bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoupled ontogeny of in vivo bite force and mandible morphology reveals effects of weaning and sexual maturation in mice
Authors: Ginot Samuel , Hautier Lionel , Agret Sylvie , Claude Julien
Published: December 2019

The link between performance, morphology and their sources of variation is a major target of evolutionary functional biology. In vertebrates, many studies have linked in vivo bite force to skull morphology, mostly at the interspecific level. Within species, however, the ontogeny of bite force, in relation to the development of the mandible, remains poorly known, despite its relevance for life history and for the co-evolution of form and function. Here, ontogenetic trajectories of bite force, correlated with mandible size and shape, are reported for the first time in a wild-derived colony of laboratory mice. Bite forces were measured in vivo and mandible morphology was assessed using geometric morphometrics. Most coordinated changes in morphology and in vivo bite force occur during the first stages of growth, prior to weaning. Mandible shape stabilizes after day 23. The increases in mandible size and body mass slow down around day 40, but still increase during adulthood. Despite slowing down after weaning, bite force increases through a second phase during sexual maturation (days 30–40). This may be linked to the progressive tempering of weaning stress, continued growth and synchronization of the muscular and osteological systems, together with hormonal changes, as we observed a concomitant appearance of sexual dimorphism.
Kidney disease and mortality in patients with respiratory tract infections: a systematic review and meta-analysis
Authors: Su Guobin , Iwagami Masao , Qin Xindong , McDonald Helen , Liu Xusheng , Carrero Juan Jesus , Stålsby Lundborg Cecilia , Nitsch Dorothea
Published: December 2019

Background

Respiratory tract infections (RTIs) are a common reason for people to seek medical care. RTIs are associated with high short-term mortality. Inconsistent evidence exists in the association between the presence of kidney disease and the risk of death in patient with RTIs.

Methods

We searched the PubMed, Cochrane Library and Embase databases from inception through April 2019 for cohort and case–control studies investigating the presence of kidney disease (defined as medical diagnosis of kidney disease, reduced estimated glomerular filtration rate or creatinine clearance, elevated serum creatinine and proteinuria) on mortality in adults with RTIs in different settings including community, inpatient and intensive care units. We assessed the quality of the included studies using Cochrane Collaboration’s tool and conducted a meta-analysis on the relative risk (RR) of death.

Results

Of 5362 records identified, 18 studies involving 16 676 participants met the inclusion criteria, with 15 studies investigating pneumonia and 3 studies exploring influenza. The risk of bias in the available evidence was moderate. Most [17/18 (94.5%)] of studies reported positive associations of underlying chronic kidney disease with mortality. The pooled adjusted risk for all-cause mortality in patients with RTIs almost doubled [RR 1.96 (95% confidence interval 1.48–2.59)] in patients with kidney disease. Associations were consistent across different timings of kidney disease assessment and provenances of RTIs (community-acquired or healthcare-associated).

Conclusions

The presence of kidney disease is associated with higher mortality among people with RTIs, especially in those with pneumonia. The presence of kidney disease might be taken into account when considering admission for patients who present with RTIs.
Trends in preadmission oral anticoagulant use and clinical outcome in atrial fibrillation patients admitted with acute stroke in Denmark
Authors: Larsen Laura Kathrine , Ovesen Christian , Frost Lars , Damgaard Dorte , Christensen Hanne , Johnsen Søren Paaske
Published: December 2019

Aims

Use of oral anticoagulation (OAC) therapy has increased in recent years among patients with atrial fibrillation (AF). However, it remains uncertain whether this translates into improved clinical outcomes. We aimed to examine time trends in preadmission OAC use and clinical outcomes among AF patients admitted with stroke.

Methods and results

We used nationwide registries to perform a follow-up study of 14 999 patients with AF who were admitted with acute stroke to a Danish hospital between 2008 and 2016. The proportion of AF-related stroke was 16.1% in 2008 and 17.6% in 2016. Among patients with AF-related stroke, the overall proportion of preadmission OAC users increased from 22.6% in 2008 to 41.5% in 2016. Between 2008 and 2016, the proportion of patients with AF admitted with severe stroke declined from 32.4% to 27.4% [adjusted odds ratio (OR) = 0.78, 95% confidence interval (CI): 0.75–0.81], the median length of hospital stay (LOS) decreased from 12 to 8 days (adjusted hazard ratio of discharge = 1.32, 95% CI: 1.30–1.34) and 30-day mortality decreased from 19.2% to 13.7% (adjusted OR = 0.72, 95% CI: 0.68–0.75).

Conclusion

The incidence of AF-related strokes remains high although preadmission use of OAC has increased substantially in recent years. Despite the proportion of OAC users almost doubled from 2008 to 2016, a sizeable proportion of AF patients is still without OAC when admitted with stroke. The increased use of OAC has been accompanied by a lower proportion of patients with severe stroke, shorter LOS, and lower mortality.
Transcriptome-Wide Patterns of the Genetic and Expression Variations in Two Sympatric Schizothoracine Fishes in a Tibetan Plateau Glacier Lake
Authors: Chen Juan , Yang Liandong , Zhang Renyi , Uebbing Severin , Zhang Cunfang , Jiang Haifeng , Lei Yi , Lv Wenqi , Tian Fei , Zhao Kai , He Shunping
Published: December 2019

Sympatric speciation remains a central focus of evolutionary biology. Although some evidence shows speciation occurring in this way, little is known about the gene expression evolution and the characteristics of population genetics as species diverge. Two closely related Gymnocypris fish (Gymnocypris chui and Gymnocypris scleracanthus), which come from a small glacier lake in the Tibetan Plateau, Lake Langcuo, exist a possible incipient sympatric adaptive ecological speciation. We generated large amounts of RNA-Seq data from multiple individuals and tissues from each of the two species and compared gene expression patterns and genetic polymorphisms between them. Ordination analysis separated samples by organ rather than by species. The degree of expression difference between organs within and between species was different. Phylogenetic analyses indicated that the two closely related taxa formed a monophyletic complex. Population structure analysis displayed two distinctly divergent clusters of G. chui and G. scleracanthus populations. By contrast, G. scleracanthus population genetic diversity is higher than that of G. chui. Considerable sites of the two populations were differentiated with a coefficient of FST = 0.25–0.50, implying that a small proportion of loci nevertheless exhibited deep divergence in two comparisons. Concomitantly, putatively selected genes during speciation revealed functional categories are enriched in bone morphogenesis, cell growth, neurogenetics, enzyme activity, and binding activity in G. chui population. In contrast, nutrition and localization were highlighted in G. scleracanthus. Collectively, morphological traits and dietary preference combine with genetic variation and expression variation, probably contributed to the incipient speciation of two sympatric populations.
Genus Six Curves, K3 Surfaces, and Stable Pairs
Authors: Goluboff J Ross
Published: December 2019

A general smooth curve of genus six lies on a quintic del Pezzo surface. Artebani and Kondō [4] construct a birational period map for genus six curves by taking ramified double covers of del Pezzo surfaces. The map is not defined for special genus six curves. In this paper, we construct a smooth Deligne–Mumford stack ${\mathfrak{P}}_0$ parametrizing certain stable surface-curve pairs, which essentially resolves this map. Moreover, we give an explicit description of pairs in ${\mathfrak{P}}_0$ containing special curves.
Reproductive Biology and Evidence of Diapause in the Cowpea Curculio (Coleoptera: Curculionidae)
Authors: Riley David G , Barwick Sydni , Sparks Alton N , Harty Thomas , Hamadi Negin
Published: December 2019

Chalcodermus aeneus Boheman (Coleoptera: Curculionidae) has been the most destructive insect pest of black-eyed peas or cowpeas, Vigna unguiculata L. (Fabales: Fabaceae), over the last century in the southeastern United States. The historical distribution of this semitropical pest suggests the likelihood that diapause plays a key role in the overwintering success in parts of the United States. However, this report is the first to document biological evidence for diapause in C. aeneus. Our study assessed larval emergence from cowpea pods in the summer to fall growing seasons, egg development in female adults over the first (summer) and second (fall) generations, and adult emergence from infested soil after the first and second generations. There was a clear reduction in larval emergence from summer to fall. Egg and follicle development in female C. aeneus dropped off dramatically by September of each year. There was an extended emergence pattern of weevil adults from the soil in the fall as compared to the summer generation. Any future regional management of cowpea curculio will have to take into account the ability of this insect to diapause, thereby increasing its capacity to overwinter in regions where the cowpea crop, a warm-season, semitropical plant, is terminated with winter freezing temperatures.
Revisiting separation: Algorithms and complexity
Authors: Oliveira Daniel , Rasga João
Published: December 2019

Linear temporal logic (LTL) with Since and Until modalities is expressively equivalent, over the class of complete linear orders, to a fragment of first-order logic known as FOMLO (first-order monadic logic of order). It turns out that LTL, under some basic assumptions, is expressively complete if and only if it has the property, called separation, that every formula is equivalent to a Boolean combination of formulas that each refer only to the past, present or future. Herein we present simple algorithms and their implementations to perform separation of the LTL with Since and Until, over discrete and complete linear orders, and translation from FOMLO formulas into equivalent temporal logic formulas. We additionally show that the separation of a certain fragment of LTL results in at most a double exponential size growth.
Spatiotemporal dynamics in vital rates of Humboldt’s flying squirrels and Townsend’s chipmunks in a late-successional forest
Authors: Weldy Matt , Epps Clinton W , Lesmeister Damon B , Manning Tom , Forsman Eric D
Published: December 2019

Knowledge of the spatiotemporal variability of abundance and vital rates is essential to the conservation of wildlife populations. In Pacific Northwest forests, previous small mammal research has focused on estimating abundance; few studies have focused on vital rates. We used robust design temporal symmetry models and live-trapping data collected 2011–2016 at nine sites to estimate apparent annual survival, population growth rate, and recruitment of Humboldt’s flying squirrels (Glaucomys oregonensis) and Townsend’s chipmunks (Neotamias townsendii) in a late-successional forest of the Cascade Mountains of Oregon, United States. We also estimated the proportional contribution of apparent annual survival and recruitment to population growth rate. Covariates previously associated with abundance were also associated with vital rates for Townsend’s chipmunks, but less so for Humboldt’s flying squirrels. Apparent annual survival was nearly constant (range = 0.47 to 0.51) among years and sites for Humboldt’s flying squirrels but was consistently lower and more variable among years for Townsend’s chipmunks (range = 0.13 to 0.31). Recruitment was variable among years for both species. Apparent annual survival generally contributed more than recruitment to the population growth rate of Humboldt’s flying squirrels. For Townsend’s chipmunks, recruitment consistently contributed more than apparent annual survival to population growth rate. These findings suggest that life history strategies differed for these co-occurring species. This study demonstrates substantial temporal variation in vital rates and some differences in abundance and vital rate habitat associations, suggesting that habitat suitability inferences based on short time series or variation in abundance could be misleading.
A Prospective Study of Circulating Chemokines and Angiogenesis Markers and Risk of Multiple Myeloma and Its Precursor
Authors: Hofmann Jonathan N , Landgren Ola , Landy Rebecca , Kemp Troy J , Santo Loredana , McShane Charlene M , Shearer Joseph J , Lan Qing , Rothman Nathaniel , Pinto Ligia A , Pfeiffer Ruth M , Hildesheim Allan , Katki Hormuzd A , Purdue Mark P
Published: December 2019

Background

Experimental and clinical studies have implicated certain chemokines and angiogenic cytokines in multiple myeloma (MM) pathogenesis. To investigate whether systemic concentrations of these markers are associated with future MM risk and progression from its precursor, monoclonal gammopathy of undetermined significance (MGUS), we conducted a prospective study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Methods

We measured concentrations of 45 immunologic and pro-angiogenic markers in sera from 241 MM case patients, 441 participants with nonprogressing MGUS, and 258 MGUS-free control participants using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. We also evaluated absolute risk of progression using weighted Kaplan-Meier estimates. All statistical tests were two-sided.

Results

Prediagnostic levels of six markers were statistically significantly elevated among MM case patients compared with MGUS-free control participants using a false discovery rate of 10% (EGF, HGF, Ang-2, CXCL12, CCL8, and BMP-9). Of these, three angiogenesis markers were associated with future progression from MGUS to MM: EGF (fourth vs first quartile: OR = 3.01, 95% CI = 1.61 to 5.63, Ptrend = .00028), HGF (OR = 2.59, 95% CI = 1.33 to 5.03, Ptrend = .015), and Ang-2 (OR = 2.14, 95% CI = 1.15 to 3.98, Ptrend = .07). A composite angiogenesis biomarker score substantially stratified risk of MGUS progression to MM beyond established risk factors for progression, particularly during the first 5 years of follow-up (areas under the curve of 0.71 and 0.64 with and without the angiogenesis marker score, respectively).

Conclusions

Our prospective findings provide new insights into mechanisms involved in MM development and suggest that systemic angiogenesis markers could potentially improve risk stratification models for MGUS patients.
Cancer-Attributable Medical Costs for Colorectal Cancer Patients by Phases of Care: What Is the Effect of a Prior Cancer History?
Authors: Mariotto Angela B , Warren Joan L , Zeruto Chris , Coughlan Diarmuid , Barrett Michael J , Zhao Lirong , Yabroff K Robin
Published: December 2019

Medical care costing studies have excluded patients with a prior cancer history. This study aims to update methods for estimating medical care costs attributable to cancer and to evaluate the effect of a prior history of cancer on costs for colorectal cancer (CRC) patients. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and matched cancer patients to controls without cancer to estimate cancer-attributable costs by phases of care using Medicare 2007–2013 claims. CRC annualized average cancer-attributable costs were $56.0 K, $5.3 K, $92.5 K, and $24.3 K in the initial, continuing, and end-of-life cancer and noncancer death phases, respectively, in 2014 dollars. Costs were higher for patients diagnosed with more advanced stage, younger ages, and nonwhite races. Costs for patients with prior cancers were consistently higher than patients without prior cancers, especially in the continuing (4.9 K vs 7.2 K) and end-of-life noncancer death (22.7 K vs 30.0 K). Our CRC costs improve previous estimates by using more recent data and updated methods.
Development and Evaluation of a Process to Link Cancer Patients in the SEER Registries to National Medicaid Enrollment Data
Authors: Warren Joan L , Benner Suzie , Stevens Jennifer , Enewold Lindsey , Huang Bin , Zhao Lirong , Tilahun Negussie , Bradley Cathy J
Published: December 2019

Cancer patients receiving Medicaid have worse prognosis. Patients in 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries were linked to national Medicaid enrollment files, 2006–2013, to determine enrollment status during the year before and after diagnosis. A deterministic algorithm based on Social Security number, Medicare Health Insurance Claim number, sex, and date of birth was utilized. Results were compared with an independent linkage of Kentucky-based SEER and Medicaid data. A total 559 484 cancer cases were linked to national Medicaid enrollment files, representing 15–17% of persons with cancer yearly. About 60% of these cases were a complete match on all variables. There was 99% agreement on enrollment status compared with the Kentucky linked data. SEER data were successfully linked to national Medicaid enrollment data. NCI will make the linked data available to researchers, allowing for more detailed assessments of the impact Medicaid enrollment has on cancer diagnosis and outcomes.
A critical legal history of French banking and industrialisation: an alternative to the law and development framework
Authors: Moudud Jamee K
Published: December 2019

Money is central to production and the constitutional theory of money has emphasised its fundamentally public foundations, with flows of credit being demand-determined. Using France as a case study, this paper challenges the Law and Development framework by discussing law’s constitutive role in promoting industrialisation via the mobilisation of credit.
Crafting the lawful truth: Chile’s 1990 Truth Commission, international human rights and the museum of memory
Authors: Vázquez Guevara Valeria
Published: December 2019

This article examines the relationship between Chile’s 1990 Truth Commission (TC) and international human rights law (IHRL) through an ethnography of Chile’s Memory Museum. It shows how the Museum gives continuity to the TC’s lawful truth and subordinates lawful truths that are not informed, mediated and grounded by IHRL.
Surgical Nuances of Endoscopic Endonasal Resection of Craniopharyngiomas: 2-Dimensional Operative Video
Authors: Almeida Joao Paulo , Vescan Allan , Gentili Fred
Published: December 2019

Understanding of the microsurgical anatomy of the sella and suprasellar space is necessary for successful selection of surgical approaches and resection of craniopharyngiomas. Endoscopic endonasal surgery provides excellent exposure of the suprasellar space and has become the approach of choice for most of those tumors. In this video, we discuss the anatomical and surgical nuances for resection of craniopharyngiomas via an endoscopic transtuberculum transplanum approach. Anatomical dissections and a clinical case are used to illustrate the technique.

This is the case of a 52-yr-old woman who presented to our clinic with a history of progressive visual decline and headaches, but no hormonal deficiencies. Magnetic resonance imaging demonstrated the presence of a sella suprasellar solid cystic lesion suggestive of a craniopharyngioma. The lesion was mainly located anterior to the chiasm, preinfundibular and medial to the posterior-communicating artery. Considering the patient presented with no hormonal deficits, it was decided to proceed with an endoscopic extended approach for maximum tumor resection while attempting to preserve the pituitary stalk and gland and its function. The patient provided consent to undergo the procedure and for the surgical video. After a binostril approach and harvesting of vascularized flap, a large sphenoidotomy was performed, followed by a transtuberculum transplanum approach. The tumor was resected with blunt and sharp dissection with careful preservation of the branches of the superior hypophyseal and posterior-communicating arteries. Closure was performed in a multilayer fashion, with dura substitute, fascia lata, and vascularized flap. The patient had visual improvement after surgery and was discharged at postoperative day 5 with no complications.

Anatomical dissection pictures © 2019 Joao Paulo Almeida, MD. Used with permission.
Neural Compensation Mechanisms of Siblings of Schizophrenia Patients as Revealed by High-Density EEG
Authors: da Cruz Janir R , Shaqiri Albulena , Roinishvili Maya , Favrod Ophélie , Chkonia Eka , Brand Andreas , Figueiredo Patrícia , Herzog Michael H
Published: December 2019

Visual backward masking (VBM) deficits are candidate endophenotypes of schizophrenia indexing genetic liability of the disorder. In VBM, a target is followed by a mask that deteriorates target perception. Schizophrenia patients and, to a lesser extent, their unaffected relatives show strong and reproducible VBM deficits. In patients, VBM deficits are associated with strongly decreased amplitudes in the evoked-related potentials (ERPs). Here, to unveil the neural mechanisms of VBM in schizophrenia, circumventing illness-specific confounds, we investigated the electroencephalogram correlates of VBM in unaffected siblings of schizophrenia patients. We tested 110 schizophrenia patients, 60 siblings, and 83 healthy controls. As in previous studies, patients showed strong behavioral deficits and decreased ERP amplitudes compared to controls. Surprisingly, the ERP amplitudes of siblings were even higher than the ones of controls, while their performances were similar. ERP amplitudes in siblings were found to correlate with performance. These results suggest that VBM is deteriorated in patients and siblings. However, siblings, unlike patients, can partially compensate for the deficits by over-activating a network of brain regions.
Bridging the Divide: Student Grand Rounds at the Interface of Basic Science and Clinical Medicine
Authors: Hollenhorst Marie A. , Braun David A. , Burtner Christopher R. , Cajigas Iahn , Cunningham-Bussel Amy C. , Eser Pinar Ö. , Nabel Christopher S. , Tsai Frederick D. , Weeks Lachelle D. , Michel Thomas , Yialamas Maria A.
Published: December 2019

Problem

As biomedical research and clinical medicine become increasingly complex, physician–scientists and clinically oriented biomedical researchers play important roles in bridging the gap between disciplines. A lack of educational programming that addresses the unique needs of students preparing for careers at the interface of basic science and clinical medicine may contribute to trainee attrition.

Approach

The MD–PhD/LHB Grand Rounds was introduced in 2008 as a trainee-driven collaborative effort of the Harvard/Massachusetts Institute of Technology MD–PhD program at Harvard Medical School (HMS MD–PhD program), Harvard’s Leder Human Biology and Translational Medicine (LHB) program, and the Brigham and Women’s Hospital (BWH) Internal Medicine Department. Each of the program’s approximately 4 sessions per year begins with dinner, followed by a clinical case presentation led by a BWH MD–PhD resident with a master clinician faculty discussant, then a research presentation by an LHB PhD student or an MD–PhD student on a basic science topic related to the clinical case, and time for socialization.

Outcomes

In a July 2017 survey of participating students and residents, respondents reported being highly satisfied with the program. Mean satisfaction ratings were 4.3 (SD 0.5) for 12 MD–PhD students, 4.2 (SD 0.7) for 31 LHB students, and 4.4 (SD 0.9) for 5 residents on a 5-point scale (5 = very satisfied). Free-text responses suggested MD–PhD students valued opportunities for active engagement with the resident presenter and faculty discussant. LHB students appreciated the absence of medical jargon in the clinical presentations. Residents’ reported reasons for participating included enjoyment of teaching and interaction with students.

Next Steps

The Harvard MD–PhD/LHB Grand Rounds can serve as a template for developing similar programs at other institutions. Research is needed to determine whether such grand rounds programs can help fix the leaky pipeline in the training of future physician–scientists and clinically oriented biomedical researchers.
Oral Dimethyl Fumarate Reduces Peripheral Neuropathic Pain in Rodents via NFE2L2 Antioxidant Signaling
Authors: Li Jiahe , Ma Jiacheng , Lacagnina Michael J. , Lorca Sabina , Odem Max A. , Walters Edgar T. , Kavelaars Annemieke , Grace Peter M.
Published: December 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Available treatments for neuropathic pain have modest efficacy and significant adverse effects, including abuse potential. Because oxidative stress is a key mechanistic node for neuropathic pain, the authors focused on the master regulator of the antioxidant response—nuclear factor erythroid 2-related factor 2 (NFE2L2; Nrf2)—as an alternative target for neuropathic pain. The authors tested whether dimethyl fumarate (U.S. Food and Drug Administration-approved treatment for multiple sclerosis) would activate NFE2L2 and promote antioxidant activity to reverse neuropathic pain behaviors and oxidative stress-dependent mechanisms.

Methods

Male Sprague Dawley rats, and male and female wild type and Nfe2l2
-/- mice were treated with oral dimethyl fumarate/vehicle for 5 days (300 mg/kg; daily) after spared nerve injury/sham surgery (n = 5 to 8 per group). Allodynia was measured in von Frey reflex tests and hyperalgesia in operant conflict-avoidance tests. Ipsilateral L4/5 dorsal root ganglia were assayed for antioxidant and cytokine/chemokine levels, and mitochondrial bioenergetic capacity.

Results

Dimethyl fumarate treatment reversed mechanical allodynia (injury-vehicle, 0.45 ± 0.06 g [mean ± SD]; injury-dimethyl fumarate, 8.2 ± 0.16 g; P < 0.001) and hyperalgesia induced by nerve injury (injury-vehicle, 2 of 6 crossed noxious probes; injury-dimethyl fumarate, 6 of 6 crossed; P = 0.013). The antiallodynic effect of dimethyl fumarate was lost in nerve-injured Nfe2l2
-/- mice, but retained in nerve-injured male and female wild type mice (wild type, 0.94 ± 0.25 g; Nfe2l2
-/-, 0.02 ± 0.01 g; P < 0.001). Superoxide dismutase activity was increased by dimethyl fumarate after nerve injury (injury-vehicle, 3.96 ± 1.28 mU/mg; injury-dimethyl fumarate, 7.97 ± 0.47 mU/mg; P < 0.001). Treatment reduced the injury-dependent increases in cytokines and chemokines, including interleukin-1β (injury-vehicle, 13.30 ± 2.95 pg/mg; injury-dimethyl fumarate, 6.33 ± 1.97 pg/mg; P = 0.022). Injury-impaired mitochondrial bioenergetics, including basal respiratory capacity, were restored by dimethyl fumarate treatment (P = 0.025).

Conclusions

Dimethyl fumarate, a nonopioid and orally-bioavailable drug, alleviated nociceptive hypersensitivity induced by peripheral nerve injury via activation of NFE2L2 antioxidant signaling. Dimethyl fumarate also resolved neuroinflammation and mitochondrial dysfunction—oxidative stress-dependent mechanisms that drive nociceptive hypersensitivity after nerve injury.
Functional Outcomes of Unstable Ankle Fractures in Adolescents
Authors: Lurie Benjamin M. , Bomar James D. , Edmonds Eric W. , Pennock Andrew T. , Upasani Vidyadhar V.
Published: December 2019

Background:

The purpose of this study was to describe the functional outcomes and complications of unstable supination external rotation (SER) and pronation external rotation (PER) ankle fractures in adolescents. A secondary outcome was to compare functional outcomes of SER stage IV injuries that were treated definitively with closed reduction and cast application to a similar group of minimally displaced fractures treated with open reduction and internal fixation (ORIF).

Methods:

A retrospective review of adolescents aged 10 to 18 years with unstable ankle fractures treated at a single institution between 2009 and 2017 was conducted. All patients had functional outcomes data from the Foot and Ankle Ability Measure obtained at a minimum of 1-year follow-up.

Results:

In total, 67 adolescents (41 SER, 26 PER) were included (mean follow-up: 52.3±24.8 mo). A total of 56 were treated with ORIF and 11 were closed reduced and casted. No patients treated nonsurgically had a loss of reduction and none required subsequent surgical intervention. Preoperative radiographic predictors of syndesmotic injury (>6 mm of tibiofibular clear space or <2 mm of tibiofibular overlap) were not sensitive and only moderately specific predictors of intraoperative syndesmotic injury. There was no difference in functional outcome between the 11 SER stage IV fractures treated nonoperatively and a group of minimally displaced SER injuries treated with ORIF. Patients with open or partially open physes had better functional outcomes. Patients with syndesmotic injuries, medial malleolus fractures, or fracture-dislocations were not associated with lower functional outcome scores in our adolescent cohort.

Conclusions:

Unstable SER and PER injuries in adolescents have favorable functional outcomes at intermediate-term follow-up, though a minority continue to have impaired ankle function. Minimally displaced SER stage IV injuries with near anatomic alignment after closed reduction can be successfully treated with continued closed management, and have no difference in functional outcomes compared with similar injuries treated with ORIF.

Level of Evidence:

Level III.
Risk Factors for Contralateral Slipped Capital Femoral Epiphysis: A Meta-analysis of Cohort and Case-control Studies
Authors: Swarup Ishaan , Goodbody Christine , Goto Rie , Sankar Wudbhav N. , Fabricant Peter D.
Published: December 2019

Background:

Slipped capital femoral epiphysis (SCFE) is an important cause of hip pain and disability in pediatric patients. SCFE occurs bilaterally in 12% to 80% of cases, and the risk of contralateral SCFE is noted to be 2335 times higher than the index SCFE. Several studies have reported risk factors for contralateral SCFE; however, these studies have not been systematically analyzed. The purpose of this systematic review and meta-analysis was to review and analyze risk factors for subsequent contralateral SCFE and identify the strongest risk factors for a subsequent slip.

Methods:

A systematic review was performed of all observational studies focusing on risk factors for subsequent contralateral SCFE indexed in Medline, Embase, and Cochrane databases. Data extraction was performed and summarized using descriptive statistics. Meta-analysis was performed for risk factors with sufficient constituent study data. Quality assessment was performed using the Newcastle-Ottawa Scale, and funnel plots were generated to assess publication bias.

Results:

The initial search strategy identified 226 references, and after exclusions, 20 studies were included in this analysis. Demographic risk factors included age, sex, weight, body mass index, ethnicity, and urban/rural residence; clinical risk factors included endocrine abnormality, duration of symptoms, slip stability, and slip chronicity; and radiographic risk factors included slip angle, triradiate cartilage, alpha angle, posterior sloping angle (PSA), physeal sloping angle, modified Oxford score, and bone age. Younger patient age, body mass index≥95th percentile, presence of an endocrine abnormality, higher PSA of the unaffected hip, and lower modified Oxford score have been noted to be significant risk factors for contralateral SCFE. Meta-analysis showed that younger age (−0.9; confidence interval, −1.1, −0.6), and higher PSA (4.7 degrees; 95% confidence interval, 3.3-6.2 degrees) of the unaffected hip were predictive of subsequent contralateral SCFE. The majority of studies were of good quality.

Conclusion:

There are several risk factors for subsequent contralateral SCFE. On the basis of the available data, younger patients with a high PSA of the unaffected hip would most likely benefit from prophylactic fixation of the unaffected hip.

Level of Evidence:

Level II.
Prospective Evaluation of a Treatment Protocol Based on Fracture Displacement for Pediatric Lateral Condyle Humerus Fractures: A Preliminary Study
Authors: Nazareth Alexander , VandenBerg Curtis D. , Sarkisova Natalya , Goldstein Rachel Y. , Andras Lindsay M. , Lightdale-Miric Nina R. , Pace James Lee , Skaggs David L.
Published: December 2019

Background:

To prospectively evaluate a displacement-based classification system and an outcome-derived algorithm in the treatment of children with lateral condyle fractures.

Methods:

All children with a lateral condyle fracture were prospectively enrolled at our institution between 2013 and 2016. Fractures were classified and treated on the basis of the following classification system: type 1: <2 mm; treated with long arm casting, type II: 2 to 4 mm; treated with closed reduction and percutaneous pinning (CRPP), and type III: >4 mm; open reduction and percutaneous pinning (ORPP). Functional outcomes were assessed at 6 to 12 weeks and at 1-year follow-ups using the Pediatric Outcomes Data Collection Instrument (PODCI).

Results:

A total of 55 patients (mean age, 6 y; range 2 to 12 y) were prospectively enrolled. There were 17 (31%) type I fractures treated with a long arm cast, 8 (15%) type II treated with CRPP, and 30 (54%) type III treated with ORPP. Postoperative complications included delayed union (N=5) and pin site infection (N=3). Delayed unions on the basis of fracture type was type I (1/17, 6%), type II (1/8, 13%), and type III (3/30, 10%) (P=0.85). The rate of delayed unions in type II and III fractures fixed with k-wires was 11% (4/38). Four patients required a second operation with screw fixation. No significant differences were found across PODCI domains at 1-year follow-up when comparing our study population with normative data.

Conclusions:

This is the first prospective study of a treatment protocol for pediatric lateral condyle fractures and validates the use of displacement as a guide for best evidence-based treatment. Children with a lateral condyle fracture can achieve excellent functional outcomes in all classification types with comparable complication rates when radiographic fracture displacement is used to guide surgical and clinical decision making.

Level of Evidence:

Level II.
The conversion factor for predicting adenoma detection rate from polyp detection rate varies according to colonoscopy indication and patient sex
Authors: Vojtechova Gabriela , Ngo Ondrej , Grega Tomas , Kmochova Klara , Voska Michal , Buckova Barbora , Majek Ondrej , Zavoral Miroslav , Suchanek Stepan
Published: December 2019

The adenoma detection rate (ADR) is the primary quality indicator for colonoscopies. The polyp detection rate (PDR) is available from administrative data and does not depend on histology verification. The correlation between PDR and ADR and the ADR/PDR conversion factor in preventive colonoscopies were evaluated. In the prospective study, asymptomatic individuals aged 45–75 years with preventive colonoscopy in 2012–2016 were included. Spearman’s correlation coefficient was used to assess PDR/ADR for each endoscopist. Conversion factor predicting ADR from PDR was obtained by linear regression and subsequently compared with adenoma to polyp detection rate quotient. One thousand six hundred fourteen preventive colonoscopies performed by 16 endoscopists in 8 screening colonoscopy centres in the Czech Republic were analysed. Correlation between PDR and ADR in all preventive colonoscopies was high and statistically significant (Rs 0.82; P < 0.001). There was a strong correlation between PDR and ADR in men (Rs 0.74; P = 0.002) and in screening colonoscopies (Rs 0.85; P < 0.001). The conversion factor to convert ADR from PDR was 0.72 in all preventive colonoscopies, 0.76 in FOBT+ colonoscopies and 0.67 in screening colonoscopies. ADR may be replaced by PDR in the assessment of colonoscopy quality. The value of the conversion factor varies according to colonoscopy indication and gender of examined individuals; in this Czech study, it was 0.72 in all preventive colonoscopies. The minimum requested ADR of 25 % corresponds to a PDR of 35 %, when converted with the appropriate conversion factor.
Senotherapeutics for HIV and aging
Authors: Szaniawski Matthew A. , Spivak Adam M.
Published: December 2019

Purpose of review

To summarize the state of chronic, treated HIV infection and its contribution to accelerated aging, and to evaluate recent research relevant to the study and treatment of aging and senescence.

Recent findings

Chronic treated HIV-1 infection is associated with significant risk of end-organ impairment, non-AIDS-associated malignancies, and accelerated physiologic aging. Coupled with the chronologic aging of the HIV-1-positive population, the development of therapies that target these processes is of great clinical importance. Age-related diseases are partly the result of cellular senescence. Both immune and nonimmune cell subsets are thought to mediate this senescent phenotype, a state of stable cell cycle arrest characterized by sustained release of pro-inflammatory mediators. Recent research in the field of aging has identified a number of ‘senotherapeutics’ to combat aging-related diseases, pharmacologic agents that act either by selectively promoting the death of senescent cells (‘senolytics’) or modifying senescent phenotype (‘senomorphics’).

Senescence is a hallmark of aging-related diseases that is characterized by stable cell cycle arrest and chronic inflammation. Chronic HIV-1 infection predisposes patients to aging-related illnesses and is similarly marked by a senescence-like phenotype. A better understanding of the role of HIV-1 in aging will inform the development of therapeutics aimed at eliminating senescent cells that drive accelerated physiologic aging.
Sensation seeking, sexual orientation, and drug abuse symptoms in a community sample of emerging adults
Authors: Regan Timothy , Thamotharan Sneha , Hahn Hunter , Harris Bethany , Engler Solangia , Schueler Jordan , Fields Sherecce A.
Published: December 2019

Increased use of drugs is associated with a number of factors including high sensation seeking and sexual minority status (through group-specific minority stress). We sought to examine how personality traits like sensation seeking may influence drug abuse among sexual minority individuals. Participants were 217 emerging adults (M

age
= 20.23, SD = 0.85) recruited from Amazon Mechanical Turk (MTurk). Of these participants, 67.7% identified as heterosexual, 9.7% as gay or lesbian, 21.2% as bisexual, and 1.4% indicated other sexual orientations. Sensation seeking and drug abuse were self-reported using the Brief Sensation Seeking Scale and the Drug Abuse Screening Test, respectively. A preliminary multiple analysis of variance indicated no significant mean differences for these variables as a function of sex or sexual orientation. Next, sexual minority status, Brief Sensation Seeking Scale scores, sex and their interactions were entered into a linear regression predicting Drug Abuse Screening Test scores. Results revealed a significant moderation, such that the positive relationship between Brief Sensation Seeking Scale total scores and Drug Abuse Screening Test total scores was stronger for sexual minorities (β = 0.14, P = 0.00) compared to heterosexuals (β = 0.04, P = 0.04), controlling for sex. These results demonstrate, while sensation seeking and sexual minority status may selectively indicate risk for drug use, sexual minorities high in sensation seeking may be at especially high risk for problems related to drug abuse. More research examining the addiction etiology of sexual minority individuals would inform targeted interventions for this population.
A Review of Imaging Biomarkers of the Ocular Surface
Authors: Binotti William W. , Bayraktutar Betul , Ozmen M. Cuneyt , Cox Stephanie M. , Hamrah Pedram
Published: December 2019

A biomarker is a “characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions.” Recently, calls for biomarkers for ocular surface diseases have increased, and advancements in imaging technologies have aided in allowing imaging biomarkers to serve as a potential solution for this need. This review focuses on the state of imaging biomarkers for ocular surface diseases, specifically non-invasive tear break-up time (NIBUT), tear meniscus measurement and corneal epithelial thickness with anterior segment optical coherence tomography (OCT), meibomian gland morphology with infrared meibography and in vivo confocal microscopy (IVCM), ocular redness with grading scales, and cellular corneal immune cells and nerve assessment by IVCM. Extensive literature review was performed for analytical and clinical validation that currently exists for potential imaging biomarkers. Our summary suggests that the reported analytical and clinical validation state for potential imaging biomarkers is broad, with some having good to excellent intra- and intergrader agreement to date. Examples of these include NIBUT for dry eye disease, ocular redness grading scales, and detection of corneal immune cells by IVCM for grading and monitoring inflammation. Further examples are nerve assessment by IVCM for monitoring severity of diabetes mellitus and neurotrophic keratitis, and corneal epithelial thickness assessment with anterior segment OCT for the diagnosis of early keratoconus. However, additional analytical validation for these biomarkers is required before clinical application as a biomarker.
Biophysical Agent Curriculum in Entry-Level Physical Therapist Education Programs Across the United States: A Survey
Authors: Greco Jamie L. , Lamberg Eric M.
Published: December 2019

Introduction:

The literature supporting the use of biophysical agents (BPAs) for patient care in Physical Therapy is conflicting. Although some guidelines exist, the academic institution makes decisions as to which individual BPAs are included in the Doctor of Physical Therapy curriculum. This study investigated current BPA curricular content in physical therapist education programs.

Subjects/Methods:

Two hundred thirty-eight emails were sent to program directors and/or individuals with an identified role of teaching BPAs at accredited physical therapist education programs across the United States. Eighty-six people completed the survey (response rate 35%). The survey consisted of 4 sections: instructor demographics (teaching responsibilities and role), institutional demographics (geographical location, and cohort size), curricular content (timing of course, contact hours, curricular changes, student assessment, and importance of BPA inclusion), and one open-ended response question.

Results:

For most programs, BPA is a stand-alone course (72.3%) taught in the first year of curriculum (72.0%). The most common instructional method included a combination of lecture and laboratory (89.2%). A combined percentage of 77% of respondents reported changes to the BPA curriculum in the past 5 years (ie, decrease in contact hours, change in content, or change in delivery method).

Discussion and Conclusion:

Evidence and clinical practice patterns were referenced by respondents as factors contributing to changes. Certain BPAs are taught using multiple methods, assessed in a variety of ways, and perceived by instructors to be more important to include in the curriculum than others. In addition, there is variation among BPAs regarding the expected levels of competency for students. Overall, the extent to which each BPA is taught in physical therapist education program curriculum aligns with current need for instruction in safe, appropriate operation and clinical usage. However, educators need to be cognizant of both clinical practice patterns and changing evidence and to be willing to alter curriculum as needed to graduate competent physical therapists.
Relevance of Microvascular Flow Assessments in Critically Ill Neonates and Children: A Systematic Review
Authors: Maitoza Laura A. , Neeman Eitan , Funaro Melissa , Pierce Richard W.
Published: December 2019

Objectives:

Resolution of impaired microvascular flow may lag the normalization of macrocirculatory variables. The significance of microcirculatory dysfunction in critically ill children and neonates is unknown, but microcirculatory variables can be measured using Doppler or videomicroscopy imaging techniques. We outline the current understanding of the role of the microcirculation in critical illness, review methods for its assessment, and perform a systematic review of how it has been monitored in critically ill neonates and children.

Design:

Systematic review (PROSPERO CRD42019117993).

Setting:

Not applicable.

Subjects:

Not applicable.

Interventions:

None.

Measurements and Results:

We systematically searched MEDLINE, EMBASE, PubMed, and Web of Science. We included studies of critically ill patients 0 to 18 years old investigating microcirculatory blood flow. Two reviewers analyzed abstracts and articles. Results were qualitatively analyzed due to study heterogeneity. A total of 2,559 abstracts met search criteria, of which 94 underwent full-text review. Of those, 36 met inclusion criteria. Seven studies investigated microcirculatory changes in critically ill children. Twenty studies investigated the microcirculatory changes in neonates with variable diagnoses compared with a diverse set of clinical endpoints. Nine studies assessed the effects of age, sex, and birth weight on microvascular flow in neonates. Across all studies, microcirculatory dysfunction was associated with poor outcomes and may not correlate with observed macrovascular function.

Conclusions:

Assessment of microvascular flow in critically ill children and neonates is possible, although significant challenges remain. In many such patients, microvascular blood flow is disrupted despite medical management targeting normalized macrovascular variables. Future studies are needed to define normal pediatric microvascular flow variables and to assess the impact of patient and treatment factors on its function.
Using the North Dakota IIS to Assess the Response of Health Care Providers to the ACIP Recommendation for Tdap Vaccination During Pregnancy
Authors: Woinarowicz Mary , Howell Molly
Published: December 2019

Objectives:

To evaluate the response of North Dakota health care providers to follow the recommendation set forth by the Advisory Committee on Immunization Practices (ACIP) to administer a dose of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine to women during each pregnancy using the North Dakota Immunization Information System (NDIIS).

Methods:

Data from the NDIIS for North Dakota infants born during calendar years 2013-2018 were extracted. Mother's name was taken from the newborn records and matched to NDIIS female client records to identify the population of mothers of newborns who would have been recommended to receive Tdap during their pregnancy. Doses of Tdap vaccine administered after October 1, 2012, were extracted from the NDIIS, and the dose records were matched back to the mother's record. The time from baby's birthdate back to the doses of Tdap vaccine administered to the mother was measured to find any doses that would have been administered during pregnancy.

Results:

The percentage of women receiving Tdap vaccine during pregnancy increased from 31.5% in 2013 to 60.6% in 2018. Of those women who received Tdap during pregnancy, 94% received the vaccine during the ACIP-recommended interval of 27 to 36 weeks' gestation, using the assumption that all babies were born at 40 weeks' gestation.

Conclusions:

North Dakota health care providers have responded positively to the recommendation of the ACIP to administer a dose of Tdap vaccine to women during each pregnancy and have increased their administration of the vaccine to their patients.