In vivo Ca2+ dynamics during cooling after eccentric contractions in rat skeletal muscle.
The effect of cooling on in vivo intracellular calcium ion concentration [Ca2+]i after eccentric contractions (ECs) remains to be determined. We tested the hypothesis that cryotherapy following ECs promotes an increased [Ca2+]i and induces greater muscle damage in two muscles with substantial IIb and IIx fiber populations. The thin spinotrapezius (SPINO) muscles of Wistar rats were used for in vivo [Ca2+]i imaging, and tibialis anterior (TA) muscles provided greater fidelity and repeatability of contractile function measurements. SPINO [Ca2+]i was estimated using fura 2-AM and the magnitude, location, and temporal profile of [Ca2+]i determined as the temperature near the muscle surface post-ECs was decreased from 30°C (control) to 20°C or 10°C. Subsequently, in the TA, the effect of post-ECs cooling to 10°C on muscle contractile performance was determined at 1 and 2 days after ECs. TA muscle samples were examined by hematoxylin and eosin staining to assess damage. In SPINO, reducing the muscle temperature from 30°C to 10°C post-ECs resulted in a 3.7-fold increase in the spread of high [Ca2+]i sites generated by ECs (P < 0.05). These high [Ca2+]i sites demonstrated partial reversibility when rewarmed to 30°C. Dantrolene, a ryanodine receptor Ca2+ release inhibitor, reduced the presence of high [Ca2+] sites at 10°C. In the TA, cooling exacerbated ECs-induced muscle strength deficits via enhanced muscle fiber damage (P < 0.05). By demonstrating that cooling post-ECs potentiates [Ca2+]i derangements, this in vivo approach supports a putative mechanistic basis for how postexercise cryotherapy might augment muscle fiber damage and decrease subsequent exercise performance.


Ethnobotanical studies of fodder grass resources for ruminant animals, based on the traditional knowledge of indigenous communities in Central Punjab Pakistan.
Traditional knowledge of indigenous plants is pivotal in developing strategies to feed livestock sustainably in low input systems. Likewise, in Pakistan the indigenous people of Central Punjab have been using their regional grasses as a ruminant fodder for centuries. This study evaluated the indigenous traditional knowledge to ascertain the value of various fodder grasses to optimise their use to feed livestock in Central Punjab. The snowball technique was employed to identify key informants who had relevant knowledge about different grasses in the study area. Semi-structured questionnaires, face-to-face interviews and site visits were used for describing the fodder grasses. The data were then analysed by using relative frequency citation and pairwise comparison methods to determine the order of priority among the listed fodder grasses. Furthermore, SPSS 22 software was used for descriptive statistics and interpretation of associations among studied parameters. Microsoft Excel was used to present data as % values and graphs. Overall, 53 grasses were described with ethnobotanical information regarding their uses for fodder, ethnoveterinary and other purposes. All these grasses belonged to the family Poaceae where the subfamily Panicoideae had the maximum number of 30 grasses. We categorized these grasses into high (A), medium (B) and low priority (C) groups where the group A grasses were reported as not only the most abundant but also the most palatable forages to all ruminants. Their higher demand was reflected by the feeding systems of both ad libitum grazing and feeding after cutting and mixing with other feeds. The study also revealed 37 previously unreported ethnoveterinary uses of these grasses. The results have reinforced the value of conserving ethnobotanical knowledge, being poorly documented previously, in developing strategies to feed livestock. It indicated the preferred fodder grasses as well as the possible reasons of their preference. The reported data need to be validated for nutritional and health benefits. This information could help the smallholder farmers in association with regional governments to propagate suitable fodder grasses for their use in sustainable livestock feeding to produce safe and healthy food for indigenous communities.


[Evaluation of a community-oriented health promotion project "Mauren Aktiv"].
In the year 1996, "Mauren Aktiv"--a community health promotion project in Liechtenstein--was evaluated. The methods used were as follows: Interviews with key-persons of the community, group-discussions, written questionnaire, telephone-interviews and analysis of documents. The evaluation showed the following results: "Mauren Aktiv" works. It has increased the offer of health promotion activities by more than 100 percent. The offer is well received by the population. The flexible organisational structure proved to be functional. But "Mauren Aktiv" only partly achieves its claim to be a co-ordinating agent for all health promotion activity within the community. Favourable factors for the project are the co-operation of numerous volunteers and the conditions offered by the municipality. On the contrary the co-operation of the volunteers and the lack of professional support cause problems, for example regarding the documentation of the activities of "Mauren Aktiv".


Integrated bioinformatic analysis to understand the association between phthalate exposure and breast cancer progression.
Phthalates have been extensively used as plasticizers while manufacturing plastic-based consumer products. Estradiol mimicking properties and association studies suggest phthalates may contribute to breast cancer (BC). We performed an in-silico analysis and functional studies to understand the association between phthalate exposure and BC progression. Search for phthalate-responsive genes using the comparative toxicogenomics database identified 20 genes as commonly altered in response to multiple phthalates exposure. Of the 20 genes, 12 were significantly differentially expressed between normal and BC samples. In BC samples, 9 out of 20 genes showed a negative correlation between promoter methylation and its expression. AHR, BAX, BCL2, CAT, ESR2, IL6, and PTGS2 expression differed significantly between metastatic and non-metastatic BC samples. Gene set enrichment analysis identified metabolism, ATP-binding cassette transporters, insulin signaling, and type II diabetes as highly enriched pathways. The diagnostic assessment based on 20 genes expression suggested a sensitivity and a specificity >0.91. The aberrantly expressed phthalate interactive gene influenced the overall survival of BC patients. Drug-gene interaction analysis identified 14 genes and 523 candidate drugs, including 19 BC treatment-approved drugs. Di(2-ethylhexyl) phthlate (DEHP) exposure increased the growth, proliferation, and migration of MCF-7 and MDA-MB-231 cells in-vitro. DEHP exposure induced morphological changes, actin cytoskeletal remodeling, increased ROS content, reduced basal level lipid peroxidation, and induced epithelial to mesenchymal transition (EMT). The present approach can help to explore the potentially damaging effects of environmental agents on cancer risk and understand the underlined pathways and molecular mechanisms.


Micturition in the toilet compared with bedpan in laboring Nulliparas: a randomized controlled trial.
Bladder overdistension in labor may lead to prolonged postpartum urinary retention. We hypothesized that nulliparas mobilizing to toilet is more likely to achieve satisfactory micturition. One hundred sixteen (58 in each arm) term nulliparas in labor with filled bladders were randomized to mobilizing to the toilet or using bedpan to micturate. Primary outcome was satisfactory micturition defined as ultrasound derived post-void bladder volume < 150 ml. Following unsatisfactory micturition, participants crossover to the opposed intervention. Participants were catheterized if after crossover, residual bladder volume was ≥250 ml. Satisfactory micturition rates were 55/58 (95%) vs. 43/58 (74%) RR 1.28 95%CI 1.08-1.51 NNTb 4.8 95%CI 3.0-12.4 P = 0.008, failure to micturate 1/58 (2%) vs. 8/58 (14%) RR 0.13 95%CI 0.02-0.97 NNTb 8.3 95%CI 4.6-38.7 P = 0.047. After cross over following unsatisfactory bladder voiding, satisfactory micturition rates were 0/3 (0%) vs 13/15 (87%) P = 0.024, bladder catheterization rates were 3/58 (5%) vs. 2/58 (4%) RR 95%CI 1.5 (0.26-8.65) P = 0.648, maternal satisfaction with allocated intervention 55/58 (95%) vs. 9/58 (16%) RR 95%CI 6.1 (3.3-11.2) NNTb 95%CI 1.3 (1.1-1.5) P < 0.0001 and preference for mobilizing to the toilet if micturition was needed again during labor 55/58 (95%) vs. 53/58 (92%) for mobilizing to the toilet compared to bedpan use arms respectively. Labor and neonatal outcomes were similar. Satisfactory micturition was more frequently achieved with mobilization to the toilet than bedpan use. Women in both arms overwhelmingly prefer to mobilize to the toilet to urinate. This study was registered with ISRCTN on 17/07/2019 with trial identification number: ISRCTN17787339 . First participant was recruited on 31/07/2019. The last patient was recruited on 18/12/2019.


Potential applications for cell regulatory factors in liver progenitor cell therapy.
Orthotopic liver transplant represent the state of the art treatment for terminal liver pathologies such as cirrhosis in adults and hemochromatosis in neonates. A limited supply of transplantable organs in relationship to the demand means that many patients will succumb to disease before an organ becomes available. One promising alternative to liver transplant is therapy based on the transplant of liver progenitor cells. These cells may be derived from the patient, expanded in vitro, and transplanted back to the diseased liver. Inborn metabolic disorders represent the most attractive target for liver progenitor cell therapy, as many of these disorders may be corrected by repopulation of only a portion of the liver by healthy cells. Another potential application for liver progenitor cell therapy is the seeding of bio-artificial liver matrix. These ex vivo bioreactors may someday be used to bridge critically ill patients to other treatments. Conferring a selective growth advantage to the progenitor cell population remains an obstacle to therapy development. Understanding the molecular signaling mechanisms and micro-environmental cues that govern liver progenitor cell phenotype may someday lead to strategies for providing this selective growth advantage. The discovery of a population of cells within the bone marrow possessing the ability to differentiate into hepatocytes may provide an easily accessible source of cells for liver therapies.


Efficiency of follicle-stimulating hormone, commenced in the luteal phase, for overcoming a poor response in assisted reproduction.
The efficacy of commencement of recombinant follicle-stimulating hormone (recFSH) during the luteal phase in the long-protocol gonadotropin-releasing hormone (GnRH) agonist regimen in poor responders was compared with the conventional protocol in a prospective, randomized, controlled study. Forty-two women who responded poorly to previous conventional controlled ovarian hyperstimulation were included in the study. Recombinant FSH (150 IU) was started simultaneously with the GnRH agonist long protocol in the study group. The control group was started recFSH on Day 2 of menstruation in the long-protocol GnRH agonist regimen. The number of metaphase (M) II oocytes, the number of embryos transferred, and the pregnancy rate were analyzed as main outcome measures. Patients in the study group had a higher number of MII oocytes compared with the control group (6.8 vs 3.2, respectively; P < 0.005), received a higher number of embryos (2.7 vs 1.2, respectively; P < 0.05), and had higher pregnancy rates (38% vs 15%, respectively; P < 0.005). Commencement of recFSH during the luteal phase simultaneously with the long-protocol GnRH agonist regiment in poor responder women produces better results compared with the conventional long-protocol GnRH agonist plus high-dose recFSH regimen.


Lysosomal cell death mechanisms in aging.
Lysosomes are degradative organelles essential for cell homeostasis that regulate a variety of processes, from calcium signaling and nutrient responses to autophagic degradation of intracellular components. Lysosomal cell death is mediated by the lethal effects of cathepsins, which are released into the cytoplasm following lysosomal damage. This process of lysosomal membrane permeabilization and cathepsin release is observed in several physiopathological conditions and plays a role in tissue remodeling, the immune response to intracellular pathogens and neurodegenerative diseases. Many evidences indicate that aging strongly influences lysosomal activity by altering the physical and chemical properties of these organelles, rendering them more sensitive to stress. In this review we focus on how aging alters lysosomal function and increases cell sensitivity to lysosomal membrane permeabilization and lysosomal cell death, both in physiological conditions and age-related pathologies.


[Extent of fenestration in one-level operations for lateral herniation of the intervertebral disk of the lumbar segment of the spine].
In the years 1969-1986 operations were carried out in 1650 cases of lateral prolapse of the lumbar nucleus pulposus at one level, they accounted for 75% of patients operated on for symptomatic sciatic pains. The operations were done in lateral recumbent position. In 29% of cases it was necessary to extend the typical fenestration by reducing the size of one or two halves of the vertebral arches, and in 12% of cases full hemilaminectomy was done. The most frequent cause of fenestration extension was narrow yellow ligament and massive broad vertebral arches at the level of the prolapsed nucleus, as well as congenital or acquired narrowing of the lateral recess of the vertebral canal. In only 4% of cases the necessity of fenestration extension was due to displacement of the free fragments of the prolapsed nucleus far from the intervertebral space or their falling into the meningeal sac.


Atypical presentation of herpes simplex (chronic hypertrophic herpes) in a patient with HIV infection.
A 46-year-old man with HIV infection and AIDS presented with a large perianal ulcerated vegetative lesion that developed over a 1-year period. He had a past history of recurrent genital herpes infection, treated successfully each time with acyclovir. The perianal lesion developed while he was taking prophylactic acyclovir. Clinically, there were features suspicious of a carcinoma and a biopsy was reported as showing dysplasia. Therefore, the lesion was resected in its entirety. Histologically, there were prominent pseudo-epitheliomatous hyperplasia and chronic ulceration associated with herpesvirus infection. There was no evidence of dysplasia or malignancy. It is important to be aware of chronic vegetant herpesvirus infection, as clinical appearances are unusual and some methods of identification, such as smears or biopsy, may not be sufficient for diagnosis. Viral culture or PCR may need to be performed for a definite diagnosis to alleviate prolonged discomfort and avoid unnecessary radical surgery.


Advances in CD30- and PD-1-targeted therapies for relapsed or refractory Hodgkin lymphoma.
The current standard approach for relapsed or refractory (R/R) Hodgkin lymphoma (HL) is salvage chemotherapy, followed by autologous stem cell transplantation (ASCT). However, this therapeutic regimen is successful in only half of patients with relapsed or refractory classical HL. In addition, some patients with R/R HL are ineligible for ASCT. To improve survival time and quality of life and decrease the acute and long-term toxicities of therapy, many schemes for the treatment of R/R HL have emerged. Recently, the use of targeted therapy and immunotherapy represents an important advance in the treatment of R/R HL. The CD30 antibody drug conjugate brentuximab vedotin (BV) and programmed death-1 (PD-1) receptor checkpoint inhibitors nivolumab and pembrolizumab are effective and well-tolerated treatments for R/R HL patients, broadening treatment options for these patients. BV and anti-PD-1 antibodies can be used as monotherapy or combined with other chemotherapy regimens for rescue treatment, consolidation treatment and second-line treatment of R/R HL. In this article, we review current pathobiology knowledge of R/R HL and summarize recent advances in therapy schemes.


Prevalence of synchronous colorectal neoplasms in surgically treated gastric cancer patients and significance of screening colonoscopy.
The existence of other primary tumors during the treatment and management of gastric cancer (GC) is an important issue. The present study investigated the prevalence and management of synchronous colorectal neoplasms (CRN) in surgically treated GC patients. Of 381 surgically treated GC patients, 332 (87.1%) underwent colonoscopy to detect CRN before surgery or within a year after surgery. CRN were synchronously observed in 140 patients (42.2%). Adenoma was observed in 131 patients (39.4%). Endoscopic resection was done in 18 patients with adenoma. Colorectal cancer (CRC) was observed in 16 patients (4.8%), superficial CRC in 13 and advanced CRC in three patients. Endoscopic resection of superficial CRC was carried out in seven patients, whereas simultaneous surgical resection of CRC was done in nine patients. CRN were more frequently observed in men. CRC was more frequently observed in GC patients with distant metastasis, albeit without significance. The overall survival of GC patients with CRN or CRC was poorer than that of patients without CRN or CRC. Synchronous CRN were commonly associated with GC and screening colonoscopy should be offered to patients with GC.


The influence of total knee arthroplasty geometry on mid-flexion stability: an experimental and finite element study.
Fluoroscopic evaluation of total knee arthroplasty (TKA) has reported sudden anterior translation of the femur relative to the tibia (paradoxical anterior motion) for some cruciate-retaining designs. This motion may be tied to abrupt changes in the femoral sagittal radius of curvature characteristic of traditional TKA designs, as the geometry transitions from a large load-bearing distal radius to a smaller posterior radius which can accommodate femoral rollback. It was hypothesized that a gradually reducing radius may attenuate sudden changes in anterior-posterior motion that occur in mid-flexion with traditional discrete-radius designs. A combined experimental and computational approach was employed to test this hypothesis. A previously developed finite element (FE) model of the Kansas knee simulator (KKS), virtually implanted with multiple implant designs, was used to predict the amount of paradoxical anterior femoral slide during a simulated deep knee bend. The model predicted kinematics demonstrated that incorporating a gradually reducing radius in mid-flexion reduced the magnitude of paradoxical anterior translation between 21% and 68%, depending on the conformity of the tibial insert. Subsequently, both a dual-radius design and a modified design incorporating gradually reducing radii were tested in vitro in the KKS for verification. The model-predicted and experimentally observed kinematics exhibited good agreement, while the average experimental kinematics demonstrated an 81% reduction in anterior translation with the modified design. The FE model demonstrated sufficient sensitivity to appropriately differentiate kinematic changes due to subtle changes in implant design, and served as a useful pre-clinical design-phase tool to improve implant kinematics.


The diagnostic effectiveness of serum sialic acid predicts both qualitative and quantitative prostate cancer in patients with prostate-specific antigen between 4 and 20 ng/mL.
This study aimed to evaluate the predictive value of the serum biochemical index, including alkaline phosphatase (AKP), lactate dehydrogenase (LDH), α-L-fucosidase (AFU), serum sialic acid (SA), and fibrinogen (FIB), for prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) in patients with a prostate-specific antigen (PSA) value between 4 and 20 ng/mL. This study retrospectively examined the clinical data of 408 eligible patients who underwent prostate biopsies in our hospital between March 2015 and July 2022. CSPCa was defined as a "Gleason grade group of≥2". For analyzing the association between PCa/CSPCa and serum biochemical index, univariable logistic regression and multivariable logistic regression were conducted. Based on the multivariable logistic regression model, we constructed models and compared the area under the curve (AUC). We generated the nomogram, the ROC curve, the DCA curve, and the calibration curve for PCa. Overall, we studied 271 patients with PCa (including 155 patients with CSPCa) and 137 non-PCa patients. Patients with PCa were more likely to consume alcohol, have higher total PSA (TPSA) values, and have lower free PSA (FPSA) and free/total PSA (f/T) values. There were higher TPSA values and lower f/T values in the CSPCa group when compared with the non-CSPCa group. The univariate logistic regression analyses did not show significant results. However, AKP, AFU, SA, TPSA, and FPSA all retain significant significance when all factors are included in multifactor logistic regression analysis. This finding suggests that the exposure factor exhibited an independent effect on the outcome after controlling for other factors, including the potential confounding effects that may have been underestimated. Through ROC curves, we found that SA and TPSA levels are more powerful predictors. In contrast, there is a lack of excellent predictive value for PCA and CSPCa using Age, AFU, FIB, and FPSA. In our study, serum biochemical index is a potential prediction tool for PCa and CSPCa for patients with PSA values between 4 and 20 ng/mL. Additionally, the new serum biochemical index SA is also useful when diagnosing PCa and CSPCa, as we conclude in our study.


Point-prevalence surveillance of healthcare-associated infections in Swedish hospitals, 2008-2014. Description of the method and reliability of results.
In 2007 the Swedish Association of Local Authorities and Regions (SALAR) decided to establish a nationwide system for point-prevalence surveillance of healthcare-associated infections (HCAIs) among hospitalized patients. Surveillance started in 2008 and has since then been performed twice a year (April and October). The documentation of HCAIs is performed by regular clinical physicians and nurses on each hospital ward aided by oral and written instructions. All Swedish publicly financed hospitals (>95% of all hospitals) are included (25,862 beds in 2008 and 24,905 beds in 2013). A total of 88-92% of all inpatients has been covered in each survey. The overall prevalence of HCAI (including psychiatric inpatients) has ranged from 7.8% to 10.0%. In 2012 SALAR decided to assess the reliability of the prevalence data. In all, 1216 patients were assessed for HCAIs by both the regular surveillance teams and teams with expert knowledge on HCAI independently of each other. The prevalence of HCAI was 8.3% (95% confidence interval: 6.7-9.9) according to the regular teams and 13.1% (11.2-15.0) according to the expert teams. The sensitivity of the regular point-prevalence surveillance was 47% and the specificity 97%. The Swedish system for repeated nationwide point-prevalence surveillance of HCAI has had a high coverage of about 90% since it commenced. However, the surveys underestimate the true prevalence of HCAI.


InPrePPI: an integrated evaluation method based on genomic context for predicting protein-protein interactions in prokaryotic genomes.
Although many genomic features have been used in the prediction of protein-protein interactions (PPIs), frequently only one is used in a computational method. After realizing the limited power in the prediction using only one genomic feature, investigators are now moving toward integration. So far, there have been few integration studies for PPI prediction; one failed to yield appreciable improvement of prediction and the others did not conduct performance comparison. It remains unclear whether an integration of multiple genomic features can improve the PPI prediction and, if it can, how to integrate these features. In this study, we first performed a systematic evaluation on the PPI prediction in Escherichia coli (E. coli) by four genomic context based methods: the phylogenetic profile method, the gene cluster method, the gene fusion method, and the gene neighbor method. The number of predicted PPIs and the average degree in the predicted PPI networks varied greatly among the four methods. Further, no method outperformed the others when we tested using three well-defined positive datasets from the KEGG, EcoCyc, and DIP databases. Based on these comparisons, we developed a novel integrated method, named InPrePPI. InPrePPI first normalizes the AC value (an integrated value of the accuracy and coverage) of each method using three positive datasets, then calculates a weight for each method, and finally uses the weight to calculate an integrated score for each protein pair predicted by the four genomic context based methods. We demonstrate that InPrePPI outperforms each of the four individual methods and, in general, the other two existing integrated methods: the joint observation method and the integrated prediction method in STRING. These four methods and InPrePPI are implemented in a user-friendly web interface. This study evaluated the PPI prediction by four genomic context based methods, and presents an integrated evaluation method that shows better performance in E. coli.


Generation of a prostate from a single adult stem cell.
The existence of prostate stem cells (PSCs) was first postulated from the observation that normal prostate regeneration can occur after repeated cycles of androgen deprivation and replacement in rodents. Given the critical role of PSCs in maintaining prostate tissue integrity and their potential involvement in prostate tumorigenesis, it is important to define specific markers for normal PSCs. Several cell-surface markers have been reported to identify candidate PSCs, including stem cell antigen-1 (Sca-1, also known as Ly6a), CD133 (Prom1) and CD44 (refs 3-10). However, many non-PSCs in the mouse prostate also express these markers and thus identification of a more defined PSC population remains elusive. Here we identify CD117 (c-kit, stem cell factor receptor) as a new marker of a rare adult mouse PSC population, and demonstrate that a single stem cell defined by the phenotype Lin(-)Sca-1(+)CD133(+)CD44(+)CD117(+) can generate a prostate after transplantation in vivo. CD117 expression is predominantly localized to the region of the mouse prostate proximal to the urethra and is upregulated after castration-induced prostate involution-two characteristics consistent with that of a PSC marker. CD117(+) PSCs can generate functional, secretion-producing prostates when transplanted in vivo. Moreover, CD117(+) PSCs have long-term self-renewal capacity, as evidenced by serial isolation and transplantation in vivo. Our data establish that single cells in the adult mouse prostate with multipotent, self-renewal capacity are defined by a Lin(-)Sca-1(+)CD133(+)CD44(+)CD117(+) phenotype.


Protective effect of aged garlic extract against the oxidative stress induced by cisplatin on blood cells parameters and hepatic antioxidant enzymes in rats.
Cisplatin (CP) is one of the most active cytotoxic drugs. However, it has several side effects that are associated with increased oxidative stress. Aged garlic extract (AGE) is a natural product containing different compounds with antioxidant activity. The present study aimed to evaluate the effect of AGE on CP-induced hepatotoxicity. Four equally male rat groups: control, AGE-treated (250 mg/kg once for 21 days), CP-treated (7.5 mg/kg, once intraperitoneal), combined AGE and CP-treated were used. Blood samples were collected to investigate blood picture and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin (TSB) and albumin. The liver of each rat was excised, cleaned, weighed, rinsed in ice-cold saline and homogenized for assessment malondialdehyde (MDA) level, catalase (CAT) and superoxide dismutase (SOD) activities and level of reduced glutathione (GSH). Histological examination was also carried out. AGE-pretreated rats revealed significant reduction in serum levels of AST, ALT & TSB and increase serum albumin level induced by CP administration. Furthermore, AGE significantly ameliorated CP-induced increase in MDA level and decrease in GSH level, CAT and SOD activities in liver tissue homogenates. Additionally, histopathological and blood picture examinations revealed markedly ameliorated CP-induced toxicity on blood cells parameters and liver structure. Our results prove that AGE has antioxidant and protective effects against CP-induced oxidative stress and changes in parameters of blood cells and liver structure in rats. Thus, it could be used as a dietary supplementation to reduce toxic side effects of anticancer drugs.


Evolution of a patient education program in a rural hospital.
An interdisciplinary Patient Education Committee developed strategies which would ensure adequate and consistent patient education. Four major projects merged: 1) a Patient and Family Teaching Policy; 2) in-house development of teaching handouts; 3) a Patient Education Television network, and 4) a Patient Education Materials list available on the Hospital Information System. Soon all teaching handouts will also be available in that format.


MYC and BCL2 overexpression is associated with a higher class of Memorial Sloan-Kettering Cancer Center prognostic model and poor clinical outcome in primary diffuse large B-cell lymphoma of the central nervous system.
Primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) is a distinct clinicopathological entity with a poor prognosis. Concurrent MYC and BCL2 overexpression predicts inferior prognosis in systemic DLBCLs. However, the prognostic significance of MYC and BCL2 in PCNS-DLBCL remains elusive. Immunohistochemistry (IHC) of MYC, BCL2 and BCL6 was performed on tumor samples from 114 patients with PCNS-DLBCL. IHC score was assigned based on the proportion of immunostained cells. MYC, BCL2, and BCL6 IHC scores were 18.16 ± 19.58, 58.86 ± 35.07, and 39.39 ± 37.66 % (mean ± SD), respectively. Twenty-one cases (18.1 %) were designated as MYC-positive with a cutoff score of 40. BCL2 positivity was found in 87 cases (75.0 %) using a cutoff score of 30. MSKCC (Memorial Sloan-Kettering Cancer Center prognostic model) class 2 and 3 had higher rates of MYC and/or BCL2 positivity (MYC, P = 0.012; BCL2, P = 0.008; dual-positive, P = 0.022). Poor KPS (Karnofsky Performance Status score <70), multifocal disease, Nottingham-Barcelona score ≥2, and MSKCC class 2 and 3 were related to shorter progression-free survival (PFS) (P = 0.001, 0.037, 0.001, and 0.008, respectively). Patients with older age (>60 years) showed poorer overall survival (OS) (P = 0.020). MYC positivity was associated with poor PFS (P = 0.027), while patients with BCL2 positivity exhibited a shorter OS (P = 0.010). Concomitant MYC and BCL2 positivity was related to poor PFS (P = 0.041), while the lack of both MYC and BCL2 expression was related to prolonged OS (P = 0.014). MYC and BCL2 expression had no independent prognostic implication by multivariate analysis in overall patients with PCNS-DLBCL. However, among patients treated with combined high-dose methotrexate, vincristine and procarbazine and radiotherapy, dual MYC and BCL2 overexpression (a cutoff score of 60) was an independent poor prognostic indicator (P = 0.010). Evaluation of MYC and BCL2 expression may be helpful for the determination of PCNS-DLBCL prognosis.


Synthesis of Functionalized 6,5- and 7,5-Azabicycloalkane Amino Acids by Metathesis Reactions.
Azabicyclo[4.3.0]- and [5.3.0]alkanone amino acid derivatives were easily prepared by submitting the same starting dipeptide to a direct ring-closing enyne metathesis or an ethylene-mediated cross-enyne metathesis/ring-closing metathesis, respectively. The reactivity of the newly synthesized 6,5- and 7,5-fused bicyclic scaffolds was then investigated to obtain variously functionalized derivatives with potential applications in the field of peptides/peptidomimetics.


A study on the membrane potential and pH gradient in chromatophores and intact cells of photosynthetic bacteria.
Generation of membrane potential (delta psi) and transmembrane pH difference (delta pH) was studied in PPi-energized chromatophores of Rhodospirillum rubrum by means of measurements of carotenoid and bacteriochlorophyll absorption changes, atebrin and 8-anilinonaphthalene-1-sulphonate fluorescence responses, and phenyldicarbaundecaborane transport. The data obtained are consistent with the suggestion that carotenoid, bacteriochlorophyll and phenyldicarbaundecaborane responses are indicators of delta psi, while an atebrin response is an indicator of delta pH. The fluorescence of 8-anilinonaphthalene-1-sulphonate is affected both by delta psi and delta pH.


Encountering Chronic Sore Throat: How Challenging is it for the Otolaryngologists?
Objective To explore and diagnose the underlying causes of chronic, recalcitrant sore throat. Methodology In this descriptive, cross-sectional study spanning 3 years (January 2014-December 2016), 1580 patients with chronic sore throat (>12 weeks duration, despite conventional medication) were evaluated for the possible cause(s) in a tertiary care teaching institute of eastern India, through proper history, appropriate investigations, and a self-designed algorithm. Results The common causes for chronic sore throat were chronic tonsillopharyngitis, gastroesophageal reflux disorder, submandibular sialadenitis, and laryngopharyngeal reflux disorder, respectively. Allergy, psychiatric illnesses, oral submucous fibrosis, systemic comorbidities (diabetes mellitus, hypothyroidism, uremia, arthritides), stylalgia, Koch's pneumonitis, recurrent aphthous ulcers, and dietary deficiencies formed the other major causes. There was a minimal female preponderance, the female: male ratio being 1.25. About 39% patients were chronic smokers, and 31% addicted to alcohol. Forty-three (2.72%) patients were reactive to HIV 1/2. Conclusion The study provided with a detailed account of the heterogeneous etiology of chronic sore throat, and an overall structured idea on how to approach to its work-up and diagnosis. Proper history taking and appropriate structured investigations are the keys. Chronic tonsillopharyngitis, gastroesophageal reflux disorder, submandibular sialadenitis, and laryngopharyngeal reflux disorder were the chief causes of chronic sore throat.


Import of rat liver mitochondrial malate dehydrogenase. Synthesis, transport, and processing in vitro of its precursor.
Rat liver total RNA was translated in a reticulocyte lysate, and the precursor of rat liver mitochondrial malate dehydrogenase was identified by a monospecific antibody against the denatured mature enzyme. The precursor is about Mr = 1500 to 2000 larger than the monomeric form of the mature protein. The major spots of the two-dimensional peptide map of the two proteins were identical. The precursor was synthesized on free polysomes, but not membrane-bound polysomes. Upon fractionation by molecular sieve chromatography on Sephadex G-100, the size of the precursor was slightly larger than the dimeric form of the mature protein. Incubation of the precursor with isolated mitochondria from Chinese hamster ovary cells resulted in uptake and processing of the precursor to the mature size. The processed form was resistant to trypsin indicating that it was translocated into mitochondria. Processing was complete in 10 to 30 min at 30 degrees C. Rapid binding of the precursor to mitochondria was also observed at 0 or 30 degrees C. Processing but not binding was inhibited by an uncoupler.


Evaluation of interaction between Piriformospora indica, animal manure and NPK fertilizer on quantitative and qualitative yield and absorption of elements in sunflower.
Microbial endophytes are considered as one of the most important soil microorganisms which increase their yield per unit area by generating genetic, physiological, and ecological changes in their host plants. We conducted an experiment as factorial in a completely randomized manner with three replications at the Ghasre Shirin greenhouse of Kermanshah province in order to evaluate the interaction of Piriformospora indica (inoculation-noninoculation) with manure (25% of the flowerpot volume-without using manure as a control) and NPK chemical fertilizer (10 g per flowerpot-without the use of fertilizer as a control), the quantitative and qualitative yield and absorption of elements in sunflower. The results showed that the interaction of P. indica, manure, and chemical fertilizer on the colonization percentage, seed oil percentage, nitrogen concentration, phosphorus concentration, and the 1000-seed weight was significant at 1% probability level, and on yield index, growth, plant height, and concentration of potassium element it was at 5% probability level. Bilateral effects of P. indica with chemical fertilizer and the manure treated with chemical fertilizer on the budding time were significant at the probability level of 1% and 5%, respectively. It seems that the coexistence between sunflower root and P. indica increases the growth of the root system of the plant; thereby it increases the height of plant because of the absorption of essential elements such as nitrogen, phosphorus, and potassium by the root, and increases the quantitative and qualitative yield of sunflower.


Sulfur functionality-modified starches: Review of synthesis strategies, properties, and applications.
Starch is the second most abundant naturally-occurring polymer after cellulose that possess superior physicochemical and biological features with numerous practical applications ranging from industrial to biomedical. Despite, native starch suffer from some drawbacks, including difficult processability, low shear and thermal stability, weak mechanical properties, and tendency to easily retrograde and undergo syneresis. Therefore, modification of native starch is necessary for circumvent the above-mentioned problems and expanding application ranges. This natural polymer can be modified using chemical, physical, enzymatic, and genetic engineering strategies. Amongst, chemical approaches have received more attention owing to enhancing physicochemical and biological features that lead to higher performance than those of the other strategies. In this context, incorporation of sulfur functionality-containing groups (sulfonation and sulfation) can be considered as an efficient approach due to significant enhancement in physiochemical properties, including zeta potential (move to negative values), molecular weight, processiability (e.g., solubility and meltability), and rheology. Furthermore, this strategy can modified some biological features, such as hemocompatibility, protein sorption, biostability, adhesion and proliferation of numerous cells, antithrombogenicity, antiinflammatory, antiviral, antimicrobial, antioxidant, antifungal, anticoagulant and antifouling properties. Accordingly, this review highlight's the synthesis strategies, physiochemical and biological properties, as well as applications of sulfur functionality-modified starches in numerous practical fields.


Monocyte chemoattractant protein production in red cell incompatibility.
Mononuclear phagocytes play a central role in hemolytic transfusion reactions by erythrophagocytosis and production of inflammatory mediators. Factors that affect the number or function of monocyters would be expected to alter the clinical course of hemolytic transfusion reactions, and thus the production of monocyte chemoattractant protein-1 (MCP-1), a recently described chemotactic and activating cytokine specific for monocytes, was investigated in two distinct settings of red cell (RBC) incompatibility. Fresh heparinized whole blood was incubated with ABO-compatible or -incompatible RBCs. Isolated peripheral blood mononuclear cells were incubated with anti-D-coated or uncoated RBCs. MCP-1 was measured in the plasma or culture medium by enzyme-linked immunosorbent assay. MCP-1 gene expression was detected by Northern blot analysis of buffy coat or mononuclear cell total RNA. Significant levels of MCP-1 protein in plasma or medium were detected 24 hours after the addition of incompatible RBCs, but not in the first 6 hours. Nonimmune hemolysis of added RBCs did not stimulate MCP-1 production. The inactivation of complement by heat treatment of plasma prior to the addition of RBCs to whole blood did not prevent MCP-1 production. Nor did neutralizing antibodies to tumor necrosis factor prevent MCP-1 production in ABO incompatibility. MCP-1 production was associated with increased steady-state levels of white cell MCP-1 mRNA, which occurred more rapidly in ABO than Rh incompatibility. The monocyte-specific chemotactic cytokine MCP-1 is produced by peripheral blood leukocytes in response to RBC incompatibility. MCP-1 may act in a positive feedback loop to recruit and activate monocytes during hemolytic transfusion reactions, thus contributing to the maintenance of these reactions.


A novel dataset on a culture of cooperation and inclusive political institutions in 90 European historical regions observed between 1000 and 1600.
A culture of cooperation, which is the implicit reward from cooperating in any prisoner's dilemma and investment types of activity, and inclusive political institutions, which enable the citizenry to better select public-spirited representatives and check their decisions, are key for economic development. To foster research on the determinants and impact of these institutions, we illustrate a novel data set employed in [1] and [4] and gathering a measure of the activity of the Cistercians and the Franciscans, which is a proxy for the citizens' culture, and a constraints on the elite's decision-making power score, which is a proxy for the inclusiveness of political institutions, for a panel of 90 European historical regions spanning the 1000-1600 period.


Incidence of Huntington disease in a northeastern Spanish region: a 13-year retrospective study at tertiary care centre.
Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases. Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100,000 inhabitants per year during the period 2007-2019 in Aragon (Spain). 50 (27.9%) incident cases of HD (CAG repeat length ≥ 36) were identified from a total of 179 persons studied. The remaining 129/179 (72.1%) were HD negative (CAG repeat length < 36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 0.648 per 100,000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 9 and the most common CAG length among HD negative individuals was 16. Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.


An artificial intelligence ultrasound system's ability to distinguish benign from malignant follicular-patterned lesions.
To evaluate the application value of a generally trained artificial intelligence (AI) automatic diagnosis system in the malignancy diagnosis of follicular-patterned thyroid lesions (FPTL), including follicular thyroid carcinoma (FTC), adenomatoid hyperplasia nodule (AHN) and follicular thyroid adenoma (FTA) and compare the diagnostic performance with radiologists of different experience levels. We retrospectively reviewed 607 patients with 699 thyroid nodules that included 168 malignant nodules by using postoperative pathology as the gold standard, and compared the diagnostic performances of three radiologists (one junior, two senior) and that of AI automatic diagnosis system in malignancy diagnosis of FPTL in terms of sensitivity, specificity and accuracy, respectively. Pairwise t-test was used to evaluate the statistically significant difference. The accuracy of the AI system in malignancy diagnosis was 0.71, which was higher than the best radiologist in this study by a margin of 0.09 with a p-value of 2.08×10-5. Two radiologists had higher sensitivity (0.84 and 0.78) than that of the AI system (0.69) at the cost of having much lower specificity (0.35, 0.57 versus 0.71). One senior radiologist showed balanced sensitivity and specificity (0.62 and 0.54) but both were lower than that of the AI system. The generally trained AI automatic diagnosis system can potentially assist radiologists for distinguishing FTC from other FPTL cases that share poorly distinguishable ultrasonographical features.


Clinical significance of rapid (accelerated) gastric emptying.
The purpose of this study was to determine the significance and frequency of rapid gastric emptying (RGE) in clinical practice and to examine its relationship to age, gender, and presenting symptoms. The review included 750 patients who underwent scintigraphic gastric emptying studies (GES) within the past 11 years. In 80 patients with RGE, the mean gastric emptying time (GET) in female and male patients was compared with study gender differences. Similarly, the mean GET in young and old patients was compared with study age differences. The presenting symptoms and conditions indicating GES were noted. RGE was found in 80 of 750 study patients (10.7%). RGE was equally common in both sexes. Younger patients (mean age, 34.3 +/- 9.5 years) and older patients (mean age, 67.3 +/- 11.6 years) had similar mean GETs. Most patients with RGE presented with symptoms that mimicked gastroparesis. RGE has no relationship to age or gender. RGE may be representative of early dumping syndrome in most patients. GES help make a clear distinction between early dumping syndrome and gastroparesis, which can present with similar symptoms.


New carbon/ZnO/Li2O nanocomposites with enhanced photocatalytic activity.
Our study was focused on the synthesis of photocatalytic materials for the degradation of organic dyes based on the valorization of biomass resources. The biochar resulted from pyrolysis process of cherry pits wastes was activated by CO2 flow. Activated and inactivated carbon was used to obtain carbon-based photocatalysts impregnated with different zinc salt precursors. The activation of carbon had no significant influence on the photodegradation process. The doping procedure used Li2CO3 and Zn(CH3COO)2 of different concentrations to impregnate the biochar. The carbon-ZnO-Li2O based nanomaterials were analysed by TEM and SEM, while the presence of hexagonal wurtzite ZnO was investigated by XRD. The solid samples were analysed by PL at 360 nm excitation fixed wavelength to correlate their morphology with the optical and photocatalytic properties. The presence of Li atoms led to photocatalytic activities of the doped ZnO similar to the undoped ZnO obtained at higher concentrations of zinc acetate precursor.


Computational Analysis of a Prebiotic Amino Acid Synthesis with Reference to Extant Codon-Amino Acid Relationships.
Novel density functional theory calculations are presented regarding a mechanism for prebiotic amino acid synthesis from alpha-keto acids that was suggested to happen via catalysis by dinucleotide species. Our results were analysed with comparison to the original hypothesis (Copley et al., PNAS, 2005, 102, 4442-4447). It was shown that the keto acid-dinucleotide hypothesis for possible prebiotic amino acid synthesis was plausible based on an initial computational analysis, and details of the structures for the intermediates and transition states showed that there was wide scope for interactions between the keto acid and dinucleotide moieties that could affect the free energy profiles and lead to the required proto-metabolic selectivity.


Experience Profiling of Fluorescence-Guided Surgery II: Non-Glioma Pathologies.
Only sporadic reports of fluorescence-guided surgery (FGS) have been published for non-glioma conditions. In this study, we focus on epidemiological data of fluorescence patterns and report the diverse experiences of FGS in non-gliomas. During 8.5 years between July 2010 and January 2019, 900 FGS for brain tumor performed in Seoul National University Hospital. Among them, a total of 73 histologically proven non-glioma patients were analyzed. Indications for FGS have been the possibility of anaplastic tumor in intra-axial tumors in preoperative MRI and an attempt to reproduce known anecdotal experiences of 5-Aminolevulinic Acid (5-ALA) fluorescence. In cases of brain tumors except for gliomas, the most frequent cases were brain metastasis (23 cases) followed by lymphomas (9 cases) and meningeal tumors (8 cases). And there were embryonal tumors (6 cases), hemangioblastomas (4 cases), and solitary fibrous tumor/hemangiopericytomas (3 cases). Most brain metastases, meningiomas, primary central nervous system lymphomas, and treatment effect cases showed positive fluorescence. Moreover, some non-tumorous conditions also showed positive fluorescence. However, hemangioblastoma and germ cell tumor did not observe any fluorescence at all. 5-ALA induced fluorescence is not limited to glioma but is also evident in non-glioma and non-neoplastic conditions. This 5-ALA-induced fluorescence may be used as an intraoperative tool for various brain conditions.


Coping when a child has a disability: exploring the impact of parent-to-parent support.
To explore the impact of parent-to-parent support when a child is born with a disability. The research approach was qualitative. Data were collected retrospectively and were derived from in-depth interviews with parents. The audio-taped interviews were transcribed and then analysed using constant comparative procedures. Scotland. The parents of 63 children born with a congenital upper limb deficiency. The early weeks and months following the birth of their baby was a difficult and emotional time for most parents. Feelings of isolation were common and there was a lot of concern about what the future would hold. Although a certain amount of support was derived from contact with family, friends and health professionals, parents did not generally obtain the level of support that was required from these sources. Contact with other parents of limb-deficient children, however, clearly exerted a powerful stress-buffering influence, providing much needed emotional, social and practical support. This study suggests that parents of children with special needs are uniquely qualified to help each other. The challenge is to ensure that health professionals are aware of the potential benefits of parent-to-parent support and provide parents with information about appropriate local organizations/ contacts.


Random effects inducing heart pathological dynamics: An approach based on mathematical models.
This work deals with an investigation of randomness effects on heart rhythm analysis. A mathematical model composed by three-coupled nonlinear oscillators coupled by time-delayed connections is employed for this aim. In this regard, heart rhythm is governed by delayed-differential equations. Nondeterministic aspects are incorporated considering random connections among oscillators. The main idea is to show that nonlinearities and randomness define together the great variety of possibilities in the heart dynamical system. In general, results corroborate that the model is able to capture the main behaviors of the cardiac system showing that pathological behaviors can evolve from normal rhythms due to random couplings. Experimental data corroborate this argues pointing that nonlinear dynamical analysis is useful for a proper physiological comprehension.


Galectin-1 is implicated in the protein kinase C epsilon/vimentin-controlled trafficking of integrin-beta1 in glioblastoma cells.
Cell motility and resistance to apoptosis characterize glioblastoma (GBM) growth and malignancy. In our current work we report that galectin-1, a homodimeric adhesion molecule and carbohydrate-binding protein with affinity for beta-galactosides, is linked with cell surface expression of integrin beta1 and the process of integrin trafficking. Using immunofluorescence, depletion of galectin-1 through both stable knockdown and transient-targeted small interfering RNA (siRNA) treatment induces an intracellular accumulation of integrin-beta1 coincident with a diminution of integrin-beta1 at points of cellular adhesion at the cell membrane. Galectin-1 depletion does not alter the gene expression level of integrin-beta1. Transient galectin-1 depletion effectuates as well the perinuclear accumulation of protein kinase C epsilon (PKCepsilon) and the intermediate filament vimentin, both of which have been shown to mediate integrin recycling in motile cells. Our results argue for the involvement of galectin-1 in the PKCepsilon/vimentin-controlled trafficking of integrin-beta1. The understanding of molecular mediators such as galectin-1 and the pathways through which they drive the cell invasion so descriptive of GBM is anticipated to reveal potential therapeutic targets that promote glioma malignancy.


Predictors of restenosis after implantation of 2.5 mm stents in small coronary arteries.
The results of stent implantation for small coronary disease have been inconclusive. The purpose of the present study was to evaluate the factors in predicting the risk of angiographic restenosis after 2.5-mm stent implantation for small coronary arteries. The study group comprised 134 consecutive patients who had a reference small coronary artery with diameter from 1.8 mm to 2.5 mm on quantitative coronary angiography and who had been successfully treated by stent implantation with a 2.5-mm stent. Of the 134 patients, 55 had angiographic restenosis (41%). The rate of target lesion revascularization was 32%. Diabetes mellitus, acute coronary syndrome, lesion length, bifurcation lesion, lower left ventricular ejection fraction (LVEF), stent strut, stent/artery ratio, and stent length were identified as predictors of restenosis by univariate analysis. Subsequent multivariate analysis revealed that lower LVEF (odds ratio (OR) 3.37, p=0.01), bifurcation lesion (OR 2.47, p=0.04), thicker stent strut (OR 2.30, p=0.04), and longer stent length (OR 1.05, p=0.02) were significant predictors of restenosis. Two pre-interventional factors (reduced left ventricular function and bifurcated lesion) and 2 procedure-related factors (thickness of stent strut and total stent length) were identified as predictors of restenosis. These factors should be taken into account when deciding on the percutaneous coronary intervention strategy for small coronary artery disease.


Developmental Changes in Coarticulation Degree Relate to Differences in Articulatory Patterns: An Empirically Grounded Modeling Approach.
Coarticulatory effects in speech vary across development, but the sources of this variation remain unclear. This study investigated whether developmental differences in intrasyllabic coarticulation degree could be explained by differences in children's articulatory patterns compared to adults. To address this question, we first compared the tongue configurations of 3- to 7-year-old German children to those of adults. The observed developmental differences were then examined through simulations with Task Dynamics Application, a Task Dynamics simulation system, to establish which articulatory modifications could best reproduce the empirical results. To generate syllables simulating the lack of tongue gesture differentiation, we tested three simulation scenarios. We found that younger speakers use less differentiated articulatory patterns to achieve alveolar constrictions than adults. The simulations corresponding to undifferentiated control of tongue tip and tongue body resulted in (a) tongue shapes similar to those observed in natural speech and (b) higher degrees of intrasyllabic coarticulation in children when compared to adults. Results provide evidence that differences in articulatory patterns contribute to developmental differences in coarticulation degree. This study further shows that empirically informed modeling can advance our understanding of changes in coarticulatory patterns across age.


Current outcomes and predictors of treatment failure in patients with surgical site infection after elective colorectal surgery. A multicentre prospective cohort study.
To determine current outcomes and predictors of treatment failure among patients with surgical site infection (SSI) after colorectal surgery. A multicentre observational prospective cohort study of adults undergoing elective colorectal surgery in 10 Spanish hospitals (2011-2014). Treatment failure was defined as persistence of signs/symptoms of SSI or death at 30 days post-surgery. Of 3701 patients, 669 (18.1%) developed SSI; 336 (9.1%) were organ-space infections. Among patients with organ-space SSI, 81.2% required source control: 60.4% reoperation and 20.8% percutaneous/transrectal drainage. Overall treatment failure rate was 21.7%: 9% in incisional SSIs and 34.2% in organ-space SSIs (p < 0.001). Median length of stay was 15 days (IQR 9-22) for incisional SSIs and 24 days (IQR 17-35) for organ-space SSIs (p < 0.001). One hundred and twenty-seven patients (19%) required readmission and 35 patients died (5.2%). Risk factors for treatment failure among patients with organ-space SSI were age ≥65 years (OR 1.83, 95% CI: 1.07-1.83), laparoscopy (OR 1.7, 95% CI: 1.06-2.77), and reoperation (OR 2.8, 95% CI: 1.7-4.6). Rates of SSI and treatment failure in organ-space SSI after elective colorectal surgery are notably high. Careful attention should be paid to older patients with previous laparoscopy requiring reoperation for organ-space SSI, so that treatment failure can be identified early.


Comparison of complement-dependent cytotoxic and flow-cytometry crossmatch results before cadaveric kidney transplantation.
The presence of HLA donor-specific antibodies (DSA) before kidney transplantation decreases graft survival. In this study, we compared crossmatch results of kidney transplantation candidates, for cadaveric renal donation between March 10, 2012, and September 7, 2012. The 47 kidney transplantation candidates tested for crossmatch included 10 for cadaveric donor organs. Two crossmatch methods were performed: complement-dependent cytotoxic crossmatch (CDCXM) and flow cytometry crossmatch (FCXM). Spleen cells were used as the source of lymphocytes for all crossmatch tests. The T and B cell ratios isolated from spleen were 38.8% and 34.8%, respectively. The concordance ratio of the two methods was 76.6% with 23.4% discordant results. Regarding the discordant results, 4.2% were positive CDCXM but negative FCXM; 191%, negative CDCXM but positive FCXM. All patients displaying positive crossmatches had a previous immunization history. As a result, we speculated that the positive CDCXM but negative FCXM results were due to the washing procedures in the FCXM disturbing antigen-antibody complexes. We suggest at least two different methods to be performed for crossmatch tests before kidney transplantation. CDCXM detects immunoglobulin G1 (IgG1) and IgG3, which are critical for rejection. FCXM is able to detect all IgG subgroups because of its high sensivity. As a result we suggest that both CDCXM and FCXM are preferrable strategies to detect DSAs.


Hemoglobin Richmond. Subunit dissociation and oxygen equilibrium properties.
In hemoglobin Richmond (beta102 leads to Lys), amino acid substitution has occurred at the same site as the mutation in hemoglobin Kansas (beta102 Asn leads to Thr), a variant with very low oxygen affinity. Although hemoglobin Richmond has been shown to have increased tetramer-dimer dissociation, its oxygen affinity has been inferred to be normal from studies on hemolysates of carriers. We have isolated hemoglobin Richmond and have further studied its properties. We confirm that the oxygen affinity of pure hemoglobin Richmond under conditions similar to those found in vivo is normal. However, the Bohr effect of the variant hemoglobin is markedly abnormal. Its oxygen affinity is low at high pH and high at low pH, relative to hemoglobin A. The tetramer-dimer equilibrium displays a strong pH dependence such that protons promote dissociation. A model is presented in which the structural change in hemoglobin Richmond results in low oxygen affinity, like hemoglobin Kansas. However, the close linkage between tetramer-dimer dissociation and proton concentration seen with hemoglobin Richmond results in normal oxygen affinity at intracellular pH and hemoglobin concentration, and carriers display no hematological abnormalities.


Usefulness of Leifson staining method in diagnosis of Helicobacter pylori infection.
The Leifson staining method was used to diagnose Helicobacter pylori infection and was compared to histology, culture, and the rapid urease test (RUT). Histology gave the best sensitivity (98%), compared to Leifson staining (97%), culture (92%), and RUT (85%) (P < 0.005). Leifson staining is a sensitive, rapid, economical method for diagnosis of H. pylori infection in dyspeptic patients.


Characterization of an Lyt-1+ cytolytic T-cell clone specific for a polymorphic domain of the I-Ak molecule.
We have characterized a cytolytic T-cell clone, isolated from a A.TH anti-A.TL mixed lymphocyte culture, which recognized a private determinant of the I-Ak molecule. This specificity has been confirmed by inhibition of effector-target cell interaction by anti-I-Ak monoclonal antibody (mAb). Comparison of the inhibitory capacity of various mAb and the spatial arrangement of their epitopes (defined in previous studies by antibody-binding competition) indicated that the antigenic site recognized by this cytolytic T-cell clone was topologically related to one of the major polymorphic domains of the Ak molecule. This clone expressed the Thy-1.2+, Lyt-1.+, Lyt-1.2+low and I-As- cell surface phenotype. Testing of several rat mAb, screened for their ability to inhibit H-2K/D-specific cytolysis at the level of the effector cells, revealed that two anti-p94, 180 mAb but not various anti-Lyt-2 mAb inhibited the lytic function of this anti-I-Ak T-cell clone.


Cytochrome P450 1B1 polymorphism drives cancer cell stemness and patient outcome in head-and-neck carcinoma.
Cytochrome P450 1B1 (CYP1B1) is mostly expressed in tumours and displays unusual properties. Its two polymorphic forms were differently associated with anticancer drug sensitivity. We decipher here the role of this polymorphism in anticancer drug efficacy in vitro, in vivo and in the clinical setting. From head-and-neck squamous cell carcinoma cell lines not expressing CYP1B1, we generated isogenic derivatives expressing the two forms. Proliferation, invasiveness, stem cell characteristics, sensitivity to anticancer agents and transcriptome were analysed. Tumour growth and chemosensitivity were studied in vivo. A prospective clinical trial on 121 patients with advanced head-and-neck cancers was conducted, and a validation-retrospective study was conducted. Cell lines expressing the variant form displayed high rates of in vitro proliferation and invasiveness, stemness features and resistance to DNA-damaging agents. In vivo, tumours expressing the variant CYP1B1 had higher growth rates and were markedly drug-resistant. In the clinical study, overall survival was significantly associated with the genotypes, wild-type patients presenting a longer median survival (13.5 months) than the variant patients (6.3 months) (p = 0.0166). This frequent CYP1B1 polymorphism is crucial for cancer cell proliferation, migration, resistance to chemotherapy and stemness properties, and strongly influences head-and-neck cancer patients' survival.


Is graft-versus-host disease a reliable model for scleroderma?
There are both similarities and differences between chronic graft-versus-host disease (GVHD) and scleroderma. The similarities include chronic fibrosis, immunological (autoimmune) abnormalities and perhaps mast cell involvement. The differences include the type of collagen laid down and its precise location, and the distribution of organ involvement. However, a common thread appears to be an immunologically-mediated fibrotic process, involving T cells, fibroblasts and perhaps mast cells. For this reason, we believe that important insights for scleroderma will come from the study of GVHD, in spite of the differences between the two syndromes. Indeed, it would not be expected that GVHD and scleroderma would be identical.


Relationship of cholesterolgenesis to DNA synthesis and proliferation by lens epithelial cells in culture.
Cholesterolgenesis could be important for both cell growth and DNA synthesis in many cell types. Since the ocular lens seems at least partially dependent upon biosynthesis to supply its required cholesterol, cholesterolgenesis could have a special role in control of cell proliferation and DNA synthesis in the lens. We thus examined the effects of inhibiting sterol synthesis with mevinolin upon cell proliferation, upon accumulation of DNA, sterol and protein mass and upon DNA synthesis by bovine lens epithelial cells cultured in lipoprotein-deficient media. All DNA synthesis in the ocular lens occurs in the monolayer of epithelial cells which covers the anterior surface of this organ. Concentrations of mevinolin which largely prevented synthesis and accumulation of sterol by the cultured lens epithelial cells and stopped proliferation of these cells had no effect on the cell's DNA synthesis or accumulation of DNA mass. The inhibition of proliferation by mevinolin could be completely reversed by cholesterol added to the culture media in the form of low density lipoprotein. These findings indicate that an adequate supply of cholesterol is required by lens epithelial cells to proceed through the cell cycle. Inhibition of cholesterolgenesis by the lens in vivo could have profound effects upon lens growth and development.


Caudal Septal Extension Graft Sutured with Absorbable Material and Not Fixed to the Nasal Spine Region Compared with the Conventional Fixation Method: A Retrospective Study.
The caudal septal extension graft (CSEG) is a predictable method for positioning the tip and columella during rhinoplasty, and it is commonly performed using permanent sutures and in some cases fixating the graft to the nasal spine region (NSR) (conventional method). Whether this predictability is preserved when using absorbable sutures has yet to be determined. We performed a retrospective assessment of 1146 patients who underwent rhinoplasty performed by the same surgeon using the CSEG method from 2008 through 2017 in an academic setting. We utilized a computer-based patient record system for automatic data collection comparing outcomes of two groups: a group of patients who were operated on using the conventional fixation method (2008-2011) (group 1) with a second group in which absorbable sutures were used without fixation to the NSR (2011-2017) (group 2). The average follow-up period was 33.2 months. Patients operated on using a combination of methods and patients with less than 6 months of follow-up were excluded. All cases had the same septum-to-extension graft suturing technique with either permanent or absorbable suture material. This technique was side-to-side fixation with simple interrupted stitches. Outcomes were measured in terms of reoperation rates and complication rates grouped in 10 categories. There were no statistical differences in complication or reoperation rates between group 1 and group 2 except for suture extrusion and/or foreign body reaction (3.9% and 0.2%, respectively, P < 0.0001). Tip deprojection was of rare and similar occurrence in both groups (0.9% and 0.8%, respectively, P 0.88). Suturing CSEG with absorbable material and not fixing it to the NSR is a reliable variation in the conventional technique. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Spinal cord compression in myelomatosis: response to chemotherapy alone.
Current management of spinal cord compression due to multiple myeloma usually involves irradiation with or without decompressive surgery. We report five patients (three of whom were severely affected) with a neurological deficit due to spinal cord compression by multiple myeloma, who regained ambulation and sphincter control with melphalan and prednisone alone. The dramatic response in these cases, as well as other evidence presented, suggests that systemic treatment may have a major role in the management of spinal cord compression by sensitive malignant tumours.


Does second-scale intertrial interval affect motor evoked potentials induced by single-pulse transcranial magnetic stimulation?
To determine whether a second-scale intertrial interval (ITI) of single-pulse transcranial magnetic stimulation (TMS) affects the measured amplitude of motor-evoked potentials (MEPs) representing individual corticospinal excitability. This was performed to challenge the common assumption of time invariance of such amplitudes. Navigated TMS was used to map the dominant hemisphere of nine healthy subjects for the cortical representation focus of the contralateral thenar muscle, and resting motor threshold (MT) was determined. Single-trial MEP amplitudes were analyzed from trains of 30 responses induced at an intensity of 120% of the MT, and constant ITIs were investigated at 1, 2, 3, 5, and 10 seconds as well as randomized at ranges of 1-3 seconds, 3-5 seconds, and 5-10 seconds. MEP responses were divided into three blocks of 10 consecutive responses within each stimulation train. Repeated samples ANOVA was used to assess whether the individual characteristic MEP amplitudes were time invariant, i.e., not affected by the different ITIs and stimulus blocks. The individual single-trial MEP amplitudes were affected significantly (P < 0.05) by the ITI (8/8 subjects), block number (5/8 subjects), and ITI by block number interaction (6/8 subjects). One subject was excluded as the sphericity of the variances could not be confirmed. Consequently, the found time variant nature of the individual single-trial MEP amplitudes affected the estimates (means) of individual characteristic MEP amplitudes. This was also observed as a significant block number effect (P < 0.05) across all subjects. The individual characteristic MEP amplitudes are time variant, contrary to the common assumption. Hence, individual characteristic MEP amplitude estimates should be used cautiously, as erroneous conclusions could be made when assuming those as time invariant.


Purkinje neurons: What is the signal for complex spikes?
Cerebellar Purkinje neurons generate characteristic complex spikes; but are these bursts of activity generated by somatic or dendritic excitability? A recent study may have settled this debate by giving the soma the dominant role, but it does not fully resolve the question of what information is transmitted downstream of the Purkinje cells.


Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.
Transcriptomic analysis showed that the central circadian pathway genes had significantly altered expression in fracture calluses from mice fed a low phosphate diet. This led us to hypothesize that phosphate deficiency altered the circadian cycle in peripheral tissues. Analysis of the expression of the central clock genes over a 24-36 hour period in multiple peripheral tissues including fracture callus, proximal tibia growth plate and cardiac tissues after 12 days on a low phosphate diet showed higher levels of gene expression in the hypophosphatemia groups (p < 0.001) and a 3 to 6 hour elongation of the circadian cycle. A comparative analysis of the callus tissue transcriptome genes that were differentially regulated by hypophosphatemia with published data for the genes in bone that are diurnally regulated identified 1879 genes with overlapping differential regulation, which were shown by ontology assessment to be associated with oxidative metabolism and apoptosis. Network analysis of the central circadian pathway genes linked their expression to the up regulated expression of the histone methyltransferase gene EZH2, a gene that when mutated in both humans and mice controls overall skeletal growth. These data suggest that phosphate is an essential metabolite that controls circadian function in both skeletal and non skeletal peripheral tissues and associates its levels with the overall oxidative metabolism and skeletal growth of animals.


AHPBA graduated fellows' assessments of strengths, weaknesses, opportunities and threats facing fellowship training in HPB surgery: "HPB training excellence means volume, knowledge, and mentorship".
Many fellowship programs in North America prepare surgeons for a career in Hepato-Pancreato-Biliary (HPB) surgery. Recent fellowship graduates were surveyed as part of a strengths, weaknesses, opportunities, and threats (SWOT) analysis commissioned by Americas Hepato-Pancreato-Biliary Association (AHPBA). This was a cross-sectional study surveying AHPBA-certified fellowship graduates conducted August-December 2021. Survey data were analyzed using descriptive statistics. Free-text answers were analyzed using both grounded theory principles and thematic network analyses. Four main themes were identified: (i) concerns regarding the lack of standardization between HPB fellowship curricula (ii) concern for job market oversaturation, (iii) need to emphasize the value in HPB fellowship training and (iv) importance of diversity, inclusion, and equity in HPB training. Based on themes identified, the strengths of AHPBA-certified HPB programs include superior case volume and technical training. Areas of weakness and growth opportunities include standardizing training experiences. According to AHPBA-certificate awardees, optimizing future HPB fellowships would include strong sponsorship for job placement after graduation, and more intentional investments in diversity, equity, and inclusion.


Posaconazole vs fluconazole or itraconazole for prevention of invasive fungal diseases in patients with acute myeloid leukemia or myelodysplastic syndrome: a cost-effectiveness analysis in an Asian teaching hospital.
Posaconazole is superior to fluconazole/itraconazole in preventing invasive fungal diseases (IFDs) in neutropenic patients. Whether the higher cost of posaconazole is offset by decreases in IFDs in a given institute requires cost-effective analysis encompassing the spectrum of IFDs and socioeconomic factors specific to that geographic area. This study performed a cost-effective analysis of posaconazole prophylaxis for IFDs in an Asian teaching hospital, employing decision modeling and data of IFDs and medication costs specific to the institute, in neutropenic patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). In the cost-effectiveness analysis, the higher cost of posaconazole was partially offset by a reduction in the cost of treating IFDs that were prevented, resulting in an incremental cost of 125,954 Hong Kong dollars/16,148 USD per IFD avoided. Over a lifetime horizon, assuming same case fatality rate of IFDs in both groups, use of posaconazole results in 0.07 discounted life years saved. This corresponds to an incremental cost of 116,023 HKD/14,875 USD per life year saved. This incremental cost per life year saved in posaconazole prophylaxis fulfilled the World Health Organization defined threshold for cost-effectiveness. Posaconazole prophylaxis was cost-effective in Hong Kong.


Experience of childhood sexual violence and its associations with depressive symptoms among university students in Guangdong, China.
Sexual violence, especially childhood sexual violence, is a serious social issue, yet the prevalence of childhood sexual violence among university students is unknown. We aimed to investigate the prevalence of these experiences and assess their associations with depressive symptoms. The study included 29,311 participants, mean (SD) age 20.5 (1.4) years, from a cross-sectional survey of a multi-stage stratified cluster random sample from all universities in Guangdong province of China. Data were obtained through an anonymous electronic questionnaire from December 2 to 15, 2019. Undergraduates' experiences of childhood sexual violence were self-reported. Current depressive symptoms were measured by Center for Epidemiological Studies Depression Scale (CESD-10). Stress measures in recent months were measured by the College Student Stress Scale. The prevalence of childhood sexual violence experience among university students was 4.8 % (95 % confidence interval (CI) = 4.6 %-5.0 %), 7.3 % (95 % CI = 6.9 %-7.7 %) for female students and 1.8 % (95 % CI = 1.6 %-2.0 %) for male students. Sexual violence in childhood was related to students' current depressive symptoms after adjustment for stress and socio, demographic characteristics (adjusted prevalence ratio (PRa) = 1.36, 95 % CI = 1.30-1.42). Significant differences in the association between childhood sexual violence and depressive symptoms were also found by sex. Experiences of childhood sexual violence among university students are not negligible and associated with their current depressive symptoms. The association between childhood sexual violence and depressive symptoms among female and male students is different. Schools, families, and society as a whole should be encouraged to provide education on healthy sexual behavior preventive interventions related to sexual violence for childhood students.


Combined effect of ultraviolet-B radiation and cadmium contamination on nutrient uptake and photosynthetic pigments in Brassica campestris L. seedlings.
Environmental and industrial pollution along with increase in ground level UV-B radiation, because of stratospheric ozone depletion, present multiple stresses, which may affect crop photosynthesis and productivity. The present study was undertaken to see interactive effects of heavy metal contamination (Cd(2+)) and UV-B exposure on essential nutrient (Ca(2+), Mg(2+), K(+)) uptake, biomass, and chlorophyll content in mustard (Brassica campestris L.) seedlings. Plants grown in 0.5, 1.0, 2.5, and 5.0 mg L(-1) Cd(2+) supplemented medium were exposed to UV-B for 30 min (0.4 mW cm(-2)) per day. The interactive effect of two stresses measured after 5 and 10 days showed an overall decline in biomass. Under dual stress (5 mg Cd(2+) L(-1)) significant (P < 0.001) decrease in chlorophyll a (43%), chlorophyll b (23%), and carotenoid (53%) was observed. Ca(2+) uptake was reduced by 51% in roots under high doses of Cd(2+) (5 mg L(-1)) and simultaneous exposure to 0.4 mW cm(-2) UV-B for 10 days. Mg(2+) content was reduced by 48% and K(+) by 62% under similar exposure conditions. Decline in nutrient uptake in Brassica campestris L. seedlings was observed both in root and shoot leaf in the initial growth period under controlled lab conditions. Cadmium ion (Cd(2+)) uptake was significantly enhanced by 33% (P < 0.001) in the presence of UV-B. The findings are significant as multiple stress conditions prevalent in the environment play an important role during the early growth period, a period critical for crop yield.


Schistosoma japonicum: heterogeneity in paramyosin genes.
Paramyosin is an integral muscle protein found in many invertebrates including schistosomes, and is considered an important candidate vaccine antigen in schistosomiasis. The characterisation of natural molecular variation in vaccine antigens including paramyosin is important because strain-specific vaccination may be necessary against schistosomiasis japonica. We have isolated partial cDNAs encoding paramyosin from an adult, Chinese strain Schistosoma japonicum gene library. Two of these cDNAs (B6 and Y6) encode the same region of paramyosin but their nucleotide sequences differ at eight positions and their deduced amino acid sequences differ by an arginine/cysteine substitution, demonstrating intrastrain variation in paramyosin. Southern blot analysis of genomic DNA from the Chinese and Philippine strains of S. japonicum demonstrated strain-related RFLPs at the paramyosin locus, and suggested that more than one copy of the paramyosin gene was present in the S. japonicum genome. PCR-based RFLP analysis which exploited restriction site differences between B6 and Y6 showed that paramyosin genotype B6 was much more common in schistosome populations and verified the existence of introns in the paramyosin gene(s) of S. japonicum.


Transition-metal nanoparticles in imidazolium ionic liquids: recyclable catalysts for biphasic hydrogenation reactions.
1-n-Butyl-3-methylimidazolium hexafluorophosphate room-temperature ionic liquid is not only suitable as a medium for the preparation and stabilization of iridium nanoparticles but also ideal for the generation of recyclable biphasic catalytic systems for hydrogenation reactions. Thus, Ir(0) nanoparticles with a mean diameter of 2 nm have been prepared by reduction of Ir(I) dissolved in the ionic liquid with H2. This catalytic solution can be reused several times for the biphasic hydrogenation of olefins under mild reaction conditions.


Validation of the Abbreviated Westmead Post-traumatic Amnesia Scale: a brief measure to identify acute cognitive impairment in mild traumatic brain injury.
To validate the use of the Abbreviated Westmead Post-traumatic Amnesia Scale (A-WPTAS) in the assessment of acute cognitive impairment in mild traumatic brain injury (mTBI). Data previously collected from 82 mTBI and 88 control participants using the Revised Westmead Post-traumatic Amnesia Scale (R-WPTAS) was converted to A-WPTAS scores and pass/fail classifications were calculated for both scales. The proportion of failures on the R-WPTAS and the A-WPTAS did not differ and a similar number of mTBIs were classified on each. For mTBIs the relationship between the independent memory test and a pass/fail classification was the same for both scales. Bivariate logistic regressions revealed that mTBIs, relative to controls, were around 8 times more likely to fail the assessment (R-WPTAS: 95% CI: 3.70-18.87; A-WPTAS: 95% CI: 3.70-20.14). As verbal learning improved the likelihood of failure was reduced. Greater education was associated with a decreased likelihood of failure. The relationship between education and a fail performance was not sustained when education was adjusted for the effect of age, prior mTBI, blood alcohol level, injury status, verbal learning, and morphine administration. The A-WPTAS is a valid measure. The A-WPTAS may reduce the risk of failing to classify patients with mTBI by identifying and documenting acute cognitive impairment.


Probing the geometric constraints of RNA binding via dynamic covalent chemistry.
Dynamic Combinatorial Chemistry (DCC) has proven to be a reliable method for identifying hit compounds for target nucleic acid (DNA and RNA) sequences. Typically, these hit compounds are subjected to a lengthy process of optimization via traditional medicinal chemistry. Here, we examine the potential of DCC to also generate and test variations on a hit compound as a method for probing the binding site of an RNA-targeted compound. Specifically, we demonstrate that addition of linker dithiols to a disulfide library containing a known binder to the HIV-1 frameshift-stimulatory RNA (a critical regulator of the HIV life cycle) can yield a mixture of new bridged structures incorporating the dithiol, depending on dithiol structure. Equilibration of this library with the HIV FSS RNA resulted in selection of the original disulfide in preference to bridged structures, suggesting incorporation of the bridge is not compatible with this particular binding site. Application of this strategy to other RNA targets should allow for rapidly profiling the affinity of modified compounds.


T3-mediated expression of PGC-1alpha via a far upstream located thyroid hormone response element.
Thyroid hormone (T3) has a profound influence on normal development, differentiation and metabolism. T3 induces complex gene expression patterns raises the question of how these expression patterns might be regulated. Since the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) induces very similar cellular energy metabolic pathways, we investigated the molecular mechanism of T3 regulation of PGC-1alpha. PGC-1alpha is rapidly regulated by T3, both in vivo and in cell culture. Transient transfection experiments demonstrated binding of the thyroid hormone receptor (TR) to a response element located at -4kb upstream of the transcriptional start site within the PGC-1alpha gene. Introducing of a single copy of the -4kb TRE in a heterologous promoter context is sufficient to maintain T3 responsiveness. Chromatin immunoprecipitation analysis revealed increased histone acetylation upon stimulation of T3. Finally, TR binds the -4kb TRE in electrophoretic mobility shift assays, identifying PGC-1alpha as a direct target of TR action. Since T3 directly regulates PGC-1alpha and PGC-1alpha coactivates liganded TR, we suggest an autoregulatory feed-forward loop of PGC-1alpha activation upon T3 treatment.


DEER experiments reveal fundamental differences between calmodulin complexes with IQ and MARCKS peptides in solution.
Calmodulin (CaM) is a calcium-binding protein that regulates the function of many proteins by indirectly conferring Ca2+ sensitivity, and it undergoes a large conformational change on partners' binding. We compared the solution binding mode of the target peptides MARCKS and IQ by double electron-electron resonance (DEER) distance measurements and paramagnetic NMR. We combined nitroxide and Gd(III) spin labels, including specific substitution of one of the Ca2+ ions in the CaM mutant N60D by a Gd(III) ion. The binding of MARCKS to holo-CaM resulted neither in a closed conformation nor in a unique relative orientation between the two CaM domains, in contrast with the crystal structure. Binding of IQ to holo-CaM did generate a closed conformation. Using elastic network modeling and 12 distance restraints obtained from multiple holo-CaM/IQ DEER data, we derived a model of the solution structure, which is in reasonable agreement with the crystal structure.


Attributions of survival and methods of coping of long-term ovarian cancer survivors: a qualitative study.
Only 8-23% of advanced epithelial ovarian cancer patients survive for 10 years or longer. Given the need for targeted interventions to improve survival, we interviewed this relatively rare survivor population to gain personalized insights into the reasons for their survival. The aim of this study was to characterize subjective attributions of survival and specific coping mechanisms long-term survivors of ovarian cancer. Twenty-two semi-structured, qualitative interviews assessing survival attributions and coping strategies were conducted from April to November 2014. Data were analyzed in a multistep process using ATLAS.ti.8: codes were identified during review of the transcripts and refined with literature review; the frequency of codes and code co-occurrence was calculated, and codes were grouped into themes. Resulting themes were checked by a national leader of an ovarian cancer advocacy organization and compared against available literature. Thematic analysis found that participants credited their long-term survival to a variety of factors including medical, social, religious/spiritual, and lifestyle/personal characteristics. Some participants rejected these same attributions, concluding that the reason for survival was due to luck or unknowable. Several of Carver et al.'s theoretical dimensions of coping were evident in our sample: planning, positive reinterpretation, social support, religion and acceptance whereas three relatively new strategies were uncovered: conserving emotional energy, value-based activity coping, and self-care. Long-term survivors' perspectives were largely consistent with those of newly diagnosed ovarian cancer patients and ovarian cancer survivors of shorter duration. However, the long-term survivors were also willing to reject conventional attributions for survival and recognized the importance of disciplined self-preservational coping strategies.


Communicating by Catcalling: Power Dynamics and Communicative Motivations in Street Harassment.
To understand the frequencies and communicative motivations of men engaging in street harassment, men's tolerance of sexual harassment, and the relationship between power and street harassment experiences for both men and women using the frameworks of dyadic power theory and feminist theories, we surveyed 348 undergraduate participants at a university in the Pacific United States. Results indicated that men who believe they have lower power than women were the most likely to report engaging in street harassment. Results also indicated a positive relationship between men's reported tolerance for sexual harassment and men's reports of engaging in street harassment.


Breast cancer in southern Brazil: association with past dietary intake.
To determine possible associations between the risk of breast cancer in Brazilian women and demographic, social and economical variables, and past dietary intake. A case-control study was conducted in Joinville, Santa Catarina, Brazil, between june and november 2003 involving a group of 33 women recently diagnosed with breast cancer and a control group of 33 healthy women volunteers. Personal details, health history and past dietary intake were obtained via questionnaires and interviews. Data between groups were compared using chi2, Fisher, and Student's t test, whilst associations were evaluated using a non-conditional logistic regression method and odds ratio (OR). Statistically significant differences between the two groups were revealed with respect to age distribution (P = 0.007), family income level (P = 0.02), educational level (P < 0.0001) and attainment of menopause (P < 0.0001). After adjustment, with regard to family income level, of the data concerning past dietary intake, the consumption of pig lard (OR = 6.32) and fatty red meat (OR = 3.48) were found to be associated with an increase in the risk of breast cancer. The regular ingestion of apples (OR = 0.30), watermelons (OR = 0.31), tomatoes (OR = 0.16), plain cakes (OR = 0.30) and desserts (OR = 0.20) afforded some degree of protection against the development of the disease. Age (> 45 years), low family income (< $520/month), poor educational level (primary school level or lower) and past regular consumption of pork fat and fatty meat may be factors associated with an increased risk of breast cancer.


Referred pain elicited by manual exploration of the lateral rectus muscle in chronic tension-type headache.
To analyze the presence of referred pain elicited by manual examination of the lateral rectus muscle in patients with chronic tension-type headache (CTTH). A case-control blinded study. It has been found previously that the manual examination of the superior oblique muscle can elicit referred pain to the head in some patients with migraine or tension-type headache. However, a referred pain from other extraocular muscles has not been investigated. Fifteen patients with CTTH and 15 healthy subjects without headache history were included. A blinded assessor performed a manual examination focused on the search for myofascial trigger points (TrPs) in the right and left lateral rectus muscles. TrP diagnosis was made when there was referred pain evoked by maintained pressure on the lateral corner of the orbit (anatomical projection of the lateral rectus muscle) for 20 seconds, and increased referred pain while the subject maintained a medial gaze on the corresponding side (active stretching of the muscle) for 15 seconds. On each side, a 10-point numerical pain rate scale was used to assess the intensity of referred pain at both stages of the examination. Ten patients with CTTH (66.6%) had referred pain that satisfied TrPs diagnostic criteria, while only one healthy control (0.07%) reported referred pain upon the examination of the lateral rectus muscles (P < 0.001). The elicited referred pain was perceived as a deep ache located at the supraorbital region or the homolateral forehead. Pain was evoked on both sides in all subjects with TrPs, with no difference in pain intensity between the right and the left. The average pain intensity was significantly greater in the patient group (P < 0.001). All CTTH patients with referred pain recognized it as the frontal pain that they usually experienced during their headache attacks, which was consistent with active TrPs. In some patients with CTTH, the manual examination of lateral rectus muscle TrPs elicits a referred pain that extends to the supraorbital region or the homolateral forehead. Nociceptive inputs from the extraocular muscles may sustain the activation of trigeminal neuron, thus sensitizing central pain pathways and exacerbating headache.


The timing of mentally represented actions.
The performance of subjects walking blindly to previously inspected visual targets (located at 5, 10 or 15 m from the subjects) was studied in 2 experiments. In Expt. 1, subjects selected as good visual imagers were instructed to build up a mental representation of the target. Then they had to either actually walk or imagine themselves walking to the target. Walking time was measured in both the actual and the mental performance. It was found that subjects took almost exactly the same time in the two conditions. Accuracy of these subjects was also measured in the actual walking task. They were found to make no direction errors and to slightly overshoot target location. Subjects from another, control, group, who received no instructions about visual imagery made much larger errors. In Expt. 2, actual and mental walking times were measured in the same subjects as in Expt. 1, while they carried a 25-kg weight on their shoulders. In this condition, actual walking time was the same as in Expt. 1, although mental walking time was found to increase systematically by about 30%. These results are discussed in terms of the neural parameters encoded in the motor program for actually executing or mentally performing an action.


SMILE: Cost-sensitive multi-task learning for nuclear segmentation and classification with imbalanced annotations.
High throughput nuclear segmentation and classification of whole slide images (WSIs) is crucial to biological analysis, clinical diagnosis and precision medicine. With the advances of CNN algorithms and the continuously growing datasets, considerable progress has been made in nuclear segmentation and classification. However, few works consider how to reasonably deal with nuclear heterogeneity in the following two aspects: imbalanced data distribution and diversified morphology characteristics. The minority classes might be dominated by the majority classes due to the imbalanced data distribution and the diversified morphology characteristics may lead to fragile segmentation results. In this study, a cost-Sensitive MultI-task LEarning (SMILE) framework is conducted to tackle the data heterogeneity problem. Based on the most popular multi-task learning backbone in nuclei segmentation and classification, we propose a multi-task correlation attention (MTCA) to perform feature interaction of multiple high relevant tasks to learn better feature representation. A cost-sensitive learning strategy is proposed to solve the imbalanced data distribution by increasing the penalization for the error classification of the minority classes. Furthermore, we propose a novel post-processing step based on the coarse-to-fine marker-controlled watershed scheme to alleviate fragile segmentation when nuclei are with large size and unclear contour. Extensive experiments show that the proposed method achieves state-of-the-art performances on CoNSeP and MoNuSAC 2020 datasets. The code is available at: https://github.com/panxipeng/nuclear_segandcls.


Aurora-A kinase phosphorylation of Aurora-A kinase interacting protein (AIP) and stabilization of the enzyme-substrate complex.
Aurora-A is an oncogenic kinase that plays essential roles in mitosis as well as cell survival. Aurora-A interacting protein (AIP) was identified as a negative regulator of Aurora-A with its ectopic over expression inducing destabilization of Aurora-A protein. Here we present evidence that in human cells, contrary to the earlier report, AIP functions in stabilizing rather than destabilizing Aurora-A. Furthermore, AIP is phosphorylated on Serine 70 by Aurora-A but not Aurora-B and expression of phosphorylation mimic mutant of AIP results in prolonged protein stability compared to unphosphorylatable mutant. We observed that when co-expressed with AIP, protein levels of both Aurora-A and Aurora-B are markedly elevated regardless of their kinase activities and phosphorylation state of AIP. Interaction of Aurora kinases with AIP is necessary for this elevated stability. This phenomenon is commonly detected in several human cancer cell lines used in this study. Depletion of AIP by RNA interference decreased Aurora-A but not Aurora-B in two of the three cell lines analyzed, indicating that under physiological condition, AIP functions in stabilization of Aurora-A but not Aurora-B, though this regulation may be dependent on additional factors as well. Further, AIP siRNA induced cell cycle arrest at G2/M, which is consistent with anticipated loss of function of Aurora-A in these cells. Thus, our study provides the first evidence of a role for AIP in G2/M cell cycle progression by cooperatively regulating protein stabilization of its up-stream regulator, Aurora-A kinase through protein-protein interaction as well as protein phosphorylation.