bluuebunny/crossref_metadata_2025 huggingface dataset:
Undergraduate Laboratory Exercises Specific to Food Spoilage Microbiology
Authors: Snyder Abigail B. , Worobo Randy W. , Orta‐Ramirez Alicia
Published: June 2016

Food spoilage has an enormous economic impact, and microbial food spoilage plays a significant role in food waste and loss; subsequently, an equally significant portion of undergraduate food microbiology instruction should be dedicated to spoilage microbiology. Here, we describe a set of undergraduate microbiology laboratory exercises that focus specifically on food spoilage which were taught in 2 lab periods as part of the undergraduate food microbiology lab curriculum at Cornell University. The lab was broken down into 3 exercises. Two exercises lead students to determine the likely source of contamination in a canned salsa through (exercise 1a) plating and observation of colony morphology and (exercise 1b) determination of the thermal resistance for those isolates. The final exercise (2) involved detection of the spoilage bacterium Alicyclobacillus in apple juice. Spoiled juice demonstrations were also prepared in this exercise for students to observe sensorial changes resulting from spoilage, emphasizing that spoilage is not always visually detectable. Students were able to successfully determine the source of contamination based on the results of their laboratory findings, which they used to make recommendations for production to reduce microbial food spoilage in the canned salsa product. Based on student answers to discussion questions provided following lab exercises, participants were able to (a) identify the significance of microbial spoilage and how spoilage is principally different from food safety, (b) describe varying sensorial changes associated with microbial spoilage, and (c) employ methods and analysis to evaluate sources and type of contamination. Downloadable handouts and stepwise instructions are available as supporting information.
Phosphate Removal During Long Nocturnal Hemodialysis/Hemodiafiltration: A Study With Total Dialysate Collection
Authors: Zupančič Tina , Ponikvar Rafael , Gubenšek Jakob , Buturović‐Ponikvar Jadranka
Published: June 2016

The aim of our prospective study was to quantify phosphate removal during long nocturnal high‐flux hemodialysis or hemodiafiltration (HD) with total dialysate collection. Eight patients (two women) were studied for the first‐in‐the‐week HD session that lasted 7–8 h. Total dialysate was collected. Serum and collected dialysate phosphate concentrations were measured every hour. Phosphate removal as assessed from the serum concentration was most important during the first 2 h of HD, and then a plateau was reached. The highest average phosphate concentration in the total dialysate was in the 1st hour, thereafter the concentration decreased but remained stable. The average total removed mass of phosphate quantified from hourly collected dialysate was 5195.7 ± 1898 mg. Phosphate had been removed in a consistent manner during the whole duration of nocturnal HD as assessed through dialysate (despite stable serum phosphate concentration). This could indicate phosphate transfer from intracellular space. The total removed phosphate quantified from the total dialysate collection was higher than previously reported and exceeded the normal phosphate food intake.
Chronic Hemodialysis in Small Children
Authors: Novljan Gregor , Rus Rina R , Premru Vladimir , Ponikvar Rafael , Battelino Nina
Published: June 2016

When peritoneal dialysis is inapplicable, chronic hemodialysis (HD) becomes the only available treatment option in small children. Due to small patient size, central venous catheters (CVC) are mainly used for vascular access. Over the past 4 years, four children weighing less than 15 kg received chronic HD in our unit. A total of 848 dialysis sessions were performed. Altogether, 21 catheters were inserted. In all but one occasion, uncuffed catheters were used. Catheter revision was performed 15 times during the study period, either due to infection or catheter malfunction. The median number of catheter revisions and the median line survival was 3.0/patient‐year and 53 days (range; 6–373 days), respectively. There were 14 episodes of catheter related infections requiring 11 CVC revisions (78.6%). The median rate of line infections was 2.8/patient‐year. Chronic HD in small children is demanding and labor intensive. Issues pertain mainly to CVCs and limit its long‐term use.
End‐Stage Renal Disease in an Infant With Hajdu‐Cheney Syndrome
Authors: Battelino Nina , Writzl Karin , Bratanič Nevenka , Irving Melita D , Novljan Gregor
Published: June 2016

Hajdu‐Cheney syndrome (HJCYS) is a rare, autosomal dominant, skeletal disorder caused by mutations in the NOTCH2 signaling pathway for which genetic testing has recently become available. Renal abnormalities are associated in at least 10% of cases. We present an 8‐year‐old Caucasian boy, born with multiple dysmorphic features consistent with HJCYS. Imaging of the urinary tract revealed bilateral cystic dysplastic kidneys with associated vesicoureteral reflux. Renal function has been impaired since birth and deteriorated progressively to end‐stage renal disease (ESRD) by the age of two and a half years, when peritoneal dialysis was initiated and only recently renal transplantation was performed. Additional congenital abnormalities and multisystem involvement in HJCYS further complicated management, and he developed refractory anemia. Molecular diagnosis was confirmed by identification of a truncating mutation in exon 34 of NOTCH2. Although, renal abnormalities are considered an integral part of the HJCYS, published reports on ESRD are scarce. In those few published cases, where ESRD was recognized, renal failure developed either in late adolescence or adulthood. This is the first report of early ESRD occurring in a child. Patients with HJCYS may need chronic renal replacement therapy even in early childhood. The management of these children can be challenging given the multisystemic manifestations of HJCYS.
Effects of the Polysaccharide from the Sporophyll of Brown Alga Undaria Pinnatifida on Serum Lipid Profile and Fat Tissue Accumulation in Rats Fed a High‐Fat Diet
Authors: Kim Byoung‐Mok , Park Jae‐Ho , Kim Dong‐Soo , Kim Young‐Myung , Jun Joon‐Young , Jeong In‐Hak , Chi Young‐Min
Published: June 2016

We investigated the effects of the polysaccharide from the sporophyll of a selected brown alga Undaria pinnatifida on serum lipid profile, fat tissue accumulation, and gastrointestinal transit time in rats fed a high‐fat diet. The algal polysaccharide (AP) was prepared by the treatment of multiple cellulase‐producing fungi Trichoderma reesei and obtained from the sporophyll with a yield of 38.7% (dry basis). The AP was mostly composed of alginate and fucoidan (up to 89%) in a ratio of 3.75:1. The AP was added to the high‐fat diet in concentrations of 0.6% and 1.7% and was given to male Sprague–Dawley rats (5‐wk‐old) for 5 wk. The 1.7% AP addition notably reduced body weight gain and fat tissue accumulation, and it improved the serum lipid profile, including triglycerides, total cholesterol, and very low‐density lipoprotein‐cholesterol. The effects were associated with increased feces weight and shortened gastrointestinal transit time. In addition, the lipid peroxidation of the liver was decreased in both groups.
Efficacy of Slightly Acidic Electrolyzed Water and UV‐Ozonated Water Combination for Inactivating Escherichia Coli O157:H7 on Romaine and Iceberg Lettuce during Spray Washing Process
Authors: Pang Yu‐Hsin , Hung Yen‐Con
Published: June 2016

Spray washing is a common sanitizing method for the fresh produce industry. The purpose of this research was to investigate the antimicrobial effect of spraying slightly acidic electrolyzed water (SAEW) and a combination of ozonated water with ultraviolet (UV) in reducing Escherichia coli O157:H7 on romaine and iceberg lettuces. Both romaine and iceberg lettuces were spot inoculated with 100 μL of a 3 strain mixture of E. coli O157:H7 to achieve an inoculum of 6 log CFU/g on lettuce. A strong antimicrobial effect was observed for the UV‐ozonated water combination, which reduced the population of E. coli by 5 log CFU/g of E. coli O157:H7 on both lettuces. SAEW achieved about 5 log CFU/g reductions in the bacterial counts on romaine lettuce. However, less than 2.5 log CFU/g in the population of E. coli O157:H7 was reduced on iceberg lettuce. The difference may be due to bacteria aggregation near and within stomata for iceberg lettuce but not for romaine lettuce. The UV light treatment may stimulate the opening of the stomata for the UV‐ozonated water treatment and hence achieve better bacterial inactivation than the SAEW treatment for iceberg lettuce. Our results demonstrated that the combined treatment of SAEW and UV‐ozonated water in the spray washing process could more effectively reduce E. coli O157:H7 on lettuce, which in turn may help reduce incidences of E. coli O157:H7 outbreaks.
An East Asian subgroup analysis of PROCLAIM, a phase III trial of pemetrexed and cisplatin or etoposide and cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non–small cell lung cancer
Authors: Wang Luhua , Wu Yi‐Long , Lu Shun , Deng Lei , Ahn Myung‐Ju , Hsu Feng‐Ming , Iscoe Neill , Hossain Anwar , Puri Tarun , Zhang Pinghai , Orlando Mauro
Published: June 2016

Aim

PROCLAIM, a phase III trial of patients with nonsquamous non–small cell lung cancer comparing concurrent pemetrexed‐cisplatin and thoracic radiation therapy followed by consolidation pemetrexed, did not meet its primary endpoint of superior overall survival versus etoposide‐cisplatin and thoracic radiation therapy followed by a consolidation platinum doublet of choice. The results from an East Asian subgroup analysis are presented here.

Methods

A subgroup analysis was performed for all patients randomized from China (n = 61), Taiwan (n = 25), and Korea (n = 11).

Results

Baseline characteristics were balanced between treatment arms for East Asian patients. In the 97 randomized East Asian patients, median overall survival was 26.8 months for the pemetrexed‐cisplatin arm and 36.3 months for the etoposide‐cisplatin arm (hazard ratio: 1.23; 95% confidence interval: 0.70–2.14; P = 0.469). Median progression‐free survival was 10.0 months for the pemetrexed‐cisplatin arm and 7.6 months for the etoposide‐cisplatin arm (hazard ratio: 0.97; 95% confidence interval: 0.61–1.54; P = 0.890). The objective response rate was 47.7% in the pemetrexed‐cisplatin arm and 34.0% in the etoposide‐cisplatin arm (P = 0.167). In the 90 treated East Asian patients, the overall incidence of drug‐related grade 3–4 treatment‐emergent adverse events was significantly lower in the pemetrexed‐cisplatin arm versus the etoposide‐cisplatin arm (61.4% vs 91.3%; P = 0.001).

Conclusion

For East Asian patients, pemetrexed‐cisplatin combined with thoracic radiation therapy, followed by consolidation pemetrexed, did not improve overall survival but did have a good safety profile with a trend for improved progression‐free survival and objective response rate compared to standard chemoradiotherapy for stage III unresectable nonsquamous non–small cell lung cancer.
Yield of adenomas and colorectal cancers within 5 years of a negative colonoscopy: are the guidelines guiding?
Authors: Tee Chin Li , Stephensen Bree , Sloss Andrew , Grieve David A.
Published: June 2016

Background

Screening for colorectal cancers outside the recommended guidelines presents a considerable burden to resource management in many public hospitals. The aim of this study is to evaluate the frequency, indications and outcomes for repeat colonoscopy performed within 5 years of a negative colonoscopy.

Methods

A retrospective review of all colonoscopies at Nambour Hospital in 2008 was performed to identify those with a negative colonoscopy. The charts of patients undergoing repeat colonoscopy at the same institution within 5 years of a negative colonoscopy were examined further, and data obtained regarding indications and outcomes of subsequent colonoscopies.

Results

A total of 616 colonoscopies were identified, 427 (69.3%) were negative for adenoma and carcinoma. Of these patients, 74 (17.3%) underwent a repeat colonoscopy at Nambour Hospital within 5 years. Eighteen out of 74 (24.3%) were outside guideline recommendation. Overall, one patient (1.4%) had cancer and 11 patients (14.9%) had polyps detected at repeat colonoscopy. Most of the polyps detected had low‐risk features and were detected in the fourth and fifth years of the study period.

Conclusion

The yield of a second colonoscopy within 5 years of a good‐quality negative colonoscopy is low but not zero. In the absence of new concerning symptoms or other risk factors, patients can be reassured and guidelines adhered to.
Liver fibrosis and fatty liver in Asian HIV‐infected patients
Authors: Lui G. , Wong V. W.‐S. , Wong G. L.‐H. , Chu W. C.‐W. , Wong C.‐K. , Yung I. M. H. , Wong R. Y. K. , Yeung S.‐L. , Yeung D. K.‐W. , Cheung C. S. K. , Chan H.‐Y. , Chan H. L.‐Y. , Lee N.
Published: June 2016

Background

Little is known about the importance of liver fibrosis and fatty liver in HIV‐monoinfected individuals without hepatitis virus co‐infection, particularly among the Asian population.

Aim

To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV‐monoinfected individuals.

Methods

Eighty asymptomatic HIV‐monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV‐uninfected healthy controls. Transient elastography and proton‐magnetic resonance spectroscopy (1H‐MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin‐18).

Results

All HIV‐infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4–13 years) were stable on anti‐retrovirals (PI‐based 58.7%, NNRTI‐based 25.0% integrase‐inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1–6.2) kPa vs. 4.2 (IQR 3.6–5.0) kPa, P < 0.001], and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29–12.41, P = 0.016). HIV‐infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected.

Conclusions

HIV‐monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV‐related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.
Toward a Comprehensive Understanding of the Factors Underlying Multiracial Person Perception
Authors: Chen Jacqueline M. , Norman Jasmine B.
Published: June 2016

Young and colleagues’ recent article substantially contributes to the understanding of multiracial perception generally and in the context of affirmative action. Their introduction of socioeconomic status as a relevant factor in the perception of Latino‐White biracials highlights our need for additional research identifying which target characteristics and perceiver motives influence the perception of multiracials and under what conditions these relationships occur. We outline how future research can incorporate and expand on Young et al.’s work to better understand multiracial person perception and specify the most appropriate contexts in which these findings could be applied by practitioners.
Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma
Authors: Lee Lydia , Bounds Danton , Paterson Jennifer , Herledan Gaelle , Sully Katherine , Seestaller‐Wehr Laura M. , Fieles William E. , Tunstead James , McCahon Lee , Germaschewski Fiona M. , Mayes Patrick A , Craigen Jenny L. , Rodriguez‐Justo Manuel , Yong Kwee L.
Published: June 2016

B‐cell maturation antigen (BCMA, also termed TNFRSF17) is an attractive therapeutic target due to its restricted expression on normal and malignant plasma cells (PC). GSK2857916 (or J6M0‐MMAF) is a BCMA‐specific antibody conjugated to the microtubule‐disrupting agent monomethyl auristatin F (MMAF) via a protease‐resistant linker. To evaluate the clinical potential of this agent, tumour cells from seventy multiple myeloma (MM) patients were assessed for BCMA expression by immunohistochemistry and flow cytometry. All patients tested expressed BCMA, at varying levels, and both surface and intracellular expression were observed. BCMA expression is maintained through relapse, extramedullary spread and in residual disease post therapy. BCMA levels may also be prognostically useful as higher levels of BCMA were associated with poorer outcomes, even taking into account genetic risk. We observed rapid internalization of surface BCMA and newly expressed protein by 1 h, suggesting a mechanism for J6M0‐MMAF activity even with low surface antigen. J6M0‐MMAF mediated cytotoxicity of MM cells varied with dose and antigen levels, with clonogenic progenitors killed at lower doses than mature cells. In comparison, J6M0‐MMAF killing of primary CD138+ myeloma cells occurred with slower kinetics. Our observations support BCMA to be a promising therapeutic target in MM for novel therapies such as J6M0‐MMAF.
Stains of the Past: Space, Memory, and Postdictatorship in Luis Fernando Veríssimo'sA mancha
Authors: RAJCA ANDREW C.
Published: June 2016

This article examines the relationship between space, memory, and the effects of Brazil's military dictatorship (1964–1985) presented in Luis Fernando Veríssimo's 2004 short story, A mancha (‘The Stain’). Although simple in structure, the narrative touches upon complex themes in postdictatorship: engaging with past trauma and political differences that cut across family relationships, conflicting notions of betrayal, the urban processes associated with capitalism, and the commodification of memory itself. I argue that the ‘stain’ traced in A mancha goes beyond the normalised rhetoric of postdictatorial memory, as the narrative both maintains and traces marginalised subjectivities of postdictatorship through its engagement with material and discursive spatial production in Brazil.
Long non‐coding RNA ROR promotes proliferation, migration and chemoresistance of nasopharyngeal carcinoma
Authors: Li Li , Gu Miao , You Bo , Shi Si , Shan Ying , Bao Lili , You Yiwen
Published: June 2016

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies of the head and neck. It arises from the nasopharynx epithelium and is associated with high morbidity and mortality. Long non‐coding RNA (lncRNA) have been reported to regulate gene interaction and play critical roles in carcinogenesis and progression. LncRNA‐ROR, a recently identified lncRNA, has been shown to be involved in initiation, progression and metastasis of several tumors, including hepatocellular carcinoma, breast cancer and glioma. However, whether lncRNA‐ROR is associated with the progression of NPC remains unknown. Resistance to radiotherapy and chemotherapy is the primary cause of NPC patients’ death. In this study, we found that lncRNA‐ROR was significantly upregulated in NPC tissues compared with normal tissues. Next, our study proved that lncRNA‐ROR was highly associated with the proliferation, metastasis and apoptosis of NPC. The enrichment of lncRNA‐ROR played a critucal functional role in chemoresistance. The mechanism by which NPC resists chemotherapy might be that lncRNA‐ROR suppress p53 signal pathway. Taken together, these data suggested that lncRNA‐ROR played an important role in the progression of NPC; thereby it might become a therapeutic target and reduce chemoresistance for NPC.
Characteristics of young adults of Belarus with post‐Chernobyl papillary thyroid carcinoma: a long‐term follow‐up of patients with early exposure to radiation at the 30th anniversary of the accident
Authors: Fridman Mikhail , Lam Alfred King‐yin , Krasko Olga
Published: June 2016

Objectives

Studies of thyroid cancer related to the Chernobyl accident have focused on children as they are the most vulnerable group with the highest risk of developing radiation‐associated cancer. In contrast, our research aimed to look at the clinical and pathological features of patients with post‐Chernobyl papillary thyroid carcinoma that were 2 years old or less at the time of the Chernobyl accident.

Design

The study subjects were patients (n = 359) aged 0 to 2 at the time of the Chernobyl accident and aged ≥19 years at presentation/surgery who were treated in Belarus for papillary thyroid carcinoma during the period 2003–2013.

Results

In conventional or oncocytic variant of papillary thyroid carcinoma, the prevalence of extra‐thyroidal extension, nodal disease, infiltrative growth or lymphatic vessel invasion was above 50%. These features were less pronounced when compared to tall cell or diffuse sclerosing variants of papillary thyroid carcinoma. The highest frequency of central lymph node metastases was found in patients aged 1–2 years at exposure (P = 0·004). Subjects exposed in utero were characterized by absent/insignificant lymphocytic infiltration around the carcinoma (P = 0·025), predominance of conventional papillary architecture and an association with lymphocytic thyroiditis.

Conclusions

A number of features were associated with this group of patients that were very young at the time of radiation exposure. In addition, the incidence and basic characteristics of adult papillary thyroid carcinoma varied depending on the types of exposure conditions.
Materials in the vitreous during cataract surgery: nature and incidence, with two cases of histological confirmation
Authors: Kam Andrew W , Chen Tony S , Wang Sarah B , Jain Neeranjali S , Goh Aaron YJ , Douglas Christopher P , McKelvie Penny A , Agar Ashish , Osher Robert H , Francis Ian C
Published: June 2016

Background

To identify and classify materials in the vitreous observed during phacoemulsification cataract surgery (phaco).

Design

Prospective, consecutive, observational case series at one ophthalmic day surgery in Sydney, Australia.

Participants

A total of 767 consecutive phaco cases. Cases were excluded if there was posterior capsule rupture or vitreous loss intraoperatively.

Methods

For each patient, age, gender, baseline corrected distance visual acuity, presence of pseudoexfoliation, nuclear sclerosis grade and phacoemulsification ultrasound time were recorded. The relationship between these variables and materials in the vitreous was evaluated with regression analysis. Two patients with materials in the vitreous developed an acute intraoperative rock‐hard eye syndrome. In these two patients, pars plana needle aspiration of retrolenticular fluid was performed to re‐establish normal intraocular pressure. Histology was undertaken to compare this fluid with known lens material retrieved from the Fluid Management System bags in two unrelated cases.

Main Outcome Measurements

Presence of materials in the vitreous during phaco.

Results

Materials in the vitreous were observed in either Berger's space or the anterior vitreous in 386 eyes (50.3% of cases); the majority was putatively lens material (46.5% of all cases). Pigment and ophthalmic viscoelastic device were seen in the anterior vitreous in 9.8% and 1.7% of cases, respectively. Logistic regression analysis demonstrated that higher nuclear sclerosis grade (P = 0.025), male gender (P = 0.003) and greater age (P = 0.016) were predictive of the presence of materials in the vitreous. Histological assessment with light microscopy and birefringence techniques identified the materials in the vitreous as lens material.

Conclusion

Materials in the vitreous were seen in 50.3% of phaco cases. It has been histologically demonstrated that lens materials can be introduced into the anterior vitreous during phaco.
Effects of past and present livestock grazing on herpetofauna in a landscape‐scale experiment
Authors: Kay Geoffrey M. , Mortelliti Alessio , Tulloch Ayesha , Barton Philip , Florance Daniel , Cunningham Saul A. , Lindenmayer David B.
Published: June 2016

Livestock grazing is the most widespread land use on Earth and can have negative effects on biodiversity. Yet, many of the mechanisms by which grazing leads to changes in biodiversity remain unresolved. One reason is that conventional grazing studies often target broad treatments rather than specific parameters of grazing (e.g., intensity, duration, and frequency) or fail to account for historical grazing effects. We conducted a landscape‐scale replicated grazing experiment (15,000 km2, 97 sites) to examine the impact of past grazing management and current grazing regimes (intensity, duration, and frequency) on a community of ground‐dwelling herpetofauna (39 species). We analyzed community variables (species richness and composition) for all species and built multiseason patch‐occupancy models to predict local colonization and extinction for the 7 most abundant species. Past grazing practices did not influence community richness but did affect community composition and patch colonization and extinction for 4 of 7 species. Present grazing parameters did not influence community richness or composition, but 6 of the 7 target species were affected by at least one grazing parameter. Grazing frequency had the most consistent influence, positively affecting 3 of 7 species (increased colonization or decreased extinction). Past grazing practice affected community composition and population dynamics in some species in different ways, which suggests that conservation planners should examine the different grazing histories of an area. Species responded differently to specific current grazing practices; thus, incentive programs that apply a diversity of approaches rather than focusing on a change such as reduced grazing intensity should be considered. Based on our findings, we suggest that determining fine‐scale grazing attributes is essential for advancing grazing as a conservation strategy.
miRNA‐34a promotes proliferation of human pulmonary artery smooth muscle cells by targeting PDGFRA
Authors: Wang Peng , Xu Jie , Hou Zhiling , Wang Fangfang , Song Yingli , Wang Jiao , Zhu Hui , Jin Hongbo
Published: June 2016

Objectives

Pulmonary arterial hypertension (PAH) is a fast progressing vascular disease characterized by uncontrolled cell proliferation of pulmonary artery smooth muscle cells (PASMCs). Some studies have suggested that PAH and cancers share an apoptosis‐resistant state, featuring excessive cell proliferation. The miR‐34 family consists of tumour‐suppressive miRNAs, and its reduced expression has been reported in numerous cancers; however, its role in hypoxia‐induced PAH has not been previously studied.

Materials and methods

miR‐34 family expression was evaluated in a rat model with hypoxia and in cultured hypoxic PASMCs, using real‐time quantitative PCR (RT‐qPCR). Function of miR‐34 family was assessed by transfecting miR‐34 mimics and inhibitors. Dual luciferase reporter gene assays, RT‐qPCR and Western blotting were performed to validate target genes of miR‐34.

Results

Significant down‐regulation of miR‐34a in hypoxic lung tissue, pulmonary artery and PASMCs was identified and then effects of miR‐34a in modulating cell proliferation in human pulmonary artery smooth muscle cells (hPASMCs) was investigated in vitro. Reduction of miR‐34a levels in hPASMCs caused increased proliferation and these effects were reversed by overexpression of miR‐34a. miR‐34a overexpression down‐regulated platelet‐derived growth factor receptor alpha (PDGFRA) expression, which is a key factor in PAH development. These results suggest that miR‐34a is a potential regulator of proliferation in PASMCs, and that it could be used as a novel treatment strategy in PAH.
Leucocyte‐bound apolipoprotein B in the circulation is inversely associated with the presence of clinical and subclinical atherosclerosis
Authors: de Vries Marijke A. , Klop Boudewijn , van der Meulen Noëlle , van de Geijn Gert‐Jan M. , Prinzen Lenneke , van der Zwan Ellen , Birnie Erwin , Cohen Tervaert Jan W. , Liem Anho H. , de Herder Wouter W. , Castro Cabezas Manuel
Published: June 2016

Background

Atherosclerosis is a pro‐inflammatory condition, in which leucocyte activation plays an important role. The interaction between circulating leucocytes and apolipoprotein (apo) B‐containing lipoproteins results in pro‐inflammatory changes of these cells. We aimed to evaluate the relationship between apo B bound to circulating leucocytes and atherosclerosis.

Methods

Apo B on circulating leucocytes was measured by flow cytometry in subjects with and without cardiovascular disease (CVD), expressed as mean fluorescent intensity in arbitrary units (au). Carotid intima–media thickness (cIMT) was measured using B‐mode ultrasound. Data are given as median (interquartile range).

Results

A total of 396 subjects were included, of whom 183 had a history of CVD. Compared to subjects without CVD, patients with CVD had lower apo B bound to neutrophils (12·7 au (9·8–16·2) and 14·2 au (10·1–17·5), respectively, P = 0·038) and to monocytes (2·5 au (1·7–3·1) and 2·7 (1·9–3·6) au, respectively, P = 0·025). No differences were found for lymphocyte‐bound apo B. Neutrophil‐ and monocyte‐bound apo B were inversely correlated with cIMT (Spearman's rho: −0·123, P = 0·017 and −0·108, P = 0·035, respectively). Both monocyte‐ and neutrophil‐bound apo B were inversely associated with different factors related to the metabolic syndrome, such as body mass index, triglycerides and complement C3. There was a positive association between erythrocyte‐bound apo B and apo B bound to each of the leucocyte classes, possibly reflecting a similar mechanism. Discontinuation of statins in 54 subjects did not influence leucocyte‐bound apo B.

Conclusion

Unexpectedly, the presence of noninternalized apo B‐containing lipoproteins on circulating neutrophil and monocyte membranes may represent a protective mechanism against atherosclerosis.
Expression of possible targets for new proteasome inhibitors in diffuse large B‐cell lymphoma
Authors: Delforoush Maryam , Berglund Mattias , Edqvist Per‐Henrik , Sundström Christer , Gullbo Joachim , Enblad Gunilla
Published: June 2016

Objectives

Investigating expression of possible targets for proteasome inhibitors in patients with diffuse large B‐cell lymphoma (DLBCL) and correlating the findings to clinical parameters and outcome.

Methods

Tumour material from 92 patients with DLBCL treated with either R‐CHOP like (n = 69) or CHOP like (n = 23) regimens were stained for possible targets of proteasome inhibitors.

Results

The primary target molecule of bortezomib, proteasome subunit beta, type 5 (PSMB5), was not detected in the tumour cells in any of the cases but showed an abundant expression in cells in the microenvironment. However, the deubiquitinases (DUBs) of the proteasome, the ubiquitin carboxyl‐terminal hydrolase L5 (UCHL5) and the ubiquitin specific peptidase 14 (USP14), were detected in the cytoplasm of the tumour cells in 77% and 74% of the cases, respectively. The adhesion regulating molecule 1 (ADRM1) was detected in 98% of the cases. There was no correlation between the expression of any of the studied markers and clinical outcome or GC/non‐GC phenotype.

Conclusions

We suggest that UCHL5 and/or USP14 should be further evaluated as new targets for proteasome inhibitors in DLBCL. The lack of expression of PSMB5 on the tumour cells might provide an explanation of the relatively poor results of bortezomib in DLBCL.
Review of the genus Eumonopyta (Lepidoptera: Yponomeutidae) with descriptions of two new species
Authors: Sohn Jae‐Cheon
Published: June 2016

The yponomeutid genus Eumonopyta is reviewed by examination of the type species, E. unicornis, from Japan and Taiwan and descriptions of two new congeners, E. tucki from India and E. viridigigas from Thailand. Eumonopyta unicornis is first reported from Taiwan. The previously proposed diagnostic characters for Eumonopyta are re‐evaluated. The female genitalia of Eumonopyta are described for the first time, based on E. unicornis and E. viridigigas. Photographs of imagoes and genitalia, if available, are provided for all three species of Eumonopyta.
Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology
Authors: Ahmed A. Razzaque , Carrozzo Marco , Caux Frédéric , Cirillo Nicola , Dmochowski Marian , Alonso Agustín España , Gniadecki Robert , Hertl Michael , López‐Zabalza Maria J. , Lotti Roberta , Pincelli Carlo , Pittelkow Mark , Schmidt Enno , Sinha Animesh A. , Sprecher Eli , Grando Sergei A.
Published: June 2016

This viewpoint highlights major, partly controversial concepts about the pathogenesis of pemphigus. The monopathogenic theory explains intra‐epidermal blistering through the “desmoglein (Dsg) compensation” hypothesis, according to which an antibody‐dependent disabling of Dsg 1‐ and/or Dsg 3‐mediated cell–cell attachments of keratinocytes (KCs) is sufficient to disrupt epidermal integrity and cause blistering. The multipathogenic theory explains intra‐epidermal blistering through the “multiple hit” hypothesis stating that a simultaneous and synchronized inactivation of the physiological mechanisms regulating and/or mediating intercellular adhesion of KCs is necessary to disrupt epidermal integrity. The major premise for a multipathogenic theory is that a single type of autoantibody induces only reversible changes, so that affected KCs can recover due to a self‐repair. The damage, however, becomes irreversible when the salvage pathway and/or other cell functions are altered by a partnering autoantibody and/or other pathogenic factors. Future studies are needed to (i) corroborate these findings, (ii) characterize in detail patient populations with non‐Dsg‐specific autoantibodies, and (iii) determine the extent of the contribution of non‐Dsg antibodies in disease pathophysiology.
Microscale decoupling of sediment oxygen consumption and microbial biomass in an oligotrophic lake
Authors: Jeske Jan Torsten , Müller Roger A. , Wendeberg Annelie , Bertilsson Stefan
Published: June 2016

Sediments of aquatic ecosystems are hotspots for biological activity. Here, we address the question if, within surface sediments, oxygen consumption is linearly related to cell abundance. In addition, we identify habitat‐specific factors influencing underlying microbial processes.

Sediment microcosms were established from three sites within oligotrophic Lake Ånnsjön, Sweden, to use microsensors for measuring oxygen profiles and estimate spatially resolved oxygen consumption rates at the water–sediment interfaces. To evaluate differences between habitats, we measured sediment carbon content and C : N : P as a proxy for diagenetic state and organic matter bioavailability. Epifluorescence microscopy was used to assess the microscale distribution and size of surface‐colonising microorganisms.

There was no linear correlation between oxygen consumption rates and microbial cell abundances. Cell‐specific respiration rates were highest in the profundal compared to the littoral‐ and inflow‐sediment microcosms, whereas vertical variability in all these parameters was highest at the inflow, intermediate in the littoral and least variable in profundal sediments.

Illumina sequencing of spatially resolved 16SrRNA genes was used to test for possible influence of bacterial diversity on spatially resolved oxygen consumption rates. Bacterial α‐diversity decreased over depth at each site, but was also lower in sediments from the most active profundal zones of the lake compared to the inflow.

We suggest that bacteria in profundal sediments mainly use highly oxidised organic compounds, resulting in overall low growth yield despite high metabolic activity. In the lake inflow and the littoral, more reduced organic substrates of terrestrial origin are used at lower rates but with higher yield.
Prevalence and prognostic influence of bacterial pyuria in elderly patients with pneumonia: A retrospective study
Authors: Oka Hiroaki , Komiya Kosaku , Ohama Minoru , Kawano Yoshiyuki , Uchida Masahiro , Miyajima Hajime , Iwashita Tomohiko , Okabe Eiji , Kawamura Tadao , Yasuda Kazuhiro , Matsumoto Taisuke , Kadota Jun‐ichi
Published: June 2016

Aim

The number of elderly patients with pneumonia is significantly increasing as the populations in many countries age. Although elderly patients with pneumonia are at risk of developing urinary tract infections, no studies have examined the prevalence or the prognostic impact of this complication. The aim of the present study was to investigate the prevalence of comorbid bacterial pyuria and the impact on the prognosis of elderly patients with pneumonia.

Methods

We retrospectively evaluated 132 patients aged >65 years who were hospitalized for pneumonia and who underwent a urinary sediment test on admission. The background characteristics, laboratory results and treatment regimens were documented, and the risk factors for the complication of bacterial pyuria and its association with 90‐day mortality in pneumonia patients were elucidated.

Results

A total of 37 (28%) of 132 patients were complicated by bacterial pyuria. The patients with bacterial pyuria were more often women, showed a poorer performance status, were more frequently fed by percutaneous endoscopic gastrostomy, and more frequently used diapers and/or a bladder catheter. Regarding first‐line drugs, 82.6% of the patients received beta‐lactamase inhibitors and extended‐spectrum penicillins. The use of a bladder catheter and a poor performance status were associated with bacterial pyuria. A multivariate analysis showed that a poor performance status was the only factor associated with 90‐day mortality.

Conclusions

Bacterial pyuria did not affect the prognosis of patients who were treated with penicillin‐based regimens. Thus, broad‐spectrum antibiotics are not necessarily required for elderly patients with pneumonia complicated by urinary tract infection. Geriatr Gerontol Int 2017; 17: 1076–1080.
The use of enhanced half‐life coagulation factor concentrates in routine clinical practice: guidance from UKHCDO
Authors: Collins P. , Chalmers E. , Chowdary P. , Keeling D. , Mathias M. , O'Donnell J. , Pasi K. J. , Rangarajan S. , Thomas A.
Published: June 2016

Enhanced half‐life factor VIII and IX products are being introduced into routine clinical practice. Published data report on clinical trials and there are limited data available on how to use these products in routine clinical practice. Many patients, for example, those with a past history of an inhibitor, have been excluded from clinical trials and there are limited data published on children. This guidance document is a consensus statement from the UK Haemophilia Centres Doctors' Organisation and aims to give pragmatic advice on the use of these products in routine practice.
Ordinary risks and accepted fictions: how contrasting and competing priorities work in risk assessment and mental health care planning
Authors: Coffey Michael , Cohen Rachel , Faulkner Alison , Hannigan Ben , Simpson Alan , Barlow Sally
Published: June 2016

Background

Communication and information sharing are considered crucial to recovery‐focused mental health services. Effective mental health care planning and coordination includes assessment and management of risk and safety.

Objective

Using data from our cross‐national mixed‐method study of care planning and coordination, we examined what patients, family members and workers say about risk assessment and management and explored the contents of care plans.

Design

Thematic analysis of qualitative research interviews (n = 117) with patients, family members and workers, across four English and two Welsh National Health Service sites. Care plans were reviewed (n = 33) using a structured template.

Findings

Participants have contrasting priorities in relation to risk. Patients see benefit in discussions about risk, but cast the process as a worker priority that may lead to loss of liberty. Relationships with workers are key to family members and patients; however, worker claims of involving people in the care planning process do not extend to risk assessment and management procedures for fear of causing upset. Workers locate risk as coming from the person rather than social or environmental factors, are risk averse and appear to prioritize the procedural aspects of assessment.

Conclusions

Despite limitations, risk assessment is treated as legitimate work by professionals. Risk assessment practice operates as a type of fiction in which poor predictive ability and fear of consequences are accepted in the interests of normative certainty by all parties. As a consequence, risk adverse options are encouraged by workers and patients steered away from opportunities for ordinary risks thereby hindering the mobilization of their strengths and abilities.
Serum amyloid A immunohistochemical staining patterns in hepatitis
Authors: Piotti Kathryn C , Yantiss Rhonda K , Chen Zhengming , Jessurun Jose
Published: June 2016

Aims

Serum amyloid A is an acute phase reactant that is produced by hepatocytes in response to either inflammatory or neoplastic conditions. Because inflammatory adenomas produce this protein, serum amyloid A immunohistochemistry has been used in the evaluation of hepatocellular neoplasms. However, studies evaluating the expression of this protein in hepatitis are lacking. The aim of this study was to perform serum amyloid A immunostains on medical liver biopsy specimens of patients with common chronic liver diseases and correlate them with disease activity and stage.

Methods and results

We performed serum amyloid A immunostains on 160 medical liver biopsies, including 100 cases of hepatitis C virus infection at different stages (20 cases of each) and 20 cases each of hepatitis B viral infection, steatohepatitis and autoimmune hepatitis. The extent and location of staining was recorded and correlated with grade, stage and laboratory values (transaminases, bilirubin and viral load). Data were analysed using the Cochran–Mantel–Haenszel χ2 test for trend. Serum amyloid A staining was present in 130 (81%) cases and was limited to zone 3 perivenular hepatocytes in 66 (41%). Biopsy specimens with less fibrosis and/or mild portal inflammation showed significantly more staining than those with cirrhosis (P < 0.001), or at least moderate inflammatory activity (P < 0.001). There was no significant association between lobular inflammation (P = 0.06), bilirubin levels or viral load and immunohistochemical staining for serum amyloid A.

Conclusions

Our results show that liver biopsy specimens with mildly active chronic hepatitis, early fibrosis and normal serum transaminases show more serum amyloid A immunopositivity compared with cases with more inflammatory activity, fibrosis or transaminitis. These findings indicate that serum amyloid A is expressed primarily in the early phases of disease and might influence progression and/or response to treatment.
Electricity saving behavior of households by making efforts, replacing appliances, and renovations: empirical analysis using a multivariate ordered probit model
Authors: Nakamura Eri
Published: June 2016

This study empirically explores the determinants of household electricity saving behavior based on a sample of Japanese households. Our study makes four contributions. First, we examine the short‐term saving action of making efforts, the medium‐term saving action of replacing appliances, and the long‐term saving action of undertaking renovations. Second, we consider not only the physical characteristics of households but also behavioral characteristics, such as their understanding of the importance of energy saving and willingness to save energy. Third, in our analysis, we assume that appliances and housing facilities have the electricity‐saving capability and service‐providing capability. While previous studies focus on the former, consumers in reality consider both capabilities. Fourth, we consider the optimization by households and include broad types of appliances and renovations. Using a multivariate ordered probit model with data on 518 Japanese households in 2012, we obtain the following results. First, in addition to the demand response, the effort level is determined by behavioral, rather than by physical characteristics. Second, the motivation behind appliance replacement is durability, rather than electricity‐saving and service‐providing capabilities. Third, appliance replacement is enhanced by an understanding of the importance of energy saving, rather than by the willingness to save energy. Households can replace appliances because of social pressure, even if they are not so concerned about saving energy. Fourth, households are willing to renovate housing facilities even though they pay a higher cost for the greater saving capability rather than for the service‐providing capability. However, such renovation is not influenced by internal incentives, but by physical aspects of the house, such as size, age, and type.
History of diapers and diapering
Authors: Krafchik Bernice
Published: June 2016

For centuries, diapering has been a global practice. Most cultures around the world have historically implemented mechanisms to cover the genital area, both for privacy and to contain waste. The latest and most important innovation was the advent of the disposable diaper in the mid‐twentieth century. Modern disposable diapers have considerably decreased the incidence of irritant diaper dermatitis through their design and construction. Disposable diaper use continues to grow globally. This article reviews the history of diaper practices worldwide.
A novel HLA‐B*40 allele, B*40:01:40, identified in a Chinese individual
Authors: Pei Y. F. , Huang H. N. , Li H. C. , Shen W. D.
Published: June 2016

A new allele, officially named B*40:01:40, was detected in a Chinese individual by sequence‐based typing (SBT). The new allele differs from B*40:01:01 by a single nucleotide exchange at position 99 in codon 9, which results in synonymous substitution and seems not to compromise the HLA complex and T‐cell receptor interaction.
Androgen receptor targeted therapies in castration‐resistant prostate cancer: Bench to clinic
Authors: Imamura Yusuke , Sadar Marianne D
Published: June 2016

The androgen receptor is a transcription factor and validated therapeutic target for prostate cancer. Androgen deprivation therapy remains the gold standard treatment, but it is not curative, and eventually the disease will return as lethal castration‐resistant prostate cancer. There have been improvements in the therapeutic landscape with new agents approved, such as abiraterone acetate, enzalutamide, sipuleucel‐T, cabazitaxel and Ra‐223, in the past 5 years. New insight into the mechanisms of resistance to treatments in advanced disease is being and has been elucidated. All current androgen receptor‐targeting therapies inhibit the growth of prostate cancer by blocking the ligand‐binding domain, where androgen binds to activate the receptor. Persuasive evidence supports the concept that constitutively active androgen receptor splice variants lacking the ligand‐binding domain are one of the resistant mechanisms underlying advanced disease. Transcriptional activity of the androgen receptor requires a functional AF‐1 region in its N‐terminal domain. Preclinical evidence proved that this domain is a druggable target to forecast a potential paradigm shift in the management of advanced prostate cancer. This review presents an overview of androgen receptor‐related mechanisms of resistance as well as novel therapeutic agents to overcome resistance that is linked to the expression of androgen receptor splice variants in castration‐resistant prostate cancer.