bluuebunny/crossref_metadata_2025 huggingface dataset:
Misreading Narcissus
Authors: Tyminski Robert
Published: July 2016

This article explores the myth of Narcissus as told by Ovid. The author examines why one scene in the story became the focus for the term ‘narcissism’, which has been extrapolated to become a theoretical concept as well a diagnosis. Closer reading of the myth suggests this may have been a distortion. Narcissus as a mythological figure may tell us more about late male adolescence than we have given him credit for. Freud’s paper ‘On Narcissism’ is contrasted with Jung’s views on libido. One legacy of the way in which Freud conceptualized narcissism was to pathologize the development of gay men and women. Two cases are presented to show an alternative understanding of sexual development for young men in mid and late adolescence. The author proposes that a dawning awareness of feminine aspects of sexuality can be experienced as a kind of potentially harmful ‘flowering’, about which young men can feel considerable shame and anxiety.
Modulation of release kinetics by plasma polymerization of ampicillin-loaded β-TCP ceramics
Authors: Labay C , Buxadera-Palomero J , Avilés M , Canal C , Ginebra M P
Published: July 2016

Beta-tricalcium phosphate (β-TCP) bioceramics are employed in bone repair surgery. Their local implantation in bone defects puts them in the limelight as potential materials for local drug delivery. However, obtaining suitable release patterns fitting the required therapeutics is a challenge. Here, plasma polymerization of ampicillin-loaded β-TCP is studied for the design of a novel antibiotic delivery system. Polyethylene glycol-like (PEG-like) coating of β-TCP by low pressure plasma polymerization was performed using diglyme as precursor, and nanometric PEG-like layers were obtained by simple and double plasma polymerization processes. A significant increase in hydrophobicity, and the presence of plasma polymer was visible on the surface by SEM and quantified by XPS. As a main consequence of the plasma polymerisation, the release kinetics were successfully modified, avoiding burst release, and slowing down the initial rate of release leading to a 4.5 h delay in reaching the same antibiotic release percentage, whilst conservation of the activity of the antibiotic was simultaneously maintained. Thus, plasma polymerisation on the surface of bioceramics may be a good strategy to design controlled drug delivery matrices for local bone therapies.
Eps15 membrane-binding and -bending activity acts redundantly with Fcho1 during clathrin-mediated endocytosis
Authors: Wang Lei , Johnson Adam , Hanna Michael , Audhya Anjon
Published: July 2016

Clathrin coat assembly on membranes requires cytosolic adaptors and accessory proteins, which bridge triskeleons with the lipid bilayer and stabilize lattice architecture throughout the process of vesicle formation. In Caenorhabditis elegans, the prototypical AP-2 adaptor complex, which is activated by the accessory factor Fcho1 at the plasma membrane, is dispensable during embryogenesis, enabling us to define alternative mechanisms that facilitate clathrin-mediated endocytosis. Here we uncover a synthetic genetic interaction between C. elegans Fcho1 (FCHO-1) and Eps15 (EHS-1), suggesting that they function in a parallel and potentially redundant manner. Consistent with this idea, we find that the FCHO-1 EFC/F-BAR domain and the EHS-1 EH domains exhibit highly similar membrane-binding and -bending characteristics in vitro. Furthermore, we demonstrate a critical role for EHS-1 when FCHO-1 membrane-binding and -bending activity is specifically eliminated in vivo. Taken together, our data highlight Eps15 as an important membrane-remodeling factor, which acts in a partially redundant manner with Fcho proteins during the earliest stages of clathrin-mediated endocytosis.
Influence of Harvest Date on Bull’s Eye Rot of ‘Cripps Pink’ Apple and Control Chemical Strategies
Authors: Cameldi Irene , Neri Fiorella , Ventrucci Daria , Ceredi Gianni , Muzzi Enrico , Mari Marta
Published: July 2016

The influence of four different harvest times on the bull’s eye rot of ‘Cripps Pink’ apple caused by Neofabraea spp. was investigated in two orchards harvested at four different times. In addition, a control strategy based on chemical treatments performed in preharvest or postharvest was evaluated. Regression analysis between harvest time and disease incidence revealed high r2 values (>0.75). All preharvest fungicide treatments significantly (P < 0.0085) reduced the bull’s eye rot incidence; however, thiophanate-methyl (achieving >87% control) was more effective than a mixture of pyraclostrobin and boscalid (<80.7%) or fludioxonil (<57.6%), in all trials. Compared with nontreated control fruit, a postharvest treatment with the ethylene inhibitor 1-methylcyclopropene (1-MCP) halved the incidence of infection in three of four experiments. However, a combination of two preharvest treatments with a mixture of pyraclostrobin plus boscalid and one postharvest 1-MPC treatment suppressed bull’s eye rot to a significantly (P < 0.00001) greater degree (achieving >87.5% control) than the single treatments with pyraclostrobin and boscalid (<65%) and 1-MCP (<80%) tested alone.
Barriers to Knowledge Translation Regarding the Use of Probiotics as a Risk-Reduction Strategy for Necrotizing Enterocolitis
Authors: Anderson Sharon
Published: July 2016

Background:

Increasingly, evidence supports enteral probiotics are an important risk-reduction strategy for necrotizing enterocolitis (NEC) among very low birth-weight and extremely low birth-weight preterm infants. Yet, the majority of providers remain reluctant to implement practice changes.

Purpose:

The aim of this study was to better understand the discrepancy between the available evidence and clinical practice regarding the use of probiotics and other NEC prevention strategies in New Jersey.

Methods:

Using an exploratory descriptive design, a multimodal interprofessional survey was developed and executed to elicit intensive care nursery provider knowledge, views, and current practice.

Results:

Although the sample size was small (N = 29), approximately one-half of respondents familiar with the literature rated the quality of the evidence regarding probiotics as “above average” to “excellent.” These respondents were “very likely” to “extremely likely” to recommend probiotics as an NEC prevention strategy; however, none actually prescribed this intervention. The most important reason respondents did not prescribe probiotics was the focus on providing exclusive maternal and donor breast milk feedings. Other confounding factors included provision of oral colostrum care, standardized feeding protocols, and withholding feedings during blood transfusion.

Implications for Practice:

Study results suggested that some providers (primarily nurses) were not familiar with probiotic literature, which may contribute to deficits in knowledge translation to practice.

Implications for Research:

Areas for future study include identifying improved mechanisms for knowledge dissemination, recognizing and addressing barriers and facilitators to knowledge translation, and understanding how probiotics fit and/or contrast with other NEC risk-reduction strategies in the research and clinical settings.
Histologic Chorioamnionitis and Funisitis After Laser Surgery for Twin–Twin Transfusion Syndrome
Authors: Zhao Depeng , Cohen Danielle , Middeldorp Johanna M. , van Zwet Erik W. , De Paepe Monique E. , Oepkes Dick , Lopriore Enrico
Published: July 2016

OBJECTIVE:

To estimate the incidence of histologic chorioamnionitis and funisitis after fetoscopic laser surgery for the management of twin–twin transfusion syndrome.

METHODS:

A case–control study was performed at the Leiden University Medical Center from 2013 to 2014. All patients with twin–twin transfusion syndrome managed with laser surgery during the study period were included and compared with a control group of all monochorionic twins not treated with laser surgery. We excluded patients with fetal demise or higher order pregnancies. Placentas were reviewed for the presence and degree of chorioamnionitis and presence or absence of fetal inflammatory response. The primary outcome was the incidence of histologic chorioamnionitis and funisitis after laser surgery. Odds ratios (ORs) and 95% confidence intervals (CIs) for primary outcomes were calculated. A P value of <.05 was considered as statistical significance.

RESULTS:

Sixty-two patients treated with laser surgery were included in the study group and compared with 64 patients in the control group. The incidence of histologic chorioamnionitis was 13% (8/62) in the laser group compared with 5% (3/64) in the control group (OR 3.0, 95% CI 0.8–11.9, P=.12). Funisitis occurred in 8% (10/124) in the laser group compared with 0% in the control group (OR 11.1, 95% CI 1.3–96.9, P=.03). Histologic chorioamnionitis with or without funisitis after laser surgery was associated with a shorter laser-to-delivery interval (median 6.6 [range 3.4–14.1] compared with 13.6 [4.4–20.1] weeks, P<.01) and lower gestational age at birth (median 28.1 [range 23.1–32.6] compared with 32.7 [24.4–37.0] weeks, P<.01).

CONCLUSION:

These findings suggest that laser surgery for twin–twin transfusion syndrome is associated with an increased risk of funisitis.
Sharing of Snorting Straws and Hepatitis C Virus Infection in Pregnant Women
Authors: Fernandez Noelle , Towers Craig V. , Wolfe Lynlee , Hennessy Mark D. , Weitz Beth , Porter Stephanie
Published: July 2016

OBJECTIVE:

To evaluate possible modes of hepatitis C virus (HCV) acquisition in pregnant women found to be HCV-infected in the prenatal period and to assess transmission risk factors.

METHODS:

This was a prospective cohort study conducted from March 2014 through June 2015 involving the distribution of an anonymous survey to HCV-infected pregnant women that assessed for numerous modes of potential HCV transmission involving, intravenous drug use, blood transfusion, organ transplant, sexual contact, tattoos, and snorting drugs with a straw. Participants were drawn from our institutional obstetric high-risk clinic. Statistical analysis involved simple percentages and χ2 comparisons where appropriate; P<.05 was considered significant. To test biologic plausibility, snorting utensils confiscated by law enforcement authorities from patients not in this study were tested for the presence of human blood.

RESULTS:

A total of 189 HCV-infected pregnant patients completed the survey, and no approached patients declined. Of these, 136 (72%, 95% confidence interval [CI] 65–78%) admitted to intravenous drug use, of whom 89 (65%, 95% CI 57–73%) reported sharing needles. Of the 178 (94%, 95% CI 90–97%) who admitted snorting drugs, 164 (92%, 95% CI 87–96%) reported sharing straws. The difference between the proportion reporting sharing of snorting utensils compared with the proportion sharing intravenous drug use utensils was significant (P<.001). Twenty-nine patients (15%, 95% CI 11–21%) reported snorting drugs and sharing straws but denied any other risk factor except sexual contact. Of the 54 straws confiscated by law enforcement authorities, 13 (24%, 95% CI 13–38%) tested positive for the presence of human blood.

CONCLUSION:

Sharing snorting utensils (straws) in noninjection drug use may be an additional risk factor for HCV and other virus transmission.
Diagnostic Biomarkers in Women With Suspected Preeclampsia in a Prospective Multicenter Study
Authors: Duckworth Suzy , Griffin Melanie , Seed Paul T. , North Robyn , Myers Jenny , Mackillop Lucy , Simpson Nigel , Waugh Jason , Anumba Dilly , Kenny Louise C. , Redman Christopher W. G. , Shennan Andrew H. , Chappell Lucy C.
Published: July 2016

OBJECTIVE:

To evaluate 47 biomarkers (selected from the current medical literature), in isolation or in combination with placental growth factor (PlGF), to determine the need for delivery within 14 days, in women presenting with suspected preterm preeclampsia.

METHODS:

In a prospective, multicenter observational study, 47 biomarkers were measured in 423 women presenting with suspected preterm preeclampsia (in two prespecified groups: group 1 at less than 35 weeks of gestation and group 2 presenting between 35 0/7 and 36 6/7 weeks of gestation) to evaluate their ability to determine the primary endpoint: preeclampsia requiring delivery within 14 days. Using factor analysis and stepwise logistic regression, we sought one or more additional biomarkers for optimal determination of the primary endpoint.

RESULTS:

In women presenting at less than 35 weeks of gestation (n=286), the best performing combination of PlGF, podocalyxin, endoglin, procalcitonin (receiver operating curve [ROC] area 0.90, 95% confidence interval [CI] 0.86–0.93) was not statistically better than PlGF alone (ROC 0.87, 95% CI 0.83–0.92; P=.43) for preeclampsia requiring delivery within 14 days. Two other single markers had test performance that was not significantly different to PlGF (soluble fms-like tyrosine kinase-1 [sFlt-1] ROC 0.83, 95% CI 0.78–0.88; endoglin ROC 0.83, 95% CI 0.79–0.88). Similar findings were found in women presenting between 35 0/7 and 36 6/7 weeks of gestation (n=137): ROC for PlGF alone 0.75 (95% CI 0.67–0.83); ROC for PlGF, cystatin, pregnancy-associated plasma protein A in combination 0.81 (95% CI 0.74–0.88; P=.40).

CONCLUSION:

This study supports the growing body of evidence that a single angiogenesis-related biomarker (PlGF, sFlt-1, or endoglin) alone represents a useful diagnostic test for women presenting with suspected preterm preeclampsia.
Cryopreserved Human Umbilical Cord for In Utero Myeloschisis Repair
Authors: Papanna Ramesha , Fletcher Stephen , Moise Kenneth J. , Mann Lovepreet K. , Tseng Scheffer C. G.
Published: July 2016

BACKGROUND:

There is an urgent need is for a regenerative patch for in utero repair of spina bifida in situations in which primary closure is difficult.

CASES:

We present two cases of large myeloschisis defects that underwent in utero spina bifida repair at midgestation with closure of the skin defect by using a cryopreserved human umbilical cord patch. The pregnancies were uncomplicated, and the births occurred at 37 weeks by planned cesarean delivery. The repair sites were intact with no evidence of cerebrospinal fluid leakage, with skin regenerated after delivery over a period of 3–4 weeks. The short-term outcomes after delivery showed reversal of hindbrain herniation, minimal spinal cord tethering, and normal function of the lower extremities.

CONCLUSION:

Cryopreserved human umbilical cord may be a suitable patch system for the spina bifida closure.
A Sanitary Pad for Self-Assessment of Rupture of Membranes
Authors: Mor Amir , Haberman Shoshana , Kalgi Bharati , Minkoff Howard
Published: July 2016

BACKGROUND:

Multistep immunoassay kits for the diagnosis of rupture of membranes are relatively complex and are not designed to be used by pregnant women themselves. These kits require procedural steps of specimen extraction and preparation. We evaluated the ability of a sanitary pad containing a qualitative immunoassay for alpha-fetoprotein (AFP) to serve as a one-step self-test to detect amniotic fluid leakage.

TECHNIQUE:

Four sets of pads were evaluated. The pads in the study set were worn by 288 pregnant women with confirmed rupture of membranes. Three controls were evaluated: 1) pads worn by 93 pregnant women with intact membranes, 2) additional pads instilled with urine specimens obtained from the 381 women described previously (study set plus control set 1), and 3) pads instilled with semen collected from 40 men.

EXPERIENCE:

All 288 pads that absorbed amniotic fluid had positive results. Approximately half of the pads absorbed with normal vaginal discharge had a sufficient amount to yield valid results, which were all negative. All 381 pads with instilled urine and all 40 pads with instilled semen had negative results.

CONCLUSION:

An immunoassay for AFP, embedded in a pad, appears to be a feasible and reproducible self-test for the detection of rupture of membranes.
Early Compared With Delayed Physician Rounds on Patient Satisfaction of Postpartum Women
Authors: Roberts Robyn P. , Blackwell Sean C. , Brown Kelly M. , Pedroza Claudia , Sibai Baha M. , Tyson Jon E.
Published: July 2016

OBJECTIVE:

To investigate whether delayed timing of physician rounds improves patient satisfaction for postpartum women.

METHODS:

Women were randomized to early (5–7 am) or delayed (8–10 am) physician rounding. Women with stillbirth, high-risk pregnancy, or complications precluding delayed rounding were excluded. At discharge, women completed a modified Hospital Consumer Assessment of Healthcare Providers and Systems survey. The primary outcome was rating of the hospital. Secondary outcomes included patient assessment of patient–physician communication, various hospital experiences, and timing of maternal and neonatal discharge. We estimated that 74 women were needed to detect a 20% difference in rating of the hospital (0–10 score) between groups (assumption P=.05, power 90%). Given limited information on primary outcome, an a priori plan was in place to conduct the study for 2 months.

RESULTS:

One hundred fifty-two women were randomized (n=76 early rounding; n=76 delayed rounding). More women had a cesarean delivery in the early compared with the delayed rounding group (47.4% compared with 22.4%). Median rating of the hospital was higher in the delayed as compared with the early rounding group (9.0 [7.0–9.0] compared with 7.0 [6.0–8.0]; P<.01). Median scores regarding physician communication and perception of hospital experiences were higher in the delayed compared with the early group (8.0 [7.0–9.0] compared with 6.0 [5.0–7.0]; P<.001). Adjustment for delivery mode did not alter results (P<.01). No differences in timing of maternal (P=.47) or neonatal hospital discharge (P=.35) were observed.

CONCLUSION:

Postpartum women receiving delayed physician rounding were more satisfied with their hospital experience and patient–physician communication without prolonging maternal or neonatal discharge.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, https://clinicaltrials.gov, NCT02432573.
Failure of tension band plating: a case series
Authors: Masquijo Julio J. , Firth Gregory B. , Sepúlveda Dalia
Published: July 2016

Growth modulation with tension band plates (TBP) has been shown to be a very useful method for the treatment of angular deformities in growing children. Recently, we have observed cases of failure where the epiphyseal screw was drawn through the physis into the metaphysis. This study describes a series of children who developed this complication. Patients who developed TBP failure after operative treatment of lower limb angular deformities were identified from the databases at four institutions over a 5-year period. The medical records were reviewed to record demographics, primary diagnoses, details of the operative procedure, development of physeal arrest, and recurrence of the original deformity. Six patients (five girls) with nine implant failures were identified. The mean age of the children at the time of implant insertion was 7.2 years (range, 4–10 years). The primary diagnoses included hypophosphatemic rickets (n=7), congenital pseudoarthrosis of the tibia associated with neurofibromatosis 1 (n=1), and post-traumatic malunion after distal tibial fracture (n=1). Of the nine TBP that presented with the complication, four were inserted into the medial distal femur (one bilateral case), two into the medial proximal tibia (one bilateral case), two into the lateral distal tibia, and one into the medial distal tibia. None of these patients developed physeal growth arrest at the last follow-up as assessed on the latest radiographs. The use of TBP for guided growth in patients younger than 10 years old with rickets, neurofibromatosis, or other conditions that produce osteopenia leads to an increased risk for implant failure. In these cases, it is important to confirm that the epiphyseal screw has good purchase. Patients with these features should be monitored closely for early detection of this complication.
The fate of hips that are conservatively treated in multiple epiphyseal dysplasia
Authors: Kim Seung-Ju , Ramanathan Ashok K. , Jeon Young-Sik , Song Hae-Ryong
Published: July 2016

We reviewed the radiologic and clinical outcomes of hip joints affected by multiple epiphyseal dysplasia in 40 patients. The average patient age was 9.6 years. All patients were followed up for an average of 7.2 years. No patient underwent surgical treatment. The variances of the center-edge angle and femoral head coverage had the greatest tendency to increase with conservative treatment and follow-up (P=0.011 and 0.015, respectively). The acetabular angle and the acetabular depth index at the first visit and the latest follow-up were statistically significantly different (P=0.046 and 0.027, respectively). According to the Stulberg classification, the severity of hip deformity became less severe with age, but this was not statistically significant (P=0.090). Larger improvements in Harris hip scores were identified after conservative treatment (P=0.003). Favorable midterm outcomes were obtained for the treatment of hip deformity in multiple epiphyseal dysplasia patients by conservative treatment.
The effectiveness of posterior knee capsulotomies and knee extension osteotomies in crouched gait in children with cerebral palsy
Authors: Taylor Daveda , Connor Justin , Church Chris , Lennon Nancy , Henley John , Niiler Tim , Miller Freeman
Published: July 2016

Crouched gait is common in children with cerebral palsy (CP), and there are various treatment options. This study evaluated the effectiveness of single-event multilevel surgery including posterior knee capsulotomy or distal femoral extension osteotomy to correct knee flexion contracture in children with CP. Gait analyses were carried out to evaluate gait preoperatively and postoperatively. Significant improvements were found in physical examination and kinematic measures, which showed that children with CP and crouched gait who develop knee flexion contractures can be treated effectively using single-event multilevel surgery including a posterior knee capsulotomy or distal femoral extension osteotomy.
Primary Signet-Ring Cell/Histiocytoid Carcinoma of the Eyelid: A “Binocle” Presentation of the “Monocle Tumor”
Authors: Bernárdez Claudia , Macías del Toro Elena , Ramírez Bellver Jose Luis , Martinez Menchón Teresa , Martinez Barba Enrique , Molina-Ruiz Ana María , Requena Luis
Published: July 2016

Primary cutaneous signet-ring cell carcinoma is a rare and aggressive neoplasm which diffusely involves dermis and subcutis of the eyelid or axillae. Neoplastic cells show a signet-ring cell or histiocytoid morphology in variable number, and can be found intermingled among collagen bundles, sparing the epidermis. This neoplasm typically appears in the eyelids of elderly men, in the form of a painless infiltration and swelling but with no other specific clinical feature, and frequently causes diagnostic retardation and worse prognosis. Frequent involvement of both eyelids of the same eye has given it the name of monocle tumor. Only 29 cases have been described in English literature to date, of which 7 developed metastases, mainly on regional lymph nodes. The authors present a case of involvement of contralateral eyelid, which has only been described previously in 2 cases. The immunohistochemical profile of the involvement in the contralateral eye, and the absence of other metastasis, suggest that it is locally spread from the initial lesion. However the possibility of being a second primary tumor or metastasis cannot be readily ruled out.
High Relative Expression of Pannexin 3 (PANX3) in an Axillary Sweat Gland Carcinoma With Osteosarcomatous Transformation
Authors: Romano Ryan C. , Gardner Jerad M. , Shalin Sara C. , Ram Roopa , Govindarajan Rang , Montgomery Corey O. , Gilley Jasen H. , Nicholas Richard W.
Published: July 2016

Primary cutaneous sweat gland carcinomas (SGCs) are rare tumors that commonly involve axillae, have a high local recurrence rate, and rarely show sarcomatoid transformation. A 68-year-old man presented with rapid enlargement of a previously stable, asymptomatic pea-sized nodule in the left axilla. Initial excision (with positive surgical margins) at another institution showed characteristic histologic features of a high-grade osteosarcoma and molecular analysis using a 92-gene real-time quantitative reverse transcription–polymerase chain reaction assay confirmed a diagnosis of osteosarcoma with 96% certainty. Notably, the molecular assay demonstrated consistently high relative expression of pannexin 3 (PANX3), a gene involved in normal osteoblast differentiation which, when highly expressed, strongly predicts osteosarcoma per the assay's algorithm. However, on further histologic review, the tumor also contained focal cystic areas, nests, and ducts composed of malignant epithelial cells reminiscent of SGC; these areas directly transitioned into the osteosarcomatous component and were strongly positive for pancytokeratin, CK7, and p63. Within 2 weeks, the lesion recurred and grew rapidly, prompting complete resection, histologic sections of which showed high-grade osteosarcoma without residual epithelial elements. This is the fifth report, to our knowledge, of osteosarcomatous transformation in a SGC, and the only report to date including molecular data. This case demonstrates that osteosarcoma arising from a SGC has a similar molecular profile to de novo primary osteosarcoma of bone. It also emphasizes the importance of histopathologic findings as the established diagnostic gold standard and the need to interpret molecular results within the clinical context.
Atypical Spitzoid Neoplasms in Childhood: A Molecular and Outcome Study
Authors: Lee Christina Y. , Sholl Lauren M. , Zhang Bin , Merkel Emily A. , Amin Sapna M. , Guitart Joan , Gerami Pedram
Published: July 2016

The natural history of atypical Spitz neoplasms remains poorly understood, resulting in significant patient and clinician anxiety. We sought to better characterize outcomes that correlated with molecular features by performing a prospective cohort study of pediatric atypical spitzoid neoplasms in which fluorescence in situ hybridization studies were obtained for diagnosis. Cases with sufficient tissue underwent additional retrospective assessment for translocations inALK,NTRK1,BRAF,RET, andROS1. Among 246 total patients assessed, 13% had a positive fluorescence in situ hybridization result. Follow-up data was available in 85 patients. Two patients had a recurrence of whom 1 had distant metastasis. Both patients had homozygous deletions in 9p21. Homozygous deletions in 9p21 significantly correlated with recurrence of disease (P= 0.027). Fifteen (36%) of 42 cases were found to have a kinase fusion protein. However, the presence of kinase fusions was nonprognostic of recurrence (P> 0.99). This study was limited by the availability and length of follow-up data and the number of adverse outcomes. The majority of atypical spitzoid neoplasms in childhood have indolent behavior. Although the subgroup of patients with homozygous deletions in 9p21 is at higher risk for aggressive clinical behavior, their prognosis seems considerably better than similarly staged conventional melanoma.
Mitotic Activity in Juvenile Benign Nevi
Authors: Brown Megan Anne , Tallon Ben
Published: July 2016

Melanocytic nevi are submitted for histological evaluation primarily to exclude a malignant process. Mitotic figures are one of the factors used in this assessment. However, there is a lack of data on mitotic activity in juvenile benign nevi. The authors assessed 114 cases of benign melanocytic nevi in children aged 0–15 (inclusive) years old by counting the mitoses present in 2 sections of hematoxylin and eosin–stained tissue. The authors then calculated the proportion of cases in which mitotic activity was present, and the average number of mitoses per case for each age group to get the mitotic rate. The authors found that there was at least 1 mitoses present in 40.4% of cases, and that the mitotic rate decreases in older children compared with younger children. This highlights the need for careful consideration of the significance of a mitotic figure in juvenile pigmented lesions, to ensure the lesion is not overinterpreted as malignant.
Do Cancer-Related Beliefs Influence the Severity, Incidence, and Persistence of Psychological Symptoms?
Authors: Desautels Caroline , Trudel-Fitzgerald Claudia , Ruel Sophie , Ivers Hans , Savard Josée
Published: July 2016

Background:

Previous studies have suggested that negative beliefs about cancer may impair patients’ psychological well-being, but only a few of these studies focused on specific psychological symptoms, and many were cross-sectional.

Objective:

The aim of this study was to investigate longitudinally the relationship of cancer-related cognitions with the severity, incidence, and persistence of anxiety, fear of cancer recurrence, depression, and insomnia symptoms during an 18-month period.

Methods:

Patients scheduled to undergo surgery for cancer (N = 962) completed a questionnaire assessing cancer-related cognitions at baseline (T1), the Hospital Anxiety and Depression Scale, the severity subscale of the Fear of Cancer Recurrence Inventory, and the Insomnia Severity Index at baseline (T1) and 2 (T2), 6 (T3), 10 (T4), 14 (T5), and 18 (T6) months later.

Results:

Group × time factorial analyses using mixed models revealed that participants endorsing more negative cancer-related cognitions consistently reported more severe symptoms throughout the 18-month period. Logistic regression analyses suggested that endorsing more negative cancer-related cognitions at T1 significantly increased incidence and persistence rates of clinical levels of psychological symptoms.

Conclusions:

These findings suggest that the endorsement of negative cancer-related beliefs at the perioperative period influences the longitudinal evolution of anxiety, fear of cancer recurrence, depression, and insomnia symptoms in the following months.

Implications for Practice:

These results highlight the relevance of using cognitive restructuring early during the cancer care trajectory to potentially revise erroneous beliefs about cancer and prevent the incidence and persistence of psychological disturbances over time.
Effect of Botulinum Toxin Type A on TGF-β/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation
Authors: Kim Sena , Ahn Moonsang , Piao Yibo , Ha Yooseok , Choi Dae-Kyoung , Yi Min-Hee , Shin Nara , Kim Dong Woon , Oh Sang-Ha
Published: July 2016

Background:

One of the most serious complications of breast surgery using implants is capsular contracture. Several preventive treatments have been introduced; however, the mechanism of capsule formation has not been resolved completely. The authors previously identified negative effects of botulinum toxin type A on capsule formation, expression of transforming growth factor (TGF)-β1, and differentiation of fibroblasts into myofibroblasts. Thus, the authors investigated how to prevent capsule formation by using botulinum toxin type A, particularly by means of TGF-β1 signaling, in human fibroblasts.

Methods:

In vitro, cultured human fibroblasts were treated with TGF-β1 and/or botulinum toxin type A. Expression of collagen, matrix metalloproteinase, and Smad was examined by Western blotting. The activation of matrix metalloproteinase was observed by gelatin zymography. In vivo, the effect of botulinum toxin type A on the phosphorylation of Smad2 in silicone-induced capsule formation was evaluated by immunocytochemistry.

Results:

In vitro, the phosphorylation of Smad2 was inhibited by botulinum toxin type A treatment. The expression levels of collagen types 1 and 3 were inhibited by botulinum toxin type A treatment, whereas those of matrix metalloproteinase-2 and matrix metalloproteinase-9 were enhanced. Gelatin zymography experiments confirmed enhanced matrix metalloproteinase-2 activity in collagen degradation. In vivo, botulinum toxin type A treatment reduced capsule thickness and Smad2 phosphorylation in silicone-induced capsules.

Conclusion:

This study suggests that botulinum toxin type A plays an important role in the inhibition of capsule formation through the TGF-β/Smad signaling pathway.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Autologous Fat Grafting for Pedal Fat Pad Atrophy: A Prospective Randomized Clinical Trial
Authors: Gusenoff Jeffrey A. , Mitchell Ryan T. , Jeong Kwonho , Wukich Dane K. , Gusenoff Beth R.
Published: July 2016

Background:

Pedal fat pad atrophy is associated with pain, decreased tissue thickness, and increased foot pressures. To date, no objective studies investigating the use of fat grafting to the forefoot have been performed. The authors hypothesize that pedal fat grafting can reduce pain, increase tissue thickness, and decrease pedal pressures.

Methods:

A prospective randomized study was performed to assess tissue thickness, pain, and foot pressures. Group 1 underwent fat grafting immediately with 1-year follow-up, and group 2 underwent conservative management for 1 year.

Results:

Thirteen patients (two men and 11 women) constituted group 1 and 12 patients (four men and eight women) constituted group 2. Ten patients in group 1 underwent bilateral injections with a mean volume of 4.8 cc per foot. Mean follow-up time was 11.1 ± 5.4 months for group 1 and 13.8 ± 4.2 months for group 2. At 1 year, group 1 demonstrated improved foot function (p= 0.022), pain (p= 0.022), and work/leisure activities (p= 0.021). Group 1 had no change in tissue thickness, whereas in group 2, the right third metatarsal tissue thickness decreased significantly (p= 0.036). Foot pressures in group 1 did not improve; however, group 2 had a significant increase in left foot pressure (p= 0.011). When comparing the groups at 1 year, group 2 had significantly higher foot pressures and forces than group 1 (p< 0.05).

Conclusions:

Pedal fat grafting significantly improves pain and disability outcomes, and prevents against worsening foot pressures. Future analysis will reveal whether fat grafting has lasting efficacy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Metabolic Syndrome After HIV Acquisition in South African Women
Authors: Sobieszczyk Magdalena E. , Werner Lise , Mlisana Koleka , Naicker Nivashnee , Feinstein Addi , Gray Clive M. , Masson Lindi , Passmore Jo-Ann S. , Williamson Carolyn , Abdool Karim Quarraisha , Abdool Karim Salim S. , Garrett Nigel J.
Published: July 2016

Background:

Noncommunicable diseases are common among chronically infected patients with HIV in the developed world, but little is known about these conditions in African cohorts. We assessed the epidemiology of metabolic syndrome among young South African women during the first 3 years after HIV acquisition.

Methods:

A total of 160 women were followed prospectively in the CAPRISA 002 Acute Infection study. Metabolic syndrome was defined as a constellation of hyperlipidemia, hypertension, hyperglycemia/diabetes, and abdominal obesity. Time trends were assessed using generalized estimation equation models.

Results:

Median age was 24 years and body mass index 27 kg/m2. Prevalence of metabolic syndrome at infection was 8.7% increasing to 19.2% over 36 months (P = 0.001). The proportion of women with body mass index >30 kg/m2 increased from 34.4% to 47.7% (P = 0.004), those with abnormal waist circumference and elevated blood pressure increased from 33.5% to 44.3% (P = 0.060) and 23.8% to 43.9% (P < 0.001), respectively. Incidence of metabolic syndrome was 9.13/100 person-years (95% CI: 6.02 to 13.28). Predictors of metabolic syndrome were age (per year increase odds ratio (OR) = 1.12; 95% CI: 1.07 to 1.16), time postinfection (per year OR = 1.47; 95% CI: 1.12 to 1.92), family history of diabetes (OR = 3.13; 95% CI: 1.71 to 5.72), and the human leukocyte antigen (HLA)-B*81:01 allele (OR = 2.95; 95% CI: 1.21 to 7.17), whereas any HLA-B*57 or B*58:01 alleles were protective (OR = 0.34; 95% CI: 0.15 to 0.77). HIV-1 RNA (OR = 0.89; 95% CI: 0.62 to 1.27) and CD4 count (OR = 1.03; 95% CI: 0.95 to 1.11) did not predict metabolic syndrome.

Conclusions:

The high burden of metabolic conditions in young South African HIV-infected women highlights the need to integrate noncommunicable disease and HIV care programs. Interventions to prevent cardiovascular disease must start at HIV diagnosis, rather than later during the disease course.
Optimizing Infant HIV Diagnosis in Resource-Limited Settings: Modeling the Impact of HIV DNA PCR Testing at Birth
Authors: Chiu Alexander , Modi Surbhi , Rivadeneira Emilia D. , Koumans Emilia H.
Published: July 2016

Background:

Early antiretroviral therapy (ART) initiation in HIV-infected infants significantly improves survival but is often delayed in resource-limited settings. Adding HIV testing of infants at birth to the current recommendation of testing at age 4–6 weeks may improve testing rates and decrease time to ART initiation. We modeled the benefit of adding HIV testing at birth to the current 6-week testing algorithm.

Methods:

Microsoft Excel was used to create a decision-tree model of the care continuum for the estimated 1,400,000 HIV-infected women and their infants in sub-Saharan Africa in 2012. The model assumed average published rates for facility births (42.9%), prevention of mother-to-child HIV transmission utilization (63%), mother-to-child-transmission rates based on prevention of mother-to-child HIV transmission regimen (5%–40%), return of test results (41%), enrollment in HIV care (52%), and ART initiation (54%). We conducted sensitivity analyses to model the impact of key variables and applied the model to specific country examples.

Results:

Adding HIV testing at birth would increase the number of infants on ART by 204% by age 18 months. The greatest increase is seen in early ART initiations (543% by age 3 months). The increase would lead to a corresponding increase in survival at 12 months of age, with 5108 fewer infant deaths (44,550, versus 49,658).

Conclusion:

Adding HIV testing at birth has the potential to improve the number and timing of ART initiation of HIV-infected infants, leading to a decrease in infant mortality. Using this model, countries should investigate a combination of HIV testing at birth and during the early infant period.
Inosine Triphosphate Pyrophosphohydrolase Expression: Decreased in Leukocytes of HIV-Infected Patients Using Combination Antiretroviral Therapy
Authors: Peltenburg N. Chantal , Leers Mathie P. G. , Bakker Jaap A. , Lowe Selwyn H. , Vroemen Wim H. M. , Paulussen Aimée D. C. , van den Bosch Bianca J. C. , Bierau Jörgen , Verbon Annelies
Published: July 2016

Objective:

In HIV-infected patients, the enzyme Inosine triphosphate pyrophosphohydrolase (ITPase), involved in purine nucleotide homeostasis, was found to be decreased in erythrocytes. Since purine analogues are pivotal in the HIV treatment, a better understanding of ITPase expression in CD4+ lymphocytes may lead to better understanding of nucleotide metabolism and (adverse) effects.

Design:

Cross-sectional, cohort, observational study.

Methods:

HIV-infected and control patients above 18 years were included. All DNA samples were genotyped for the 2 functional ITPA SNPs; c.94C>A (rs1127354) and g.IVS+21A>C (rs7270101). ITPase expression was determined by flow cytometry in all leukocyte subsets.

Results:

Fifty-nine HIV-infected patients and 50 controls were included. Leukocyte subtype distribution showed no difference in monocytes and granulocytes, but lymphocytes were higher in HIV-infected patients (P < 0.001). ITPase expression was highest in activated monocytes and lowest in lymphocytes. In HIV-infected patients, the percentage of ITPase positive cells was less in all leukocyte and lymphocyte subsets compared with controls (P < 0.01). In HIV-infected patients, 97.4% of CD4+ lymphocytes were ITPase positive versus 99.9% in controls (P = 0.002) and 85.9% versus 99.6% of CD8+ lymphocytes (P < 0.0001), respectively. Stratification according to genotype revealed no significant differences in ITPase expression in leukocytes in HIV-infected and control patients.

Conclusions:

HIV-infection seems to be interfering with the nucleotide metabolism in leukocytes, including CD4+ lymphocytes, by decreasing ITPase expression, independently of ITPA genotype. Given that active metabolites of purine-analogue reverse transcriptase inhibitors are potential substrates for ITPase, these results warrant further research towards effectiveness and adverse events of purine analogues and ITPase activity.
Research Registries: A Tool to Advance Understanding of Rare Neuro-Ophthalmic Diseases
Authors: Blankshain Kimberly D. , Moss Heather E.
Published: July 2016

Background:

Medical research registries (MRR) are organized systems used to collect, store, and analyze patient information. They are important tools for medical research with particular application to the study of rare diseases, including those seen in neuro-ophthalmic practice.

Evidence Acquisition:

Evidence for this review was gathered from the writers' experiences creating a comprehensive neuro-ophthalmology registry and review of the literature.

Results:

MRR are typically observational and prospective databases of de-identified patient information. The structure is flexible and can accommodate a focus on specific diseases or treatments, surveillance of patient populations, physician quality improvement, or recruitment for future studies. They are particularly useful for the study of rare diseases. They can be integrated into the hierarchy of medical research at many levels provided their construction is well organized and they have several key characteristics including an easily manipulated database, comprehensive information on carefully selected patients, and comply with human subjects regulations. MRR pertinent to neuro-ophthalmology include the University of Illinois at Chicago neuro-ophthalmology registry, Susac Syndrome Registry, Intracranial Hypertension Registry, and larger-scale patient outcome registries being developed by professional societies.

Conclusion:

MRR have a variety of forms and applications. With careful planning and clear goals, they are flexible and powerful research tools that can support multiple different study designs, and this can provide the potential to advance understanding and care of neuro-ophthalmic diseases.
Primary transmission of chronic wasting disease versus scrapie prions from small ruminants to transgenic mice expressing ovine or cervid prion protein
Authors: Madsen-Bouterse Sally A. , Schneider David A. , Zhuang Dongyue , Dassanayake Rohana P. , Balachandran Aru , Mitchell Gordon B. , O'Rourke Katherine I.
Published: July 2016

Development of mice expressing either ovine (Tg338) or cervid (TgElk) prion protein (PrP) have aided in characterization of scrapie and chronic wasting disease (CWD), respectively. Experimental inoculation of sheep with CWD prions has demonstrated the potential for interspecies transmission but, infection with CWD versus classical scrapie prions may be difficult to differentiate using validated diagnostic platforms. In this study, mouse bioassay in Tg338 and TgElk was utilized to evaluate transmission of CWD versus scrapie prions from small ruminants. Mice (≥5 per homogenate) were inoculated with brain homogenates from clinically affected sheep or goats with naturally acquired classical scrapie, white-tailed deer with naturally acquired CWD (WTD-CWD) or sheep with experimentally acquired CWD derived from elk (sheep-passaged-CWD). Survival time (time to clinical disease) and attack rates (brain accumulation of protease resistant PrP, PrPres) were determined. Inoculation with classical scrapie prions resulted in clinical disease and 100 % attack rates in Tg338, but no clinical disease at endpoint (>300 days post-inoculation, p.i.) and low attack rates (6.8 %) in TgElk. Inoculation with WTD-CWD prions yielded no clinical disease or brain PrPres accumulation in Tg338 at endpoint (>500 days p.i.), but rapid onset of clinical disease (~121 days p.i.) and 100 % attack rate in TgElk. Sheep-passaged-CWD resulted in transmission to both mouse lines with 100 % attack rates at endpoint in Tg338 and an attack rate of ~73 % in TgElk with some culled due to clinical disease. These primary transmission observations demonstrate the potential of bioassay in Tg338 and TgElk to help differentiate possible infection with CWD versus classical scrapie prions in sheep and goats.
Are foundation species effects different than those of dominant species? A case study of ant assemblages in northeastern North American forests
Authors: Record Sydne , McCabe Tempest , Baiser Benjamin , Ellison Aaron M.
Published: July 2016

Foundation species uniquely control associated biodiversity through non-trophic effects, whereas dominant species are locally abundant but are replaceable in ecological systems. Long-term data on ant assemblages at the Harvard Forest Hemlock Removal Experiment (HF-HeRE) and the Black Rock Future of Oak Forests Experiment (BRF-FOFE) provide insights into how ant assemblages change and reassemble following the loss of a foundation species (Tsuga canadensis) or a dominant genus (Quercus). At HF-HeRE, removal ofT. canadensistrees resulted in taxonomic and functional shifts in ant assemblages relative to control stands. In contrast, ant assemblages at BRF-FOFE varied little regardless of whether oaks or non-oaks were removed from the canopy. Non-trophic effects of foundation species were stronger than indirect trophic effects on taxonomic and functional diversity of ant assemblages. In contrast, non-trophic effects of dominant species were weaker than indirect trophic effects on ant taxonomic diversity and some measures of ant functional diversity.

Statement of authorship

A.M. Ellison and S. Record conceived the study. A.M. Ellison, T. 17 McCabe, and S. Record collected field data. T. McCabe and S. Record did the taxonomic diversity analyses. B. Baiser and S. Record did the functional diversity analyses. All authors contributed to drafts of the manuscript.

Data accessibility

All data (i.e., ant and trait) and R code are available from the Harvard Forest Data Archive (http://harvardforest.fas.harvard.edu/data-archive), datasets HF-118 (HF-HeRE) and HF-097 (BRF-FOFE). Nomenclature follows Bolton (2016); voucher specimens are stored at the Harvard Forest and at the Museum of Comparative Zoology.
Chaotic provinces in the kingdom of the Red Queen
Authors: Schenk Hanna , Traulsen Arne , Gokhale Chaitanya S.
Published: July 2016

The interplay between parasites and their hosts is found in all kinds of species and plays an important role in understanding the principles of evolution and coevolution. Usually, the different genotypes of hosts and parasites oscillate in their abundances. The well-established theory of oscillatory Red Queen dynamics proposes an ongoing change in frequencies of the different types within each species. So far, it is unclear in which way Red Queen dynamics persists with more than two types of hosts and parasites. In our analysis, an arbitrary number of types within two species are examined in a deterministic framework with constant or changing population size. This general framework allows for analytical solutions for internal fixed points and their stability. For more than two species, apparently chaotic dynamics has been reported. Here we show that even for two species, once more than two types are considered per species, irregular dynamics in their frequencies can be observed in the long run. The nature of the dynamics depends strongly on the initial configuration of the system; the usual regular Red Queen oscillations are only observed in some parts of the parameter region.