bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic Ultrasound-Guided Fine-Needle Aspiration Cytology Combined With Automated Quantitative DNA Cytometry Can Improve the Value in the Detection of Pancreatic Malignancy
Authors: Zhao Min , Yang Li , Fu Xin , Yang Qiao , Liu Na , Guo Changcun , Ke Xiaoru , Wang Xin , Guo Xuegang , Wu Kaichun , Fan Daiming , Zhang Hongbo , Zhang Xiaoyin
Published: December 2017

Objectives

Quantitative DNA-image cytometry (ICM) is used to diagnose malignancy via detecting changes in DNA content. We aimed to estimate the value of cytology, DNA-ICM, and their combination in diagnosing pancreatic malignancy.

Methods

One hundred twenty-one endoscopic ultrasound-guided fine-needle aspiration samples from 116 patients suspected for pancreatic malignancy were examined by cytology and DNA-ICM. Their results and the final diagnoses (malignancy or not) were collected. Diagnostic values were compared among cytology, DNA-ICM, and their combination.

Results

The DNA-ICM had a lower sensitivity and accuracy than cytology (64.2% vs 81.1%; 71.9% vs 85.1%). The combination of the techniques significantly improved the diagnostic accuracy compared with that of cytology or DNA-ICM alone (0.932 vs 0.905, P = 0.02; 0.932 vs 0.821, P < 0.0001). Using the Youden index, we determined that one cell with DI (DNA index) ≥2.5 is the optimal cutoff value for DNA-ICM to diagnose pancreatic malignancy. After adoption of this criterion, the sensitivity and accuracy were improved to 74.7% and 80.2% with DNA-ICM and 90.5% and 92.6% with the combined method.

Conclusions

The DNA-ICM is an effective complementary method to cytology in diagnosing pancreatic malignancy. Although the diagnostic value for DNA-ICM is lower than that of cytology, an improved value was obtained after their combination.
Fungal Infections in Patients With Infected Pancreatic Necrosis and Pseudocysts
Authors: Reuken Philipp A. , Albig Hanna , Rödel Jürgen , Hocke Michael , Will Uwe , Stallmach Andreas , Bruns Tony
Published: December 2017

Objectives

Fungal infections in patients with acute pancreatitis are common and potentially life threatening. Data on fungal pancreatic infections are inconsistent. Therefore, the aim of this study was to identify risk factors for fungal infection and to determine their impact on survival.

Methods

This was a retrospective analysis of pathogen spectrum and outcome of infected pancreatic necrosis or pseudocysts from 3 German hospitals from 2002 to 2016.

Results

A total of 187 fine-needle aspirations were performed in 113 patients. Fungal pancreatic infections, predominantly caused by Candida species, were identified in 52 patients (46%). Antibiotic treatment before fine-needle aspiration (84.6% vs 49.2%, P = 0.003) and the duration of therapy (9 vs 2 days, P = 0.024) identified patients at an increased risk of fungal infection. Patients with fungal pancreatic infections had a longer hospital stay (34 vs 14 days, P < 0.001), received intensive care treatment more often (55.8% vs 27.9%, P = 0.002), and had a lower 365-day survival (78.4 [SE, 6.6%] vs 95.0 [SE, 2.0%], P = 0.035) than patients with bacterial pancreatic infections only.

Conclusions

Fungal infections are common in patients with infected pancreatic necrosis and pseudocysts and indicate patients with a higher risk of mortality in the long term.
Total Pancreatectomy With Intraportal Islet Autotransplantation as a Treatment of Chronic Pancreatitis in Patients With CFTR Mutations
Authors: Colling Kristin P. , Bellin Melena D. , Schwarzenberg Sarah J. , Berry Louise , Wilhelm Joshua J. , Dunn Ty , Pruett Timothy L. , Sutherland David E.R. , Chinnakotla Srinath , Dunitz Jordan M. , Beilman Greg J.
Published: December 2017

Objectives

Chronic pancreatitis (CP) is an infrequent but debilitating complication associated with CFTR mutations. Total pancreatectomy with islet autotransplantation (TPIAT) is a treatment option for CP that provides pain relief and preserves β-cell mass, thereby minimizing the complication of diabetes mellitus. We compared outcomes after TPIAT for CP associated with CFTR mutations to CP without CTFR mutations.

Methods

All TPIATs performed between 2002 and 2014 were retrospectively reviewed: identifying 20 CFTR homozygotes (cystic fibrosis [CF] patients), 19 CFTR heterozygotes, and 20 age-/sex-matched controls without CFTR mutations. Analysis of variance and χ2 tests were used to compare groups.

Results

Baseline demographics were not different between groups. Postoperative glycosylated hemoglobin and C-peptide levels were similar between groups, as were islet yield and rate of postoperative complications. At 1 year, 40% of CF patients, 22% of CFTR heterozygotes, and 35% of control patients were insulin independent.

Conclusion

Total pancreatectomy with islet autotransplantation is a safe, effective treatment option for CF patients with CP, giving similar outcomes for those with other CP etiologies.
Long‐term Results and Quality of Life Assessment in Biliary Atresia Patients
Authors: Wong Carol Wing Yan , Chung Patrick Ho Yu , Tam Paul Kwong Hang , Wong Kenneth Kak Yuen
Published: December 2017

Objectives:

To review long‐term transplant‐free survival and quality of life (QOL) of patients with biliary atresia (BA).

Methods:

A retrospective study reviewing all patients with Kasai operation between January 1, 1980 and December 31, 2015 was performed to evaluate the transplant‐free survival. Subgroup analysis of patients older than 20 years was carried out to assess the QOL using the Short Form‐36 Health Survey and incidences of disease‐related complications. Comparison between patients with native and transplanted liver was performed using two‐tailed independent samples t‐test (P value < 0.05, significant).

Results:

The 20‐year Kaplan‐Meier transplant‐free survival of the 141 patients in our study was 51%. The subgroup analysis of long‐term survivors revealed a trend of increased prevalence of complications like esophageal varices, portal hypertension, and recurrent admissions in the patient groups with raised serum bilirubin (SB).

Thirty‐one patients were successfully contacted for QOL assessment, 26 (16 with native liver and 10 with transplanted liver) responded (76.5%). BA patients who were documented to have active complications have a significantly lower vitality score (50.7 vs 57.5, P = 0.015). There was no statistically significant difference in the scores between the transplanted group and the disease‐free control group. However, the native liver group achieved a lower score in both the general health section (42.9 vs 49.6, P = 0.029) and the overall physical component (49.6 vs 54.4, P = 0.037).

Conclusions:

A significant proportion of our patients survive with their native liver for more than 20 years. These long‐term survivors may suffer from complications that impair their QOL. They require continuous life‐long care.
Educating Future Health Care Professionals About Cybercivility
Authors: De Gagne Jennie C. , Conklin Jamie L. , Yamane Sandra S. , Kang Hee Sun , Hyun Myung-Sun
Published: December 2017

As misbehaviors online in higher education have been widely addressed in recent research, the discourse on cyberincivility has become a contemporary issue in health professions education. However, studies regarding cybercivility, particularly from an interprofessional education standpoint, are few. This study assessed the knowledge, experience, and perceptions about cyberincivility among students in 4 health care disciplines. Their preferred means of learning about cybercivility and the perceived benefits of such education are also discussed.
Use of a Telehealth System to Enhance a Home Exercise Program for a Person With Parkinson Disease: A Case Report
Authors: Chatto Charlotte A. , York Paul T. , Slade Catherine P. , Hasson Scott M.
Published: December 2017

Background and Purpose:

This case addresses feasibility of a home-based telehealth system to enhance home exercise program (HEP) adherence for a patient with Parkinson disease (PD). We describe START—System for Technology-Augmented Rehabilitation and Training—and discuss outcomes after integrating START into the HEP component of an established therapy protocol, Lee Silverman Voice Technique BIG (LSVT BIG).

Case Description:

The participant was a 67-year-old woman with PD at Hoehn and Yahr Stage II.

Intervention:

During the first 4 weeks of a 4-month intervention, a physical therapist guided the participant through the LSVT BIG protocol. START was introduced at week 3; the participant was encouraged to complement her daily HEP through the end of the fourth month with START.

Outcomes:

Improvements in gait, endurance, balance confidence, and quality of life were observed from the start of the assessment to the end of month 1. By month 4, the participant maintained or improved with respect to these outcomes. Monitored by START, the rate of adherence to her twice-daily HEP prescription was 24%, but her daily participation rate was 78%. The participant's satisfaction with the START system was high, although autonomous feedback provided by START was a limiting concern. There were no technical issues or adverse events reported.

Discussion:

This case supports START as a feasible HEP telehealth solution for physical therapy, given that increased long-term exercise adherence may improve health outcomes for people with PD. The outcomes of this case study support further investigation into the use of START for people with PD.

Video Abstract available for more insights from the authors (see Video; Supplemental Digital Content 1, http://links.lww.com/JNPT/A192).
Standardization of Pediatric Interfacility Transport Handover: Measuring the Development of a Shared Mental Model*
Authors: Sochet Anthony A. , Ryan Kelsey S. , Bartlett Jennifer L. , Nakagawa Thomas A. , Bingham Ladonna
Published: December 2017

Objectives:

To determine if standardization of pediatric interfacility transport handover is associated with the development of a prototypical shared mental model between healthcare providers.

Design:

A single center, prepost, retrospective cohort study.

Settings:

A 259-bed, tertiary care, pediatric referral center.

Patients:

Children 0 to 18 years old transferred to our critical care units or emergency center from October 2016 to February 2017.

Interventions:

Standardization of interfacility handover using a multidisciplinary checklist, didactic teaching, and simulation conducted midway through the study period.

Measurements and Main Results:

The primary outcome was a shared mental model index defined as percent congruence among handover participants regarding key patient healthcare data including patient identification, diagnoses, transport interventions, immediate postadmission care plans, and anticipatory guidance for ongoing care. Secondary outcomes were handover comprehensiveness and teaming metrics such as efficiency, attendance, interruption frequency, and team member inclusion. During the study period, 100 transport handovers were observed of which 50 were preintervention and 50 post. A majority of handovers represented transfers to the emergency center (41%) or PICU (45%). There were no observable differences between prepost intervention cohorts by general characteristics, admission diagnoses, or severity of illness metrics including Pediatric Index of Mortality-3-Risk of Mortality, length of stay, mortality, frequency of invasive and noninvasive ventilation, and vasoactive use. The shared mental model index increased from 38% to 78% following standardization of handover. Attendance (76% vs 94%), punctuality (91.5% vs 98%), attention (82% vs 92%), summarization (42% vs 72%), and provision of anticipatory guidance (42% vs 58%) also improved. Efficiency was unchanged with a mean handover duration of 4 minutes in both cohorts.

Conclusions:

Considerable enhancements in handover quality, team participation, and the development of a shared mental model after standardization of interfacility transport handover were noted. These findings were achieved without compromising handover efficiency.
Understanding the Impact of Fluid Restriction on Growth Outcomes in Infants Following Cardiac Surgery*
Authors: Li Melissa , Campa Adriana , Huffman Fatma G. , Rossi Anthony F.
Published: December 2017

Objective:

Fluid restriction is reported to be a barrier in providing adequate nutrition following cardiac surgery. The specific aim of this study was to evaluate the adequacy of nutritional intake during the postoperative period using anthropometrics by comparing preoperative weight status, as measured by weight-for-age z scores, to weight status at discharge home.

Design:

Prospective cohort study.

Setting:

Cardiac ICU at Miami Children’s Hospital.

Patients:

Infants from birth to 12 months old who were scheduled for cardiac surgery at Miami Children’s Hospital between December 2013 and September 2014 were followed during the postoperative stay.

Interventions:

Observational study.

Measurements and Main Results:

Preoperative and discharge weight-for-age z scores were analyzed. The Risk Adjustment for Congenital Heart Surgery 1 categories were obtained to account for the individual complexity of each case. In patients who had preoperative and discharge weights available (n = 40), the mean preoperative weight-for-age z score was –1.3 ± 1.43 and the mean weight-for-age z score at hospital discharge was –1.89 ± 1.35 with a mean difference of 0.58 ± 0.5 (p < 0.001). A higher Risk Adjustment for Congenital Heart Surgery 1 category was correlated with a greater decrease in weight-for-age z scores (r = –0.597; p = 0.002).

Conclusions:

Nutritional status during the postoperative period was found inadequate through the use of objective anthropometric measures and by comparing them with normal growth curves. Increase in surgical risk categories predicted a greater decrease in weight-for-age z scores. The development of future protocols for nutritional intervention should consider surgical risk categories.
Time of Day When Type 1 Diabetes Patients With Eating Disorder Symptoms Most Commonly Restrict Insulin
Authors: Merwin Rhonda M. , Moskovich Ashley A. , Honeycutt Lisa K. , Lane James D. , Feinglos Mark , Surwit Richard S. , Zucker Nancy L. , Dmitrieva Natalia O. , Babyak Michael A. , Batchelder Heather , Mooney Jan
Published: December 2017

Objective

Restricting insulin to lose weight is a significant problem in the clinical management of type 1 diabetes (T1D). Little is known about this behavior or how to effectively intervene. Identifying when insulin restriction occurs could allow clinicians to target typical high-risk times or formulate hypotheses regarding factors that influence this behavior. The current study investigated the frequency of insulin restriction by time of day.

Methods

Fifty-nine adults with T1D and eating disorder symptoms completed 72 hours of real-time reporting of eating and insulin dosing with continuous glucose monitoring. We used a generalized estimating equation model to test the global hypothesis that frequency of insulin restriction (defined as not taking enough insulin to cover food consumed) varied by time of day, and examined frequency of insulin restriction by hour. We also examined whether patterns of insulin restriction for 72 hours corresponded with patients' interview reports of insulin restriction for the past 28 days.

Results

Frequency of insulin restriction varied as a function of time (p = .016). Insulin restriction was the least likely in the morning hours (6:00–8:59 AM), averaging 6% of the meals/snacks consumed. Insulin restriction was more common in the late afternoon (3:00–5:59 PM), peaking at 29%. Insulin was restricted for 32% of the meals/snacks eaten overnight (excluding for hypoglycemia); however, overnight eating was rare. Insulin restriction was associated with higher 120-minute postprandial blood glucose (difference = 44.4 mg/dL, 95% confidence interval = 22.7–68.5, p < .001) and overall poorer metabolic control (r = 0.43–0.62, p's < .01). Patients reported restricting insulin for a greater percentage of meals and snacks for the past 28 days than during the 72 hour real-time assessment; however, the reports were correlated (Spearman's ρ = 0.46, p < .001) and accounted for similar variance in HbA1c (34% versus 35%, respectively).

Conclusions

Findings suggest that insulin restriction may be less likely in the morning, and that late afternoon is a potentially important time for additional therapeutic support. Results also suggest that systematic clinical assessment and treatment of overnight eating might improve T1D management.
Viral Drug Resistance Through 48 Weeks, in a Phase 2b, Randomized, Controlled Trial of the HIV-1 Attachment Inhibitor Prodrug, Fostemsavir
Authors: Lataillade Max , Zhou Nannan , Joshi Samit R. , Lee Sangil , Stock David A. , Hanna George J. , Krystal Mark ,   for the AI438011 study team
Published: December 2017

Background:

Fostemsavir is a prodrug of temsavir, an attachment inhibitor that binds to HIV-1 gp120, blocking viral attachment to host CD4+ T-cells. The phase 2b trial AI438011 investigated the safety, efficacy, and dose–response of fostemsavir vs ritonavir-boosted atazanavir (ATV/r) in treatment-experienced, HIV-1–infected subjects.

Methods:

Two hundred fifty-one treatment-experienced subjects with baseline (BL) susceptibility to study drugs [temsavir half-maximal inhibitory concentration (IC50) <100 nM, PhenoSense Entry assay] received fostemsavir or ATV/r, each with tenofovir disoproxil fumarate + raltegravir. Subjects meeting resistance-testing criteria were assessed for emergent viral drug resistance. Changes in temsavir IC50 from BL was given a conservative technical cutoff (>3-fold increase).

Results:

66/200 fostemsavir and 14/51 ATV/r subjects had resistance testing performed; 44/66 and 9/14 were successfully tested using the PhenoSense GT assay. No subjects had emergent tenofovir disoproxil fumarate or ATV resistance. Six fostemsavir-treated subjects developed emergent raltegravir resistance. 29/66 fostemsavir-treated subjects had an evaluable phenotype using PhenoSense Entry (which tests for viral susceptibility to temsavir) and 13/29 exhibited >3-fold increase in temsavir IC50 from BL. gp120 population sequencing was successful in 11/13 subjects and 7 had emergent substitutions in gp120 associated with reduced temsavir susceptibility (S375, M426, or M434). However, 5/13 fostemsavir-treated subjects achieved subsequent suppression to <50 copies/mL before the week 48 database lock, regardless of key gp120 substitutions.

Conclusions:

Response rates remained similar across study arms regardless of BL nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, and protease inhibitor resistance-associated mutations. Emergent changes in viral susceptibility occurred more frequently with fostemsavir compared with ATV/r. However, the full impact of temsavir IC50 changes and emergent HIV-1 gp120 substitutions, and thus appropriate clinical cutoffs, requires further study. Fostemsavir is being evaluated in a phase 3 trial in heavily treatment-experienced subjects.
Recruitment of Female Sex Workers in HIV Prevention Trials: Can Efficacy Endpoints Be Reached More Efficiently?
Authors: Wood Daniel , Lancaster Kathryn E. , Boily Marie-Claude , Powers Kimberly A. , Donnell Deborah , Cohen Myron S. , Dimitrov Dobromir T.
Published: December 2017

Background/Setting:

Randomized controlled trials (RCTs) of HIV biomedical prevention interventions often enroll participants with varying levels of HIV exposure, including people never exposed to HIV. We assessed whether enrolling larger proportion of participants with consistently high exposure to HIV, such as female sex workers (FSWs), might reduce trial duration and improve the accuracy of product efficacy estimates in future HIV prevention trials.

Methods:

We used an individual-based stochastic model to simulate event-driven RCTs of an HIV prevention intervention providing 80% reduction in susceptibility per act under different proportions of FSW enrolled. A 5% annual dropout rate was assumed for both FSW and non-FSW in our main scenario, but rates of up to 50% for FSW were also explored.

Results:

Enrolling 20% and 50% FSW reduced the median-simulated trial duration from 30 months with 0% FSW enrolled to 22 months and 17 months, respectively. Estimated efficacy increased from 71% for RCTs without FSW to 74% and 76% for RCTs with 20% and 50% FSW enrolled, respectively. Increasing the FSW dropout rate to 50% increased the duration of RCTs by 1–2 months on average and preserved the gain in estimated efficacy.

Conclusions:

Despite the potential logistical challenges of recruiting and retaining FSW, trialists should revisit the idea of enrolling FSW in settings where HIV incidence among FSW is higher than among non-FSW. Our analysis suggests that enrolling FSW would increase HIV incidence, reduce trial duration, and improve efficacy estimates, even if the annual dropout rate among FSW participants is high.
123I-FP-CIT SPECT Accurately Distinguishes Parkinsonian From Cerebellar Variant of Multiple System Atrophy
Authors: Nicastro Nicolas , Garibotto Valentina , Burkhard Pierre R.
Published: December 2017

Purpose

Dopamine transporter SPECT imaging is a valuable tool to estimate the integrity of presynaptic dopaminergic pathways in degenerative parkinsonisms. Evidence about SPECT differential pattern between parkinsonian and cerebellar forms of multiple system atrophy (MSA-P and MSA-C) is lacking. We aimed at assessing whether MSA-P and MSA-C variants have a distinct semiquantitative 123I-FP-CIT SPECT pattern.

Methods

We studied a unicentric 13-year (2003–2016) retrospective cohort of subjects with possible or probable MSA and scanned with the same acquisition and reconstruction SPECT protocol. Age-dependent semiquantitative reference limits for striatal volumes of interest, asymmetry indices, and caudate/putamen ratio were previously established with a percentile approach on a cohort of subjects with nondegenerative conditions and normal visual scan.

Results

Thirty-four subjects with clinical MSA (28 MSA-P and 6 MSA-C) were identified (mean age, 68.2 ± 10.1 years; male/female ratio 1.00; disease duration, 2.5 ± 2.2 years; Movement Disorders Society Unified Parkinson's Disease Rating Scale III score, 33.8 ± 12.4). The MSA-P subjects exhibited lower uptake values for all volumes of interest, for example, striatal uptake on the more affected side (1.10 ± 0.51) compared with MSA-C (2.30 ± 0.41, P = 0.0005), as well as significantly higher asymmetry indices % (24.7 ± 24.8 vs 6.3 ± 4.5, P = 0.028) and caudate/putamen ratio (2.26 ± 1.23 vs 1.13 ± 0.17, P = 0.00148).

Conclusions

The MSA-P and MSA-C subjects exhibited significantly distinct semiquantitative SPECT pattern with severe uptake impairment and high asymmetry for MSA-P and borderline uptake values for MSA-C. Clinical distinction of these 2 phenotypical entities is necessary in order to evaluate SPECT potential to discriminate between degenerative parkinsonisms.
Focal 18F-DOPA Uptake in Brain Parenchyma Surrounding Developmental Venous Anomalies
Authors: Condon Lee , Blazak John
Published: December 2017

We report the finding of increased 18F-DOPA uptake within parenchyma surrounding a developmental venous anomaly, found incidentally in a 64-year-old woman undergoing PET scan to assess for Parkinson’s disease. Not identified on previous T1/T2 MRI, susceptibility-weighted imaging MRI performed post–PET scan demonstrated the presence of developmental venous anomaly within the left cerebellar hemisphere. Focal uptake of 18F-DOPA may suggest the presence of a brain tumor and prompt invasive diagnostic investigations. Nuclear medicine physicians should be aware of this finding when interpreting 18F-DOPA PET and consider appropriate imaging to identify venous anomalies prior to more invasive investigations for possible brain tumors.
FDG-PET/CT Guided Biopsy in Angiosarcoma of Bone
Authors: Matti Antonella , Farolfi Andrea , Frisoni Tommaso , Fanti Stefano , Nanni Cristina
Published: December 2017

Primary angiosarcoma of the bone (PAB) is a particularly rare and aggressive form of malignancy in the spectrum of vascular tumours, and it accounts for less than 1% of sarcomas. This case of PAB, diagnosed thanks to FDG-PET/CT guided biopsy, is a paradigm of how powerful are clinical informations that can be derived by a 18F-FDG PET/CT, in view of negative or inconclusive imaging of conventional radiology, starting from the metabolic characterization of an equivocal finding, the possibility to drive the biopsy towards the most active site, the accurate total body staging, the stratification of prognosis and early therapy assessment.
Serial FDG-PET/CT Imaging in the Management of Cardiac Sarcoidosis
Authors: Bremer William , Sweiss Nadera J. , Lu Yang
Published: December 2017

A 60-year-old woman with biopsy-proven cardiac sarcoidosis status post implantable cardioverter defibrillator placement presented with periodic dizziness and dyspnea on exertion. Myocardial perfusion scan demonstrated a moderate sized, fixed perfusion defect along the mid to proximal anteroseptal wall of the left ventricle, with better perfusion on stress images. FDG-PET/CT demonstrated corresponding focal FDG avidity of the mid to proximal anteroseptal wall, suggestive of active cardiac sarcoidosis. Because of severe side effects, mycophenolate mofetil was discontinued, and the patient received low-dose steroid therapy. At 7-month follow-up FDG PET/CT, there was increased FDG avidity in the same regions, indicating worsening cardiac sarcoidosis.
Cardiac Fibroma
Authors: Pittman Sarah , Sethi Pooja , Flavell Robert R. , Pampaloni Miguel Hernandez
Published: December 2017

A 66-year-old woman was referred for evaluation of coronary artery disease. Myocardial perfusion imaging (MPI) was performed, and showed a medium-sized, severe fixed perfusion defect in the inferior and inferolateral wall from apex to midcavity. On review of prior imaging, it was noted that the patient had an incidental finding of an intramural cardiac mass on chest CT performed 8 years prior. Subsequent cardiac MRI showed findings consistent with a cardiac fibroma in the left ventricle, at the location of the perfusion defect on MPI. Our case demonstrates an uncommon cause of a fixed perfusion defect on MPI.
Management of Rare Craniofacial Anomalies With Soft Tissue Reconstruction on Humanitarian Missions
Authors: Abulezz Tarek , Fadaak Hussein A.
Published: December 2017

In poor communities, patients may suffer from health problems requiring special management that cannot be provided locally because of lack of equipment and/or expertise. Children with craniofacial anomalies represent one of these challenging problems. Visiting medical missionary teams have attempted to address these issues for a long time. This article highlights healthcare difficulties in one of the third-world countries with personally based trials for providing free surgeries in tough situation and with hardly available diagnostic and therapeutic facilities. During 15 years, >5000 surgeries were performed in repeated missionary visits. The majority of operations were to correct post-burn complications or to repair cleft lip and/or palate. Of 33 cases of rare craniofacial anomalies, 14 patients were treated with simple soft tissue reconstruction without interference in the underlying bone deformities. This may not be optimal; however, it can give good results even with the limited resources.
An Applied Anatomical Study of the Ethmoidal Arteries: Computed Tomographic and Direct Measurements in Human Cadavers
Authors: Felding Ulrik Ascanius , Karnov Kirstine , Clemmensen Anne , Thomsen Carsten , Darvann Tron A. , Buchwald Christian von , Tranum-Jensen Jørgen
Published: December 2017

Computed tomography (CT) images have been used in very few studies on distances to the ethmoidal arteries in the orbit. Most other studies have included direct measurements on cadavers and frequently quote the 24–12–6 mm rule to describe distances from the anterior lacrimal crest to the anterior and posterior ethmoidal foramina (AEF and PEF), optic canal (OC), respectively. However, the large interindividual variation of distances renders absolute values less applicable in a clinical setting. Preoperative measurements on CT images may provide more precise distances than absolute rules and thus lead to safer orbital surgery. The authors hypothesize that the distances to the ethmoidal arteries and the length of the medial wall are positively correlated and that measurements of the distances from the posterior lacrimal crest (PLC) on CT images are feasible with a low intra- and interobserver variability.

Fifty intact orbits from 25 Caucasian cadavers were exenterated and examined. In additional, high-resolution CT scans of 48 orbits from 24 other Caucasian nonexenterated cadavers were examined. Distances were measured from 4 different anterior landmarks to the AEF and PEF and the OC.

Distances from the most anterior landmarks to the arteries were positively correlated with the length of the medial wall. Measurements of the distances from the PLC to the ethmoidal arteries on CT images were feasible with a low intra- and interobserver variability. In conclusion, iatrogenic damage to the ethmoidal arteries in the orbit may be best avoided by using CT measurements in presurgical planning.
Comprehensive Evaluation of Visual Function in Patients With Orbital Fracture by Visual Electrophysiology and Visual Field Examination
Authors: Liu Shao-Rui , Li Mao , He Fang-Lin , Li Zheng-Kang , Fan Xian-Qun
Published: December 2017

Objective:

At present, the effect of the visual electrophysiology and vision field examination in patients with orbital blowout fracture is rarely studied. So, the authors investigate the value of visual electrophysiology and vision field examination in the diagnosis of ocular contusion.

Methods:

The position and range of fracture of 81 patients were determined by computed tomography (CT) scanning. Visual evoked potential (VEP), electroretinogram (ERG), and mfERG were vision field examination detected in 81 patients and the results were compared with those of contralateral healthy eyes. In addition, visual electrophysiology and vision field examination in diagnosis of eye contusion was analyzed and the correlation of the VEP, ERG, mfERG injury duration, and visual acuity was further analyzed.

Results:

The visual acuity of orbital fractures was significantly decreased compared with that in the uninjured eyes (t = 2.181, P = 0.032). Compared injured eyes and normal eyes in 54 patients, b wave of Max-ERG and Cone-ERG implied value extension (t = −2.426, P = 0.025; t = −2.942, P = 0.014), P-VEP P100 Peak duration and amplitude significantly extended (t = 3.162, P = 0.007; t = 9.314, P = 0.000), and F-VEP P1 amplitude decreased significantly (t = 3.362, P = 0.004). mfERG showed that the injured eye central reaction was significantly decreased (t = 8.727, P = 0.000). There was a significant correlation between P-VEP P100 amplitude and visual acuity (r = 0.067, P = 0.000). But there was no significant correlation between the P100 peak value, amplitude of P-VEP, mfERG central reaction, and injured days, respectively. There was significant difference between 2 groups with average visual acuity and mean defect value (t = 3.253, 3.461, P = 0.006, 0.003). There was statistical means the difference in P-VEP abnormal group, visual field abnormal group, and combined detection abnormal groups, the abnormal rate increased significantly (χ2 = 3.931, P < 0.01).

Conclusion:

Orbital floor fracture can lead to optic nerve damage and also may be associated with decreased macular function. The combination analysis of visual electrophysiology and vision field examination is beneficial to early diagnosis of ocular trauma and can improve the positive rate in clinic practice.
Long-term Outcome and Causes of Death for Working-age Patients Hospitalized Due to Acute Pancreatitis With a Median Follow-up of 10 Years
Authors: Karjula Heikki , Saarela Arto , Ohtonen Pasi , Ala-Kokko Tero , Mäkelä Jyrki , Liisanantti Janne H.
Published: December 2017

Objective:

To examine long-term survival and causes of death among working-age patients with acute pancreatitis (AP) compared with the normal population.

Summary of Background Data:

Few studies have investigated long-term survival after AP and recurrent AP compared with the normal population; moreover, results from those studies are difficult to compare, due to suboptimal control populations and wide variations in follow-up times.

Methods:

This retrospective, registry-based study included 1644 patients with AP, aged 18 to 64 years, admitted to Oulu University Hospital in 1995 to 2012. Patient data were compared with data from 8220 age- and sex-matched controls that resided in the hospital district area.

Results:

Alcohol was the main etiologic factor causing 71.4% of the cases. During the median follow-up time of 9.5 years, mortality was 24.2% in the study group and 6.3% in the control group (P < 0.001). Alcohol-related factors caused 39.4% of deaths and alcohol AP was the main single cause of death (16.3%) in the study group. Of all fatal AP cases, 42.9% were related to recurrence. Survival was similar among patients with nonalcohol AP and controls.

Conclusion:

The long-term mortality among patients admitted to the hospital due to (mainly alcohol induced) AP was 4 times higher than that in the age- and sex-matched control population. The significant difference in the causes of death between patients with alcohol AP and controls could be explained by alcohol-related diseases. Occurrences of AP without an alcohol etiology had a minimal impact on survival.
Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective
Authors: Edkins Adrienne L. , Price John T. , Pockley A. Graham , Blatch Gregory L.
Published: December 2017

Many heat shock proteins (HSPs) are essential to survival as a consequence of their role as molecular chaperones, and play a critical role in maintaining cellular proteostasis by integrating the fundamental processes of protein folding and degradation. HSPs are arguably among the most prominent classes of proteins that have been broadly linked to many human disorders, with changes in their expression profile and/or intracellular/extracellular location now being described as contributing to the pathogenesis of a number of different diseases. Although the concept was initially controversial, it is now widely accepted that HSPs have additional biological functions over and above their role in proteostasis (so-called ‘protein moonlighting’). Most importantly, these new insights are enlightening our understanding of biological processes in health and disease, and revealing novel and exciting therapeutic opportunities. This theme issue draws on therapeutic insights from established research on HSPs in cancer and other non-communicable disorders, with an emphasis on how the intracellular function of HSPs contrasts with their extracellular properties and function, and interrogates their potential diagnostic and therapeutic value to the prevention, management and treatment of chronic diseases.

This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
Extracellular cell stress (heat shock) proteins—immune responses and disease: an overview
Authors: Pockley A. Graham , Henderson Brian
Published: December 2017

Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory ‘danger signals’ for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells. The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals/non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining/regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins, therefore, form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease.

This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
Protein moonlighting: what is it, and why is it important?
Authors: Jeffery Constance J.
Published: December 2017

Members of the GroEL/HSP60 protein family have been studied for many years because of their critical roles as ATP-dependent molecular chaperones, so it might come as a surprise that some have important functions in ATP-poor conditions, for example, when secreted outside the cell. At least some members of each of the HSP10, HSP70, HSP90, HSP100 and HSP110 heat shock protein families are also ‘moonlighting proteins’. Moonlighting proteins exhibit more than one physiologically relevant biochemical or biophysical function within one polypeptide chain. In this class of multifunctional proteins, the multiple functions are not due to gene fusions or multiple proteolytic fragments. Several hundred moonlighting proteins have been identified, and they include a diverse set of proteins with a large variety of functions. Some participate in multiple biochemical processes by using an active site pocket for catalysis and a different part of the protein's surface to interact with other proteins. Moonlighting proteins play a central role in many diseases, and the development of novel treatments would be aided by more information addressing current questions, for example, how some are targeted to multiple cellular locations and how a single function can be targeted by therapeutics without targeting a function not involved in disease.

This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis
Authors: Dai Chengkai
Published: December 2017

The heat-shock, or HSF1-mediated proteotoxic stress, response (HSR/HPSR) is characterized by induction of heat-shock proteins (HSPs). As molecular chaperones, HSPs facilitate the folding, assembly, transportation and degradation of other proteins. In mammals, heat shock factor 1 (HSF1) is the master regulator of this ancient transcriptional programme. Upon proteotoxic insults, the HSR/HPSR is essential to proteome homeostasis, or proteostasis, thereby resisting stress and antagonizing protein misfolding diseases and ageing. Contrasting with these benefits, an unexpected pro-oncogenic role of the HSR/HPSR is unfolding. Whereas HSF1 remains latent in primary cells without stress, it becomes constitutively activated within malignant cells, rendering them addicted to HSF1 for their growth and survival. Highlighting the HSR/HPSR as an integral component of the oncogenic network, several key pathways governing HSF1 activation by environmental stressors are causally implicated in malignancy. Importantly, HSF1 impacts the cancer proteome systemically. By suppressing tumour-suppressive amyloidogenesis, HSF1 preserves cancer proteostasis to support the malignant state, both providing insight into how HSF1 enables tumorigenesis and suggesting disruption of cancer proteostasis as a therapeutic strategy. This review provides an overview of the role of HSF1 in oncogenesis, mechanisms underlying its constitutive activation within cancer cells and its pro-oncogenic action, as well as potential HSF1-targeting strategies.

This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
Therapeutic potential of heat shock protein induction for muscular dystrophy and other muscle wasting conditions
Authors: Thakur Savant S. , Swiderski Kristy , Ryall James G. , Lynch Gordon S.
Published: December 2017

Duchenne muscular dystrophy is the most common and severe of the muscular dystrophies, a group of inherited myopathies caused by different genetic mutations leading to aberrant expression or complete absence of cytoskeletal proteins. Dystrophic muscles are prone to injury, and regenerate poorly after damage. Remorseless cycles of muscle fibre breakdown and incomplete repair lead to progressive and severe muscle wasting, weakness and premature death. Many other conditions are similarly characterized by muscle wasting, including sarcopenia, cancer cachexia, sepsis, denervation, burns, and chronic obstructive pulmonary disease. Muscle trauma and loss of mass and physical capacity can significantly compromise quality of life for patients. Exercise and nutritional interventions are unlikely to halt or reverse the conditions, and strategies promoting muscle anabolism have limited clinical acceptance. Heat shock proteins (HSPs) are molecular chaperones that help proteins fold back to their original conformation and restore function. Since many muscle wasting conditions have pathophysiologies where inflammation, atrophy and weakness are indicated, increasing HSP expression in skeletal muscle may have therapeutic potential. This review will provide evidence supporting HSP induction for muscular dystrophy and other muscle wasting conditions.

This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
Hsp90 and FKBP51: complex regulators of psychiatric diseases
Authors: Criado-Marrero Marangelie , Rein Theo , Binder Elisabeth B. , Porter James T. , Koren John , Blair Laura J.
Published: December 2017

Mood disorders affect nearly a quarter of the world's population. Therefore, understanding the molecular mechanisms underlying these conditions is of great importance. FK-506 binding protein 5 (
FKBP5
) encodes the FKBP51 protein, a heat shock protein 90 kDa (Hsp90) co-chaperone, and is a risk factor for several affective disorders. FKBP51, in coordination with Hsp90, regulates glucocorticoid receptor (GR) activity via a short negative feedback loop. This signalling pathway rapidly restores homeostasis in the hypothalamic–pituitary–adrenal (HPA) axis following stress. Expression of
FKBP5
increases with age through reduced DNA methylation. High levels of FKBP51 are linked to GR resistance and reduced stress coping behaviour. Moreover, common allelic variants in the
FKBP5
gene are associated with increased risk of developing affective disorders like anxiety, depression and post-traumatic stress disorder (PTSD). This review highlights the current understanding of the Hsp90 co-chaperone, FKBP5, in disease from both human and animal studies. In addition,
FKBP5
genetic implications in the clinic involving life stress exposure, gender differences and treatment outcomes are discussed.

This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
DNAJ Proteins in neurodegeneration: essential and protective factors
Authors: Zarouchlioti Christina , Parfitt David A. , Li Wenwen , Gittings Lauren M. , Cheetham Michael E.
Published: December 2017

Maintenance of protein homeostasis is vitally important in post-mitotic cells, particularly neurons. Neurodegenerative diseases such as polyglutamine expansion disorders—like Huntington's disease or spinocerebellar ataxia (SCA), Alzheimer's disease, fronto-temporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease—are often characterized by the presence of inclusions of aggregated protein. Neurons contain complex protein networks dedicated to protein quality control and maintaining protein homeostasis, or proteostasis. Molecular chaperones are a class of proteins with prominent roles in maintaining proteostasis, which act to bind and shield hydrophobic regions of nascent or misfolded proteins while allowing correct folding, conformational changes and enabling quality control. There are many different families of molecular chaperones with multiple functions in proteostasis. The DNAJ family of molecular chaperones is the largest chaperone family and is defined by the J-domain, which regulates the function of HSP70 chaperones. DNAJ proteins can also have multiple other protein domains such as ubiquitin-interacting motifs or clathrin-binding domains leading to diverse and specific roles in the cell, including targeting client proteins for degradation via the proteasome, chaperone-mediated autophagy and uncoating clathrin-coated vesicles. DNAJ proteins can also contain ER-signal peptides or mitochondrial leader sequences, targeting them to specific organelles in the cell. In this review, we discuss the multiple roles of DNAJ proteins and in particular focus on the role of DNAJ proteins in protecting against neurodegenerative diseases caused by misfolded proteins. We also discuss the role of DNAJ proteins as direct causes of inherited neurodegeneration via mutations inDNAJfamily genes.

This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
Comparative genomics of bdelloid rotifers: evaluating the effects of asexuality and desiccation tolerance on genome evolution
Authors: Nowell Reuben W. , Almeida Pedro , Wilson Christopher G. , Smith Thomas P. , Fontaneto Diego , Crisp Alastair , Micklem Gos , Tunnacliffe Alan , Boschetti Chiara , Barraclough Timothy G
Published: December 2017

Bdelloid rotifers are microscopic invertebrates that have existed for millions of years apparently without sex or meiosis. They inhabit a variety of temporary and permanent freshwater habitats globally, and many species are remarkably tolerant of desiccation. Bdelloids offer an opportunity to better understand the evolution of sex and recombination, but previous work has emphasized desiccation as the cause of several unusual genomic features in this group. Here, we evaluate the relative effects of asexuality and desiccation tolerance on genome evolution by comparing whole genome sequences for three bdelloid species:Adineta ricciae(desiccation tolerant),Rotaria macruraandRotaria magnacalcarata(both desiccation intolerant) to the only published bdelloid genome to date, that ofAdineta vaga(also desiccation tolerant). We find that tetraploidy is conserved among all four bdelloid species, but homologous divergence in obligately aquaticRotariagenomes is low, well within the range observed between alleles in obligately sexual, diploid animals. In addition, we find that homologous regions inA. ricciaeare largely collinear and do not form palindromic repeats as observed in the publishedA. vagaassembly. These findings are contrary to current understanding of the role of desiccation in shaping the bdelloid genome, and indicate that various features interpreted as genomic evidence for long-term ameiotic evolution are not general to all bdelloid species, even within the same genus. Finally, we substantiate previous findings of high levels of horizontally transferred non-metazoan genes encoded in both desiccating and non-desiccating bdelloid species, and show that this is a unique feature of bdelloids among related animal phyla. Comparisons within bdelloids and to other desiccation-tolerant animals, however, again call into question the purported role of desiccation in horizontal transfer.