bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic imaging patterns in posterior cortical atrophy and Lewy body dementia
Authors: Gupta Vanshika , Verma Ritu , Ranjan Rajeev , Belho Ethel S. , Seniaray Nikhil , Dinand Veronique , Malik Dharmender , Mahajan Harsh
Published: October 2019

Purpose

To study the imaging patterns of Posterior cortical atrophy (PCA) and Dementia with Lewy bodies (DLB) on fluoro-deoxyglucose positron emission tomography computed tomography ([18F]FDG PET/CT), identify areas of overlap and differences and to develop a prediction model to assist in diagnosis using univariate and multivariate analysis.

Methods

A retrospective analysis of 72 patients clinically suspected of having posterior dementia was done. All patients underwent [18FF]FDG PET/CT of the brain and dopamine transporter imaging with [[99mTc]TRODAT-1 SPECT scan on separate days. The patients were divided into PCA with normal TRODAT uptake (n=34) and DLB with abnormal TRODAT uptake (n=38). The FDG PET/CT uptake patterns were recorded and areas of significant hypometabolism by z score analysis were considered as abnormal. Receiver operator characteristics (ROC) curve analysis was used to determine cutoff z scores and binary logistic regression analysis was used to determine the Odds ratio of being in the predicted groups.

Results

Significantly hypometabolism was found in parieto-temporo-occipital association cortices and cingulate cortices in PCA patients. DLB patients showed significantly reduced uptake in the visual cortex. No significant difference was found between z score of occipital association cortex which showed hypometabolism in both groups. The cut-off z-score values derived from the ROC curve analysis were as follows- parietal association (cut-off-3, sensitivity-65.6%, specificity - 68.7%), temporal association (cut-off-2, sensitivity-78%, specificity-75%) and posterior cingulate (cut-off-0.5, sensitivity-93.7%, specificity-40.6%), their respective Odds ratio (with 95% confidence interval) for being in the PCA group as derived from univariate logistic regression were 3.66 (1.30–10.32), 10.71 (3.36–34.13) and 7.85 (1.57–39.17). The cut-off z score of primary visual cortex as derived from ROC curve was zero with sensitivity of 87.5%, specificity of 71.9%, and the Odds ratio for being the in the DLB group was 24.7 with 95% confidence interval of 5.99–101.85.

Conclusion

[18F]FDG PET may be useful as a non-invasive diagnostic modality in differentiating the two posterior cortical dementias, despite significant overlap. Primary visual cortical hypometabolism can serve as an independent diagnostic marker for DLB, even in the absence of TRODAT imaging.
Pediatric ossiculoplasty: optimizing outcomes
Authors: Kaffenberger Thomas M. , Eichar Bradley , Chi David H.
Published: October 2019

Purpose of review

Despite years of research, pediatric ossiculoplasty remains a challenging surgery with numerous variables factoring into successful outcomes. The aim of this review is to summarize recent publications on surgical technique, timing, and reconstruction materials.

Recent findings

The cause behind ossicular discontinuity does not seem to play a role in hearing results after ossiculoplasty; however, revision surgery is associated with worsening outcomes. The status of the ossicles remains an active area of interest, but the data remain mixed in terms of them playing a role in predicting outcomes in adults and pediatric patients. There remains debate regarding the utility of staging the reconstruction and is often undertaken on a case-by-case basis. Other recent publications highlight positive outcomes associated with canal wall-up procedures, titanium prostheses, and partial ossicular reconstruction prostheses. Endoscopic middle ear surgery in ossiculoplasty has been shown to be successful in monitoring and removal of disease and helpful in reconstruction.

Pediatric ossiculoplasty remains a challenging yet rewarding procedure. The bulk of publications are retrospective making much of the literature difficult to interpret. There remains a need for prospective and well controlled studies in both adult and pediatric populations.
Effects of visual feedback training and visual targets on muscle activation, balancing, and walking ability in adults after hemiplegic stroke: a preliminary, randomized, controlled study
Authors: Pak Noh-Wook , Lee Joon-Hee
Published: October 2019

The aim of this randomized, controlled study was to investigate the effect of visual feedback through visual targets on muscle activity, balance, and gait in stroke patients. Patients were recruited from the inpatient unit of a rehabilitation hospital. Twenty-one patients who had experienced hemiplegic stroke were randomly assigned to two groups: an experimental group (visual feedback training with visual targets on gradual weight shifting), and a control group (visual feedback training on gradual weight shifting). All patients performed 30 minutes of comprehensive rehabilitation therapy followed by an additional 20 minutes of gradual weight shifting using visual feedback training with or without visual targets: three sets per day, five times a week, for 4 weeks. Significantly larger gains were identified in the experimental group compared to the control group due to gluteus medius muscle activation and the weight-bearing ability of the paretic side. Visual feedback training with visual targets during gradual weight bearing on the paretic side appears to improve the muscle activation and balancing abilities of hemiplegic stroke patients compared to visual feedback training alone.
Death by Wheat-Loaded Cartridge
Authors: Okdemir Erdem , Keten Alper , Avşar Abdullah , Kaya Ömer
Published: October 2019

The materials used to produce shotgun ammunition can have different properties depending on the purpose, and ammunition can be fabricated or loaded manually. In Turkey, wheat-loaded cartridges are manufactured for use as sound cartridges. This ammunition is understood by the public to be harmless. However, we present a case of a 13-year-old adolescent boy who was wounded from a contact shot to the chest. An entrance wound measuring 7 cm and 5 cm in diameter was seen on the skin. Wheat grains could not be detected in the internal organs and were only observed between the chest muscles around the entrance wound. A plastic wad was also found in this area. The cause of death was internal bleeding due to internal organ injury. Wheat-loaded cartridges are not visible on x-ray and are difficult to detect visually in the wound.
Steroid Receptor Coactivator-1 Expression in Pheochromocytoma: Clinicopathologic Correlation and Potential Diagnostic Pitfall
Authors: Xiong Meng-Jun , Osunkoya Adeboye O.
Published: October 2019

Pheochromocytoma is a relatively uncommon tumor, and the histomorphologic and biochemical features that may portend malignant behavior have poor overall consensus across various proposed classification systems. Steroid receptor coactivator-1 (SRC-1) is a nuclear protein that mediates transcriptional activity. Current diagnostic applications of SRC-1 are limited, and include distinguishing adrenocortical carcinoma (ACC) from renal cell carcinoma, and other mimickers. SRC-1 expression in pheochromocytoma has not been previously studied. Pheochromocytoma cases were retrieved from our Urological Pathology database and expert consultation files of the senior author, from 2015 to 2019. Clinicopathological data were obtained. SRC-1 expression was scored systematically. Thirty-eight cases were included, with a female predominance, and a mean age of 52 years (range, 16 to 75 y). Seven patients had heritable mutations including RET (n=3), VHL (2), SDHB (1), and ATM and PDGFRA (1). Two patients developed clinical metastasis, who individually had ATM and PDGFRA mutations, and SDHB p.V140F mutation. All heritable tumors were positive for SRC-1, including diffuse/strong staining and intensity in the VHL cases, and diffuse staining with variable intensity in RET cases. Diffuse positivity was seen in most of our heritable cases, providing evidence for a putative link between RET and downstream SRC-1 signaling. An inverse relationship was observed between SRC-1 expression and Pheochromocytoma of the Adrenal Gland Scaled Score/tumor size, suggesting that SRC-1 phenotype may become muted in pheochromocytomas that have malignant potential. SRC-1 expression in aggressive pheochromocytomas, may also be a potential diagnostic pitfall in view of the fact that these tumors may be misinterpreted as ACC in the primary or metastatic setting.
The Effect of Astaxanthin on Random Pattern Skin Flaps
Authors: Gürsoy Koray , Teymur Hakan , Koca Gökhan , Tanas Işikçi Özlem , Göktaş Demircan Fethiye Berna , Kankaya Yüksel , Koçer Uğur
Published: October 2019

Background

Skin flaps are the first-line treatment modality for skin defect reconstruction. With the increased importance and use of flap surgery, a growing number of studies have investigated the ways for the prevention of ischemia-reperfusion injury. The aim of this study was to investigate the effect of astaxanthin, which is an antioxidant molecule from the xanthophyll family, on the survival of random pattern skin flaps.

Methods

Thirty-two Sprague-Dawley rats with a caudally based random pattern skin flap (3 × 9 cm) were divided into 4 groups: group A (astaxanthin orally 1 mg/kg per day), group B (astaxanthin orally 4 mg/kg per day), group C (astaxanthin orally 16 mg/kg per day), and the control group. On postoperative day 7, the flaps were evaluated by photographic, scintigraphic, and histological methods. Photographs were taken to investigate the total flap, necrotic flap, and surviving flap areas. A scintigraphic evaluation was undertaken to analyze the surviving area. The flaps were evaluated histopathologically for vascularization, acute inflammation, and chronic inflammation.

Results

The rate of surviving flap areas was observed to increase in parallel to the increase in the astaxanthin dose. Surviving flap areas and flap perfusion values were higher in group C compared with the control group and group A (P < 0.05). The values were also significantly higher in group B compared with control group (P < 0.05). All study groups were shown to have statistically significantly higher vascular density than the control group (P < 0.05), whereas lymphocyte and neutrophil densities were similar among all groups (P > 0.05). The photographic and scintigraphic evaluations for the viable area percentages of the flaps correlated with each other (r
s = 0.913, P < 0.001).

Conclusions

Orally administered astaxanthin, if given at doses higher than 4 mg/kg, increases flap viability rates and vascularization and can be used as an adjunctive agent.
A Sequential Thoracoacromial Artery Perforator Flap for Reconstructing the Donor Site of Sternocleidomastoid Myocutaneous Flaps
Authors: Song Dajiang , Pafitanis Georgios , Reissis Dimitris , Koshima Isao , Zhang Yixin , Narushima Mitsunaga , Zhou Xiao , Li Zan
Published: October 2019

Background

The current study introduces and demonstrates our experience of using asequentialthoracoacromial artery perforator (TAAP) flap to repair the sternocleidomastoid (SCM) flap donor site in this context. The aims of this technique are to optimize both esthetic and functional outcomes and to reduce postoperative complications for patients.

Methods

Between September 2013 and March 2017, the SCM flap combined with sequential TAAP flap was used for reconstruction postradical parotidectomy in 12 patients. Flap characteristics, patient outcomes, and postoperative complications were monitored and objectively measured, with 10 to 24 months of follow-up.

Results

There were no incidences of total flap loss. All TAAP flap donor sites were closed directly, and all healed without any complications. The SCM flap and TAAP flap donor areas were esthetically acceptable, with good esthetic and functional outcomes achieved in all 12 patients.

Conclusions

The sequential TAAP flap has a consistent vascular supply and provides a reliable surgical approach to reconstruct the SCM flap donor site with good esthetic and functional outcomes.
Gliding Tissue Reconstruction Using a Dorsal Digital Adipofascial Flap in Complex Extensor Injury
Authors: Hosomi Kento , Iwasawa Motonao , Mishima Yoshito , Kawamura Tatsuya , Nagai Fumio
Published: October 2019

Background

Postoperative scar adhesions between tendons and phalanx bones cause persistent disability in complex injuries involving tendons and bones of the hand. Although gliding tissue reconstruction is effective in preventing peritendinous adhesion formation and a dorsal digital adipofascial flap is a reliable method to prevent scar adhesion between tendon and bone after extensor tendon repair, no comparative clinical reports exist. This study aimed to determine the usefulness of a gliding tissue reconstruction method by comparing postoperative range of motion between patients who underwent gliding tissue reconstruction and those who did not.

Methods

Medical records of patients with complex extensor tendon injury who underwent extensor repair between April 2005 and March 2018 were retrospectively analyzed. Ten patients underwent extensor repair with gliding tissue reconstruction using a dorsal digital adipofascial flap and 13 underwent only extensor repair. A triangular flap was separated after zig-zag incision to expose the injured extensor tendon into dermal and adipofascial flaps. The adipofascial flap, based on a dorsal branch of the digital artery, was placed on the injured bone as the tendon gliding surface. The same extensor tendon suture method and rehabilitation protocol were used in both groups. All patients were followed up for 6 to 12 months.

Results

The mean ± SD % total active movements were 84.1% ± 12.4% and 57.6% ± 13.0% in the groups with and without gliding tissue reconstruction, respectively. Significant differences were found between the 2 groups (P < 0.05).

Conclusions

Patients with gliding tissue reconstruction had better functional recovery. This reconstruction is recommended to restore the extensor function in cases of complex extensor injury involving finger tendons and bones.
Evaluation of Direct Surgical Remodeling of Frontal Bossing in Patients With Sagittal Synostosis
Authors: Yen Debra W. , Nguyen Dennis C. , Skolnick Gary B. , Naidoo Sybill , Smyth Matthew D. , Patel Kamlesh B. , Woo Albert S.
Published: October 2019

Background:

The need for surgical correction of frontal bossing in patients with sagittal synostosis is currently debated. The authors retrospectively analyzed frontal bossing in patients with isolated, nonsyndromic sagittal synostosis who underwent calvarial remodeling with and without frontal craniotomy and compared with control subjects.

Methods:

The authors analyzed computed tomography (CT) scans of patients with sagittal synostosis <9 months of age (6.2 ± 1.6 months) who underwent modified-pi procedure either with frontal craniotomy (FC, n = 15) or without frontal craniotomy (NFC, n = 10). Only patients treated with both pre-operative and 1-year post-operative CT scans were included. Non-synostotic age-matched control scans were also analyzed. Cephalic index (CI), 3 previously validated measures of frontal bossing (bossing angle, horizontal bossing ratio, and vertical bossing ratio), and pre-nasion volume ratio were obtained. Additionally, three-dimensional photographs of 10 FC patients were evaluated for frontal bossing between 1 and 8 years post-operatively.

Results:

Pre-operatively, no significant differences were found between the 2 groups (.064<P < 0.940). Both groups showed greater scaphocephaly and frontal bossing compared to controls (P < 0.001). One-year post-operatively, all measures improved but remained significantly different than normal values except: CI of NFC patients (P = 0.296); bossing angle (P = 0.068) and horizontal bossing ratio (P = 0.129) of FC patients. Compared to NFC patients, horizontal bossing ratio was significantly improved in FC patients (P = 0.017, mean difference of 0.047). No other statistically significant differences were found between the 2 techniques (0.127<P < 0.637).

In our long-term study of FC patients up to 9 years of age (n = 10), the authors analyzed forehead inclination as our measure of frontal bossing in three-dimensional photographs. A linear regression analysis showed a significant reduction in forehead inclination with age, decreasing 1.3 ± 0.4 degrees per year (P = 0.021). Forehead inclination for controls did not change significantly with age (P = 0.558).

Conclusions:

At 1-year following modified-pi procedure, FC patients approached normalization of their forehead morphology to a greater extent than NFC patients. However, neither group completely normalized during this time period. Frontal bossing in FC patients continued to decrease with age, which reveals the post-operative dynamic nature of frontal bone morphology during childhood for these patients.
Temporomandibular Joint Ankylosis Following Mandibular Distraction Osteogenesis: A Dreadful Complication
Authors: Schlund M. , Touzet-Roumazeille S. , Nicot R. , Ferri J.
Published: October 2019

Introduction:

Mandibular distraction osteogenesis (MDO) is an effective treatment for severe micrognathia, as it helps to avoid tracheostomy but has some adverse effects on the temporomandibular joint (TMJ). TMJ ankylosis is a serious condition leading to feeding difficulties and growth impairment, and could result in worse consequences in cases with micrognathia who already have limited growth potential. Here, we aimed to report on cases with TMJ ankylosis—a rare but devastating complication of MDO. In total, we described 3 syndromic cases with TMJ ankylosis that developed after MDO and reviewed the associated literature.

Material and Methods:

We retrospectively enrolled 3 patients who presented with TMJ ankylosis following MDO at the Oral and Maxillofacial Surgery Department of the University Hospital of Lille, France.

Results:

All 3 patients had craniofacial syndrome with micrognathia. MDO was performed at least twice in each case, and the 3 patients developed subsequent TMJ ankylosis. They all presented with TMJ ankylosis and micrognathia in our Department.

Discussion:

MDO leads to a certain amount of stress on the TMJ, and in cases with congenital TMJ deformation, such stress could lead to TMJ ankylosis. To our knowledge, 12 cases of TMJ ankylosis after MDO have been described in studies involving 309 patients while it is not reported in other publications. They were all syndromic patients. Thus, TMJ health should be carefully monitored during and after MDO to avoid TMJ ankylosis, and alternative treatments such as costochondral grafts should be considered.
Pituitary Adenoma Deposit in the Nasolabial Region Following Sublabial Transsphenoidal Surgery in the Setting of Nelson Syndrome
Authors: Wallace Aaron , Liu Palmila , Cipriani Nicole A. , Ginat Daniel , Portugal Louis
Published: October 2019

Pituitary adenomas are a group of tumors arising from the anterior pituitary gland, and with the exception of prolactin-secreting adenomas, transsphenoidal resection is the cornerstone of treatment. Although most adenomas are located within the pituitary fossa, ectopic adenomas have been reported, primarily occurring along the route of embryologic development. In this article, we present the case of an ectopic pituitary adenoma in the nasolabial fold that likely resulted from seeding during transsphenoidal resection via sublabial approach.
Trends in the Use of Medications and Supplements to Treat or Prevent Dementia
Authors: Stoehr Gary P. , Jacobsen Erin , Jia Yichen , Snitz Beth E. , Ganguli Mary
Published: October 2019

Objective:

To examine older adults’ use over time of agents to treat or prevent dementia or enhance memory.

Design:

Longitudinal community study with 10-year annual follow-up (2006-2017).

Setting:

Population-based cohort.

Participants:

A total of 1982 individuals with a mean (SD) age of 77 (7.4) years at baseline.

Measurements:

Demographics, self-report, direct inspection of prescription antidementia drugs and nonprescription supplements, cognitive and functional assessments, Clinical Dementia Rating (CDR®) Dementia Staging Instrument.

Results:

Supplement use was reported by 27% to 42% of participants over 10 years. Use was associated with younger age, high school or greater education, good to excellent self-reported health, higher memory test scores, and absence of cognitive impairment or dementia (CDR=0). Over the same period, about 2% to 6% of participants took prescription dementia medications over 10 years. Use was associated with lower memory test scores, at least mild cognitive impairment (CDR≥0.5), fair to poor self-rated health, and high school or lesser education.

Conclusions:

The use of both prescription drugs and supplements increased over time, except for decreases in ginkgo and vitamin E. Prescription drug use appeared in line with prescribing guidelines. Supplement use was associated with higher education and better self-rated health; it persists despite a lack of supportive evidence.
Clustering and Additive Effects of Nongenetic Risk Factors in Non–Autosomal-Dominant Degenerative and Vascular Young Onset Dementia
Authors: Cations Monica , Withall Adrienne , Low Lee-Fay , Radford Kylie , Trollor Julian , Brodaty Henry , Sachdev Perminder , Gonski Peter , Broe Gerald Anthony , Cumming Robert G. , Draper Brian
Published: October 2019

Introduction:

Both genetic and nongenetic factors contribute to the risk profile of young onset dementia (YOD), but risk factors often co-occur. This matched case-control study examined whether nongenetic risk factors cluster together, to inform targeted prevention efforts.

Methods:

Ninety-six participants with non–autosomal-dominant degenerative and/or vascular YOD and 175 controls were recruited to 2 Australian epidemiological studies. Risk exposure was retrospectively self-reported and/or informant-reported.

Results:

Each additional exposure increased the risk for YOD, though only where vascular dementia was included in the analysis. Cluster analysis identified 4 risk groups, one of which reported a high probability of exposure to all risks and a significantly higher risk for YOD.

Discussion:

Results suggest that combinations of nongenetic risk factors confer more risk for young onset vascular dementia, and possibly primary degenerative YOD, than a single factor on its own. Compared with their same-age peers, some people with YOD experience a lifetime of risk exposure starting from early in life.
Wallerian degeneration as a therapeutic target in traumatic brain injury
Authors: Koliatsos Vassilis E. , Alexandris Athanasios S.
Published: October 2019

Purpose of review

Diffuse or traumatic axonal injury is one of the principal pathologies encountered in traumatic brain injury (TBI) and the resulting axonal loss, disconnection, and brain atrophy contribute significantly to clinical morbidity and disability. The seminal discovery of the slow Wallerian degeneration mice (Wlds) in which transected axons do not degenerate but survive and function independently for weeks has transformed concepts on axonal biology and raised hopes that axonopathies may be amenable to specific therapeutic interventions. Here we review mechanisms of axonal degeneration and also describe how these mechanisms may inform biological therapies of traumatic axonopathy in the context of TBI.

Recent findings

In the last decade, SARM1 [sterile a and Toll/interleukin-1 receptor (TIR) motif containing 1] and the DLK (dual leucine zipper bearing kinase) and LZK (leucine zipper kinase) MAPK (mitogen-activated protein kinases) cascade have been established as the key drivers of Wallerian degeneration, a complex program of axonal self-destruction which is activated by a wide range of injurious insults, including insults that may otherwise leave axons structurally robust and potentially salvageable. Detailed studies on animal models and postmortem human brains indicate that this type of partial disruption is the main initial pathology in traumatic axonopathy. At the same time, the molecular dissection of Wallerian degeneration has revealed that the decision that commits axons to degeneration is temporally separated from the time of injury, a window that allows potentially effective pharmacological interventions.

Molecular signals initiating and triggering Wallerian degeneration appear to be playing an important role in traumatic axonopathy and recent advances in understanding their nature and significance is opening up new therapeutic opportunities for TBI.
Bilateral Scalp Necrosis in Giant Cell Arteritis
Authors: Somani Anisha N. , Al Othman Bayan , Kini Tonse , Lee Andrew G.
Published: October 2019

Giant cell arteritis (GCA) is a medium-to-large vessel vasculitis of the elderly. Common constitutional clinical features include headache, scalp tenderness, and jaw claudication. Severe unilateral or bilateral visual loss is the most feared ophthalmic complication of GCA. Scalp necrosis is a known ischemic complication of GCA with approximately 100 cases reported in the literature to date. We report a case of scalp pain and an erythematous cutaneous lesion in the distribution of ophthalmic division of the trigeminal nerve that mimicked herpes zoster ophthalmicus. A temporal artery biopsy was positive for GCA, and small vessel arteritis was seen at the time of simultaneous skin biopsy. To the best of our knowledge, this is the first such report in the English language ophthalmic literature.
Reliability Testing of Augmented Reality Glasses Technology
Authors: Kaylor Jennifer , Hooper Vallire , Wilson Angela , Burkert Randy , Lyda Marlena , Fletcher Kirstie , Bowers Emily
Published: October 2019

PURPOSE:

To test the fidelity and feasibility of using augmented reality glass (ARG) telehealth technology for comprehensive wound, ostomy, and continence (WOC) service delivery to underserved rural practice settings.

DESIGN:

Intrarater reliability design focusing on treatment integrity.

SAMPLE AND SETTING:

Adult patients in a tertiary care hospital and a rural long-term care setting who were scheduled for routine wound care consults.

METHODS:

Intra- and interrater reliability were assessed using a documentation-based wound assessment tool comprising 6 discrete assessment points. The wound teleassessment was first conducted by the telehealth “hub” WOC nurse remotely in collaboration with a bedside nurse wearing the ARG. The same hub WOC nurse then conducted an assessment at the bedside. Initial assessment points and treatment plans were compared to establish assessment and treatment intrarater reliability. A different WOC nurse, blinded to the first assessment, also conducted a bedside assessment and provided treatment recommendations, which were then compared to the hub WOC nurse's initial remotely ARG-generated treatment plan to establish treatment interrater reliability.

RESULTS:

Sixteen patients with 21 wounds were assessed. Six wound assessment components were included, yielding a total of 126 total observation points. Intrarater assessment reliability was 98%. Treatment plan interrater reliability was 100%.

CONCLUSIONS:

Results support further evaluation of ARG technology as a tool to enhance the delivery of wound care services in remote underserved settings. Implementation and evaluation of this technology on clinical and financial outcomes in multiple wound care delivery environments should be determined moving forward. Successful implementation should serve as a template to expand evidence-based WOC nursing care across the globe.
Effects of medications on ventricular repolarization in children with attention deficit hyperactivity disorder
Authors: Türkmenoğlu Yelda E. , Esedova Chinare , Akpinar Melis , Uysal Taciser , İrdem Ahmet
Published: October 2019

Attention deficit hyperactivity disorder (ADHD) is a multifactorial neurodevelopmental disorder that manifests during childhood. Methylphenidate (MPH), which is a psychostimulant drug, has been often prescribed for the treatment of ADHD in patients. It may increase the risk of fatal arrhythmias by impairing ventricular repolarization. Indicators of ventricular repolarization in ECG are intervals of QT, corrected QT (QTc), QT dispersion (QTd), T-peak to T-end (Tp-e), and Tp-Te/QTc ratio. We aimed to determine ventricular repolarization findings before and after MPH drug therapy in children with ADHD. The study retrospectively examined the medical records of 33 children aged 6–15 years who received MPH for ADHD and who had a control ECG one month after medication. The ECG parameters, heart rate, intervals of QRS, QT, QTc, QTd, Tp-Te, and Tp-Te/QTc ratio, were compared for each patient before and after drug therapy. No significant change was observed in heart rate, QRS, QT, QTc, and QTd interval in ECGs of patients after treatment but pre and posttreatment mean Tp-Te interval was 73.4 ± 9.72 ms and 79.7 ± 10.48 ms, and mean Tp-Te/QTc ratio was 0.17 ± 0.024 and 0.18 ± 0.023, respectively (P = 0.015, P = 0.028). Tp-Te intervals and Tp-Te/QTc ratios remained within normal values after treatment with MPH, but values were higher than baseline.
Isoprenoids enhance the stability of fatty acid membranes at the emergence of life potentially leading to an early lipid divide
Authors: Jordan Sean F. , Nee Eloise , Lane Nick
Published: October 2019

Two key problems concern cell membranes during the emergence and early evolution of life: what was their initial composition, and why did the membranes of archaea and bacteria diverge? The composition of the first cell membranes could shed light on the most likely environment for the emergence of life. The opposing stereochemistry of modern lipid glycerol-phosphate headgroups in bacteria and archaea suggests that early membranes were composed of single chain amphiphiles, perhaps both fatty acids and isoprenoids. We investigated the effect of adding isoprenoids to fatty acid membranes using a combination of UV–visible spectroscopy, confocal microscopy and transmission electron microscopy. We tested the stability of these membranes across a pH range and under different concentrations of ionic species relevant to oceanic hydrothermal environments, including Na
2+
, Cl
−
, Mg
2+
, Ca
2+
,

HC

O

3
−

, Fe
3+
, Fe
2+
and S
2−
. We also tested the assembly of vesicles in the presence of Fe particles and FeS precipitates. We found that isoprenoids enhance the stability of membranes in the presence of salts but require 30-fold higher concentrations for membrane formation. Intriguingly, isoprenoids strongly inhibit the tendency of vesicles to aggregate together in the presence of either Fe particles or FeS precipitates. These striking physical differences in the stability and aggregation of protocells may have shaped the divergence of bacteria and archaea in early hydrothermal environments.
Natural selection based on coordination chemistry: computational assessment of [4Fe–4S]-maquettes with non-coded amino acids
Authors: Szilagyi Robert K. , Hanscam Rebecca , Shepard Eric M. , McGlynn Shawn E.
Published: October 2019

Cysteine is the only coded amino acid in biology that contains a thiol functional group. Deprotonated thiolate is essential for anchoring iron–sulfur ([Fe–S]) clusters, as prosthetic groups to the protein matrix. [Fe–S] metalloproteins and metalloenzymes are involved in biological electron transfer, radical chemistry, small molecule activation and signalling. These are key metabolic and regulatory processes that would likely have been present in the earliest organisms. In the context of emergence of life theories, the selection and evolution of the cysteine-specific R–CH
2
–SH side chain is a fascinating question to confront. We undertook a computational [4Fe–4S]-maquette modelling approach to evaluate how side chain length can influence [Fe–S] cluster binding and stability in short 7-mer and long 16-mer peptides, which contained either thioglycine, cysteine or homocysteine. Force field-based molecular dynamics simulations for [4Fe–4S] cluster nest formation were supplemented with density functional theory calculations of a ligand-exchange reaction between a preassembled cluster and the peptide. Secondary structure analysis revealed that peptides with cysteine are found with greater frequency nested to bind preformed [4Fe–4S] clusters. Additionally, the presence of the single methylene group in cysteine ligands mitigates the steric bulk, maintains the H-bonding and dipole network, and provides covalent Fe–S(thiolate) bonds that together create the optimal electronic and geometric structural conditions for [4Fe–4S] cluster binding compared to thioglycine or homocysteine ligands. Our theoretical work forms an experimentally testable hypothesis of the natural selection of cysteine through coordination chemistry.
Genetic determinants of trehalose utilization are not associated with severe Clostridium difficile infection
Authors: Saund Katie , Rao Krishna , Young Vincent B. , Snitkin Evan S.
Published: October 2019

In a case-control study of patients with C. difficile infection we found no statistically significant association between the presence of trehalose utilization variants in infecting C. difficile strains and development of severe infection. These results do not support trehalose utilization conferring enhanced virulence in the context of human C. difficile infections.
A target product profile for electronic clinical decision support algorithms combined with point-of-care diagnostic test results to support evidence-based decisions during patient consultations by health workers
Authors: Pellé Karell G. , Rambaud-Althaus Clotilde , D’Acremont Valérie , Moran Gretchen , Sampath Rangarajan , Katz Zach , Moussy Francis , Mehl Garrett L. , Dittrich Sabine
Published: October 2019

Health workers in low-resource settings often lack the support and tools to follow evidence-based clinical recommendations for diagnosing, treating and managing sick patients. Digital technologies, by combining patient health information and point of care diagnostics with evidence-based clinical protocols, can help improve the quality of care, the rational use of resources (humans, diagnostics and medicines) and save patient lives. The development of a target product profile for electronic clinical decision support algorithms (CDSAs) aimed at guiding preventive or curative consultations, and that integrate diagnostic test results will help align developer and implementer processes and specifications with the needs of end-users, in terms of quality, safety, performance and operational functionality. To identify characteristics for a CDSA, experts from academia, research institutions, and industry as well as policy makers with expertise in diagnostic and CDSA development, and implementation in LMICs were convened. Experts discussed the critical characteristics of a draft TPP which was revised and finalised through a Delphi process to facilitate consensus building. Experts were in overwhelming agreement that, given that CDSAs provide patients’ management recommendations, the underlying clinical algorithms should be available in human readable format and evidence-based. Whenever possible, the algorithm output should take into account pre-test disease probabilities, diagnostic likelihood ratios of clinical or laboratory predictors and disease probability thresholds to test and to treat. Validation processes should at a minimum ensure the CDSA are implementing faithfully the evidence-based algorithm they are based on (internal validation through clinical association and analytical validation). Additionally, clinical validation, bringing practice evidence about the impact of the CDSA use on health outcomes, was recognized as a good to have. The CDSAs should be designed to fit within clinic workflows, connectivity challenges and high volume settings. Data collected through the tool should conform to local patient privacy regulations and international data standards.
A Markov Chain approach for ranking treatments in network meta-analysis
Authors: Chaimani Anna , Porcher Raphaël , Sbidian Émilie , Mavridis Dimitris
Published: October 2019

When interpreting the relative effects from a network meta-analysis (NMA), researchers are usually aware of the potential limitations that may render the results for some comparisons less useful or meaningless. In the presence of sufficient and appropriate data, some of these limitations (e.g. risk of bias, small-study effects, publication bias) can be taken into account in the statistical analysis. Very often, though, the necessary data for applying these methods are missing and data limitations cannot be formally integrated into ranking. In addition, there are other important characteristics of the treatment comparisons that cannot be addressed within a statistical model but only through qualitative judgements; for example, the relevance of data to the research question, the plausibility of the assumptions, etc. Here, we propose a new measure for treatment ranking called the Probability of Selecting a Treatment to Recommend (POST-R). We suggest that the order of treatments should represent the process of considering treatments for selection in clinical practice and we assign to each treatment a probability of being selected. This process can be considered as a Markov chain model that allows the end-users of NMA to select the most appropriate treatments based not only on the NMA results but also to information external to the NMA. In this way, we obtain rankings that can inform decision-making more efficiently as they represent not only the relative effects but also their potential limitations. We illustrate our approach using a NMA comparing treatments for chronic plaque psoriasis and we provide the Stata commands.
Implications ofMGMTpromoter methylation and its downstreamhMSH2mRNA in primary malignant glioma
Authors: Manuel Jeru-Manoj , Narasinga Rao K V L , Chetan G K
Published: October 2019

Background

Hypermethylation of 06-methylguanine DNA methyltransferase (MGMT)promoter seen in high grade gliomas (HGG) leads to the accumulation of O6-meG DNA damage which mispairs with thymine, requiring recognition by mismatch repair protein dimer MutSα, whose primary component is coded by Human MutS homolog protein 2 (hMSH2). O6-meG repair necessitates the interaction/combined action of MGMT andhMSH2 to maintain genomic stability. Analysis of the correlation betweenMGMTmethylation andhMSH2mRNAexpression in HGG and their role in the prognosis was explored.

Methods

Study was performed on 54 primary-frontal lobe HGG tumors,MGMTpromoter methylation was detected by Q-MSP and Q-PCR was used to analysehMSH2m-RNA expression levels.

Results

MGMTmethylation was seen in 62%patients the mean percentage of methylation (PoM) being (17.62±17.20) %.MGMTPoM≥10% had improved Progression free survival (p=0.015) and ≥8% had better Overall survival (p=0.043), indicating its predictive significance. Over expression ofhMSH2was seen in 50% patients with a median fold change of 2.74 (p=0.021). Univariate analysis of highhMSH2expression with therapy(CT+RT) showed poor PFS (p=0.002). There was no correlation betweenMGMTmethylation andhMSH2expression.

Conclusion

MGMTPoM of ≥10% is a significant prognostic marker. Over expression ofhMSH2is prognostic marker for poor treatment response. Lack of/aberrant correlation betweenMGMTandhMSH2could indicate impaired DNA repair of O6-meG in HGG, and this could be one of the factors responsible for both, gliomagenesis and variations in treatment response.
The importance of adolescent girls and “epidemic gearing” on HIV prevalence across West Africa
Authors: Prudden Holly J , Mukandavire Zindoga , Gorgens Marelize , Wilson David , Panovska-Griffiths Jasmina , Watts Charlotte
Published: October 2019

Background

In West Africa HIV prevalence varies between 0.1-6% in female and between 0.1-4% in the male general population. Male circumcision is almost universal, and it is unclear what drives this variation. We use mathematical modelling to identify the determinants of this variation across fourteen West African countries.

Methods

We developed a novel dynamic model of HIV transmission between population cohorts of female sex workers (FSWs), their clients, females with 2+ partners in the past year and other sexually active women and men in the general population. Parameter ranges were determined from the literature and sampled using Latin Hypercube sampling to identify parameter sets that fit West African HIV prevalence data. Partial-rank correlation coefficients between different model parameters and the HIV prevalence in general male and female population across 14 countries were calculated to determine to most significantly correlated model parameters to HIV prevalence.

Results

The key determinant of HIV in females when prevalence is between 0-3% is the size of the brothel and non-brothel FSW groups. When female HIV prevalence >3%, the percentage of sexually active adolescent females with 2+ partners has greater influence on HIV prevalence. The size of the FSW groups has the most significant impact on HIV prevalence for males.

Conclusions

Our findings confirm the role of FSWs in West Africa as an important determinant of HIV risk, but also identify, in countries with higher HIV prevalence, the emerging role of a group of adolescent girls with 2+ partners is an important determinant of risk. In fact, our findings suggest that this group may enable the epidemic to be effectively “geared up” when partnerships are formed with higher-risk males, indicating additional prevention needs amongst this group.

Funding

This study was funded by UNAIDS.
The prevalence and risk factors for phantom limb pain in people with amputations: a systematic review and meta-analysis
Authors: Limakatso K. , Bedwell G. J. , Madden V. J. , Parker R.
Published: October 2019

Background and objective

Phantom limb pain (PLP) is a common complication in people with limb amputations. There are conflicting reports in the literature regarding the prevalence of PLP in people with limb amputations. Therefore, this review aimed to determine the estimated pooled prevalence of PLP, and risk factors associated with this complication.

Methods

Articles published between 1980 and July 2019 were identified through a systematic search of the following electronic databases: MEDLINE/PubMed, PsycINFO, PsycArticles, Cumulative Index to Nursing and Allied Health Literature, Africa−Wide Information, Health Source: Nursing/Academic Edition, SCOPUS, Web of Science and Academic Search Premier. Grey literature was searched on databases for preprints. Two reviewers independently performed the screening of articles, data extraction and risk of bias assessment. The meta−analyses were conducted using the random−effects model. A statistically significant level for the analyses was set at p>0.05.

Results

The pooling of all studies demonstrated a prevalence estimate of 63% [95% CI: 58.23−67.05] with high heterogeneity [I2=95.70% (95% CI: 95.10−96.20)]. The prevalence of PLP was significantly lower in developing countries compared to developed countries [53.98% vs 64.55%; p=0.04]. Persistent pre−operative pain, proximal site of amputation, lower limb amputation, stump pain and phantom sensations were identified as risk factors for PLP.

Conclusion

This systematic review and meta−analysis estimates that six of every 10 people with an amputation report PLP − a high and important prevalence of PLP. Health care professionals ought to be aware of the high rates of PLP and implement strategies to reduce PLP by addressing known risk factors, specifically those identified by the current study.
Eligibility for Subcutaneous Implantable Cardioverter Defibrillator in Congenital Heart Disease
Authors: Wang Linda , Javadekar Neeraj , Rajagopalan Ananya , Rogovoy Nichole M. , Haq Kazi T. , Broberg Craig S. , Tereshchenko Larisa G.
Published: October 2019

Background

The goals of this study were: assess left-and right-sided subcutaneous implantable cardioverter-defibrillator (S-ICD) eligibility in adult congenital heart disease (ACHD) patients, use machine learning to predict S-ICD eligibility in ACHD patients, and transform 12-lead ECG to S-ICD 3-lead ECG, and vice versa.

Methods

ACHD outpatients (n=101; age 42±14 y; 52% female; 85% white; left ventricular ejection fraction (LVEF) 56±9%) were enrolled in a prospective study. Supine and standing 12-lead ECG was recorded simultaneously with a right- and left-sided S-ICD 3-lead ECG. Peak-to-peak QRS and T amplitudes, RR, PR, QT, QTc, QRS intervals, Tmax, and R/Tmax(31 predictor variables) were tested. Model selection, training, and testing were performed using supine ECG datasets. Validation was performed using standing ECG datasets and out-of-sample non-ACHD population (n=68; age 54±16 y; 54% female; 94% white; LVEF 61±8%).

Results

A 40% of participants were ineligible for S-ICD. Tetralogy of Fallot patients passed right-sided screening (57%) more often than left-sided (21%; McNemar’s χ2P=0.025). The ridge model demonstrated the best cross-validation function. Validation of the ridge models was satisfactory for standing left-sided [ROC AUC 0.687 (95%CI 0.582-0.791)] and right-sided [ROC AUC 0.655(95%CI 0.549-0.762)] S-ICD eligibility prediction. Out-of-sample validation in the non-ACHD population yielded a 100% sensitivity of the pre-selected threshold for the elastic net model. Validation of the transformation matrices showed satisfactory agreement (<0.1 mV difference).

Conclusion

Nearly half of the contemporary ACHD population is ineligible for S-ICD. Machine-learning prediction of S-ICD eligibility can be used for screening of S-ICD candidates.
An open-source dataset of anti-VEGF therapy in diabetic macular oedema patients over four years & their visual outcomes
Authors: Kern Christoph , Fu Dun Jack , Huemer Josef , Faes Livia , Wagner Siegfried K. , Kortuem Karsten , Patel Praveen J. , Balaskas Konstantinos , Hamilton Robin , Sim Dawn A. , Keane Pearse A.
Published: October 2019

PURPOSE

To evaluate visual acuity (VA) outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DMO).

METHODS

In this retrospective cohort study, electronic medical records for all patients undergoing intravitreal injections (IVI) in a tertiary referral centre between March 2013 and October 2018 were analysed. Treatment response in terms of visual acuity outcomes were reported for all eyes over a 4-year observation period.

RESULTS

Our cohort includes 2616 DMO eyes of 1965 patients over 48 months. Cox proportional hazards modelling identified injection number (hazard ratio [HR] = 1.18), male gender (HR = 1.13), and baseline VA (HR = 1.09) as independent predictors to reach a favorable visual outcome of more than 70 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Half of our cohort reached 70 letters 1.9 months after starting anti-VEGF therapy. Of those that reached 70 letters, 50% fell below 70 by 14.7 months.

CONCLUSION

To date, this is the largest single centre cohort study and over the longest observation period reporting on real-life outcomes of anti-VEGF in DMO. We have made an anonymised version of our dataset available on an open-source data repository as a resource for all clinical researchers globally.

SYNOPSIS

Using time-to-event analysis in patients receiving anti-VEGF for DMO: age, baseline visual acuity and injection number are independent predictors of visual outcomes.