bluuebunny/crossref_metadata_2025 huggingface dataset:
The Elution Kinetics of BMP-2, BMP-4, and BMP-7 From a Commercial Human Demineralized Bone Matrix Putty
Authors: Pietrzak William S. , Ali Saba N.
Published: September 2017

Bone morphogenetic proteins (BMPs) are associated with bone extracellular matrix and impart osteoinductive properties to demineralized bone matrix (DBM) grafts. The first step of the osteoinductive process is BMP release from DBM in situ; however, this has not been characterized for human DBM. The authors investigated the release of BMPs 2, 4, and 7 from a clinical human DBM putty (Bonus II DBM, Biomet Inc, Warsaw, IN). The DBM was placed in Sorensen buffer and the BMP concentrations in the Sorensen buffer and guanidine extracts of the DBM were measured concurrently by enzymelinked immunosorbant assay for up to 7 days. The baseline DBM concentrations were BMP-2: 28.1 ± 1.3 ng/g DBM, BMP-4: 0.577 ± 0.056 ng/g DBM, and BMP-7: 92.9 ± 7.5 ng/g DBM. Relative to baseline, the proportions released by 7 days were 11.1%, 3.9%, and 29.3%, respectively. The early (0–8 hour) and late (8–168 hours) elution rates were BMP-2: 0.16 ± 0.24 and 0.0089 ± 0.012 ng/(g DBM hr), and BMP-7: 1.29 ± 2.1 and 0.086 ± 0.039 ng/(g DBM hr), respectively. Little BMP-4 elution occurred over the first 24 hours, with the rate for the remaining interval being 0.00014 ± 0.00021 ng/(g DBM hr). The apparent DBM BMP profiles were counterintuitive in that the concentrations increased from baseline for some, or all, of the 7 days instead of monotonically decreasing. Similar behavior has previously been reported in bovine studies. This provides further evidence that BMPs are associated with at least 2 compartments in DBM differing by their affinity for BMPs and that guanidine extraction of BMPs is not 100% efficient.
Bilateral Submental Flap: An Innovative Modification
Authors: Gadre Kiran , Gadre Pushkar , Singh Divya , Shetty Anushri , Malu Ankit
Published: September 2017

Early management of premalignant lesions like oral submucous fibrosis cannot be underestimated in context of prevention and control of oral malignancies. Soft tissue reconstruction of the oral cavity and face is a complex undertaking. Several flaps local and distant as well as microvascular are available, each with their pros and cons. Microvascular free flaps lay a considerable burden on resources, expertise, increased operating time, and logistics. Simple and technically reproducible alternatives are needed to tackle these issues, more so in developing countries like ours. Submental flap is based on a large branch of the facial artery and was initially described in 1993 by Martin et al as an excellent option in head and neck reconstruction. We describe innovative modification of the submental flap based on concept of bilateral presence of facial and submental vasculature and thus can be used for bilateral cheek reconstruction. We use pedicled bilateral submental flap (BSF) by dividing the oval skin paddle obliquely, maintaining needed length. The best use of the BSF is in reconstruction of cheek defect, after surgical release of grade IV oral submucous fibrosis, a debilitating affliction commonly affecting young productive adults and seen in Indian subcontinent. The technique was used successfully in 20cases with minor complications.
Inflammatory Urinary Cytokine Expression and Quality of Life in Patients With Overactive Bladder
Authors: Pillalamarri Nirmala , Shalom Dara F. , Pilkinton Marjorie L. , Winkler Harvey A. , Chatterjee Prodyot K. , Solanki Malvika , Metz Christine N.
Published: September 2017

Objective

The aims of this study were to analyze levels of selected inflammatory urinary cytokines/chemokines in subjects with overactive bladder (OAB) and to determine if cytokine/chemokine levels correlate with quality of life and symptom distress.

Methods

This prospective, case-control pilot analysis included 23 women with OAB and 22 control subjects. Overactive bladder subjects were enrolled if they had symptoms of urinary frequency, urgency, or urge incontinence for more than 3 months and urodynamic evidence of detrusor overactivity. Control subjects denied urinary symptoms. Subjects and control subjects were excluded if they had known inflammatory bladder or systemic conditions, cystitis, stones, or recent anticholinergic use. Urine samples were collected from each subject and control. Subjects filled out the Incontinence Quality of Life Questionnaire and the Urinary Distress Inventory Questionnaire 6. Cytokine/chemokine levels were determined using the multiplexed Meso Scale Discovery Platform and were corrected for urinary creatinine concentrations. Statistical analysis comparing cytokine/chemokine levels was performed using the Mann-Whitney U test; relationships between cytokine/chemokine and questionnaire scores were calculated with Spearman correlation coefficient.

Results

Subjects with OAB had significantly lower urinary interleukin 10 (IL-10), IL-12-p70, and IL-13 levels compared with control subjects. Interleukin 1 correlated with worsening symptom distress on Urinary Distress Inventory Questionnaire 6.

Conclusions

To our knowledge, this is at present the only study correlating inflammatory cytokine/chemokine levels in women with OAB with quality of life and distress. Interleukin 1 signified worsening distress, whereas IL-10, IL-12p70, and IL-13 were the only cytokines found at different levels in subjects. Our findings support a larger study in order to evaluate the value of urinary cytokines/chemokines as potential biomarkers.
Expedited Assessment of Terrestrial Arthropod Diversity by Coupling Malaise Traps with DNA Barcoding
Authors: deWaard JR , Levesque-Beaudin V , deWaard SL , Ivanova NV , McKeown JTA , Miskie R , Naik S , Perez K , Ratnasingham S , Sobel CN , Sones JE , Steinke C , Telfer AC , Young AD , Young MR , Zakharov EV , Hebert PDN
Published: September 2017

Monitoring changes in terrestrial arthropod communities over space and time requires a dramatic increase in the speed and accuracy of processing samples that cannot be achieved with morphological approaches.

The combination of DNA barcoding and Malaise traps allows expedited, comprehensive inventories of species abundance whose cost will rapidly decline as high-throughput sequencing technologies advance.

Aside from detailing protocols from specimen sorting to data release, this paper describes their use in a survey of arthropod diversity in a national park that examined 20,000 specimens representing 2200 species.

These protocols can support arthropod monitoring programs at regional, national, and continental scales.
Synaptic co-transmission of acetylcholine and GABA regulates hippocampal states
Authors: Takács Virág T. , Cserép Csaba , Schlingloff Dániel , Pósfai Balázs , Szőnyi András , Sos Katalin E. , Környei Zsuzsanna , Dénes Ádám , Gulyás Attila I. , Freund Tamás F. , Nyiri Gábor
Published: September 2017

The basal forebrain cholinergic system is widely assumed to control cortical functions via non-synaptic transmission of a single neurotransmitter, acetylcholine. Yet, using immune-electron tomographic, molecular anatomical, optogenetic and physiological techniques, we find that mouse hippocampal cholinergic terminals invariably establish synapses and their vesicles dock at synapses only. We demonstrate that these synapses do not co-release but co-transmit GABA and acetylcholine via different vesicles, whose release is triggered by distinct calcium channels. This co-transmission evokes fast composite postsynaptic potentials, which are mutually cross-regulated by presynaptic auto-receptors and display different short-term plasticity. The GABAergic component alone effectively suppresses hippocampal sharp wave-ripples and epileptiform activity. The synaptic nature of the forebrain cholinergic system with differentially regulated, fast, GABAergic and cholinergic co-transmission suggests a hitherto unrecognized level of synaptic control over cortical states. This novel model of hippocampal cholinergic neurotransmission could form the basis for alternative pharmacotherapies after cholinergic deinnervation seen in neurodegenerative disorders.

Supplementary materials are attached after the main text.
The importance of geometry in the corneal micropocket angiogenesis assay
Authors: Grogan James A. , Connor Anthony J. , Pitt-Francis Joe M. , Maini Philip K. , Byrne Helen M.
Published: September 2017

The corneal micropocket angiogenesis assay is an experimental protocol for studying vessel network formation, or neovascularization,in vivo. The assay is attractive due to the ease with which the developing vessel network can be observed in the same animal over time. Measurements from the assay have been used in combination with mathematical modeling to gain insights into the mechanisms of angiogenesis. While previous modeling studies have adopted planar domains to represent the assay, the hemispherical shape of the cornea and asymmetric positioning of the angiogenic source can be seen to affect vascular patterning in experimental images. As such, we aim to better understand: i) how the geometry of the assay influences vessel network formation and ii) how to relate observations from planar domains to those in the hemispherical cornea. To do so, we develop a three-dimensional, off-lattice mathematical model of neovascularization in the cornea, using a spatially resolved representation of the assay for the first time. Relative to the detailed model, we predict that the adoption of planar geometries has a noticeable impact on vascular patterning, leading to increased vessel ‘merging’, or anastomosis, in particular when circular geometries are adopted. Significant differences in the dynamics of diffusible aniogenesis simulators are also predicted between different domains. In terms of comparing predictions across domains, the ‘distance of the vascular front to the limbus’ metric is found to have low sensitivity to domain choice, while metrics such as densities of tip cells and vessels and ‘vascularized fraction’ are sensitive to domain choice. Given the widespread adoption and attractive simplicity of planar tissue domains, bothin silicoandin vitro, the differences identified in the present study should prove useful in relating the results of previous and future theoretical studies of neovascularization toin vivoobservations in the cornea.

Author summary

Neovascularization, or the formation of new blood vessels, is an important process in development, wound healing and cancer. The corneal micropocket assay is used to better understand the process and, in the case of cancer, how it can be controlled with drug therapies for improved patient outcomes. In the assay, the hemispherical shape of the cornea can influence the way the vessel network forms. This makes it difficult to directly compare results from experiments with the predictions of mathematical models or cell culture experiments, which are typically performed on flat substrates or planar matrices. In this study, we use mathematical modeling to investigate how the hemispherical shape of the cornea affects vessel formation and to identify how sensitive different measurements of neovascularization are to geometry.
Persistent increases of PKMζ in sensorimotor cortex maintain procedural long-term memory storage
Authors: Gao Peng P. , Goodman Jeffrey H. , Sacktor Todd C. , Francis Joseph T.
Published: September 2017

Procedural memories, such as for riding a bicycle, can be maintained without practice for long periods of time and are thought to be supported by the persistent reorganization of sensorimotor cortices (S1/M1). Whereas enhanced synaptic strength and structural changes accompany the learning of motor tasks, the persistent molecular modifications that store long-term procedural memories within specific layers of sensorimotor cortex have not been identified. The persistent increase in the autonomously active, atypical PKC isoform, PKMζ, is a putative molecular mechanism for maintaining enhanced synaptic strength during long-term potentiation (LTP) and several forms of long-term memory. Here we examine whether persistent increases in PKMζ store long-term memory for a reaching task in rat sensorimotor cortex that could reveal the sites of procedural memory storage. Perturbing PKMζ synthesis with PKMζ -antisense oligodeoxynucleotides or blocking atypical PKC activity with zeta inhibitory peptide (ZIP) in S1/M1 disrupts and erases the maintenance of long-term motor memories. Only memories that are maintained without daily reinforcement are affected, indicating atypical PKCs (via ZIP) and PKMζ specifically (via antisense) stores consolidated long-term procedural memories. Analysis of changes in the amount of PKMζ in S1/M1 reveals PKMζ increases in layers II/III and V of both S1 and M1 cortices as performance improves to an asymptote during training. After storage for 1 month without reinforcement, the increase in M1 layer V but not other layers persists without decrement. Thus, the sustained increases in PKMζ reveal that the persistent molecular changes storing long-term procedural memory are localized to the descending output layer of primary motor cortex.
Sepsis: Partial least squares structural equation modelling (PLS-SEM) suggests a critical role for anti-inflammatory responses in clinical severity
Authors: Mukherjee Ratnadeep , Kanti Barman Pijus , Thatoi Pravat , Kumar Prusty Birendra , Tripathy Rina , Kumar Das Bidyut , Ravindran Balachandran
Published: September 2017

Backgorund

Despite major advances in medicine, Sepsis remains one of the major killers in critical care wards around the world. For several years it was widely believed that an early pro-inflammatory host response is followed by an overwhelming anti-inflammatory phase. The hypo-inflammatory status, termed as ‘Compensatory anti-inflammatory response syndrome’ (CARS), was proposed to be the primary cause of sepsis-associated mortality. However, this paradiam changed in recent years since there was little evidence to support the linear model of host response and pathogenesis in sepsis. Currently held view is that both inflammatory and anti-inflammatory host responses are stimulated in an overlapping manner. In this study a robust statistical model to study the complex interplay of host cytokines in human sepsis has been developed to evaluate host responses in sepsis that contribute significantly to clinical pathology.

Methods

Twentyseven cytokines/ chemokines were quantified in 139 sepsis patients and multivariate analysis of variance (MANOVA) was performed to assess differences in host responses in different categories of clinical severity. Partial least squares regression based structural equation modelling (PLS-SEM) was used to assess interactions between different groups of cytokines and their contribution to clinical pathology. An array of 23 cytokines was analysed in a mouse model of endotoxemia and a similar mathematical model was constructed.

Results

The results of MANOVA demonstrated the ability of combined cytokine response to discriminate sepsis patients according to clinical severity or outcome. Structural equation modelling revealed strong positive association between inflammatory and anti-inflammatory cytokines. In human sepsis, anti-inflammatory cytokines emerged as a significant entity associated with clinical severity as assessed by APACHE II scores.

Conclusion

PLS-SEM modeling of cytokine responses and APACHE II score in human sepsis revealed that anti-inflammatory molecules contribute significantly towards clinical severity. More critically, the model offers emperical evidence for failures of clinical trials conducted during the last two decades in which antagonists of inflammatory host responses for human Sepsis were used for sepsis. The model also provides credence to the notion that inflammatory and anti-inflammatory host responses occur concurrently in both experimental endotoxemia and in human sepsis.
Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor
Authors: Shuhaibar Leia C. , Robinson Jerid W. , Shuhaibar Ninna P. , Egbert Jeremy R. , Vigone Giulia , Baena Valentina , Kaback Deborah , Yee Siu-Pok , Feil Robert , Fisher Melanie C. , Dealy Caroline N. , Potter Lincoln R. , Jaffe Laurinda A.
Published: September 2017

Activating mutations in fibroblast growth factor (FGF) receptor 3 and inactivating mutations in the NPR2 guanylyl cyclase cause similar forms of dwarfism, but how these two signaling systems interact to regulate bone growth is poorly understood. Here, by use of a mouse model in which NPR2 cannot be dephosphorylated, we show that bone elongation is opposed when NPR2 is dephosphorylated and thus produces less cyclic GMP. By developing an in vivo imaging system to measure cyclic GMP levels in intact tibia, we show that FGF-induced dephosphorylation of NPR2 decreases its guanylyl cyclase activity in growth plate chondrocytes in living bone. Thus FGF signaling lowers cyclic GMP in the growth plate, which counteracts bone elongation. These results define a new component of the signaling network by which activating mutations in the FGF receptor inhibit bone growth.
Physicochemical analysis of Mozzarella cheese produced and developed by the novel EPS‐producing strain Lactobacillus kefiranofaciens ZW3
Authors: Rehman Rizwan‐ur , Wang Yanping , Wang Jinju , Geng Weitao
Published: September 2017

A novel exopolysaccharide‐producing strain Lactobacillus kefiranofaciens ZW3, isolated from Tibetan kefir grain, was used as an adjunct strain to compare the physicochemical, textural and structural properties of Mozzarella cheese also made with market‐available starter cultures and acetic acid‐made cheese. Stretchability, meltability and fat leakage attributes were improved in ZW3‐made cheese. Textural analysis revealed that stain ZW3 improved the hardness and chewiness of the Mozzarella cheese but had little impact on the cohesiveness, elasticity and resilience of Mozzarella cheese. Microstructure studies indicated that ZW3‐made Mozzarella cheese is more filamentous, ropy and compact when compared to the controls cheeses.
Conversion during laparoscopic anterior resection for rectal cancer with a congenital solitary pelvic kidney: A case report
Authors: Takeda Koki , Matsuda Chu , Takahashi Hidekazu , Haraguchi Naotsugu , Nishimura Junichi , Hata Taishi , Mizushima Tsunekazu , Doki Yuichiro , Mori Masaki
Published: September 2017

A 54‐year‐old female patient was hospitalized with a chief complaint of anal discomfort. Based on biopsy results, she was diagnosed with highly differentiated adenocarcinoma, and colonoscopy findings indicated a type 3 rectal tumor. We observed a right pelvic kidney on enhanced abdominal CT. We began a laparoscopic operation but converted to an open operation after resecting the right pelvic renal artery by mistake. After low anterior resection, urologists performed angioplasty of the right renal pelvic artery. The patient was discharged on postoperative day 16, after the preservation of right renal function had been confirmed. This case strongly suggests that it is important to understand the positional relationship of the inferior mesenteric and renal arteries by preoperative assessment using either 3‐D CT angiography or magnetic resonance angiography.
Age‐specific incidence and treatment patterns of head and neck cancer in the Netherlands—A cohort study
Authors: Halmos G.B. , Bras L. , Siesling S. , van der Laan B.F.A.M. , Langendijk J.A. , van Dijk B.A.C.
Published: September 2017

Objectives

To explore the incidence and treatment pattern of head and neck cancer in different age groups.

Design

Cohort study.

Setting

Netherlands Cancer Registry.

Participants

All new primary head and neck cancer cases diagnosed between 2010 and 2014 were included and categorised into different age groups.

Main outcome measures

Tumour site, stage, treatment modality, location of diagnosis and treatment.

Results

The study population was composed of 11 558 tumours. Oral cancer was the most common primary site (31%), followed by laryngeal (25%) and oropharyngeal cancer (22%). Ninety‐six per cent of the entire study population was diagnosed and/or treated in a certified head and neck oncology centre which was lower in the 80+ population (92%). Multimodality treatment was less frequently applied with increasing age (eg oral cavity: 17% in 80+ vs 34% in 60−; P < .001). The percentage of patients not receiving tumour‐directed treatment increased with age (eg oropharyngeal cancer: 25% in 80+ vs 6% in 80−; P < .001).

Conclusions

This study confirms that less multimodal and tumour‐directed treatment is applied with the increasing age of head and neck cancer patients.
Prognostic impact of pre‐treatment neutrophil‐to‐lymphocyte ratio (NLR) in nasopharyngeal carcinoma: A retrospective study of 180 Taiwanese patients
Authors: Liao L.‐J. , Hsu W.‐L. , Wang C.‐T. , Lo W.‐C. , Cheng P.‐W. , Shueng P.‐W. , Hsieh C.‐H. , Chiu Y.‐L. , Lin Y.‐C.
Published: September 2017

Objectives

Nasopharyngeal cancer (NPC) is an endemic disease in Taiwan. Prognostic factors the anatomical TNM stage are important for its prognostic stratification. An elevated neutrophil‐to‐lymphocyte ratio (NLR) has been reported to be associated with poor prognosis in various solid tumours. In this study, we analysed the prognostic impact of the NLR in NPC in Taiwan.

Design

Single‐institution retrospective study.

Setting

Medical centre.

Participants

One hundred and eighty patients with NPC treated at the Far Eastern Memorial Hospital, Taiwan, from January 2007 to December 2013.

Main outcome measures

The association between the clinical or haematological presentations and the prognosis.

Results

The majority of the 180 patients included in this study were men (80%) and were <65 years old (91.7%). A neck mass (55.6%) was the most common clinical presentation, followed by nasal (39.4%) and aural (30.6%) symptoms. In addition, the majority (75.4%) of patients had advanced stage (III and IV) disease. Patients with a high NLR (≧3.6) had significantly lower progression‐free survival, overall survival and disease‐specific survival rates. The association between high NLR and poor prognosis was more pronounced in patients with advanced disease than in those with early‐stage NPC. The results of a multivariate analysis revealed that advanced age, clinical symptoms including headache, diplopia and facial numbness, advanced disease stage, and high NLR were independent prognostic factors.

Conclusion

A high NLR is an independent poor prognostic factor of NPC in Taiwan.
Non‐ST‐elevation myocardial infarction outcomes in patients with type 2 diabetes with non‐obstructive coronary artery stenosis: Effects of incretin treatment
Authors: Marfella Raffaele , Sardu Celestino , Calabrò Paolo , Siniscalchi Mario , Minicucci Fabio , Signoriello Giuseppe , Balestrieri Maria L. , Mauro Ciro , Rizzo Maria R. , Paolisso Giuseppe , Barbieri Michelangela
Published: September 2017

There are insufficient data on the prognosis and management of people with type 2 diabetes who experience a non‐obstructive coronary artery stenosis (NOCS)–non‐ST‐elevation myocardial infarction (NSTEMI) event. We evaluated the 12‐month prognosis of patients with diabetes and NOCS (20%‐49% luminal stenosis) who experience a first NSTEMI as compared with patients without diabetes. In addition, we investigated the 12‐month prognosis in patients with diabetes and NSTEMI‐NOCS previously treated with incretin‐based therapy compared with a matched cohort of patients with NSTEMI‐NOCS never treated with such therapy. We categorized the patients with diabetes as current incretin users (6 months’ treatment with glucagon‐like peptide‐1 agonists or dipeptidyl peptidase‐4 inhibitors) and non‐users of incretins. The endpoint was all‐cause mortality, cardiac death, recurrent acute coronary syndrome (ACS), and heart failure. The unadjusted Kaplan–Meier analysis, and a risk‐adjusted hazard analysis showed that, all‐cause mortality, cardiac death, readmission for ACS and heart failure rates during the 12‐month follow‐up were higher in patients with diabetes and NOCS‐NSTEMI than in those with NOCS‐NSTEMI without diabetes. Among the patients with diabetes, the current incretin users had a significantly lower rate of all‐cause mortality, cardiac death and readmission for ACS at 12 months. In patients with type 2 diabetes and NOCS‐NSTEMI, we observed a higher incidence of 1‐year mortality and adverse cardiovascular outcomes, as compared with patients without diabetes with NOCS‐NSTEMI. In people with diabetes, non‐users of incretins had a worse prognosis than current incretin users.
Phenological and distributional shifts in ichthyoplankton associated with recent warming in the northeast Pacific Ocean
Authors: Auth Toby D. , Daly Elizabeth A. , Brodeur Richard D. , Fisher Jennifer L.
Published: September 2017

Understanding changes in the migratory and reproductive phenology of fish stocks in relation to climate change is critical for accurate ecosystem‐based fisheries management. Relocation and changes in timing of reproduction can have dramatic effects upon the success of fish populations and throughout the food web. During anomalously warm conditions (1–4°C above normal) in the northeast Pacific Ocean during 2015–2016, we documented shifts in timing and spawning location of several pelagic fish stocks based on larval fish samples. Total larval concentrations in the northern California Current (NCC) during winter (January–March) 2015 and 2016 were the highest observed since annual collections first occurred in 1998, primarily due to increased abundances of Engraulis mordax (northern anchovy) and Sardinops sagax (Pacific sardine) larvae, which are normally summer spawning species in this region. Sardinops sagax and Merluccius productus (Pacific hake) exhibited an unprecedented early and northward spawning expansion during 2015–16. In addition, spawning duration was greatly increased for E. mordax, as the presence of larvae was observed throughout the majority of 2015–16, indicating prolonged and nearly continuous spawning of adults throughout the warm period. Larvae from all three of these species have never before been collected in the NCC as early in the year. In addition, other southern species were collected in the NCC during this period. This suggests that the spawning phenology and distribution of several ecologically and commercially important fish species dramatically and rapidly changed in response to the warming conditions occurring in 2014–2016, and could be an indication of future conditions under projected climate change. Changes in spawning timing and poleward migration of fish populations due to warmer ocean conditions or global climate change will negatively impact areas that were historically dependent on these fish, and change the food web structure of the areas that the fish move into with unforeseen consequences.
Longitudinal follow‐up of academic achievement in children with autism from age 2 to 18
Authors: Kim So Hyun , Bal Vanessa H. , Lord Catherine
Published: September 2017

Objective

This study examined early predictors of and changes in school‐age academic achievement and class placement in children referred for autism spectrum disorder (ASD) at age 2.

Method

Of 111 ASD referrals, 74 were diagnosed with ASD at age 18. Regression analyses were performed to identify age 3 predictors of achievement in arithmetic, passage comprehension, word reading, and spelling at ages 9 and 18. Linear Mixed Models were used to examine predictors of academic growth between ages 9 and 18.

Results

Academic skills varied widely at 9 and 18, but were mostly commensurate with or higher than expected given cognitive levels. However, 22% (age 9) and 32% (age 18) of children with average/above average IQ showed below/low average achievement in at least one academic domain. Children who remained in general education/inclusion classrooms had higher achievement than those who moved to special education classrooms. Stronger cognitive skills at age 3 and 9 predicted better academic achievement and faster academic growth from age 9 to 18. Parent participation in intervention by age 3 predicted better achievement at age 9 and 18.

Conclusions

Many children with ASD achieve basic academic skills commensurate with or higher than their cognitive ability. However, more rigorous screening for learning difficulties may be important for those with average cognitive skills because a significant minority show relative academic delays. Interventions targeting cognitive skills and parent participation in early treatment may have cascading effects on long‐term academic development.
Quality assessment of recent evidence‐based clinical practice guidelines for management of type 2 diabetes mellitus in adults using the AGREE II instrument
Authors: Anwer Muhammad A. , Al‐Fahed Ousama B. , Arif Samir I. , Amer Yasser S. , Titi Maher A. , Al‐Rukban Mohammed O.
Published: September 2017

Rationale, aims and objectives

Type 2 diabetes mellitus (T2DM) is a worldwide and national public health problem that has a great impact on the population in Saudi Arabia. High‐quality clinical practice guidelines (CPGs) are cornerstones in improving the health care provided for patients with diabetes. This study evaluated the methodological rigour, transparency, and applicability of recently published CPGs.

Methods

Our group conducted a systematic search for recently published CPGs for T2DM. The searching and screening for Source CPGs were guided by tools from the ADAPTE methods with specific inclusion/exclusion criteria. Five reviewers using the second version of the Appraisal of Guidelines for Research and Evaluation (AGREE II) Instrument independently assessed the quality of the retrieved Source CPGs.

Results

Domains of Scope and purpose and Clarity of presentation received the highest scores in all CPGs. Most of the assessed CPGs (86%) were considered with high overall quality and were recommended for use. Rigour of development and applicability domains were together highest in 3 CPGs (43%). The overall high quality of DM CPGs published in the last 3 years demonstrated the continuous development and improvement in CPG methodologies and standards.

Conclusions

Health care professionals should consider the quality of any CPG for T2DM before deciding to use it in their daily clinical practice. Three CPGs have been identified, using the AGREE criteria, as high‐quality and trustworthy. Ideally, the resources provided by the AGREE trust including the AGREE II Instrument should be used by a clinician to scan through the large number of published T2DM CPGs to identify the CPGs with high methodological quality and applicability.
16p11.2 deletion syndrome mice perseverate with active coping response to acute stress – rescue by blocking 5‐HT2A receptors
Authors: Panzini Chris M. , Ehlinger Daniel G. , Alchahin Adele M. , Guo Yueping , Commons Kathryn G.
Published: September 2017

In humans a chromosomal hemideletion of the 16p11.2 region results in variable neurodevelopmental deficits including developmental delay, intellectual disability, and features of autism spectrum disorder (ASD). Serotonin is implicated in ASD but its role remains enigmatic. In this study we sought to determine if and how abnormalities in serotonin neurotransmission could contribute to the behavioral phenotype of the 16p11.2 deletion syndrome in a mouse model (Del mouse). As ASD is frequently associated with altered response to acute stress and stress may exacerbate repetitive behavior in ASD, we studied the Del mouse behavior in the context of an acute stress using the forced swim test, a paradigm well characterized with respect to serotonin. Del mice perseverated with active coping (swimming) in the forced swim test and failed to adopt passive coping strategies with time as did their wild‐type littermates. Analysis of monoamine content by HPLC provided evidence for altered endogenous serotonin neurotransmission in Del mice while there was no effect of genotype on any other monoamine. Moreover, we found that Del mice were highly sensitive to the 5‐HT2A antagonists M100907, which at a dose of 0.1 mg/kg normalized their level of active coping and restored the gradual shift to passive coping in the forced swim test. Supporting evidence for altered endogenous serotonin signaling was provided by observations of additional ligand effects including altered forebrain Fos expression. Taken together, these observations indicate notable changes in endogenous serotonin signaling in 16p11.2 deletion mice and support the therapeutic utility of 5‐HT2A receptor antagonists.

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Everyday task knowledge and everyday function in dementia
Authors: Roll Emily E. , Giovannetti Tania , Libon David J. , Eppig Joel
Published: September 2017

Tests of everyday action semantics were developed and piloted in a group of healthy adults (n = 53) and then administered to individuals with Alzheimer's disease (AD; n = 17) or Parkinson's disease dementia (PDD; n = 20). Relations between everyday action knowledge and everyday function were explored. Three action semantic tests were developed: Probe Test – 45 forced‐choice questions regarding task sequences, objects, and steps; Picture Sequencing Test – sequential ordering of 4–5 cards depicting task steps; Script Test – open‐ended verbal description of the steps required to complete everyday tasks. Cognitive tests, informant reports of functioning, and the Naturalistic Action Test (NAT), a performance‐based test of function, also were administered to AD and PDD participants. NAT performance was scored for omission (failure to complete steps) and commission (inaccurate performance of step) errors. The AD and PDD groups performed worse than healthy participants on all action semantic tasks. AD and PDD groups significantly differed on only the Script Test – AD participants generated fewer correct steps. Performance on each of the action semantic tests significantly correlated with NAT omission errors. Only the Sequencing Test significantly predicted omissions, commissions, and informant report of everyday functioning. In sum, task knowledge is associated with omissions in everyday tasks and is impaired in both AD and PDD. The ability to accurately sequence task steps is associated with multiple aspects of everyday function and may be easily assessed with picture arrangement.
Assessment of age‐ and sex‐related changes in baggy lower eyelids using a novel objective image analysis method: Orbital gray scale analysis
Authors: Jo Seong‐Jin , Kim Hyung Su , Park Jung Tae , Kim Bo Ri , Youn Sang Woong
Published: September 2017

Background

Baggy lower eyelids (BLEs) are a common aesthetic problem of aging. Valid and reliable assessment tools for BLEs are required to evaluate the current status and treatment outcome.

Aims

Age‐ and sex‐related changes in BLEs were assessed with the orbital gray scale (OGS), a novel objective image analysis method.

Methods

We gathered frontal‐view photographs of the faces of the patients who sought for correction of BLEs. Based on the clinical pattern, we classified the BLEs of the subjects into medial (M), medial and central (MC), and medial to lateral (MCL) types. Severity was evaluated using the OGS, a modified method of the linear gray scale analysis.

Results

The BLEs of 1034 subjects were classified. The most common types were MCL type in the men and MC type in the women, respectively. The M and MC types were common in the young subjects, whereas the MCL type was more common in the old subjects (P < .001). The measurements of OGS in 104 subjects showed positive correlation with age, a higher mean value in the men, and a trend toward higher values in the order of M, MC, and MCL types (P < .001 for central and lateral OGS scores). In a multiple linear regression analysis, central and lateral OGS values were significantly related with age, sex, and M‐C‐L classification type (P < .001).

Conclusion

The M‐C‐L classification and OGS were significantly associated with both age and sex, proving that they could be potent objective assessment tools for BLEs.
Molecular mechanisms of the co‐deposition of multiple pathological proteins in neurodegenerative diseases
Authors: Nonaka Takashi , Masuda‐Suzukake Masami , Hasegawa Masato
Published: September 2017

Intracellular inclusions composed of abnormal protein aggregates are one of the neuropathological features of neurodegenerative diseases, and the formation of intracellular aggregates is believed to be associated with neurodegeneration leading to the onset of these diseases. In typical or pure cases, characteristic pathologies with one particular protein, such as tau, alpha‐synuclein or trans‐activation response DNA protein 43 (TDP‐43), can be observed in brains of patients. On the other hand, multiple protein pathologies co‐exist in many cases, raising the possibility that they may influence each other reciprocally in the pathogenesis and progression of the diseases. However, the molecular mechanisms through which these proteins interact with each other and through which they are co‐deposited in brains of patients remain poorly understood. In this review, we focus on the mechanisms of deposition of multiple pathological proteins, such as tau, alpha‐synuclein and/or TDP‐43, and on co‐deposition models of these proteins in vitro and in vivo intended to recapitulate the multiple pathologies found in diseased brains.
Flashing a smile: Startle eyeblink modulation by masked affective faces
Authors: Duval Elizabeth R. , Lovelace Christopher T. , Gimmestad Katherine , Aarant Justin , Filion Diane L.
Published: September 2017

Affective faces are important stimuli with relevance to healthy and abnormal social and affective information processing. The aim of this study was to investigate the effect of brief presentations of affective faces on attention and emotional state across the time course of stimulus processing, as indexed by startle eyeblink response modulation. Healthy adults were presented with happy, neutral, and disgusted male and female faces that were backward masked by neutral faces. Startle responses were elicited at 300, 800, and 3,500 ms following stimulus presentation to probe early and late startle eyeblink modulation, indicative of attention allocation and emotional state, respectively. Results revealed that, at 300 ms, both face expression and face gender modulated startle eyeblink response, suggesting that more attention was allocated to masked happy compared to disgusted female faces, and masked disgusted compared to neutral male faces. There were no effects of either face expression or face gender on startle modulation at 800 ms. At 3,500 ms, target face expression did not modulate startle, but male faces elicited larger startle responses than female faces, indicative of a more negative emotional state. These findings provide a systematic investigation of attention and emotion modulation by brief affective faces across the time course of stimulus processing.
Spectral integration of English speech for non-native English speakers
Authors: Calandruccio Lauren , Buss Emily
Published: September 2017

When listening in noisy environments, good speech perception often relies on the ability to integrate cues distributed across disparate frequency regions. The present study evaluated this ability in non-native speakers of English. Native English-speaking and native Mandarin-speaking listeners who acquired English as their second language participated. English sentence recognition was evaluated in a two-stage procedure. First, the bandwidth associated with ∼15% correct was determined for a band centered on 500 Hz and a band centered at 2500 Hz. Performance was then evaluated for each band alone and both bands combined. Data indicated that non-natives needed significantly wider bandwidths than natives to achieve comparable performance with just the low or just the high band alone. Further, even when provided with wider bandwidth within each frequency region, non-natives were worse than natives at integrating information across bands. These data support the idea that greater bandwidth requirements and a reduced ability to integrate speech cues distributed across frequency may play an important role in the greater difficulty non-natives often experience when listening to English speech in noisy environments.
Genetics of Nevirapine Metabolic Pathways at Steady State in HIV-Infected Cambodians
Authors: Eloy Philippine , Tessier Adrien , Fan-Havard Patty , Chou Monidarin , Verstuyft Céline , Taburet Anne-Marie , Haas David W. , Bertrand Julie
Published: September 2017

Nevirapine is metabolized by several hepatic cytochrome P450 (CYP) isoforms to generate four primary hydroxylated metabolites: 2-hydroxynevirapine, 3-hydroxynevirapine, 8-hydroxynevirapine, and 12-hydroxynevirapine. The present study characterized associations between genetic polymorphisms and metabolite ratios in HIV-infected Cambodians. We demonstrate associations between
CYP2B6
polymorphisms and metabolite ratios for both 3-hydroxynevirapine and 8-hydroxynevirapine, suggesting involvement of CYP2B6 in generating these metabolites.
Rhesus Macaques Are More Susceptible to Progressive Tuberculosis than Cynomolgus Macaques: a Quantitative Comparison
Authors: Maiello Pauline , DiFazio Robert M. , Cadena Anthony M. , Rodgers Mark A. , Lin Philana Ling , Scanga Charles A. , Flynn JoAnne L.
Published: September 2017

In the past 2 decades, it has become increasingly clear that nonhuman primates, specifically macaques, are useful models for human tuberculosis (TB). Several macaque species have been used for TB studies, and questions remain about the similarities and differences in TB pathogenesis among macaque species, which can complicate decisions about the best species for a specific experiment. Here we provide a quantitative assessment, using serial positron emission tomography and computed tomography (PET-CT) imaging and precise quantitative determination of bacterial burdens of low-dose
Mycobacterium tuberculosis
infection in cynomolgus macaques of Chinese origin, rhesus macaques of Chinese origin, and Mauritian cynomolgus macaques. This comprehensive study demonstrates that there is substantial variability in the outcome of infection within and among species. Overall, rhesus macaques have higher rates of disease progression, more lung, lymph node, and extrapulmonary involvement, and higher bacterial burdens than Chinese cynomolgus macaques. The small cohort of Mauritian cynomolgus macaques assessed here indicates that this species is more similar to rhesus macaques than to Chinese cynomolgus macaques in terms of
M. tuberculosis
infection outcome. These data provide insights into the differences among species, providing valuable data to the field for assessing macaque studies of TB.
What makes a sustainability tool valuable, practical and useful in real-world healthcare practice? A mixed-methods study on the development of the Long Term Success Tool in Northwest London
Authors: Lennox Laura , Doyle Cathal , Reed Julie E , Bell Derek
Published: September 2017

Objectives

Although improvement initiatives show benefits to patient care, they often fail to sustain. Models and frameworks exist to address this challenge, but issues with design, clarity and usability have been barriers to use in healthcare settings. This work aimed to collaborate with stakeholders to develop a sustainability tool relevant to people in healthcare settings and practical for use in improvement initiatives.

Design

Tool development was conducted in six stages. A scoping literature review, group discussions and a stakeholder engagement event explored literature findings and their resonance with stakeholders in healthcare settings. Interviews, small-scale trialling and piloting explored the design and tested the practicality of the tool in improvement initiatives.

Setting

National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Northwest London (CLAHRC NWL).

Participants

CLAHRC NWL improvement initiative teams and staff.

Results

The iterative design process and engagement of stakeholders informed the articulation of the sustainability factors identified from the literature and guided tool design for practical application. Key iterations of factors and tool design are discussed. From the development process, the Long Term Success Tool (LTST) has been designed. The Tool supports those implementing improvements to reflect on 12 sustainability factors to identify risks to increase chances of achieving sustainability over time. The Tool is designed to provide a platform for improvement teams to share their own views on sustainability as well as learn about the different views held within their team to prompt discussion and actions.

Conclusion

The development of the LTST has reinforced the importance of working with stakeholders to design strategies which respond to their needs and preferences and can practically be implemented in real-world settings. Further research is required to study the use and effectiveness of the tool in practice and assess engagement with the method over time.
Improving health, well-being and parenting skills in parents of children with medical complexity: a scoping review protocol
Authors: Bradshaw Sally Rebecca , Shaw Karen , Bem Danai , Cummins Carole
Published: September 2017

Introduction

Less than 1% of children have complex medical conditions but account for one-third of all child health spending. The impact of suboptimal management of this group of children can have a considerable effect on families as well as services. Some families appear to cope more easily than others do, but there are compelling reasons to suggest that effective interventions may improve family coping and ultimately outcomes. Hospitalisation of their child presents a unique set of pressures and challenges for parents, but also an opportunity to intervene. However, the evidence is not well described in relation to this group of families. The primary objective of this scoping review is to identify parent and family-based interventions available to improve parental health, well-being, functioning or skills in the context of a child’s medically complex hospital admission and hospital care.

Methods and analysis

Nine bibliographic databases will be searched spanning medicine, nursing, psychology, education, social work and the grey literature using a combination of index terms and text words related to parents, childhood, chronic illness and interventions. Study eligibility will be assessed by two researchers against preset inclusion and exclusion criteria. Key information from each study will be extracted and charted including year of publication, condition, severity, geographical setting, key concepts and definitions, aims, study population and sample size, methodology/methods, interventions, outcomes and key findings. Directed qualitative content analysis will be used to make sense of narrative findings within the included studies. Results will be presented which summarise the scope of the literature and identify key findings, potential areas for evidence synthesis and research gaps.

Ethics and dissemination

Ethical approval is not required. The results of this review will be disseminated through publication in a peer-reviewed journal and feedback to stakeholders during the development of a hospital-based intervention.