bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of tofacitinib in treatment of alopecia universalis in two patients
Authors: Gupta A.K. , Carviel J.L. , Abramovits W.
Published: June 2016

Background

Autoimmune‐triggered non‐scarring hair loss is a feature of alopecia areata (AA). Initially patchy and often self‐limited, severe hair loss forms include the complete loss of scalp hair or alopecia totalis (AT) and complete loss of all hair or alopecia universalis (AU). For AT and AU a reliable treatment has remained elusive. The targeted kinase inhibitor tofacitinib, in current use for treatment of other immune diseases, has been hypothesized as a viable option for AA, AT and AU therapy and a few case reports support this.

Objective

Our study aims to provide evidence for the effectiveness of tofacitinib in the treatment of AU.

Methods

Two patients diagnosed with long‐term AU were prescribed tofacitinib citrate at a dosage of 5 mg twice daily and observed for eight months.

Results

In the first patient, beard growth was significant by 3 months of treatment. By 6 months of treatment, hair growth was apparent throughout the entire body. By 8 months of treatment, scalp hair continued to grow longer and thicker. In addition, eyelashes and eyebrows were established. In the second patient, a noticeable increase in scalp hair was present just 1 month into treatment. By 4 months into treatment, significant scalp regrowth was observed as well as eyelash, eyebrow and beard regrowth. Axillary hair regrowth and isolated leg hair was noted by 8 months.

Conclusion

In our patients, tofacitinib successfully alleviated AU in the absence of significant adverse side‐effects. We recommend that further study be required to establish safety and confirm efficacy.
Ambient humidity and the skin: the impact of air humidity in healthy and diseased states
Authors: Goad N. , Gawkrodger D.J.
Published: June 2016

Humidity, along with other climatic factors such as temperature and ultraviolet radiation, can have an important impact on the skin. Limited data suggest that external humidity influences the water content of the stratum corneum. An online literature search was conducted through Pub‐Med using combinations of the following keywords: skin, skin disease, humidity, dermatoses, dermatitis, eczema, and mist. Publications included in this review were limited to (i) studies in humans or animals, (ii) publications showing relevance to the field of dermatology, (iii) studies published in English and (iv) publications discussing humidity as an independent influence on skin function. Studies examining environmental factors as composite influences on skin health are only included where the impact of humidity on the skin is also explored in isolation of other environmental factors. A formal systematic review was not feasible for this topic due to the heterogeneity of the available research. Epidemiological studies indicated an increase in eczema with low internal (indoors) humidity and an increase in eczema with external high humidity. Other studies suggest that symptoms of dry skin appear with low humidity internal air‐conditioned environments. Murine studies determined that low humidity caused a number of changes in the skin, including the impairment of the desquamation process. Studies in humans demonstrated a reduction in transepidermal water loss (TEWL) (a measure of the integrity of the skin's barrier function) with low humidity, alterations in the water content in the stratum corneum, decreased skin elasticity and increased roughness. Intervention with a humidifying mist increased the water content of the stratum corneum. Conversely, there is some evidence that low humidity conditions can actually improve the barrier function of the skin. Ambient relative humidity has an impact on a range of parameters involved in skin health but the literature is inconclusive. Further studies are needed to better delineate the interactions that can occur in normal and diseased states. Therapeutic measures might be forthcoming especially for skin diseases such as eczema, which are regarded as being characterized by ‘skin dryness’. Further research examining the interaction between different environmental exposures thought to impact the skin, and indeed the interplay between genetic, environmental and immunological influences, are required.
Testing the cranial evolutionary allometric ‘rule’ in Galliformes
Authors: Linde‐Medina M.
Published: June 2016

Recent comparative studies have indicated the existence of a common cranial evolutionary allometric (CREA) pattern in mammals and birds, in which smaller species have relatively smaller faces and bigger braincases than larger species. In these studies, cranial allometry was tested using a multivariate regression between shape (described using landmarks coordinates) and size (i.e. centroid size), after accounting for phylogenetic relatedness. Alternatively, cranial allometry can be determined by comparing the sizes of two anatomical parts using a bivariate regression analysis. In this analysis, a slope higher or lower than one indicates the existence of positive or negative allometry, respectively. Thus, in those species that support the CREA ‘rule’, positive allometry is expected for the association between face size and braincase size, which would indicate that larger species have disproportionally larger faces. In this study, I applied these two approaches to explore cranial allometry in 83 Galliformes (Aves, Galloanserae), ranging in mean body weight from 30 g to 2.5 kg. The multivariate regression between shape and centroid size revealed the existence of a significant allometric pattern resembling CREA, whereas the second analysis revealed a negative allometry for beak size and braincase size (i.e. contrary to the CREA ‘rule’, larger galliform species have disproportionally shorter beaks than smaller galliform species). This study suggests that the presence of CREA may be overestimated when using cranium size as the standard measurement.
Large‐brained birds suffer less oxidative damage
Authors: Vágási C. I. , Vincze O. , Pătraş L. , Osváth G. , Marton A. , Bărbos L. , Sol D. , Pap P. L.
Published: June 2016

Large brains (relative to body size) might confer fitness benefits to animals. Although the putative costs of well‐developed brains can constrain the majority of species to modest brain sizes, these costs are still poorly understood. Given that the neural tissue is energetically expensive and demands antioxidants, one potential cost of developing and maintaining large brains is increased oxidative stress (‘oxidation exposure’ hypothesis). Alternatively, because large‐brained species exhibit slow‐paced life histories, they are expected to invest more into self‐maintenance such as an efficacious antioxidative defence machinery (‘oxidation avoidance’ hypothesis). We predict decreased antioxidant levels and/or increased oxidative damage in large‐brained species in case of oxidation exposure, and the contrary in case of oxidation avoidance. We address these contrasting hypotheses for the first time by means of a phylogenetic comparative approach based on an unprecedented data set of four redox state markers from 85 European bird species. Large‐brained birds suffered less oxidative damage to lipids (measured as malondialdehyde levels) and exhibited higher total nonenzymatic antioxidant capacity than small‐brained birds, whereas uric acid and glutathione levels were independent of brain size. These results were not altered by potentially confounding variables and did not depend on how relative brain size was quantified. Our findings partially support the ‘oxidation avoidance’ hypothesis and provide a physiological explanation for the linkage of large brains with slow‐paced life histories: reduced oxidative stress of large‐brained birds can secure brain functionality and healthy life span, which are integral to their lifetime fitness and slow‐paced life history.
Interpreting risk as evidence of causality: lessons learned from a legal case to determine medical malpractice
Authors: Mercuri Mathew , Baigrie Brian S
Published: June 2016

Translating risk estimates derived from epidemiologic study into evidence of causality for a particular patient is problematic. The difficulty of this process is not unique to the medical context; rather, courts are also challenged with the task of using risk estimates to infer evidence of cause in particular cases. Thus, an examination of how this is done in a legal context might provide insight into when and how it is appropriate to use risk information as evidence of cause in a medical context. A careful study of the case of Goodman v. Viljoen, a medical malpractice suit litigated in the Ontario Superior Court of Justice in 2011, reveals different approaches to how risk information is used as or might be considered a substitute for evidence of causation, and the pitfalls associated with these approaches. Achieving statistical thresholds, specifically minimizing the probability of falsely rejecting the null hypothesis, and exceeding a relative risk of 2, plays a significant role in establishing causality of the particular in the legal setting. However, providing a reasonable explanation or establishing “biological plausibility” of the causal association also seems important, and (to some) may even take precedent over statistical thresholds for a given context.
Infection routes of Aeromonas salmonicida in rainbow trout monitored in vivo by real‐time bioluminescence imaging
Authors: Bartkova S , Kokotovic B , Dalsgaard I
Published: June 2016

Recent development of imaging tools has facilitated studies of pathogen infections in vivo in real time. This trend can be exemplified by advances in bioluminescence imaging (BLI), an approach that helps to visualize dissemination of pathogens within the same animal over several time points. Here, we employ bacterial BLI for examining routes of entry and spread of Aeromonas salmonicida susbp. salmonicida in rainbow trout. A virulent Danish A. salmonicida strain was tagged with pAKgfplux1, a dual‐labelled plasmid vector containing the mutated gfpmut3a gene from Aequorea victoria and the luxCDABE genes from the bacterium Photorhabdus luminescens. The resulting A. salmonicida transformant exhibited growth properties and virulence identical to the wild‐type A. salmonicida, which made it suitable for an experimental infection, mimicking natural conditions. Fish were infected with pAKgfplux1 tagged A. salmonicida via immersion bath. Colonization and subsequent tissue dissemination was followed over a 24‐h period using the IVIS spectrum imaging workstation. Results suggest the pathogen's colonization sites are the dorsal and pectoral fin and the gills, followed by a progression through the internal organs and an ensuing exit via the anal opening. This study provides a tool for visualizing colonization of A. salmonicida and other bacterial pathogens in fish.
Noninvasive Monitoring by Ultrasound of Liquid Foodstuff to Ice Slurry Transitions Within Steel Ducts and Pipes
Authors: Lucas Edward J.K. , Brooks Sam , Hales Alastair , McBryde Daniel , Yun Xiao , Quarini Giuseppe L.
Published: June 2016

Ultrasound was assessed as a noninvasive method of detecting dynamic transitions occurring as a scouring high ice fraction ice slurry forces liquid food products through process lines. The attenuation of ultrasound waves passing through a test section was measured within a time window that captured waves with arrival time's characteristic of a direct path through the tubing and its contents. A recording transducer measuring the attenuated signal provided an output in volts, corresponding to the extent of attenuation. Water as a comparable substitute for a liquid food product gave typical values of 2.32 ± 0.07 V for mean amplitude of these waves. The passage of ice slurry reduced this value to 0.75 ± 0.03 V which represented a highly significant (P < 0.001) reduction in transmission. Tomato soup under similar circumstances gave values of 1.93 ± 0.09 V reduced to 0.64 ± 0.02 V when ice slurry flowed between the transducers. Dynamic transitions involving yoghurt and yoghurt mixtures were also detectable except when the yoghurt and the ice slurry shared similar degrees of signal attenuation. Pipe geometry was typically found to introduce systematic changes to recorded values but these did not detract from the basic finding that significant differences were always found between flowing food products and ice slurry, except in the case of pure yoghurt in a large channel. Noninvasive monitoring of dynamic product to ice slurry transitions in food grade steel pipes by ultrasound is readily achievable and could become a method of choice for product recovery systems.

Practical Applications

Ice slurries can be used to clean out foodstuffs from processing lines and offer the possibility of product recovery from within lines that would otherwise be lost by traditional cleaning methods such as water flushing. This process ideally needs noninvasive monitoring in real time using on‐line sensors. External ultrasound transducers allow noninvasive monitoring without changes to existing infrastructure. Food grade stainless steel presents a challenge to ultrasound due to the high impedance mismatch between it and liquid food products. Knowledge of the moment of transition is an advance on rudimentary timing methods and would help to minimise wastage with prevention of contamination in recovered product. Present work demonstrates that noninvasive ultrasound can detect dynamic transitions to ice slurry within steel pipes and ducts, opening the way for automated control processes to minimise wastage and maximise product recovery.
Fabrication and Characterization of Polyglycerol Fatty Acid Esters/Polyethylene Antifogging Film
Authors: Wei L.‐J. , Yang F.‐X. , Du Y.‐P. , Chen J.‐Y. , Wang H.‐L.
Published: June 2016

The antifogging polyglycerol fatty acid esters (PGFE)/polyethylene (PE) film with polyethylene wax emulsions (WE1) as a dispersant was fabricated using twin‐screw extruder and then extrusion blow molding. The study was conducted to investigate the influence that different levels of PGFE on the antifogging performance, mechanical, optical, thermostability and cross‐section microstructures of PGFE/PE film. The modified polymer film had been characterized by contact angle measurement (CAM), thermogravimetric analysis, Fourier transform infrared spectroscopy and scanning electron microscopy. The results revealed that WE1 and PGFE could mix evenly with PE resin. Compared with 100% low‐density polyethylene film, PGFE incorporation improved antifogging performance, hydrophilicity, haze and thermostability, however, decreased light transmittance and tensile strength. When the content of PGFE is 2%, PGFE/PE film has a long lasting antifogging performance, high‐quality mechanical stability and light transmittance. It has a great potential to be applied in food packaging.

Practical Applications

Because of the utilization as antifogging, antistatic additive, lubricant and plasticizer of polyglycerol fatty acid esters (PGFE) in synthetic resin and plastics processing, it is receiving much more attention. Investigation of the antifogging performance in PGFE in polymer matrix has recently been considered. Study of the antifogging and physical parameters is one of the ways to find the influence of antifoggant on the antifogging, mechanical and structural properties of the films. In this work, high‐temperature antifogging property, water contact angle, morphology of water droplets on the film surface, mechanical and optical behaviors of film samples affected by the concentration of PGFE were studied. Investigation of scanning electron microscopy and Fourier transform infrared spectroscopy in the film allows a better understanding of film structure in the process of film fabrication. More importantly, the study solves the uneven distribution of antifoggant in the polymer resin.
Identifying Patterns of Multimorbidity in Older Americans: Application of Latent Class Analysis
Authors: Whitson Heather E. , Johnson Kimberly S. , Sloane Richard , Cigolle Christine T. , Pieper Carl F. , Landerman Lawrence , Hastings Susan N.
Published: June 2016

Objectives

To define multimorbidity “classes” empirically based on patterns of disease co‐occurrence in older Americans and to examine how class membership predicts healthcare use.

Design

Retrospective cohort study.

Setting

Nationally representative sample of Medicare beneficiaries in file years 1999–2007.

Participants

Individuals aged 65 and older in the Medicare Beneficiary Survey who had data available for at least 1 year after index interview (N = 14,052).

Measurements

Surveys (self‐report) were used to assess chronic conditions, and latent class analysis (LCA) was used to define multimorbidity classes based on the presence or absence of 13 conditions. All participants were assigned to a best‐fit class. Primary outcomes were hospitalizations and emergency department visits over 1 year.

Results

The primary LCA identified six classes. The largest portion of participants (32.7%) was assigned to the minimal disease class, in which most persons had fewer than two of the conditions. The other five classes represented various degrees and patterns of multimorbidity. Usage rates were higher in classes with greater morbidity, but many individuals could not be assigned to a particular class with confidence (sample misclassification error estimate = 0.36). Number of conditions predicted outcomes at least as well as class membership.

Conclusion

Although recognition of general patterns of disease co‐occurrence is useful for policy planning, the heterogeneity of persons with significant multimorbidity (≥3 conditions) defies neat classification. A simple count of conditions may be preferable for predicting usage.
Associations Between Inflammation and Physical Function in African Americans and European Americans with Prevalent Cardiovascular Risk Factors
Authors: Windham B. Gwen , Wilkening Steven R. , Lirette Seth T. , Kullo Iftikhar J. , Turner Stephen T. , Griswold Michael E. , Mosley Thomas H.
Published: June 2016

Objectives

To examine associations between inflammation and physical function and potential mediation by white matter hyperintensities (WMHs) in African Americans (AAs) and European Americans (EAs).

Design

Cross‐sectional analysis using linear and logistic models with generalized estimating equations to account for family clustering, reporting results as regression coefficients (β) and odds ratios (ORs) adjusted for education, alcohol, exercise, body mass index, hypertension, diabetes mellitus, heart disease, cognition, ankle–brachial index, race (site), and supported interactions.

Setting

Genetic Epidemiology Network of Arteriopathy‐Genetics of Microangiopathic Brain Injury Study cohort.

Participants

AA and EA sibships with two or more siblings with hypertension before age 60 (N = 1,960; 65% female, 51% AA, aged 26–91, 50% obese, 72% hypertensive).

Measurements

Inflammation (C‐reactive protein (CRP), interleukin‐6 (IL6), soluble tumor necrosis factor receptors (sTNFRs) 1 and 2, WMH volume (cm3) according to magnetic resonance imaging), walking speed (cm/s) over 25 feet, and mobility difficulty (any self‐reported difficulty walking half a mile).

Results

In separate models, inflammatory markers were associated with walking speed (sTNFR1: β = −2.74, P < .001; sTNFR2: β = −1.23, P = .03; CRP: β = −1.95, P = .001; IL6: β = −1.24, P = .03) and mobility difficulty (sTNFR1: OR = 1.36, P = .001; sTNFR2: OR = 1.25, P = .005; CRP: OR = 1.22, P = .005; IL6: OR = 1.18, P = .02); the association between WMH volume and sTNFR1 in AA (β = 0.07, P = .06) did not reach typical statistical thresholds. WMH volume was associated with walking speed in AA (β = −3.17, P = .02) but not with mobility difficulty (OR = 1.10, P = .54). Adjusting for WMH did not change associations.

Conclusion

In young, middle‐aged, and older adults with prevalent cardiovascular risk factors, multiple inflammatory biomarkers were associated with slower walking speed independent of microvascular disease in the brain. There was little evidence of mediation by brain WMH volume. Inflammation may contribute to physical function impairments through pathways other than brain microvascular disease, particularly in AAs.
Markers of Overall Nutritional Status and Incident Hearing Impairment in Community‐Dwelling Older Japanese: The Kurabuchi Study
Authors: Michikawa Takehiro , Nakamura Takahiro , Imamura Haruhiko , Mizutari Kunio , Saito Hideyuki , Takebayashi Toru , Nishiwaki Yuji
Published: June 2016

Objectives

To examine the association between four markers of overall nutritional status (a serum biomarker (albumin) and three anthropometric indices (body mass index (BMI), midarm circumference (MAC), calf circumference (CC))) and incident hearing impairment in older Japanese adults.

Design

Community‐based prospective cohort study.

Setting

Kurabuchi Town, Gunma Prefecture, Japan.

Participants

Individuals aged 65 and older (143 men, 195 women) without hearing impairment at baseline examination (2005–06) who participated in repeated examinations 4 years later (2009–10) (N = 338).

Measurements

The three anthropometric indices were measured at baseline, and nephelometry was used to assess serum albumin levels. Hearing impairment was defined as failure to hear a 30‐dB hearing level signal at 1 kHz and a 40‐dB signal at 4 kHz in the better ear on pure‐tone audiometry.

Results

Over the 4‐year period, 16.3% of participants developed hearing impairment. Those with lower marker values had greater risk of hearing impairment than those with higher marker values (multivariable adjusted odds ratio (aOR) = 2.18, 95% confidence interval (CI) = 1.05–4.57 for albumin ≤4.0 g/dL; aOR = 2.72, 95% CI = 1.10–6.71 for BMI <19.0 kg/m2). The pattern of association showed a similar tendency for MAC and CC. Excluding obese participants did not changed the results substantially.

Conclusion

Further research is needed to determine whether interventions that improve markers of nutritional status may help prevent age‐related hearing loss in older adults.
Disparities in Age‐Associated Cognitive Decline Between African‐American and Caucasian Populations: The Roles of Health Literacy and Education
Authors: Gupta Vishal K. , Winter Michael , Cabral Howard , Henault Lori , Waite Katherine , Hanchate Amresh , Bickmore Timothy W. , Wolf Michael S. , Paasche‐Orlow Michael K.
Published: June 2016

Objectives

To examine health literacy as a mediator of racial disparities in cognitive decline as measured by executive function in elderly adults.

Design

Prospective cohort study.

Setting

Secondary analysis of ElderWalk trial in Boston, Massachusetts.

Participants

English‐speaking African‐American and Caucasian individuals in a walking intervention for community‐dwelling adults aged 65 and older without dementia at baseline who completed baseline and 12‐month evaluations (N = 198).

Measurements

Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Fluid and crystallized cognitive functions were measured at baseline and 12 months using the Trail‐Making Test Part B minus Part B (TMT B–A) and the Controlled Oral Word Association Test (COWAT). Associations between health literacy and 12‐month cognitive decline were modeled using multivariate linear regression.

Results

Participants with higher health literacy and education experienced less cognitive decline than those with limited health literacy according to the TMT B–A (P = .01). After adjusting for covariates, Caucasian participants (n = 63) experienced less decline than African‐American participants (n = 135) on TMT B–A (P = .001) and COWAT (P = .001). Adjusting for health literacy led to a 25.3% decrease in the point estimate for racial difference in TMT B–A and a 19.5% decrease in COWAT. Although independently related to cognitive decline, educational attainment did not mediate racial differences.

Conclusion

Health literacy is a partial mediator of racial disparities in cognitive decline. These results indicate the need to develop interventions to mitigate cognitive decline that individuals with low heath literacy can use and to modify the healthcare environment to better accommodate this population.
Behavioural and cognitive outcomes in young children of mothers with intellectual impairments
Authors: Powell R. M. , Parish S. L.
Published: June 2016

Background

Despite an increase in international studies examining the experiences of parents with intellectual impairments and their children, few have utilised population‐based data. This study investigated the behavioural and cognitive outcomes of 3‐year‐old US children of mothers with intellectual impairments compared with children of mothers without intellectual impairments.

Methods

This study employed a secondary analysis of the Fragile Families Child and Wellbeing Study, a longitudinal birth cohort study in the US. Our analytic sample included mothers with intellectual impairments (n = 263) and a comparison group of mothers without intellectual impairments (n = 1298), as well as each sampled mother's focal child. When weighted, Fragile Families is representative of all births in US cities with populations over 200 000.

Results

Children of mothers with intellectual impairments had poorer behavioural and cognitive outcomes in comparison to same‐age children of mothers without intellectual impairments. Notably, however, children of mothers with intellectual impairments were not at increased risk of being aggressive unless their family income was below 200% of the federal poverty level. Further, families headed by mothers with intellectual impairments experienced multiple hardships related to socioeconomic factors, limited social supports and poor self‐reported health.

Conclusion

Appropriate policies and programmes must be developed and implemented to effectively support these families, such as increased financial benefits.
Therapy and clinical trials in frontotemporal dementia: past, present, and future
Authors: Tsai Richard M. , Boxer Adam L.
Published: June 2016

Frontotemporal dementia (FTD) is a common form of dementia with heterogeneous clinical presentations and distinct clinical syndromes. This article will review currently available therapies for FTD, its related disorders and their clinical evidence. It will also discuss recent advancements in FTD pathophysiology, treatment development, biomarker advancement and their relation to recently completed or currently ongoing clinical trials as well as future implications.

image

Frontotemporal dementia (FTD) is a type of dementia with distinct clinical syndromes. Current treatments involve off‐label use of medications for symptomatic management and cannot modify disease course. Advancements in FTD pathophysiology, genetics, and biomarkers have led to development of small molecules targeting the underlying pathology in hopes of achieving a disease‐modifying effect. This article will review current therapies for FTD, discuss advancements in FTD pathophysiology, therapy development, biomarker advancement, their relation to recent clinical trials and future implications.

This article is part of the Frontotemporal Dementia special issue.
Diagnostic and prognostic value of serum human epididymis protein 4 in patients with primary fallopian tube carcinoma
Authors: Mi Dong , Zhang Yue‐Xiang , Wang Cheng‐Jin , Feng Qiang , Qi Pei , Chen Shu‐Qin
Published: June 2016

Aim

The aim of our study was to assess the levels of human epididymis protein 4 (HE4) with the common tumor marker carbohydrate antigen 125 (CA125) in the diagnosis and monitoring of therapy for primary fallopian tube carcinoma (PFTC).

Methods

Serum HE4 and CA125 levels from 82 PFTC patients and 154 patients with benign pelvic masses as the control were measured by Roche electrochemiluminescent immunoassay. HE4 determinations for surgery response and recurrence monitoring were assessed in PFTC patients.

Results

Serum HE4 and CA125 concentrations were significantly higher in PFTC patients compared with those seen in patients with benign pelvic masses (P < 0.001). Compared with CA125, HE4 had higher specificity, but lower sensitivity whether at early or advanced stage, and the combination of HE4 + CA125 led to higher sensitivity and specificity. HE4 + CA125 performed significantly better than CA125 or HE4 alone in early stage patients. In early stage the sensitivity was 35.7% for HE4 and 64.3% for CA125, while sensitivity for the combination of HE4 and CA125 could reach 71.4%. Furthermore, the two markers were associated with the progression and histology of PFTC. Serum HE4 level was closely correlated with surgical therapy. PFTC patients displayed a greater decline in the level of HE4 compared with CA125 (76.4% vs 55.7%). Combined with CA125, HE4 elevation better predicted recurrence in PFTC patients.

Conclusions

This study indicated that serum HE4 levels are closely associated with PFTC and the outcome of surgical therapy and recurrence in Chinese patients.
Genetics of parathyroid tumours
Authors: Thakker R. V.
Published: June 2016

Primary hyperparathyroidism (PHPT), due to parathyroid tumours, may occur as part of a complex syndrome or as an isolated (nonsyndromic) disorder, and both forms can occur as familial (i.e. hereditary) or nonfamilial (i.e. sporadic) disease. Syndromic PHPT includes multiple endocrine neoplasia (MEN) types 1 to 4 (MEN1 to MEN4) and the hyperparathyroidism‐jaw tumour (HPT‐JT) syndrome. Syndromic and hereditary PHPT are often associated with multiple parathyroid tumours, in contrast to sporadic PHPT, in which single parathyroid adenomas are more common. In addition, parathyroid carcinomas may occur in ~15% of patients with the HPT‐JT syndrome. MEN1 is caused by abnormalities of the MEN1 gene which encodes a tumour suppressor; MEN2 and MEN3 are due to mutations of the rearranged during transfection (RET) proto‐oncogene, which encodes a tyrosine kinase receptor; MEN4 is due to mutations of a cyclin‐dependent kinase inhibitor (CDNK1B); and HPT‐JT is due to mutations of cell division cycle 73 (CDC73), which encodes parafibromin. Nonsyndromic PHPT, which may be hereditary and referred to as familial isolated hyperparathyroidism, may also be due to MEN1, CDC73 or calcium‐sensing receptor (CASR) mutations. In addition, ~10% of patients presenting below the age of 45 years with nonsyndromic, sporadic PHPT may have MEN1, CDC73 or CASR mutations, and overall more than 10% of patients with PHPT will have a mutation in one of 11 genes. Genetic testing is available and of value in the clinical setting, as it helps in making the correct diagnosis and planning the management of these complex disorders associated with parathyroid tumours.
Targeting orphan G protein‐coupled receptors for the treatment of diabetes and its complications: C‐peptide and GPR146
Authors: Kolar G. R. , Grote S. M. , Yosten G. L. C.
Published: June 2016

G protein‐coupled receptors (GPCRs) are the most abundant receptor family encoded by the human genome and are the targets of a high percentage of drugs currently in use or in clinical trials for the treatment of diseases such as diabetes and its associated complications. Thus, orphan GPCRs, for which the ligand is unknown, represent an important untapped source of therapeutic potential for the treatment of many diseases. We have identified the previously orphan GPCR, GPR146, as the putative receptor of proinsulin C‐peptide, which may prove to be an effective treatment for diabetes‐associated complications. For example, we have found a potential role of C‐peptide and GPR146 in regulating the function of the retinal pigment epithelium, a monolayer of cells in the retina that serves as part of the blood–retinal barrier and is disrupted in diabetic macular oedema. However, C‐peptide signalling in this cell type appears to depend at least in part on extracellular glucose concentration and its interaction with insulin. In this review, we discuss the therapeutic potential of orphan GPCRs with a special focus on C‐peptide and GPR146, including past and current strategies used to ‘deorphanize’ this diverse family of receptors, past successes and the inherent difficulties of this process.
Spinal Cord MR Diffusion Properties in Patients with Degenerative Cervical Cord Compression
Authors: Keřkovský Miloš , Bednařík Josef , Jurová Barbora , Dušek Ladislav , Kadaňka Zdeněk , Kadaňka Zdeněk , Němec Martin , Kovaľová Ivana , Šprláková‐Puková Andrea , Mechl Marek
Published: June 2016

BACKGROUND AND PURPOSE

Diffusion tensor imaging (DTI) has previously been used as a biomarker of myelopathy in patients with degenerative cervical cord compression (DCCC). However, many factors may affect the diffusion properties of the spinal cord. This prospective study seeks to identify sources of variability in spinal cord DTI parameters in both DCCC patients and healthy subjects.

METHODS

The study group included 130 patients with DCCC confirmed by magnetic resonance imaging and 71 control subjects without signs of DCCC. DTI data of the cervical spine were acquired in all subjects. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured at different levels of the spinal cord (SCLs). Statistical data analysis was then used to determine diffusion parameters in terms of age, sex, SCL, and spinal cord compression.

RESULTS

Significant variations in FA and ADC values emerged when several spinal cord levels were mutually compared in the control group. FA values correlated significantly with age in the DCCC group and sex had a significant influence on ADC values in both groups. The two diffusion parameters in the DCCC group differed significantly between patients with clinical signs of mild‐to‐moderate myelopathy compared with asymptomatic patients, and correlated with measurements of spinal canal morphology.

CONCLUSIONS

Diffusion parameters of the cervical spinal cord were thus shown to respond significantly to spinal cord compression, but were subject to interaction with several other factors including sex, age, and SCL. These findings may be important to the interpretation of DTI measurements in individual patients.
Comparative genomics revealed the origin and evolution of autophagy pathway
Authors: Yang Jian , Chai Xiao‐Qiang , Zhao Xian‐Xian , Li Xiao
Published: June 2016

Autophagy is prevalent in eukaryotic organisms. Massive research efforts have focused on the mechanism and functionality of autophagy in eukaryotes, for example, their role in human diseases. However, little is known about how this fundamental pathway evolved; in particular, there is an absence of research in prokaryotes. Here, we carried out a comparative genomics analysis among 84 species ranging from eukaryotes to eubacteria and archaebacteria. We found that most of the core proteins in the autophagy pathway were ubiquitous in eukaryotes, whereas the distribution of proteins involved in selective autophagy were limited. In prokaryotes, distant homologs of autophagy‐related proteins were also found. Species in Cyanobacteria and Euryarchaeota possess relatively more of these homologs compared to other prokaryotes, which indicated the prokaryotic origin of some autophagy‐related proteins. Phylogenic tree analysis and the distribution of homologs suggested that the presence of proteins involved in autophagosome formation should be an important sign of autophagy. Furthermore, we found that distribution of mitochondrial protein importing‐related proteins was quite similar to that of autophagy‐related proteins in eukaryotes and that their phylogenic profile was closer to that of several core autophagy proteins compared with 16S/18S ribosomal RNAs, suggesting the engulfment of mitochondria may be the driving force for the evolution of autophagy. Autophagy may have evolved as a quality control system for mitochondria at the very beginning of evolution of eukaryotes. This research shed light on the prokaryotic origin of autophagy and provided a new perspective that mitochondria and autophagy may interplay during the course of eukaryotic evolution.
In Vitro and In Vivo Characterization of a Fully Felinized Therapeutic Anti‐Nerve Growth Factor Monoclonal Antibody for the Treatment of Pain in Cats
Authors: Gearing D.P. , Huebner M. , Virtue E.R. , Knight K. , Hansen P. , Lascelles B.D.X. , Gearing R.P. , Drew A.C.
Published: June 2016

Background

Limited options are available for the treatment of pain in cats. Monoclonal antibodies (mAbs) that neutralize nerve growth factor (NGF) have demonstrated analgesic capacity in rodent models, people with osteoarthritis, and dogs with degenerative joint disease.

Hypothesis/Objectives

This study describes the design and characterization of a fully felinized anti‐NGF monoclonal antibody. In vitro potency, pharmacokinetics, and the ability of the antibody to treat pain in a self‐resolving, acute inflammation model were investigated in cats.

Animals

Thirty‐eight cats at a research colony at Charles River Laboratories, Ireland.

Methods

Felinized anti‐NGF mAb, NV‐02, was produced using a complementary DNA (cDNA)‐based method (PETization). Purified NV‐02 was tested for affinity, potency, and immunoreactivity in vitro, then for safety and plasma pharmacokinetic distribution in vivo, and analgesic efficacy in a model of kaolin‐induced inflammatory pain.

Results

Anti‐NGF mAb, NV‐02 neutralized NGF with high affinity and potency and did not bind complement. NV‐02‐administered SC had a plasma half‐life of 7–15 days and was well tolerated at dosages up to 28 mg/kg. A dosage of 2 mg/kg NV‐02 SC significantly decreased signs of lameness on day 2 (P = .0027), day 3 (P = .016), day 4, (P = .0063), day 5 (P = .0085), day 6 (P = .0014), and day 7 (P = .0034) after induction of inflammation.

Conclusions and Clinical Importance

The high affinity, long plasma half‐life, safety, and analgesic efficacy of felinized anti‐NGF mAb (NV‐02) support further investigation of the analgesic potential of this antibody in the cat.
Effects of Thyroxin and Domperidone on Oocyte Maturation and Spawning Performances in the Rabbit Fish, Siganus guttatus
Authors: Pham Hung Q. , Le Hoang M.
Published: June 2016

Thyroxin (T4) is proven to have various functions in fish reproduction. In this study, we investigated oocyte maturation and spawning performance in the rabbit fish, Siganus guttatus, orally exposed to different doses of T4 (0.05, 0.25, and 0.5 mg/kg fish) during vitellogenesis. No statistically significant differences of reproductive characteristics were observed among the treatments. However, the group that was exposed to the dose of 0.5 mg/kg spawned after receiving a hormone injection. The findings suggest that feeding T4 during vitellogenesis did not advance oocyte maturation, but probably could induce spawning in rabbit fish. In a separate experiment, we investigated the effects of orally administered domperidone (DOM) on reproductive performances of the female rabbit fish. The study showed that oral administration of DOM during the early stages of the reproductive cycle had no significant effects on oocyte maturation and spawning performance. Overall, these findings suggest that DOM may not be needed for the induction of maturation and spawning of this species under aquaculture conditions. These practical investigations were conducted with a view to attempt reducing drug use, production costs, and support sustainable aquaculture.
Reflected‐light Influences the Coloration of the Peppermint Shrimp, Lysmata boggessi (Decapoda: Caridea)
Authors: Calvo Natalia S. , RoldÁn‐Luna Magaly , Argáez‐Sosa Jorge A. , Martínez‐Moreno Gemma L. , Mascaró Maite , Simões Nuno
Published: June 2016

One alternative to contribute to the reduction of the pressure on coral reef ecosystems brought about by an increasing demand for marine aquarium ornamentals is to improve and further develop the culture of desirable species for trade. Peppermint shrimp from the genus Lysmata are among the most intensively traded decapod in the trade and while several studies have been conducted to improve its culture, individuals obtained from culture facilities are generally paler than those collected from the wild. Because color is a fundamental component of the price tag on most marine ornamental live species, poorly colored animals command a lower price, reducing competitiveness. In this study, we evaluate the influence of tank background color (reflected light) on the morphological coloration change of Lysmata boggessi. In a 15‐d experiment, 30 individuals were exposed either to reflected‐red or white light and the relative change of coloration between initial and final moments was quantified with photography (RGB color model). At the end of the experimental period, shrimp exposed to red‐reflected light presented a more intense red coloration than those exposed to white‐reflected light. These results demonstrate that a simple change in background tank color can enhance shrimp external coloration. Such a cheap‐to‐implement procedure can support the culture of more colorful, hence more valuable ornamental shrimp that can compete with those captured from the wild.
Memantine‐induced sustained unconsciousness
Authors: Kitagawa Naoyuki , Sakurai Michio
Published: June 2016

Memantine, which is an N‐methyl‐d‐aspartate receptor antagonist, is used for symptomatic treatment of moderate to severe Alzheimer's disease. Here, we present two cases of sustained unconsciousness after the use of memantine. Both cases developed consciousness disturbance after administration of memantine, and one showed myoclonus in the extremities. The elevated blood concentration of memantine might have been responsible for the unconsciousness in these cases. Ketamine, which is used as an anesthetic agent, is also a non‐competitive N‐methyl‐d‐aspartate receptor antagonist. It is possible that memantine exerts a sedative effect in a similar manner to ketamine. Care should be taken in use of memantine in elderly patients or in those with renal impairment.
Can deep brain stimulation be a therapeutic option for Parkinson's disease dementia?
Authors: Kim Han‐Joon , Jeon Beomseok , Lee Jee‐Young , Paek Sun Ha
Published: June 2016

Background

Although dementia is regarded as a contraindication for deep brain stimulation in patients with Parkinson's disease, there exist patients with Parkinson's disease dementia who can benefit motorically from deep brain stimulation.

Aim

To review the clinical outcome of deep brain stimulation in patients with Parkinson's disease dementia and discuss whether deep brain stimulation can be a therapeutic option in those patients.

Methods

We report five patients who underwent bilateral subthalamic deep brain stimulation despite the presence of dementia at the preoperative evaluations because of the presence of medically intractable motor and non‐motor symptoms that could be relieved by deep brain stimulation.

Results

After surgery, motor symptoms improved greatly, and some non‐motor symptoms also improved in all patients. However, in four patients, the motor improvements lasted just 2 or 3 years, and then, the patients deteriorated with the emergence of end‐stage problems despite there being more continued benefit that could not have been achieved by medical treatment. The remaining one patient showed excellent response until the last follow‐up at 7 years after surgery.

Conclusion

Deep brain stimulation provides some benefit not provided by medical treatment alone to patients with Parkinson's disease dementia, although its benefits do not last as long as in non‐demented patients. However, this benefit does not necessarily mean that deep brain stimulation can be performed in patients with Parkinson's disease dementia. More discussion is required on whether deep brain stimulation in Parkinson's disease dementia can be justified and in which patients it should be carried out.
The Arabidopsis leaf transcriptome reveals distinct but also overlapping responses to colonization by phyllosphere commensals and pathogen infection with impact on plant health
Authors: Vogel Christine , Bodenhausen Natacha , Gruissem Wilhelm , Vorholt Julia A.
Published: June 2016

Plants are colonized by a variety of bacteria, most of which are not pathogenic. Currently, the plant responses to phyllosphere commensals or to pathogen infection in the presence of commensals are not well understood.

Here, we examined the transcriptional response of Arabidopsis thaliana leaves to colonization by common commensal bacteria in a gnotobiotic system using RNA sequencing and conducted plant mutant assays.

Arabidopsis responded differently to the model bacteria Sphingomonas melonis Fr1 (S.Fr1) and Methylobacterium extorquens PA1 (M.PA1). Whereas M.PA1 only marginally affected the expression of plant genes (< 10), S.Fr1 colonization changed the expression of almost 400 genes. For the latter, genes related to defense responses were activated and partly overlapped with those elicited by the pathogen Pseudomonas syringae DC3000 (Pst). As S.Fr1 is able to mediate plant protective activity against Pst, we tested plant immunity mutants and found that the pattern‐recognition co‐receptor mutant bak1/bkk1 showed attenuated S.Fr1‐dependent plant protection.

The experiments demonstrate that the plant responds differently to members of its natural phyllosphere microbiota. A subset of commensals trigger expression of defense‐related genes and thereby may contribute to plant health upon pathogen encounter.
Airway reflux
Authors: Johnston Nikki , Ondrey Frank , Rosen Rachel , Hurley Bryan P. , Gould Jon , Allen Jacquie , DelGaudio John , Altman Kenneth W.
Published: June 2016

An ever‐increasing number of adult and pediatric disorders have been shown to be influenced or caused by airway reflux. This has become a controversial and complicated aspect of medicine that requires a multidisciplinary approach. Evidence indicates that it is not only the acidic components of gastric refluxate that injure extraesophageal tissues but also the nonacidic components, such as pepsin and bile. There is a realization that proton pump inhibitors will not be effective when nonacidic components of refluxate are causing the problem. New in vitro and in vivo models for the study of airway reflux and new therapeutic and surgical approaches are discussed in this review article.
The virtual esophagus: investigating esophageal functions in silico
Authors: Du Peng , Yassi Rita , Gregersen Hans , Windsor John A. , Hunter Peter J.
Published: June 2016

Esophageal and gastroesophageal junction (GEJ) diseases are highly prevalent worldwide and are a significant socioeconomic burden. Recently, applications of multiscale mathematical models of the upper gastrointestinal tract have gained attention. These in silico investigations can contribute to the development of a virtual esophagus modeling framework as part of the larger GIome and Physiome initiatives. There are also other modeling investigations that have potential screening and treatment applications. These models incorporate detailed anatomical models of the esophagus and GEJ, tissue biomechanical properties and bolus transport, sensory properties, and, potentially, bioelectrical models of the neural and myogenic pathways of esophageal and GEJ functions. A next step is to improve the integration between the different components of the virtual esophagus, encoding standards, and simulation environments to perform more realistic simulations of normal and pathophysiological functions. Ultimately, the models will be validated and will provide predictive evaluations of the effects of novel endoscopic, surgical, and pharmaceutical treatment options and will facilitate the clinical translation of these treatments.
Rare tumors of esophageal squamous mucosa
Authors: Tripathi Monika , Swanson Paul E.
Published: June 2016

In spite of increasing incidence of esophageal adenocarcinoma in the last few decades, esophageal squamous cell carcinoma (SCC) still remains the dominant subtype of esophageal cancer worldwide. Apart from conventional SCC, some rare unconventional tumors of esophageal squamous mucosa are also well known. This study provides an introduction to these and presents a brief review of the literature, including the diagnostic and prognostic importance of each variant.