bluuebunny/crossref_metadata_2025 huggingface dataset:
BURIAL AND THERMAL HISTORY MODELLING OF THE MANNAR BASIN, OFFSHORE SRI LANKA
Authors: Premarathne U. , Suzuki N. , Ratnayake N. , Kularathne C.
Published: March 2016

The Mannar Basin is a Late Jurassic – Neogene rift basin located in the Gulf of Mannar between India and Sri Lanka which developed during the break‐up of Gondwana. Water depths in the Gulf of Mannar are up to about 3000 m. The stratigraphy is about 4 km thick in the north of the Mannar Basin and more than 6 km thick in the south. The occurrence of an active petroleum system in the basin was confirmed in 2011 by two natural gas discoveries following the drilling of the Dorado and Barracuda wells, located in the Sri Lankan part of the Gulf. However potential hydrocarbon source rocks have not been recorded by any of the wells so far drilled, and the petroleum system is poorly known. In this study, basin modelling techniques and measured vitrinite reflectance data were used to reconstruct the thermal and burial history of the northern part of the Mannar Basin along a 2D profile.

Bottom‐hole temperature measurements indicate that the present‐day geothermal gradient in the northern Mannar Basin is around 24.4 oC/km. Optimised present‐day heat flows in the northern part of the Mannar Basin are 30–40 mW/m2. The heat flow histories at the Pearl‐1 and Dorado‐North well locations were modelled using SIGMA‐2D software, assuming similar patterns of heat flow history. Maximum heat flows at the end of rifting (Maastrichtian) were estimated to be about 68–71 mW/m2.

Maturity modelling places the Jurassic and/or Lower Cretaceous interval in the oil and gas generation windows, and source rocks of this age therefore probably generated the thermogenic gas found at the Dorado and Barracuda wells. If the source rocks are organic‐rich and oil‐ and gas‐prone, they may have generated economic volumes of hydrocarbons.
Tannic acid activates the Kv7.4 and Kv7.3/7.5 K+ channels expressed in HEK293 cells and reduces tension in the rat mesenteric arteries
Authors: Zhang Yuanyuan , Chu Xi , Liu Ling , Zhang Nan , Guo Hui , Yang Fan , Liu Zhenyi , Dong Yongsheng , Bao Yifan , Zhang Xuan , Zhang Jianping
Published: March 2016

Objectives

This study investigated the effect of tannic acid (TA), a plant-derived hydrolyzable polyphenol, on Kv7.4 and Kv7.5 K+ channels and rat mesenteric artery.

Methods

Whole-cell patch clamp experiments were used to record the Kv7.4 and Kv7.3/7.5 K+ currents expressed in HEK293 cells; and the tension changes of mesenteric arteries isolated from rats were recorded using small vessel myography apparatus.

Key findings

Tannic acid increases the Kv7.4 and Kv7.3/7.5 K+ currents in a concentration-dependent manner (median effective concentration (EC50) = 27.3 ± 3.6 μm and EC50 = 23.1 ± 3.9 μm, respectively). In addition, 30 μm TA shifts the G–V curve of Kv7.4 and Kv7.3/7.5 K+ currents to the left by 14.18 and 25.24 mV, respectively, and prolongs the deactivation time constants by 184.44 and 154.77 ms, respectively. Moreover, TA relaxes the vascular tension of rat mesenteric arteries in a concentration-dependent manner (half inhibitory concentration (IC50) = 148.7 ± 13.4 μm).

Conclusion

These results confirms the vasodilatory effects of TA on rat mesenteric artery and the activating effects on the Kv7.4 and Kv7.3/7.5 K+ channels, which may be a mechanism to explain the vasodilatory effect and this mechanism can be used in the research of antihypertension.
A Homozygous RAB3GAP1:c.743delC Mutation in Rottweilers with Neuronal Vacuolation and Spinocerebellar Degeneration
Authors: Mhlanga‐Mutangadura T. , Johnson G.S. , Ashwini A. , Shelton G.D. , Jablonski Wennogle Sara A. , Johnson G.C. , Kuroki K. , O'Brien D.P.
Published: March 2016

Background

A variety of presumed hereditary, neurologic diseases have been reported in young Rottweilers. Overlapping ages of onset and clinical signs have made antemortem diagnosis difficult. One of these diseases, neuronal vacuolation and spinocerebellar degeneration (NVSD) shares clinical and histological features with polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV), a recently described hereditary disease in Black Russian Terriers (BRTs). Dogs with POANV harbor mutations in RAB3GAP1 which codes for a protein involved in membrane trafficking.

Hypothesis

Rottweilers with NVSD will be homozygous for the RAB3GAP1:c.743delC allele associated with POANV in BRTs.

Animals

Eight Rottweilers with NVSD confirmed at necropsy, 128 Rottweilers without early onset neurologic signs, and 468 randomly selected dogs from 169 other breeds.

Methods

Retrospective case–control study. Dogs were genotyped for the RAB3GAP1:c.743delC allele with an allelic discrimination assay.

Results

All 8 NVSD‐affected dogs were homozygous for the RAB3GAP1:c.743delC allele while the 128 NVSD‐free Rottweilers were either homozygous for the reference allele (n = 105) or heterozygous (n = 23) and the 468 genotyped dogs from other breeds were all homozygous for the reference allele.

Conclusions and Clinical Importance

The RAB3GAP1:c.743delC mutation is associated with a similar phenotype in Rottweilers and BRTs. Identification of the mutation permits a DNA test that can aid in the diagnosis of NVSD and identify carriers of the trait so that breeders can avoid producing affected dogs. Disruption of membrane trafficking could explain the neuronal vacuolation seen in NVSD and other spongiform encephalopathies.
Effects of 0.5% Timolol Maleate Ophthalmic Solution on Heart Rate and Selected Echocardiographic Indices in Apparently Healthy Cats
Authors: Gunther‐Harrington C.T. , Ontiveros E.S. , Hodge T.E. , Visser L.C. , Stern J.A.
Published: March 2016

Background

Echocardiographic assessment of diastolic function is challenging in cats, partially because of transmitral flow pattern fusion associated with high heart rates. With heart rate (HR) reduction, transmitral flow waveforms separate, allowing identification of diastolic dysfunction. Timolol, an ophthalmic, nonselective beta‐blocker used in glaucoma is safe and transiently decreases HR in clinical trials.

Hypothesis

Administration of timolol ophthalmic solution decreases HR and facilitates echocardiographic assessment of diastolic function in cats without inducing clinically relevant adverse effects.

Animals

Twenty‐five apparently healthy cats.

Methods

Electrocardiograms and echocardiograms including transmitral flow patterns were evaluated before and 20 minutes after ocular administration of 1 drop of timolol 0.5% solution. Twenty cats underwent treatment with timolol, and 5 different cats served as untreated controls to evaluate the effects of acclimation to the hospital environment on HR.

Results

Acclimation to the hospital had no effect on HR in control cats. After timolol administration, a significant median HR reduction of 25 bpm was observed (P< .0001). Timolol had no effect on E/A ratio in cats without E/A fusion (7/20,P= .44). Of the 13 cats with E and A waves that were fused before timolol application, separation of these waves was identified in 8 cats (62%) after timolol treatment. No bradyarrhythmias were noted after timolol administration, but 2 cats had first‐degree atrioventricular block. Timolol resulted in resolution of dynamic outflow tract obstruction in 6 of 6 cats.

Conclusions and clinical importance

Ocular administration of timolol safely decreases HR in cats and could facilitate assessment of diastolic function.
Characterization of equine cytochrome P450: role of CYP3A in the metabolism of diazepam
Authors: Nakayama S. M. M. , Ikenaka Y. , Hayami A. , Mizukawa H. , Darwish W. S. , Watanabe K. P. , Kawai Y. K. , Ishizuka M.
Published: March 2016

Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzyme kinetic parameters of each metabolite (temazepam [TMZ], nordiazepam [NDZ], p‐hydroxydiazepam [p‐OH‐DZP], and oxazepam [OXZ]). In both species microsomes, TMZ was the major metabolite, but the formation rate of p‐OH‐DZP was significantly less in the horse. Inhibition assays with a CYP‐specific inhibitors and antibody suggested that CYP3A was the main enzyme responsible for DZP metabolism in horse. Four recombinant equine CYP3A isoforms expressed in Cos‐7 cells showed that CYP3A96, CYP3A94, and CYP3A89 were important for TMZ formation, whereas CYP3A97 exhibited more limited activity. Phylogenetic analysis suggested diversification of CYP3As in each mammalian order. Further study is needed to elucidate functional characteristics of each equine CYP3A isoform for effective use of diazepam in horses.
Evaluation of a fibrate, specific stimulant of PPARα, as a therapeutic alternative to the treatment of clinical ovine pregnancy toxaemia
Authors: Da Silva S. , Cal‐Pereyra L. G. , Benech A. , Acosta‐Dibarrat J. , Martin M. J. , Abreu M. C. , Perini S. , González‐Montaña J. R.
Published: March 2016

Ovine pregnancy toxaemia is a metabolic disorder affecting sheep in their last 6 weeks of pregnancy as a result of their inability to maintain adequate energy homoeostasis. Different alternative treatments are available with variable results. The aim of this research was to evaluate a peroxisome proliferator‐activated receptor alpha (PPARα) stimulant as an alternative to treat clinical pregnancy toxaemia. Thirty‐three adult sheep, with known gestation date and carrying a single foetus, were fasted from day 130 of gestation until animals showed clinical disease. From that moment onwards, sheep were treated during 6 days with three different therapeutic alternatives: 10 mg/kg of 2‐methyl‐2‐phenoxy‐propionic acid; 10 mg/kg of 2‐methyl‐2‐phenoxy‐propionic acid + 100 mL of propylene glycol oral; or 100 mL of propylene glycol oral. Glycaemia and serum β‐hydroxybutyrate (BHOB) were determined daily. Liver biopsies were taken at day 130 of gestation, at the beginning and end of treatments and at 5 days postpartum, evaluating the extent and degree of the steatosis lesion. Even though in sheep treated with 2‐methyl‐2‐phenoxy‐propionic acid, serum concentrations of glucose and BHOB recovered more slowly, we conclude that 2‐methyl‐2‐phenoxy‐propionic acid alone or combined with propylene glycol can be used as an alternative to effectively treat fatty liver, and therefore pregnancy toxaemia.
Two fluoroquinolones and their combinations with hyaluronan: comparison of effects on canine chondrocyte culture
Authors: Siengdee P. , Euppayo T. , Buddhachat K. , Chomdej S. , Nganvongpanit K.
Published: March 2016

Fluoroquinolones (FQs) are frequently used for septic arthritis. Increased antibacterial activity has been associated with mammalian cell cytotoxicity that may increase the risk of developing osteoarthritis. This study compared the direct effects of two different FQs, enrofloxacin (Enro) and marbofloxacin (Mar), on normal primary canine chondrocytes and inflammatory‐stimulated chondrocytes, in addition to their administration in combination with hyaluronan (HA). Cell viability, cell apoptosis, s‐GAG production, and expression patterns of inflammatory, extracellular matrix (ECM) component and protease genes were measured. Enro co‐culturing with HA could modify s‐GAG synthesis compared with the negative control group. Co‐treatment with both FQs and HA significantly decreased cell viability and induced more total apoptotic cell death compared with the negative control and pre‐IL‐1β‐stimulated group. Enro regulated IL‐1β‐stimulated cells to overexpress IL‐1β, TNF, and MMP3, whereas Mar induced upregulation of PTGS2 and NFKB1 and enhanced the expression of ECM component genes HAS1, COL2A1, and ACAN as well as TIMP1 and MMP9. Simultaneous use of HA with Enro can effectively reduce the expression of IL‐1β, TNF, and MMP3 in pre‐IL‐1β‐stimulated chondrocytes. These results suggest the beneficial effects of HA in reducing the adverse effects of Enro treatment at the transcriptional level.
Socio‐genetic structure of short‐beaked common dolphins in southern Australia
Authors: Zanardo N. , Bilgmann K. , Parra G. J. , Möller L. M.
Published: March 2016

Delphinids show a wide range of social structures. However, studies investigating the influence of genetic relatedness and maternal kinship on school associations are limited to a small number of relatively well‐studied delphinid species. This study investigated biparental genetic relatedness and potential maternal kinship structure in schools of short‐beaked common dolphinsDelphinus delphisfrom southern Australian waters. A total of 128 biopsy samples were obtained from free‐ranging individuals within 62 schools of common dolphins. Each sample was genotyped at 13 nuclear microsatellite markers, sequenced at 438 bp of the mitochondrialDNAcontrol region, and used for genetic sexing. Pairwise analyses within and between schools showed that the average genetic relatedness between males was greater within schools than between schools. Pairs of individuals within schools were also more likely to share mtDNAhaplotypes, for both pairs of males and of females. The results suggest that both biparental relatedness and potentially maternal kinship have an impact on school associations of short‐beaked common dolphins in southern Australia, similar to social traits reported of other dolphin species inhabiting shallow coastal environments. The information provided by this study contributes to our understanding of social evolution in delphinids. It also suggests that dolphin bycatch and deaths in fisheries from this region could lead to a reduction in the genetic diversity of this population, particularly if related individuals are simultaneously killed in the nets.
Significance of mate selection and adult sex ratio in tiger reintroduction/reinforcement programs
Authors: Anuradha Reddy P. , Ramesh K. , Shekhar Sarkar M. , Srivastava A. , Bhavanishankar M. , Shivaji S.
Published: March 2016

Translocations of large carnivores like tiger to restore extirpated populations are increasingly becoming important conservation tools in the face of persistent anthropogenic pressures and relentless habitat loss. Reintroduction success in Panna Tiger Reserve, India was variously attributed to high genetic diversity, less anthropogenic disturbance and stress, efficient execution and technological integrations. Here, we establish parentage relationships and explore the potential of mate choice and appropriate adult sex ratio to explain the successful reintroduction in Panna. We used a combination of radio‐telemetry and genetic analyses to understand mating interactions of translocated tigers and their outcomes. Surprisingly, relatedness and parentage analyses of nine cubs born in 2010–2012 suggested that five cubs (55.5%) were not sired by the single translocated male tiger, emphasizing the difficulty of assessing the persistence of tiger presence over a large geographic area. Genotype data of tigers originally from Panna prior to the present reintroduced population revealed that four cubs were sired by an original Panna tiger which possibly ranged transiently within the released tigers’ home ranges. Presence of additional male for mate choice can be a strong factor for successful reintroduction of tigers in Panna. Although number of females released is a good indicator of reintroduction success, the number of males released is also a very important factor for success. We hypothesize that while tigers live in female‐dominated population structure within male territories, mate selection strategies operate strongly between sexes. Translocation programs should therefore deliberate on this aspect of mate selection and accordingly consider founder compositions to achieve desirable results. This also reinforces the need for post‐release monitoring and thorough investigations into intraspecific interactions and behavior which will facilitate proper management and revival of tiger populations.
Delta‐MELD and survival after liver transplantation: the slope matters
Authors: Colmenero Jordi , Navasa Miquel
Published: March 2016

See Article on Page 1011
Cluster analysis on the bulk elemental compositions of Antarctic stony meteorites
Authors: Miyamoto Hideaki , Niihara Takafumi , Kuritani Takeshi , Hong Peng K. , Dohm James M. , Sugita Seiji
Published: March 2016

Remote sensing observations by recent successful missions to small bodies have revealed the difficulty in classifying the materials which cover their surfaces into a conventional classification of meteorites. Although reflectance spectroscopy is a powerful tool for this purpose, it is influenced by many factors, such as space weathering, lighting conditions, and surface physical conditions (e.g., particle size and style of mixing). Thus, complementary information, such as elemental compositions, which can be obtained by X‐ray fluorescence (XRF) and gamma‐ray spectrometers (GRS), have been considered very important. However, classifying planetary materials solely based on elemental compositions has not been investigated extensively. In this study, we perform principal component and cluster analyses on 12 major and minor elements of the bulk compositions of 500 meteorites reported in the National Institute of Polar Research (NIPR), Japan database. Our unique approach, which includes using hierarchical cluster analysis, indicates that meteorites can be classified into about 10 groups purely by their bulk elemental compositions. We suggest that Si, Fe, Mg, Ca, and Na are the optimal set of elements, as this set has been used successfully to classify meteorites of the NIPR database with more than 94% accuracy. Principal components analysis indicates that elemental compositions of meteorites form eight clusters in the three‐dimensional space of the components. The three major principal components (PC1, PC2, and PC3) are interpreted as (1) degree of differentiations of the source body (i.e., primitive versus differentiated), (2) degree of thermal effects, and (3) degree of chemical fractionation, respectively.
Wealth Inequality and Economic Power: A Sequential Bargaining Analysis
Authors: Skillman Gilbert L.
Published: March 2016

This paper adapts a matching and bargaining model due to Rubinstein and Wolinsky () to analyze the connection between wealth inequality and economic power, understood as the ability to command a positive share of the net gains from given production relations. The analysis indicates that the translation of superior wealth in productive assets into economic power depends on an inverse relationship between wealth and bargaining costs at the level of individual transactions when significant exchange frictions exist and persistent capital scarcity at the level of market equilibrium as exchange frictions become small. Different interpretations of this scarcity condition are discussed.
Cryptococcal osteomyelitis: a report of 5 cases and a review of the recent literature
Authors: Medaris Leigh Ann , Ponce Brent , Hyde Zane , Delgado Dennis , Ennis David , Lapidus William , Larrison Matthew , Pappas Peter G.
Published: March 2016

Cryptococcus neoformans is a fungal pathogen associated with advanced HIV disease and other disorders associated with immune dysfunction. The pulmonary and the central nervous system are the most common manifestations of the disease. Localised osteomyelitis as the sole manifestation of extrapulmonary disease is rare. Herein, we present five cases of Cryptococcus osteomyelitis as the only manifestation of extrapulmonary disease. We also identified 84 additional cases of isolated cryptococcal osteomyelitis in the literature. Using these data, we have made some general recommendations regarding an approach to treatment of this uncommon clinical entity.
Manifestation of tranexamic acid toxicity in chronic kidney disease and kidney transplant patients: A report of four cases and review of literature
Authors: Ma Terry King‐Wing , Chow Kai Ming , Kwan Bonnie Ching‐Ha , Leung Chi Bon , Szeto Cheuk Chun , Li Philip Kam‐Tao
Published: March 2016

Aim

Tranexamic acid (TXA) is a synthetic anti‐fibrinolytic agent commonly used for the prevention and treatment of bleeding disorders. The aim of this study is to describe the clinical manifestation of TXA toxicity in chronic kidney disease (CKD) patients.

Methods

From 2005 to 2014, we encountered four CKD patients who experienced severe complications related to TXA. Clinical manifestations and outcome of these patients were recorded. We then performed a qualitative literature review of published cases of TXA toxicity in CKD patients in the PubMed database from 1 January 1972 to 31 December 2015.

Results

In our centre, two peritoneal dialysis (PD) patients developed neurotoxicity after intravenous TXA use for surgical bleeding and one PD patient developed neurotoxicity after oral TXA use for post‐polypectomy colonic bleeding. One kidney transplant recipient developed acute obstructive uropathy due to retention of blood clot at the pelvi‐ureteric junction of graft kidney after taking oral TXA for menorrhagia. Dosage of TXA was not adjusted according to renal function in all cases. All of them recovered without permanent disability after TXA was stopped. From our literature search, we identified two cases of neurotoxicity (one PD, one stage 4 CKD patient), one case of retinal toxicity in a haemolysis (HD) patient, one case of ligneous conjunctivitis in a CKD patient, and one case of toxic epidermal necrolysis in a CKD patient.

Conclusion

Neurotoxicity is a very common clinical manifestation of TXA toxicity in CKD patients. Thrombotic complication is rare. Dosage adjustment of TXA is essential in CKD patients.
Successful treatment with foscarnet for ganciclovir‐resistant cytomegalovirus infection in a kidney transplant recipient: A case report
Authors: Iwami Daiki , Ogawa Yayoi , Fujita Hiromi , Morita Ken , Sasaki Hajime , Oishi Yuichiro , Higuchi Haruka , Hatanaka Kanako , Shinohara Nobuo
Published: March 2016

Cytomegalovirus (CMV) infection is the most common infectious complication following solid organ transplantation. Ganciclovir (GCV)‐resistant CMV infection may be fatal, and is difficult to treat while avoiding allograft rejection. A 31‐year‐old woman received a second ABO‐incompatible kidney transplant, from her father. Induction therapy consisted of basiliximab and rituximab followed by maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and methylprednisolone. Her CMV serostatus was D+/R‐ at second transplant and she received prophylactic low‐dose valganciclovir (VGCV). BK polyoma virus nephropathy (BKVN) developed 7 months after transplant concurrent with CMV hepatitis and retinitis. VGCV was increased to a therapeutic dose combined with reduced immunosuppression with minimal methylprednisolone (2 mg/day) and everolimus (0.5 mg/day). However, pp65 antigenaemia continued to increase for 6 weeks. Her CMV was defined as ganciclovir (GCV)‐resistant. Foscarnet was therefore administered and her CMV disease resolved within 2 weeks. Kidney allograft dysfunction developed 9 months after transplant, and graft biopsy showed tubulointerstitial injury with crystal deposition suggesting foscarnet nephrotoxicity, with no findings of BKVN or rejection. Kidney function recovered after cessation of foscarnet and the patient had good graft function 18 months after transplant. This case demonstrates the successful use of foscarnet to treat GCV‐resistant CMV infection after ABO‐incompatible kidney transplant complicated with BKVN, without acute allograft rejection. This case further highlights the need to establish appropriate management for CMV D+/R‐ patients to avoid the acquisition of GCV‐resistant gene mutations.
Two cases of kidney transplantation‐associated thrombotic microangiopathy successfully treated with eculizumab
Authors: Ikeda Takashi , Okumi Masayoshi , Unagami Kohei , Kanzawa Taichi , Sawada Anri , Kawanishi Kunio , Omoto Kazuya , Ishida Hideki , Tanabe Kazunari
Published: March 2016

Transplantation‐associated thrombotic microangiopathy (TA‐TMA) is relatively rare and requires immediate intervention to avoid irreversible organ damage or death; however, consensus regarding the treatment approach is lacking. Atypical haemolytic uraemic syndrome (aHUS) is a rare disease caused by dysregulation of the alternative complement pathway resulting in TMA. aHUS is histologically similar to TA‐TMA; approximately 60% of TA‐TMA patients have complement dysregulation. Eculizumab, a humanized anti‐C5 monoclonal antibody, inhibits terminal membrane‐attack complex formation and TMA progression. Eculizumab has been successfully used to treat aHUS post‐transplant. We present two cases of kidney TA‐TMA due to unknown causes, suspected antibody‐mediated rejection, or calcineurin inhibitor (CNI)‐related toxicity that developed on day 1 or 2 post‐kidney transplantation. Low platelet count and haemoglobin level with red cell fragments were detected. Despite steroid pulse, plasma exchange (PE), and intravenous immunoglobulin therapy, TA‐TMA did not improve; therefore, eculizumab was administered despite no genetic testing. Laboratory data, including renal function, improved immediately. TA‐TMA treatment primarily involves PE initiation or CNI discontinuation; eculizumab can be used to safely treat TA‐TMA and then be ceased in the short term. Therefore, eculizumab administration might be beneficial for kidney TA‐TMA as early as the diagnosis of refractory to PE.
Ciliochoroidal ganglioneuroma in neurofibromatosis type 1: Report of a case and review of the literature
Authors: Abdulkader Marwah M. , Dalesandro Mark F. , Mendenhall Stephen K. , Shah Mitesh V. , Bonnin Jose M.
Published: March 2016

Orbitofacial neurofibromatosis (OFNF) is considered a variant of neurofibromatosis type 1 (NF1). OFNF most often affects the eye, orbit and one side of the face. It is characterized by the development of relatively aggressive and disfiguring lesions, including plexiform and diffuse neurofibromas. Ciliochoroidal ganglioneuromas have not been previously reported in patients with this syndrome. We report the case of a 50‐year‐old man with OFNF, ciliochoroidal ganglioneuroma and a large ipsilateral frontoethmoidal encephalocele.
Frequent globular neuronal cytoplasmic inclusions in the medial temporal region as a possible characteristic feature in multiple system atrophy with dementia
Authors: Homma Taku , Mochizuki Yoko , Komori Takashi , Isozaki Eiji
Published: March 2016

Multiple system atrophy (MSA) is an adult‐onset neurodegenerative disease, which is characterized clinically by parkinsonism, cerebellar ataxia and/or autonomic dysfunction, and pathologically by alpha‐synuclein‐related multisystem neurodegeneration, so‐called alpha‐synucleinopathy, which particularly involves the striatonigral and olivopontocerebellar systems, with glial cytoplasmic inclusions and neuronal cytoplasmic/nuclear inclusions (NCIs/NNIs). In the recent consensus criteria for the diagnosis of MSA, dementia is described as one of the features not supporting a diagnosis of MSA. However, MSA with dementia has been reported, although the location of the lesion responsible for the dementia remains unclear. In the present study, we aimed to investigate where this lesion may be found, by analyzing 12 autopsy‐proven MSA cases, with a particular focus on the medial temporal region. Three of 12 cases with MSA had dementia (MSA‐D). Compared with MSA cases without dementia, MSA‐D cases had frequent globular NCIs (G‐NCIs) in the medial temporal region, especially in their subiculum. In addition, MSA‐D cases could be divided into two types; MSA‐D with distinct fronto‐temporal lobar degeneration (FTLD type) and without distinct fronto‐temporal lobar degeneration (non‐FTLD type). There was no association between dementia and Alzheimer pathologies, such as neurofibrillary tangles and senile plaques. We suggest that frequent G‐NCIs in the medial temporal region, and particularly the subiculum, is one of the important pathological findings of MSA‐D, even when a case with MSA‐D reveals no significant cerebral atrophy.
Anticipation of thermal pain in diverticular disease
Authors: Smith J. K. , Marciani L. , Humes D. J. , Francis S. T. , Gowland P. , Spiller R. C.
Published: March 2016

Background

The relative importance of peripheral nerve injury or central pain processing in painful diverticular disease (DD) is unclear. Functional magnetic resonance imaging (fMRI) has demonstrated that dysfunctional central pain processing predominates in irritable bowel syndrome (IBS). This study aims to identify anticipatory changes in symptomatic DD (SDD) compared to asymptomatic DD (ADD) and IBS patients.

Methods

Gastrointestinal symptoms and somatization were evaluated via the Patient Health Question‐12 Somatic Symptom and the SDD group divided into low (≤6 [LSDD]) and high (≥7 [HSDD]) somatization. Cued painful cutaneous thermal stimuli were delivered to the left hand and foot during fMRI. Fixed effect group analysis of the ‘cued’ anticipatory phase was performed.

Key Results

Within the right posterior insula, greater deactivation was found in the ADD compared to other groups. In emotion processing centers, anterior and middle insula, greater activation was identified in all patient compared to the ADD group, and in LSDD compared to IBS and HSDD groups. In comparison, amygdala deactivation was greater in ADD than the IBS and HSDD groups, and in LSDD vs HSDD groups. Descending nociceptive control centers, such as the superior medial frontal and orbitofrontal cortex, also showed greater deactivation in the ADD and LSDD compared to the HSDD and IBS groups.

Conclusions & Inferences

The HSDD group have altered anticipatory responses to thermal pain, similar to IBS group. The LSDD are similar to ADD group. This suggests underlying differences in pain pathophysiology, and the need for individualized treatment strategies to target the cause of their chronic pain.
Potential association of VAMP5 polymorphisms with total colonic aganglionosis in Hirschsprung disease
Authors: Shin J.‐G. , Kim D.‐Y. , Seo J.‐M. , Oh J.‐T. , Park K.‐W. , Kim H.‐Y. , Park B. L. , Kim J.‐H. , Shin H. D.
Published: March 2016

Background

Hirschsprung disease (HSCR) is a congenital bowel disease caused by the absence of nerve cells in portions of the intestine. Our recent genome‐wide association study has identified a variant (rs1254900) of vesicle‐associated membrane protein 5 (VAMP5) as a potential risk locus for total colonic aganglionosis (TCA) in HSCR. In addition, VAMP5 is a member of the VAMP/synaptobrevin protein complex, which participates in nerve signal transduction by regulating the vesicular fusion of the neurotransmitter in synaptic transmission.

Methods

A total of 11 single nucleotide polymorphisms (SNPs), including those in the functionally important coding region, were selected on the basis of linkage disequilibrium and genotyped in 187 HSCR patients and 283 unaffected controls by using a TaqMan assay. Logistic analysis was conducted to investigate the possible association between VAMP5 SNPs and the risk of HSCR.

Key Results

Genetic variants of VAMP5 showed increased association signals in the TCA subgroup of HSCR patients (minimum p = 9.69 × 10−5, OR = 3.93 at rs10206961) compared to other subgroups, even after Bonferroni correction (pcorr = 0.002). In haplotype analysis, three haplotypes (BL1_ht1, BL2_ht1, and BL2_ht2) were associated with the risk of TCA (minimum pcorr = 0.005). In additional combined analysis after imputation based on our previous GWAS, five SNPs still retained significant associations with the TCA subtype (minimum pcorr = 0.006 at rs10206961).

Conclusions & Inferences

Considering that differential genetic effects on the development of the enteric nervous system, our results suggest that VAMP5 may be associated with the TCA of HSCR. However, further replications and functional evaluations are required.
Stimulus‐induced pacemaker activity in interstitial cells of Cajal associated with the deep muscular plexus of the small intestine
Authors: Zhu Y. F. , Wang X.‐Y. , Parsons S. P. , Huizinga J. D.
Published: March 2016

Background

The ICC‐DMP have been proposed to generate stimulus‐dependent pacemaker activity, rhythmic transient depolarizations, that take part in orchestrating segmentation and clustered propulsive motor patterns in the small intestine. However, little is known about the fundamental properties of ICC‐DMP.

Methods

This study was undertaken to increase our understanding of intrinsic properties of the ICC‐DMP through calcium imaging and intracellular electrical recordings.

Key Results

Without stimulation, most ICC‐DMP were quiescent. In some preparations ICC‐DMP generated rhythmic low‐frequency calcium oscillations (<10 cpm) with or without high frequency activity superimposed (>35 cpm). Immunohistochemistry proved the existence of NK1R on the ICC‐DMP and close contacts between ICC‐DMP and substance P‐positive nerves. Substance P (25 nM) induced low‐frequency calcium oscillations that were synchronized across the ICC‐DMP network. Substance P also induced low frequency rhythmic transient depolarizations (<10cpm) in circular muscle cells close to the ICC‐DMP. An intracellular recording from a positively identified ICC‐DMP showed rhythmic transient depolarizations with superimposed high frequency activity. To investigate if quiescent ICC‐DMP were chronically inhibited by nitrergic activity, nNOS was inhibited, but without effect.

Conclusions & Inferences

Substance P changes non‐synchronized high frequency flickering or quiescence in ICC‐DMP into strong rhythmic calcium transients that are synchronized within the network; they are associated with rhythmic transient depolarizations within the same frequency range. We hypothesize that Substance P, released from nerves, can evoke rhythmicity in ICC‐DMP, thereby providing it with potential pacemaker activity.
Role of 5‐HT1A receptor in insular cortex mediating stress – induced visceral sensory dysfunction
Authors: Sun H. , Xu S. , Yi L. , Chen Y. , Wu P. , Cao Z. , Zhou L. , Jiang Y. , Zhang D.
Published: March 2016

Background

5‐HT1A receptors (HTR1As) in the insular cortex are thought to be related with the generation of stress‐induced functional gastrointestinal disorders (FGIDs), but its mechanism is not clear. Visceral hypersensitivity is one important pathophysiological mechanism of FGIDs. This study aimed to explore the role of HTR1As in mediating stress‐induced visceral hypersensitivity and its mechanism in the insular cortex.

Methods

Visceral hypersensitivity rat model was established by water avoidance stress (WAS) and the visceral sensitivity was measured by electromyogram. The activities of HTR1As were regulated by microinjecting the HTR1A agonist and antagonist into the insular cortex. The expression levels of 5‐HT, HTR1A, N‐methyl‐d‐aspartic acid receptor subtype 2B (NR2B) and c‐fos were observed by RT‐PCR, Western Blot and immunohistochemical staining.

Key Results

In WAS rats, the expression levels of 5‐HT and HTR1As in the insular cortex were significantly lower (p < 0.05) than that in sham WAS and normal rats, but the levels of c‐fos and NR2B were significantly higher (p < 0.05). After microinjecting HTR1As agonist into the insular cortex of WAS rats, the visceral sensitivity and the expression levels of NR2B and c‐fos in insular cortex significantly decreased (p < 0.05).

Conclusions & Inferences

The HTR1As‐NR2B signal pathway of insular cortex plays an important role in regulating stress‐induced visceral hypersensitivity.
Dispersal and diversity in experimental metacommunities: linking theory and practice
Authors: Grainger Tess Nahanni , Gilbert Benjamin
Published: March 2016

There has been a recent rise in the number of experiments investigating the effect of dispersal on diversity, with many of the predictions for these tests derived from metacommunity theory. Despite the promise of linking observed relationships between dispersal and diversity to underlying metacommunity processes, empirical studies have faced challenges in providing robust tests of theory. We review experimental studies that have tested how dispersal affects metacommunity diversity to determine why shortcomings emerge, and to provide a framework for empirical tests of theory that capture the processes structuring diversity in natural metacommunities. We first summarize recent experimental work to outline trends in results and to highlight common methods that cause a misalignment between empirical studies and the processes described by theory. We then identify the undesired implications of three widely used experimental methods that homogenize metacommunity structure or species traits, and present alternative methods that have been used to successfully integrate experiments and theory in a biologically relevant way. Finally, we present methodological and theoretical insights from three related ecological fields (coexistence, food web and priority effects theory) that, if integrated into metacommunity experiments, could help isolate the independent and joint effects of local interactions and dispersal on diversity, and reveal the mechanisms underlying observed dispersal–diversity patterns. Together, these methods can provide stronger tests of existing theory and stimulate new theoretical explorations.

Synthesis

Although metacommunity experiments offer a unique opportunity to test classic and emerging theory on the relationship between dispersal and diversity, several common challenges have hindered robust tests of theory. We outline how emerging theory on the invasion criterion, food webs and priority effects could be help clarify when and how dispersal affects metacommunity diversity, and identify when experimental approaches that homogenize metacommunities fail to test existing theory. By forging better links between theoretical and empirical work, we hope to motivate novel and improved experimental approaches to understanding the joint effects of local and regional processes on diversity.
Estimating the Risks and Benefits of Implantable Cardioverter Defibrillator Generator Replacement: A Systematic Review
Authors: LEWIS KRYSTINA B. , STACEY DAWN , CARROLL SANDRA L. , BOLAND LAURA , SIKORA LINDSEY , BIRNIE DAVID
Published: March 2016

Background

Every 4–7 years an implantable cardioverter defibrillator (ICD) pulse generator must be replaced surgically. This procedure is not without risk. In some cases, the risk versus benefit ratio may be against replacement. We aimed to synthesize the evidence on risks, benefits, and costs related to ICD replacement.

Methods

A systematic review was conducted using electronic databases from 2000 onward. Literature screening, quality appraisal, and data extraction were independently conducted by two reviewers. Outcomes included major and minor complications, ICD therapies, and costs, which were synthesized descriptively.

Results

Of 1,483 citations, 17 nonrandomized studies met criteria. Median rate of major complications was 4.05% (range 0.55–7.37%) and minor complications was 3.50% (range 0.36–7.37%). Without non‐ICD control groups, the true risk reduction provided by the ICD following replacement is unknown. Following ICD replacement, annualized rate of appropriate ICD therapy was 10.52% (range 2.42–75.00%). Of these, patients without therapies during their first generator life and those no longer meeting ICD criteria received appropriate therapies at nontrivial rates.

Conclusion

Rates of complications associated with ICD replacement are substantial. No study had nonreplacement groups, hence the true risk reduction provided by the ICD following replacement is unknown. Our analysis did not identify a subgroup at low risk of therapies following replacement. Shared discussions should occur with patients about the evidence, healthcare goals, risk tolerances, and feelings about life and death trade‐offs to enable high‐quality decisions about ICD replacement.
Implied weighting and its utility in palaeontological datasets: a study using modelled phylogenetic matrices
Authors: Congreve Curtis R. , Lamsdell James C.
Published: March 2016

Implied weighting, a method for phylogenetic inference that actively seeks to downweight supposed homoplasy, has in recent years begun to be widely utilized in palaeontological datasets. Given the method's purported ability at handling widespread homoplasy/convergence, we investigate the effects of implied weighting on modelled phylogenetic data. We generated 100 character matrices consisting of 55 characters each using a Markov Chain morphology model of evolution based on a known phylogenetic tree. Rates of character evolution in these datasets were variable and generated by pulling from a gamma distribution for each character in the matrix. These matrices were then analysed under equal weighting and four settings of implied weights (k = 1, 3, 5, and 10). Our results show that implied weighting is inconsistent in its ability to retrieve a known phylogenetic tree. Equally weighted analyses are found to generally be more conservative, retrieving higher frequency of polytomies but being less likely to generate erroneous topologies. Implied weighting is found to generally resolve polytomies while also propagating errors, resulting in an increase in both correctly and incorrectly resolved nodes with a tendency towards higher rates of error compared to equal weighting. Our results suggest that equal weights may be a preferable method for parsimony analysis.
Genetic diversity and population structure of Indian melon (Cucumis melo L.) landraces with special reference to disease and insect resistance loci
Authors: Reddy D. C. Lakshamana , Venkat Sudarshini K , Reddy Anand C , Aswath C. , Avinash K. N. , Nandini H. , Sreenivasa Rao E.
Published: March 2016

This study was aimed to examine the genetic diversity and population structure of Indian melon landraces with special reference to disease and insect resistance loci. Thirty‐six simple sequence repeat (SSR) markers along with seven markers at disease and insect resistance loci were used for this purpose on a panel of 91 accessions available at Indian Institute of Horticultural Research, Bengaluru, India. Model‐based structure analysis revealed the presence of four groups that were consistent with the results of principal coordinate analysis (PCoA). The delineation of populations was mostly based on geography with improved varieties as a separate group. Ten accessions have been identified to possess beneficial alleles at all the selected disease resistance loci and shall be useful for incorporating multiple disease resistance after phenotypic validation. The results obtained in the current study demonstrate the importance of the Indian melon group as a valuable genetic reservoir and the need to plan strategies for its conservation and utilization in breeding programmes.
Biological aspects and candidate biomarkers for psychotic bipolar disorder: A systematic review
Authors: Buoli Massimiliano , Caldiroli Alice , Cumerlato Melter Claudia , Serati Marta , de Nijs Jessica , Altamura A. Carlo
Published: March 2016

Aim

We carried out a systematic review of the available literature about potential biomarkers of psychotic bipolar disorder (BD‐P), a specific subset presenting worse outcome and greater risk of relapse than non‐psychotic bipolar disorder (BD‐NP).

Methods

We searched the main psychiatric databases (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles with the main topic of BD‐P compared to schizophrenia/BD‐NP/healthy controls (HC) written in English from 1994 to 2015 were included.

Results

BD‐P patients presented higher kynurenic acid levels in the cerebrospinal fluid, elevated anti‐
S

accharomyces cerevisiae antibodies levels, and lower serum levels of dehydroepiandrosterone sulfate and progesterone than BD‐NP/HC. Event‐related potentials abnormalities have been identified in BD‐P with respect to BD‐NP. BD‐P patients also presented bigger ventricles but similar hippocampal volumes compared to BD‐NP/HC. Although the results are contrasting, some cognitive deficits seemed to be related to the psychotic dimension of bipolar affective disorder, such as impairment in verbal/logical memory, working memory, verbal and semantic fluency and executive functioning. Finally, polymorphisms of genes, such as NRG1, 5HTTLPR (s), COMT, DAOA and some chromosome regions (16p12 and 13q), were positively associated with BD‐P.

Conclusion

Data about the identification of specific biomarkers for BD‐P are promising, but most of them have not yet been replicated. They could lead the clinicians to an early diagnosis and proper treatment, thus ameliorating outcome of BD‐P and reducing the biological changes associated with a long duration of illness. Further studies with bigger samples are needed to detect more specific biological markers of the psychotic dimension of bipolar affective disorder.
Physical and chemical properties of primary defences in Tenebrio molitor
Authors: Silva Farley W. S. , Araujo Lucimar S. , Azevedo Dihego O. , Serrão José E. , Elliot Simon L.
Published: March 2016

Prevention and reaction are the foundation for any defence system. In insects, the primary defences against pathogens and parasites limit invasion; the secondary ones (e.g. immune system) act when the cuticle and other primary defences fail. Because investment in both aspects of defence may be costly, they should be regulated in a plastic or variable way in accordance with the risk of infection. The mealworm beetle Tenebrio molitor L. changes cuticle colour and its resistance to fungal infection when subject to high population density, although such resistance is a result of the primary (cuticle) defences rather than the secondary (immunological) ones. The present study tests the hypothesis that the physical and chemical properties of the primary defences in T. molitor change with cuticular darkness. Beetles expressing black phenotypes (or with darker cuticle) have a thicker cuticle, with four well organized layers (epi‐, exo‐, endocuticle and formation zone) and more melanin than tan beetles. The cuticle properties investigated in the present study are likely to be the underlying mechanisms of pathogen resistance in black beetles, including the content of carbonylated proteins, which in black beetles was almost half that of tan beetles after exposure to ultraviolet radiation. It is proposed that, in polyphenic insects (such as mealworm beetles), primary and secondary defences are regulated pleiotropically, with the genes responsible for the expression of one defence having a positive effect on others, whereas, in polymorphic insects, there is no such link and so investment in one defence may impair others.
Public Health Nurses in Israel: A Case Study on a Quality Improvement Project of Nurse's Work Life
Authors: Kagan Ilya , Shachaf Sara , Rapaport Zofia , Livne Tzipi , Madjar Batya
Published: March 2016

Public health nurses (PHNs) working in Well Baby Clinic in Israel's Haifa district were voicing great distress to inspectors—the impossibility of meeting their workload, feeling overwhelmed, poor physical, and technological conditions. They were feeling tired and frustrated and burn‐out was rising. The district's nursing management took the decision, together with Tel Aviv University's nursing research unit, to conduct a quality improvement project based on issues that arose from meetings with focus groups on the nurses’ difficulties. This paper is a case study of a quality improvement project targeting nurses daily working life. One of its chief contributions is as a study of meeting PHNs’ frustration by integrating focus groups and round‐table brainstorming (involving nurses, clinic managers and nursing inspectors) in order to identify targets for practical intervention. This strategy has been very successful. It has provided the district's nursing management a battery of forcefully argued and realistically grounded proposals for making the work of Well Baby clinics more relevant to their communities and giving nurses (a) the conditions to meet their assignments and (b) greater professional self‐respect.