decrease in April due to the uneven distribution of SCA during 2005-2015. The results revealed a strong positive correlation (R = 0.77) between SCA and SA, whereas SCA and SST were negatively correlated (R = -0.82) during the study period. The Cloud-Aerosol Lidar and Infrared Pathfinder (CALIPSO) indicated the presence of scattering and absorbing aerosols (e.g., dust, polluted dust, and smoke) both at high and low altitudes. However, the diminution of aerosol concentration was caused by their short time span in atmosphere and the occurrence of snowfall that washed them out from the snow at high altitudes. The findings indicated an increased SCA, with contrasting behavior in the ablation period. However, the presence of aerosols demands proper attention, to monitor any future threat to the high-altitude cryosphere.


DNA repair and antibody diversification: the 53BP1 paradigm.
The DNA double-strand break (DSB) repair factor 53BP1 has long been implicated in V(D)J and class switch recombination (CSR) of mammalian lymphocyte receptors. However, the dissection of the underlying molecular activities is hampered by a paucity of studies [V(D)J] and plurality of phenotypes (CSR) associated with 53BP1 deficiency. Here, we revisit the currently accepted roles of 53BP1 in antibody diversification in view of the recent identification of its downstream effectors in DSB protection and latest advances in genome architecture. We propose that, in addition to end protection, 53BP1-mediated end-tethering stabilization is essential for CSR. Furthermore, we support a pre-DSB role during V(D)J recombination. Our perspective underscores the importance of evaluating repair of DSBs in relation to their dynamic architectural contexts.


The role of dietary patterns and erythrocyte membrane fatty acid patterns on mild cognitive impairment.
Dietary fatty acids have been shown to be associated with the development of cognition. However, research on the role of fatty acid intake in dietary patterns and fatty acid patterns (FAPs) in the development of cognitive function is limited. The aim of this study was to explore the correlation between dietary patterns and FAPs and to provide available evidence for preventing mild cognitive impairment (MCI) through these patterns. The 973 participants aged between 65 and 85 were recruited from 2020 to 2021 for this multicenter research in Beijing. Neuropsychological tests were used for cognitive evaluation, and data of dietary intake in the past 12 months were collected with semi-quantitative food frequency questionnaire. The erythrocyte membrane fatty acid profile was tested by chromatography and mass spectrometry lipid profiling. Factor analysis was used to derive the main dietary patterns and FAPs. Pearson's correlation or Spearman's correlation was used to explore the association between dietary patterns and FAPs. Binary logistic regression was applied to examine the relationship between patterns and cognitive function. Six dietary patterns and six FAPs were identified, explaining 53.4 and 80.9% of the total variance separately. After adjusting all potential confounders, T3 of the pattern 1 and FAP2 were the independent protect factors for MCI, respectively (OR 0.601, 95% CI [0.395, 0.914]; OR 0.108, 95% CI [0.019, 0.623]). Rich of SM (26:0), SM (24:1), and SM (26:1) is the characteristic of FAP2. A positive correlation was found between component scores of dietary pattern1 and FAP2 (r = 0.441, p = 0.001). People who adhered to a reasonable intake of animal flesh consumed more various long-chain fatty acids as well. The erythrocyte membrane metabolites, SM (26:0), SM (24:1), and SM (26:1), might function as early biomarkers for predicting or monitoring of cognitive aging in the elderly. The dietary pattern with recommended animal flesh consumption was significantly associated with FAP characterized by very long-chain SMs. This dietary pattern affected FAP, which might achieve the ultimate goal of neuroprotection through the very long-chain SMs. A rational intake of dietary fatty acids might be an effective way on preventing MCI in the elderly.


Phenolic removal in a model olive oil mill wastewater using Pleurotus ostreatus in bioreactor cultures and biological evaluation of the process.
Pleurotus ostreatus grown in bioreactor batch cultures in a model phenolic wastewater (diluted and sterilized olive oil mill wastewater-OMW), caused significant phenolic removal. Laccase, the sole ligninolytic enzyme detected in the growth environment, was produced during primary metabolic growth. The bioprocess was simulated with the aid of a mathematical model and the parameters of growth were determined. When the fungal biomass was increased in the reactor (during repeated batch experiments) the rate of reducing sugars consumption progressively increased, but a phenolic fraction seemed of being strongly resistant to oxidation. The toxicity of OMW against the seeds of Lepidium sativum and the marine Branchiopoda Artemia sp. was significantly decreased after biotreatment. On the contrary, the toxicity against the freshwater Branchiopoda Daphnia magna was not affected by the treatment, whereas on the soil and freshwater sediments Ostracoda Heterocypris incongruens was slightly decreased. Both treated and untreated OMWs, used as water for irrigation of lettuce and tomato plants, did not significantly affect the uptake of several nutrients by the cultivated plants, but resulted in a decrease in the plant yields, which was minimized when high OMW dilutions were used. As a conclusion, P. ostreatus is able to reduce phenolic content and toxicity of sterilized OMW, in bioreactor cultures. However, high OMW dilutions should be used, and/or additional treatment should be applied before use of the OMW in the environment, e.g. as water for irrigation. Further research should be done in order to transfer this technology under industrial conditions (e.g. by using unsterilized OMW).


Activation of ATM signaling pathway is involved in oxidative stress-induced expression of mito-inhibitory p21WAF1/Cip1 in chronic non-suppurative destructive cholangitis in primary biliary cirrhosis: an immunohistochemical study.
Biliary epithelial cells (BECs) of chronic non-suppurative destructive cholangitis (CNSDC) in primary biliary cirrhosis (PBC) reportedly express p21(WAF1/Cip1) and p16(INK4a), which may induce cell cycle arrest and are related to progressive loss of BECs of PBC. Given that the ATM pathway plays a role in the induction of p21(WAF1/Cip1), we examined its possible involvement in bile duct damage of PBC. The expression of phosphorylated-ATM (p-ATM) reflecting the activation of ATM, p21(WAF1/Cip1) and 8-hydroxy-deoxyguanosine (8-OHdG), an oxidative stress marker, was examined immunohistochemically in the liver tissues of 20 cases of stage 1/2 PBC, 9 extrahepatic biliary obstruction (EBO), 35 chronic viral hepatitis (CVH), 17 nonalcoholic steatohepatitis (NASH), and 18 histologically normal liver. p21(WAF1/Cip1), p-ATM and 8-OHdG were frequently and extensively co-expressed in the nuclei of CNSDC in PBC, and their expressions were correlated. In contrast, the expression of these three molecules was absent or faint in small bile ducts in normal livers, CVH, and EBO, and these molecules were clearly expressed in the nuclei of hepatocytes of NASH, in which oxidative stress is involved in hepatocellular damage. In conclusion, oxidative stress-induced p21(WAF1/Cip1) expression in BECs in PBC is closely associated with activation of the ATM pathway and the resultant reduced regeneration or cell cycle arrest of BECs may be related to the progressive loss of small bile ducts of PBC.


Acrylamide-Induced Hepatotoxicity Through Oxidative Stress: Mechanisms and Interventions.
Significance: Acrylamide (AA) widely exists in the environment. Studies have demonstrated that AA has neurotoxicity and potential carcinogenicity in humans, and genotoxicity and severe hepatotoxicity in animals. As the critical metabolism organ, the liver is the primary attacking target of AA. This review summarizes the recent advances in hepatotoxicity mechanism through AA-induced oxidative stress in rodent livers and hepatic cell lines, and this is beneficial to assess the risks of AA exposure and explore effective intervention methods for AA hepatotoxicity. Recent Advances: Accumulating evidence has indicated that AA-induced oxidative stress is responsible for its hepatotoxicity. The changes in homological and biochemical indexes such as activities of hepatic antioxidant enzymes have been elucidated with the occurrence and development of oxidative stress. Also, the molecular mechanisms underlying AA-induced hepatotoxicity through oxidative stress have been mainly explained by apoptosis, inflammatory, and autophagic pathways. Critical Issues: This review is focusing on the molecular mechanism of hepatotoxicity through AA-induced oxidative stress, and this can provide a theoretical basis for the assessment of AA-induced health risk and finding potential intervention targets. Future Directions: Epigenetic modifications such as microRNAs (miRNAs) and modulation of the gut microbiome involved in the AA toxification pathway must be investigated, and they will provide novel insights to unravel the toxification mechanism and intervention strategy for AA hepatotoxicity. Antioxid. Redox Signal. 38, 1122-1137.


Family leadership styles and adolescent dietary and physical activity behaviors: a cross-sectional study.
Transformational leadership is conceptualized as a set of behaviors designed to inspire, energize and motivate others to achieve higher levels of functioning, and is associated with salient health-related outcomes in organizational settings. Given (a) the similarities that exist between leadership within organizational settings and parenting within families, and (b) the importance of the family environment in the promotion of adolescent health-enhancing behaviors, the purpose of this exploratory study was to examine the cross-sectional relationships between parents' transformational leadership behaviors and adolescent dietary and physical activity behaviors. 857 adolescents (aged 13-15, mean age = 14.70 yrs) completed measures of transformational parenting behaviors, healthful dietary intake and leisure-time physical activity. Regression analyses were conducted to examine relationships between family transformational leadership and adolescent health outcomes. A further 'extreme group analysis' was conducted by clustering families based on quartile splits. A MANCOVA (controlling for child gender) was conducted to examine differences between families displaying (a) HIGH levels of transformational parenting (consistent HIGH TP), (b) LOW levels of transformational parenting (consistent LOW TP), and (c) inconsistent levels of transformational parenting (inconsistent HIGH-LOW TP). Results revealed that adolescents' perceptions of family transformational parenting were associated with both healthy dietary intake and physical activity. Adolescents who perceived their families to display the highest levels of transformational parenting (HIGH TP group) displayed greater healthy eating and physical activity behaviors than adolescents who perceived their families to display the lowest levels of transformational parenting behaviors (LOW TP group). Adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) displayed the same levels of healthy eating behaviors as those adolescents from the LOW TP group. For physical activity behaviors, adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) did not differ in terms of physical activity than those in either the HIGH TP or LOW TP group. Family transformational parenting behaviors were positively associated with both healthful dietary intake and leisure-time physical activity levels amongst adolescents. The findings suggest that transformational leadership theory is a useful framework for understanding the relationship between family leadership behaviors and adolescent health outcomes.


Adverse effects of androgen deprivation therapy on persistent genitourinary complications after carbon ion radiotherapy for prostate cancer.
To determine the risk factors for persistent late genitourinary (GU) morbidity after carbon ion radiotherapy (C-ion RT) for prostate cancer. Between April 2000 and November 2003, a Phase II study of 175 prostate cancer patients was performed to assess C-ion RT with a dose fractionation (66 Gray equivalent in 20 fractions) established from previous Phase I-II studies. The effects of the clinical and dosimetric parameters on the occurrence of persistent GU toxicity in 172 patients who survived for >18 months after C-ion RT were examined retrospectively. C-ion RT alone was performed for 33 low-risk patients, and 139 high-risk patients received C-ion RT combined with androgen deprivation therapy (ADT). Grade 1 and 2 persistent GU toxicities developed in 36 (21%) and 3 (2%) patients, respectively. The use of long-course ADT (>or=24 months) and acute GU toxicity were associated with the occurrence of persistent toxicity by multivariate analysis (p = 0.016 and p = 0.048, respectively), but short-course ADT (<24 months) had no effect on the development of toxicity (p = 0.35). The 5-year actuarial complication rate of 80 patients undergoing long-course ADT was 31.1%; the corresponding rate for the 92 patients who received no ADT or short-course ADT was 22.2%. Adverse effects with long-course ADT on persistent GU morbidity were observed in this study. Additional investigation is needed to identify suitable ADT administration according to risk groups, but long-course ADT should not be adopted for non-high-risk prostate cancer patients to reduce the GU toxicity rate with C-ion RT.


Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models.
Drug-induced liver injury (DILI) is a patient-specific, temporal, multifactorial pathophysiological process that cannot yet be recapitulated in a single in vitro model. Current preclinical testing regimes for the detection of human DILI thus remain inadequate. A systematic and concerted research effort is required to address the deficiencies in current models and to present a defined approach towards the development of new or adapted model systems for DILI prediction. This Perspective defines the current status of available models and the mechanistic understanding of DILI, and proposes our vision of a roadmap for the development of predictive preclinical models of human DILI.


Carotid plaque composition in stable and unstable coronary artery disease.
Several pieces of evidence suggest that formation of complex atheromatous plaques may be influenced not only by local but also by systemic factors. Twenty-five patients (16 men/9 women, age 63 +/- 10 years) with stable coronary artery disease (sCAD) and 61 (41 men/20 women, age 66 +/- 16 years) with acute coronary syndromes (ACSs) underwent carotid ultrasonography within 2 days of cardiac catheterization. Complex coronary plaques were associated with intraluminal filling defect consistent with thrombus, ulceration, or irregularity. Complex carotid plaques had one or more of the following features: (a) ulceration, (b) irregular surface, (c) mobile thrombi on plaque surface, (d) predominant echolucency, and (e) heterogeneity with intraplaque echolucent areas. Carotid intimamedia thickness and luminal diameter were not significantly different between patients with sCAD and those with ACS (0.95 +/- 0.22 vs 1.0 +/- 0.15 mm [P = .23] and 6.1 +/- 0.89 vs 6.20 +/- 0.77 mm [P = .60], respectively), whereas the interadventitial diameter was slightly greater in the latter (7.93 +/- 1.05 vs 8.40 +/- 0.97 mm, P = .0496). Both complex coronary plaques and complex carotid plaques were more common in patients with ACS than in those with sCAD (n = 52 [85.2%] vs n = 6 [24%] [P < .0001] and n = 38 [62.3%] vs n = 5 [20%] [P = .0009], respectively). The odds of having complex carotid plaques were increased > 6-fold in patients with ACS compared with those with sCAD (OR 6.61, 95% CI 2.24-19.32). Complex coronary plaques are associated with complex carotid plaques and the high prevalence of both plaque types in patients with ACS is indicative of a systemic process contributing to complex plaque formation and instability.


Identification and characterization of a novel aac(6')-Iag associated with the blaIMP-1-integron in a multidrug-resistant Pseudomonas aeruginosa.
In a continuing study from Dec 2006 to Apr 2008, we characterized nine multi-drug resistant Pseudomonas aeruginosa strains isolated from four patients in a ward at the Hiroshima University Hospital, Japan. Pulsed-field gel electrophoresis of SpeI-digested genomic DNAs from the isolates suggested the clonal expansion of a single strain; however, only one strain, NK0009, was found to produce metallo-β-lactamase. PCR and subsequent sequencing analysis indicated NK0009 possessed a novel class 1 integron, designated as In124, that carries an array of four gene cassettes: a novel aminoglycoside (AG) resistance gene, aac(6')-Iag, blaIMP-1, a truncated form of blaIMP-1, and a truncated form of aac(6')-Iag. The aac(6')-Iag encoded a 167-amino-acid protein that shows 40% identity with AAC(6')-Iz. Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin. A conjugation experiment and subsequent Southern hybridization with the gene probes for blaIMP-1 and aac(6')-Ig strongly suggested In124 is on a conjugal plasmid. Transconjugants acquired resistance to gentamicin and were resistant to virtually all AGs, suggesting that the In124 conjugal plasmid also possesses a gene conferring resistance to gentamicin.


The role of leukocyte-generated oxidants in left ventricular remodeling.
The cellular injury that results from irreversible ischemia leads to the alteration of tissue function responsible for the phenomenon that we call left ventricular remodeling. Oxidative stress and inflammation are key elements of this process; in mice as in humans, elevation of markers of inflammation at the time of myocardial infarction (MI) is a predictor of the development of ischemic myopathy and of adverse clinical outcomes. Several leukocyte-derived enzyme systems are responsible for the release of oxidizing agents into the myocardium after ischemic injury and provide a means of better understanding MI. By identifying the oxidation products present after inflammation, the responsible leukocyte-generating oxidant systems can be elucidated. Interestingly, a key leukocyte-derived marker, myeloperoxidase (MPO), was formerly measured routinely by older-generation hematology analyzers. Patients with lower levels of MPO were noted to be at lower risk for untoward cardiovascular events, suggesting that humans are more genomically "hardwired" than previously thought. Studies with genetic knockout mice confirm the importance of these leukocyte-generated oxidants in the pathophysiologic consequences of ischemia. This clearly affects the anatomic extent of damage, the hemodynamic consequences, and ultimately, the clinical correlates and potential outcomes. An understanding of these oxidative processes and their relation to inflammation will be extremely useful in the development and understanding of potential therapeutic agents.


[Immediate and remote postactivation effects in the human motor system].
Postactivation effects (appearance of long-lasting non-voluntary contraction of muscles after 30-60 s of the sustained voluntary effort) were studied. It is shown that after contraction of distal muscles postactivation effects can appear in proximal muscles not involved in the previous voluntary activity. The testing of the motor system state by the muscle tendon vibration revealed that besides the well known immediate postactivation effects there were concealed changes lasting for 15-20 min. It is suggested that postactivation phenomena reflecting the functioning of certain central tonogenic structures activated by a voluntary effort or by an increased afferent inflow can be used as an efficient tool in the study of postural mechanisms.


[Transvenous extraction of venous katheter by Simmons-katheter (sidewinder I) (author's transl)].
Report about successful extraction of cutoff embolised venous katheter from V. jugularis with help of a SIMMONS-catheter. Further possibilities of use of superselective arteriography catheters in this connection are mentioned.


Alternative pathway of complement activation in full term and premature infants.
Classical and alternative pathway complement levels were measured in the cord blood sera of 60 newly born infants, with weights ranging from 1200--4165 g. The impact of maternal illness and infant illness on the complement levels was also evaluated. The mean values for CH50, C3, C4, PH50, factor B, and properdin were all significantly less than normal adult levels (P less than 0.0001). All of the above determinations were significantly correlated with one another except for the relationship between properdin and factor B. CH50, PH50, C4, and properdin levels were significantly correlated with birth weight although there was much residual scatter. Neither maternal illness nor mild to moderate illness in the newborn altered the birth weight-complement relationships. Severe infant illness did significantly alter the relationship between birth weight and complement. However, the impact of this variable on the birth weight-complement relationships was not consistent among the various components. These inconsistencies and the small sample size preclude drawing any strong conclusions about severe illness and complement levels.


Morphometric analysis of the endometrium of infertile patients in relation to peripheral hormone levels.
In an attempt to identify factors that may be responsible for reproductive failure, we compared endometrial biopsies taken from infertile patients during the luteal phase of spontaneous cycles (n = 18) with those taken after ovarian stimulation (n = 18). Morphometric analyses were performed and compared with peripheral estradiol (E2) and progesterone levels at the time of supposed implantation. In stimulated cycles the number of glands per square millimeter was positively correlated to the E2 level. The morphometric data point to a measurable difference between the study groups, indicating an insufficient secretory transformation of the tissue in infertile women when compared with a group of fertile women. The observations suggest that hormonal stimulation occasionally results in impaired development of the endometrial glands.


The N haplotype of the murine beta-glucuronidase gene is altered in both its systemic regulation and its response to androgen induction.
A new haplotype of the beta-glucuronidase gene complex, [Gus]N, has been characterized following its transfer from the PAC/Cr strain to the standard strain C57BL/6J. The N haplotype contains a novel structural gene allele which encodes an allozyme differing from all previously characterized allozymes in both size and charge. Altered systemic regulation is exhibited by the [Gus]N haplotype. Multiple tissues contain levels of GUS protein that are 60 +/- 15% those found in the standard B haplotype. The regulatory mechanism for reduction is complex, involving tissue-specific changes in both enzyme synthesis and enzyme turnover. The changes in GUS protein synthesis do not result from changes in GUS mRNA levels. Instead, the amount of mature enzyme formed per mRNA molecule, or translational yield, is altered. These regulatory changes parallel those seen in other systemic regulatory variants of GUS which are also altered in translational yield. A commonality of mechanism among systemic regulatory variants of this gene is suggested. The N haplotype is also exceptional in the nature of its response to androgenic induction in kidney proximal tubule epithelial cells. The time course for GUS induction consists of a lag period followed by a progressive increase in mRNA, rate of enzyme synthesis, and enzyme activity. For the [Gus]N haplotype the lag is of an exceptionally short duration and the plateau is of a greater magnitude than for any haplotype previously described.


Aggregation of 27 oral bacteria by human whole saliva. Influence of culture medium, calcium, and bacterial cell concentration, and interference by autoaggregation.
Twenty-seven oral strains of the genera Actinomyces (5), Bacteroides (3), and Streptococcus (19) were tested for aggregation by human whole saliva, as well as the effect of culture medium, Ca-ions, and bacteria concentration thereupon. Of the media tested, GF-broth gave rise to less interference by autoaggregation or higher aggregation titers than BHI and TSB, and was used throughout this study. In most cases, Ca-ions (1 mM) only enhanced the rate of induced aggregation, whereas raising the bacteria concentration increased the rate of both induced- and autoaggregation. The final titers, ranging from 1-64, were hardly affected by these parameters, except those of S. rattus HG 59 and S. mutans HG 199, which were respectively increased and decreased by Ca-ions. Saliva-induced aggregation was observed for 21 strains of A. viscosus, A. naeslundii, A. israelii, B. gingivalis, B. intermedius, S. cricetus, S. mutans, S. rattus, S. sanguis, and S. sobrinus, mostly within 15 min to 3 h. Seventeen of these strains also showed autoaggregation, usually well after the onset of induced aggregation. Any potential induced aggregation of B. gingivalis HG 91 was always masked by autoaggregation, as well as that of the S. mutans strains under a particular set of conditions. The aggregation rate and titer varied considerably in a mutually unrelated and strain-dependent way. These microtiterplate data were matched by the 5 spectrophotometric patterns observed for saliva-bacterial interaction, which moreover, gave the better differentiation between induced and autoaggregation. In conclusion, most strains tested can show rapid saliva-induced aggregation in a strain-dependent way, yet strongly affected by the experimental conditions and interference from autoaggregation.


Local and spatial spillover effects of corporate financing costs on regional carbon emissions: evidence from Chinese listed firms.
The signing of the Paris Agreement has raised concerns about global carbon emissions, which have detrimental consequences in terms of climate change. At the same time, the financing process for listed companies has begun to incorporate investigations into these firms' carbon emissions. But the current impact of financing costs on firms' carbon emissions has not been accurately assessed. There are large differences in endowments in different regions of China, and factors flow frequently among regions. To date, no empirical evidence has emerged to show the spatial effects of financing costs on carbon emissions. This study uses the STIRPAT model and a panel lag regression model for empirical testing. The results show that increasing financing costs will increase the burden imposed by carbon reduction efforts in various regions. Although this trend has obvious spillovers to surrounding areas, the location of the enterprise bears a more negative burden of externalities. Further analysis shows that reducing the financing costs of enterprises in economically developed regions can reduce both their carbon emissions and the damage to economic growth. These research conclusions can help policymakers shape carbon reduction activities through reducing corporate financing costs on the basis of regional development differences.


Mitral stenosis after mitral valve repair for non-rheumatic mitral regurgitation.
Mitral stenosis after mitral valve repair for non-rheumatic mitral regurgitation is rare. From 1990 to 1999, 478 patients had mitral valve repair for myxomatous and 40 patients had mitral valve repair for ischemic mitral regurgitation. The Carpentier annuloplasty ring (Edwards Lifesciences, Irvine, CA) was used in 72 patients, the Duran ring (Medtronic, Minneapolis, MN) in 152, a posterior band in 221 and no ring or band in 73 patients. Four patients developed mitral stenosis late after mitral valve repair: 2 for myxomatous disease and 2 for ischemic mitral regurgitation. All 4 patients had Duran annuloplasty rings (sizes 25 to 31). The diagnosis of mitral stenosis was made by Doppler echocardiography. The mitral valve area in these 4 patients decreased from 2.7 cm2 (range, 2.3 to 3.2 cm2) early postoperatively to 0.85 cm2 (0.4 to 1.2 cm2) after a mean follow-up of 66 months (range, 38 to 110 months). Three patients had mitral valve replacement and the etiology of the mitral stenosis was the same in all patients (ie, pannus overgrowth on the annuloplasty ring with extension onto both leaflets rendering them stiff and immobile). The fourth patient had a mitral valve area of 1.2 cm2, which was mildly symptomatic with normal pulmonary artery pressure, and this patient has not had reoperation. Mitral stenosis may develop after mitral valve repair for myxomatous disease or ischemic mitral regurgitation when a Duran ring is used for annuloplasty. The stenosis is caused by pannus on the annuloplasty ring with extension onto the leaflets.


The awareness and experience of healthcare providers with the use of anabolic androgenic steroids by gym users.
This study aims to evaluate healthcare providers' awareness and experience with anabolic androgenic steroid (AAS) use among gym users in Jordan and their role in mitigating AAS misuse. A cross-sectional study was conducted between November 2022 and Feb 2023. During the study period, 158 physicians involved in prescribing AAS or treating adverse effects associated with these agents were invited to participate. A questionnaire was created and uploaded on Google Forms and distributed through social media platforms to reach physicians from different medical subspecialties. Of the 158 physicians surveyed, 30.4% were general practitioners, and 63.3% reported having formal education about the risks of bodybuilding with AAS. Among the participants, 48.7% had encountered gym users who were using AAS, with the main reason for referral being the management of side effects associated with AAS use. The median knowledge score regarding AAS and their complications was 10.0 out of 14 (IQR = 7.0), indicating adequate knowledge about most AAS side effects. Around 46% of the physicians (n = 73, 46.2%) believed that gym users might struggle to disclose AAS because they lack trust in them. Finally, the most common advice to gym users was informing them about the health-associated consequences of AAS use, with 92.2% of physicians providing this advice. Although healthcare professionals in Jordan had adequate knowledge about AAS, they needed more to make them confident in dealing with AAS use. This highlights the necessity for specialized teaching and training programs to enhance their knowledge and skills in providing accurate information to AAS users.


Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases.
vitamin D is 25-hydroxylated in the liver, before being activated by 1alpha-hydroxylation in the kidney. Recently, the rat cytochrome P450 2J3 (CYP2J3) has been identified as a principal vitamin D 25-hydroxylase in the rat [Yamasaki T, Izumi S, Ide H, Ohyama Y. Identification of a novel rat microsomal vitamin D3 25-hydroxylase. J Biol Chem 2004;279(22):22848-56]. In this study, we examine whether human CYP2J2 that exhibits 73% amino acid homology to rat CYP2J3 has similar catalytic properties. Recombinant human CYP2J2 was overexpressed in Escherichia coli, purified, and assayed for vitamin D 25-hydroxylation activity. We found significant 25-hydroxylation activity toward vitamin D3 (turnover number, 0.087 min(-1)), vitamin D2 (0.16 min(-1)), and 1alpha-hydroxyvitamin D3 (2.2 min(-1)). Interestingly, human CYP2J2 hydroxylated vitamin D2, an exogenous vitamin D, at a higher rate than it did vitamin D3, an endogenous vitamin D, whereas, rat CYP2J3 hydroxylated vitamin D3 (1.4 min(-1)) more efficiently than vitamin D2 (0.86 min(-1)). Our study demonstrated that human CYP2J2 exhibits 25-hydroxylation activity as well as rat CYP2J3, although the activity of human CYP2J2 is weaker than rat CYP2J3. CYP2J2 and CYP2J3 exhibit distinct preferences toward vitamin D3 and D2.


Use of scoring systems to assess patients with surgical sepsis.
Several scoring systems for patients with severe surgical infections are described, compared, and contrasted. All show a strong relation between a high score and high mortality risk. Each has strengths and weaknesses. All of the systems need further refinement. Future investigations of patients with serious infections should incorporate one of the published severity scores as part of the patient description.


Experimental study of the efficiency of impaza on the model of chronic aseptic prostatic inflammation.
We compared the efficacy of Impaza (antibodies against endothelial NO-synthase in ultra-low doses) and Serenoa repens on the rat model of chronic aseptic prostatic inflammation. Administration of Serenoa repens in a dose of 50 mg/kg for 1.5 months prevented the development of prostate sclerosis and increased luminal area, but did delay the development of atrophic processes. In animals treated with Impaza (3 ml/kg for 1.5 months), atrophic changes in the prostate gland were practically absent. These findings indicate that Impaza can be used in complex therapy of abacterial prostatitis.


Role of Substitutions in the Hemagglutinin in the Emergence of the 1968 Pandemic Influenza Virus.
Hemagglutinin (HA) of H3N2/1968 pandemic influenza viruses differs from the putative avian precursor by seven amino acid substitutions. Substitutions Q226L and G228S are known to be essential for adaptation of avian HA to mammals. We found that introduction of avian-virus-like amino acids at five other HA positions (positions 62, 81, 92, 144, and 193) of A/Hong Kong/1/1968 virus decreased viral replication in human cells and transmission in pigs. Thus, substitutions at some of these positions facilitated emergence of the pandemic virus.


Reduced somatosensory evoked potentials and paired-pulse inhibition in the primary somatosensory cortex of athletes with chronic pain.
Chronic pain impedes athletic training and performance. However, it is challenging to identify the precise causes of chronic pain for effective treatment. To examine possible neuroplastic changes in sensory transmission and cortical processing, we compared somatosensory evoked potentials (SEPs) and paired-pulse inhibition (PPI) in primary sensory cortex (S1) between athletes with chronic pain and control athletes. Sixty-six intercollegiate athletes (39 males and 27 females) were recruited for this study, 45 control athletes and 21 reporting persistent pain for > 3 months. Sensory-evoked potentials were induced in S1 by constant-current square-wave pulses (0.2-ms duration) delivered to the right median nerve, while PPI was induced by paired stimulation at interstimulus intervals of 30 and 100 ms (PPI-30 and PPI-100 ms, respectively). All participants were randomly presented with total 1,500 (each 500 stimuli) single stimuli and stimulus pairs at 2 Hz. Both N20 amplitude and PPI-30 ms were significantly lower in athletes with chronic pain compared to control athletes, while P25 amplitude and PPI-100 ms did not differ significantly between groups. Chronic pain in athletes is associated with substantially altered excitatory-inhibitory balance within the primary somatosensory cortex, possibly due to reduced thalamocortical excitatory transmission and suppressed cortical inhibitory transmission.


Evidence of neuroaxonal degeneration in myofascial pain syndrome: a study of neuromuscular jitter by axonal microstimulation.
The mechanism of myofascial pain syndrome (MPS) is unclear. Previous reports pointed out that pathogenesis of either referred pain or local twitch response in trigger point of MPS is related to the nerve degeneration and disintegration of motor and sensory nerves in spinal cord. The purpose of the present study is to investigate the evidence of neuromuscular transmission disorders in trigger point muscles of patients with MPS by using stimulated single-fiber electromyography (SFEMG) examination. Twenty-three patients with neck MPS and 16 age-matched controls attended for the present study. The jitter or mean consecutive difference (MCD) was calculated as the mean of the absolute differences for 30 consecutive interpotential intervals between stimuli and single-fiber potentials in trapezius and levator scapulae muscles. The relationship between the MCD values and the disease duration was measured. The results showed significantly increased MCDs in trapezius and levator scapulae muscles in MPS patients. MCD values measured in the trigger point muscles were found to be positively correlated with the disease duration. The present study with axonal microstimulation and SFEMG demonstrates a prominent evidence of neuroaxonal degeneration and neuromuscular transmission disorders in the trigger point muscles of MPS patients. The mechanism of MPS is possibly implicated with the degeneration of motor neurons.


Removing the effect of SVD algorithmic artifacts present in quantitative MR perfusion studies.
Quantitative cerebral blood flow (CBF) values can be obtained from dynamic susceptibility contrast (DSC) MR perfusion studies using the standard singular value decomposition (sSVD) deconvolution algorithm. Reports in the literature from simulation and in vivo studies suggest that CBF estimates obtained using sSVD deconvolution depend on the arterial-tissue delay (ATD). By contrast, Fourier transform (FT) deconvolution produces CBF estimates that are independent of ATD. The diagnostic reliability of quantitative CBF measurements to define areas of normal tissue flow and tissue at risk is brought into doubt by such gross sensitivity to the specifics of the deconvolution approach. This variation of CBF values with ATD is shown to be an artifact associated with the current implementation of the sSVD deconvolution algorithm. A reformulated version of the SVD deconvolution algorithm (rSVD) is presented and compared to the standard SVD algorithm through simulation and patient case studies.


Technology-related knowledge, skills, and attitudes of pre- and in-service teachers: The current situation and emerging trends.
This is the introductory article for the special issue "Technology-related knowledge, skills, and attitudes of pre- and in-service teachers". It (1) specifies the concept of technology-related knowledge, skills, and attitudes (KSA) of teachers, (2) presents how these KSA are currently assessed, and (3) outlines ways of fostering them among pre- and in-service teachers. The eight articles in the special issue are structured accordingly, and we demonstrate how they contribute to knowledge in these three areas. Moreover, we show how the afterword to the special issue widens the perspective on technology integration by taking into account systems and cultures of practice. Due to their quantitative empirical nature, the eight articles investigate technology at the current state of the art. However, the potential of artificial intelligence has not yet been fully exploited in education. We provide an outlook on potential developments and their implications on teachers' technology-related KSA. To this end, we introduce the concept of augmentation strategies.


LB-Q1 and LB-Q2: two determinants defined in the primed lymphocyte test and independent of HLA-D/DR, MB/LB-E, or SB.
The primed lymphocyte test (PLT) was used to prepare reagents between HLA-D/DR identical individuals. Two sets of primed lymphocytes were obtained which recognized the new determinants referred to as LB-Q1 and LB-Q2, respectively. LB-Q2 is significantly associated with HLA-A1, -B8, and -D/DR3. Nevertheless, LB-Q1 and LB-Q2 seem to be distinct from any of the established HLA antigens. No association with any of the alleles of the SB system was observed. A recombination between HLA-D/DR and HLA-B suggested that the locus encoding LB-Q2 is situated on the telomeric side of HLA-D/DR.


Choledochal cysts: analysis of disease pattern and optimal treatment in adult and paediatric patients.
Choledochal cysts are dilations of the biliary tree. Although commonly reported in Asian populations, the incidence outside of Asia is as low as 1:150 000. The largest series of patients with choledochal cyst disease outside of Asia is this one, studying 70 patients treated in Vancouver between 1971 and 2003. This was a retrospective chart review. In all, 19 paediatric and 51 adult patients were evaluated; 21% of paediatric and 25% of adult patients were Asian. All paediatric patients had type I or IV cysts, whereas adult patients represented the different subtypes. Abdominal pain was the presenting symptom in 79% of children and 88% of adults, vomiting was present in 42% of children and 63% of adults and jaundice was seen in 31.5% of children and 39% of adults. Ultrasound was used in 94.7% of children, and ERCP in 80% of adults. In all, 84% of paediatric patients, 100% of adult patients with type I cysts and 85.7% of adult patients with type IV cysts received complete cyst excision and Roux-en-Y hepaticojejunostomy. Complications in both groups were low. Although Vancouver does have a large Asian population, this does not explain how common choledochal cysts are in this city. Although some authors argue that paediatric and adult disease are caused by different aetiologies, presentation patterns in our study between the two groups were very similar. We recommend complete cyst excision and Roux-en-Y hepaticojejunostomy as the surgery of choice, and advocate early surgery after diagnosis to promote ease of surgery and prevention of future complications.


Surveillance for Gastric Cancer.
This article discusses the current National Comprehensive Cancer Network guidelines and other available Western and Eastern guidelines for the surveillance of gastric cancer following surgical resection. It reviews the literature assessing the utility of intensive surveillance strategies for gastric cancer, which fails to show an improvement in survival. The unique issues relating to follow-up of early gastric cancer and after endoscopic resection of early gastric cancer are discussed. This article also reviews the available modalities for follow-up. In addition, it briefly discusses the advancements in treatment of recurrent and metastatic disease and the implications for gastric cancer survival and surveillance strategies.


Coagulation factor VII gene polymorphisms are not associated with the occurrence or the survival of hepatocellular carcinoma: a report of 37 cases.
: Coagulation factor VII (FVII) triggers the extrinsic pathway of blood coagulation. In our previous study, we showed that FVII plays an important role in tumorigenesis of hepatocellular carcinoma (HCC). However, the role of FVII polymorphism in HCC is still unknown. The present study aimed to investigate the relationship between HCC carcinogenesis and single nucleotide polymorphism of FVII. : Thirty-seven HCC patients and 30 healthy donors were recruited in this study. Four common FVII gene polymorphisms - a decanucleotide insertion at position -323 (-323ins10-bp), a G to T substitution at position -401 (-401G/T), a G to A substitution at position -402 (-402G/A), and a T to C substitution at position -122 (-122T/C) - were analyzed by sequencing or commercialized assays using genomic DNA isolated from blood samples. Clinicopathological parameters between control and HCC subjects were compared according to the specific genotypes. : The most common nucleotide variation was -402G/A. However, no statistically significant difference was observed between healthy controls and HCC subjects for all four polymorphisms in terms of genotype distribution and allele frequencies, indicating that these polymorphisms may not affect HCC tumorigenesis. Furthermore, no association was found between -402G/A polymorphisms and tumor stage, recurrence, and overall survival. : Our results indicate that FVII polymorphisms may not be a key factor that clinically impact tumorigenesis and outcomes of HCC, although further investigations should be conducted to confirm our findings.


Reduction potentials of anthelmintic drugs: possible relationship to activity.
Electrochemical data were acquired for several categories of anthelmintic agents, namely, iminium-type ions, metal derivatives and chelators, quinones and iminoquinones, and nitroheterocycles. Reductions usually were in the favorable range of +0.2 to -0.7 V versus normal hydrogen electrode. The drug effect is believed to result in part from either the catalytic production of oxidative stress or disruption of helminth electron transport systems. Relevant literature results are discussed.


[Human sparganosis in Ecuador: report of a case in the province of Esmeraldas].
The second case of human sparganosis in Ecuador is reported in a male patient, of an indigenous tribe Chachi, from the province of Esmeraldas, who presented with a nodule localized in the left scapular region. Upon extirpation, a cestode classified as Spirometra was found, but the species could not be determined.