bluuebunny/crossref_metadata_2025 huggingface dataset:
Charcot Foot and the Osteoclast: More Than Just Cytokines
Authors: Stephens Sébastien , Platt Simon
Published: October 2019

Category:

Basic Sciences/Biologics

Introduction/Purpose:

Charcot foot is a serious complication of diabetes present in up to 13% carrying with high morbidity (dislocations, fractures, deformities) and up to 14% mortality. In Charcot, osteoclasts are found in increased numbers and with increased activity3,4 while C-telopeptide of type I collagen (CTX) is upregulated as opposed to ALP suggesting this is indeed an osteoclast and not an osteoblast disease.

Methods:

The scientific literature was reviewed to identify relevant osteoclastic activators and their role in the hyper activated state. We will also show videos of our current micromanipulation research techniques used to study osteoclast inhibitors in the lab.

Results:

The blood of Charcot patients is different at the nano level. Micro-nano-particles are extracellular vesicles derived from cells into plasma. Microparticles are found in increased quantity in Charcot;which contain more cytokines; known osteoclast activators. MicroRNAs – Epigenetic changes also are in Charcot; 16 different circulating microRNA known osteoclast activators are associated with Charcot. Advanced glycation end products (AGE). The hyperglycemic state in Charcot is a driving force in pathogenesis. AGEs are normal proteins turned dud after hyperglycemic induced glycation, a post translational modification which is irreversible affects both intracellular and extracellular proteins. AGEs may bind receptor RAGE, increasing osteoclast activity . RANKL is the main osteoclast differentiator and activator. RANKL has been the target of osteoclast control almost since it was found in 1998 .

Conclusion:

Charcot mediated bony destruction and remodeling; both of which are mediated by the osteoclast has traditionally had a tremendous cytokine focus. Our review suggests the mechanism for modifying a Charcot response on a local and systemic level. It is interesting to note that osteoclast inhibitors Denosumab, Bisphosphonates, Calcitonin and osteoblcast activators rPTH are not completely effective in switching off the Charcot response, implying there is a far more complex interaction between the inflammatory response, osteoclastic stimulators and osteoblastic inhibitors.
Kinematics of a Pyrocarbon Ankle Spacer for the Treatment of Arthritic Disease
Authors: Sturnick Daniel R. , Saltzman Charles L. , Burstein Albert H. , Hamilton Matthew A. , Deland Jonathan T.
Published: October 2019

Category:

Ankle, Ankle Arthritis

Introduction/Purpose:

Treatment options for ankle arthritis in younger patients are currently limited. Since the longevity of modern total ankle replacements is not sufficient for this patient population, ankle arthrodesis is typically utilized when joint preserving treatment is not a viable option. A new procedure using a pyrocarbon ankle spacer has been developed as a potential alternative, allowing for talar articular resurfacing for pain relief with minimal bone resection. The objective of this study was to assess whether this pyrocarbon ankle spacer could provide normal ankle kinematics as the native ankle joint using cadaveric gait simulation.

Methods:

Five mid-tibia cadaveric specimens without deformity and no history of lower limb injury or surgery were utilized. The stance phase of gait was simulated for each specimen using a six degree-of-freedom robotic device. A force plate was moved relative to stationary specimen through an inverse tibial kinematic path calculated from in vivo data while extrinsic tendons were actuated using physiologic loads (Figure 1A). Magnitudes of load were scaled to that of 25% bodyweight. Ankle kinematics were measured from reflective markers attached to the tibia and talus via surgical pins. The pyrocarbon ankle spacer (Exactech, Gainesville, FL, USA) was implanted in a nest formed 3-4 mm in depth on the talar articular surface using a custom burring technique (Figure 1B). Ankle spacer kinematics were compared to 95% confidence intervals of native, intact ankle joint kinematics to assess agreement.

Results:

Outcomes revealed no significant difference in ankle joint kinematics between the native, intact condition and post- pyrocarbon spacer implantation (Figure 1C). This result was consistent for the sagittal, coronal and axial planes of motion.

Conclusion:

The results of this study demonstrate that a pyrocarbon spacer permits normal ankle kinematics. Further, the device was observed to be stable in the joint throughout simulations. While the testing was performed at 25% bodyweight for analyses on all specimens, load magnitudes were also increased up to 75% on a subset of specimens and the structural integrity of the device remained pristine. With these findings, we concluded that the pyrocarbon spacer device offers promising potential as a treatment option for ankle arthritis.
Interphanlangeal and First Metatarsophalangeal Joint Fusion for Osteomyelitis and Septic Arthritis in Patients with Forefoot Diabetic Foot Ulcers
Authors: Ulrich Martin K. , Iselin Lukas D
Published: October 2019

Category:

Diabetes, infection

Introduction/Purpose:

In cases of Diabetic Foot ulcers over joints with assocuated septic arthritis or osteomylitis, the erradication of the infection can be difficult to achieve. In order to avoid amputations which are often associated with reduced quality of life, we try to be as conservative as possible in order to save as many big toes as possible. The backbone of our noval treatment protocol involve performing a thorough soft tissue and bony debridement, stabilizing the infected bones or joint by fusing them in the acute phase, and closing the skin over the infected ulcer. We present our experience of this concept.

Methods:

Retrospective study between the years 2012-2016, in a single centre, treating diabetic foot patients. 29 patients, 31 feet, were identified with IPj or 1st MTPJ fusion for Infection. All patients had a combination of bone and soft tissue infections. All patients had a preoperative radiograph, 22patients had a pre-operative MRI scan to define the extent of the bony and soft-tissue infection. In all cases the involved joint was fused in the acute phase using screws, kw’s, plates, combination of the above fusion techniques. In all cases the skin was closed above the infected ulcer.

Results:

Closed ulcers of the fitst ray after fusing the infected joint were achieved in 26 patients (84%) by 12 months after surgery. The radiographic fusion rate was 55% by one year after surgery while 77% of the cases were clinically stable by 1 year after surgery. 5 patients (16%) endend up with an amputation. In 4 of them the base of the proximal phalangx could be left to ensure the biomechanical properties as good as possible. 1 patient needed a BKA. In 26 patients, pathogens could be identified; in 77%, polymicrobial flora were found.

Conclusion:

Arthrodesis of IPJ- or 1st MTPJ in diabetic foot patients presents a successful way of treatmentin order to achieve a stable situation which allow healing of bony and soft-tissue problems. Fusing an infected joint is a safe procedure that allows maintaining functional capabilities.
Peri-Implant Fractures Around Hindfoot Fusion Nails: A Systematic Literature Review and Classification System
Authors: Velasco Brian T. , Briceno Jorge , Miller Christopher , Ye Michael Y. , Savage-Elliott Ian , Ellington J. Kent , Kwon John Y.
Published: October 2019

Category:

Hindfoot

Introduction/Purpose:

Tibio-talo calcaneal (TTC) arthrodesis is increasingly performed for hindfoot arthrosis and other indications. Peri-implant fracture around hindfoot fusion nails has been previously reported and can be problematic to treat given multiple surgical considerations including the status of hind foot arthrodesis at time of fracture. We present a systematic review of the literature regarding peri-implant fractures around hindfoot fusion nails and propose a classification system to help guide treatment based on findings from the current literature as well as the collective experience of the senior authors.

Methods:

A review of the literature was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify clinical investigations in which peri-implant fractures or other hardware failures were observed as complications following TTC arthrodesis using hindfoot nails by two research assistants. The electronic database of PubMed / Medline was explored using specific search terms, Boolean operators, and field tags. The same query without field tags and under “Search All Text” was used to explore the electronic database of the Cochrane Library. Inclusion criteria was any clinical investigation that reported on outcomes after TTC arthrodesis using a hindfoot nail in at least one patient. Cadaveric and non-clinical investigations were excluded. Manuscript language for both databases was restricted to the English literature.

Results:

A total of 36 studies were identified which met inclusion criteria and reported clinical outcomes after TTC arthrodesis using a hindfoot fusion nail. Of the 36 studies, there was a total of 13 intraoperative fractures, 43 tibial stress fractures and 24 peri-implant fractures recorded in 12 of the 36 studies.

Conclusion:

Peri-implant fracture following tibio-talo calcaneal arthrodesis using a hindfoot intramedullary nail is an uncommon but problematic condition to treat. General heterogeneity of patients and indications as well as a lack of descriptive detail in the current literature makes meta-analysis difficult. Given the lack of consensus on treatment, a classification system may be helpful to guide clinical practice.
Proximal and Distal Failure Site Analysis in Percutaneous Achilles Tendon Rupture Repair
Authors: Wagner Pablo , Wagner Emilio , Lopez Mario , Etchevers Gaston , Valencia Oscar , Guzman-Venegas Rodrigo
Published: October 2019

Category:

Ankle

Introduction/Purpose:

Different techniques have been described for Achilles Tendon Rupture repair, but no biomechanical evaluation have been performed separately for proximal and distal suturing techniques.The purpose of this study was to biomechanically analyze 3 proximal and 2 distal suture configurations during a simulated cyclic load and load to failure. It was hypothesized that proximal suturing technique was stronger than the distal one and that the modified double suturing technique was the strongest of all techniques.

Methods:

A simulated, mid-substance rupture was created 6 cm proximal to the calcaneal insertion in 15 fresh-frozen cadaveric Achilles tendons, obtaining 15 proximal and 12 distal samples. Specimens were tested independently and randomly allocated to different suture techniques: proximal fixation site groups: (A1) classic Dresden technique, (A2) modified Dresden, (A3) double modified Dresden; distal fixation groups: (B1) classic distal suture and (B2) modified distal suture. Repairs were subjected to a cyclic testing (1000 cycles of 50-200 N) and load to failure. Load to failure, cause of failure and tendon elongation was evaluated. Fischer’s test was used as statistical analysis.

Results:

None of the proximal tendon and 7/12 of the distal samples failed in cyclic testing. The proximal fixation groups demonstrated significantly more strength than the distal groups (p< 0.05) with average failure loads of 598 N, 587 N and 710 N for groups A1, A2 and A3 respectively (A3 stronger than A1 and A2, p=0,035). Groups B1 and B2 failed on average at 416 N and 351 N respectively, p=0.24. The majority of all repairs failed in the suture- tendon interphase.Regarding elongation, no significant differences were found between groups (p=0.57).

Conclusion:

The distal fixation site in the Dresden percutaneous Achilles tendon repair is weaker than the proximal fixation site. A proximal modified suture configuration increased resistance to cyclic loading and load to failure significantly. A modification in the proximal and distal fixation sites can be suggested to improve repair strength and hopefully achieve a better outcome.
Brostrom-Like Procedure Augmented with Swivelock Internal Brace for the Reconstruction of Chronic Medial Ankle Ligament Complex
Authors: Wang Bibo , Xiangyang Xu
Published: October 2019

Category:

Midfoot/Forefoot

Introduction/Purpose:

The medial ligaments and joint capsules appear to stretch or rupture under the increasing stress following a tear of the PTT in patients with flat foot often leading to pain, swelling and dysfunctional foot. This study assesses the efficacy of a Brostrom like procedure augmented with Swivelock Internal Brace for the reconstruction of chronic medial ankle ligament complex.

Methods:

A retrospective study was performed reviewing 15 flat foot patients who presented with pronounced hindfoot pronation collapse of the medial longitudinal arch after injury. The procedures included exploration and direct repair of PTT, deltoid ligament and spring ligament. Our modification included Swivelock Internal Brace enhanced reconstruction of deltoid and spring ligaments, after calcaneal medializing osteotomy. Other additional procedures such as FDL transfer, subtalar arthroereisis and Cotton osteotomy were performed as needed (Fig.1). Weight bearing X-rays of the foot, AOFAS-AH and SF36 scoring were taken before and after surgery.

Results:

There were 8 males and 7 females among the 15 patients. The age was 29.8±10.1 years old. The follow-up time period was 32.6±11.4 months. Both the AOFAS-AH (52.8±15.2 to 90.4±7.5 and SF-36 (55.4±12.6 to 91.2±6.3 scores improved significantly (p<0.001). Comparing preoperative to postoperative standing radiographs, there was significant improvement in the AP talar first metatarsal angle (25.6±18.4 to 9.5±7.8 degrees（P<0.001), lateral talar first metatarsal angle (18.3±8.4 to +2.6±4.5 degrees（P<0.001）and moment arm on the Saltzman view (+15.2mm±10.8 to +2.5±3.6mm（P=0.003） (Fig.2). No recurrence of pronation deformity or foot arch collapse was observed after surgery.

Conclusion:

The medial ankle ligaments were attenuated and under the increasing stress following a tear of the PTT in patients of flat foot. Direct repair of the ligaments after rupture usually resulted in low strength and high recurrence. Simultaneous reconstruction of medial ankle ligaments with Swivelock internal brace maintained long term medial ankle stability and the longitudinal arch. This technique protects the repaired tendon and decreased the need for FDL transfer, potentially permitted earlier rehabilitation and improved function compared to traditional techniques.
Evaluation of the Anterior Talofibular Ligament Using MRI after Arthroscopic Lateral Ankle Ligament Repair
Authors: Yoshimura Ichiro , Kanazawa Kazuki , Minokawa So , Yamamoto Takuaki , Hagio Tomonobu
Published: October 2019

Category:

Ankle, Arthroscopy

Introduction/Purpose:

Ankle sprain commonly occurs in sports activities and most patients are successfully managed with conservative treatment. An incidence of 10–30% of patients will fail conservative treatment and result in chronic lateral ankle instability (CLAI) that may require surgical treatment. Recently, several systematic reviews reported that arthroscopic lateral ankle ligament repair for CLAI are provided good clinical results. However, the pathologic condition of the lateral ankle ligament after anatomical repair has not been clarified. Previous investigations have reported that ligament signal intensity using MRI has a strong negative linear relationship with material biomechanical strength properties. The purpose of this study was to report the clinical outcome and evaluation of the anterior talofibular ligament (ATFL) using MRI after arthroscopic lateral ankle ligament repair.

Methods:

We retrospectively reviewed 40 patients (40 ankles) who underwent arthroscopic lateral ankle ligament repair for CLAI. The average age at the time of surgery was 28 years (range 12–66 years). The average follow-up was 13 months (range 12– 18 months). Clinical outcomes were assessed preoperatively and 12 months postoperatively using Japanese Society for Surgery of the Foot (JSSF) ankle-hindfoot scale and Self-Administered Foot Evaluation Questionnaire (SAFE-Q). The ATFL was evaluated using 3.0-T MRI at the preoperatively, six months postoperatively and 12 months postoperatively. The ATFL characteristics classified into the following categories: nonvisualization of the ligament, discontinuity, a wavy or curved contour, or high signal intensity within the ligament.

Results:

The mean JSSF score increased from 72 preoperatively to 95 at 12 months postoperatively. The preoperative MRI findings of the ATFL were categorized as discontinuity (11 ankles), a wavy or curved contour (14 ankles), or high signal intensity within the ligament (22 ankles). The all ATFL findings at the six months postoperatively had straight band extending from the talus to the fibular malleolus, and nine of 40 ankles had high signal intensity within the ligament. The ATFL findings at the 12 months postoperatively revealed residual high signal intensity within the ligament in six of nine ankles. A comparison of the postoperative ATFL with high signal intensity and with low signal intensity group, there were no significant difference in postoperative clinical outcomes between the groups.

Conclusion:

This study demonstrated that arthroscopic lateral ankle ligament repair was an effective procedure for the treatment of CLAI and restored the condition of ATFL.
A Comparison of Fusion Rates and Risk Factors in a Cohort of 2301 Foot and Ankle Fusions Comparing the Use of No Graft and Graft
Authors: Younger Alastair S.E. , Penner Murray J. , Veljkovic Andrea , Wing Kevin
Published: October 2019

Category:

Ankle, Ankle Arthritis, Hindfoot, Midfoot/Forefoot

Introduction/Purpose:

Bone graft and bone graft substitutes may affect fusion rates and have been advocated to reduce the risk of nonunion particularly in patients with risk factors for failure of fusion. However historically they have not been used in all patients but tend to be used in patients at risk for nonunion. This paper analyses the union rates of patients with and without graft for a large retrospective cohort in which no graft, autograft and bone graft substitute, and summarizes the risk factors for nonunion.

Methods:

2301 fusions performed in 1320 patients were reviewed with a minimum of 2 years follow up to determine the risk of repeat surgery for nonunion. The records were reviewed to determine which patients underwent revision surgery of the primary site for nonunion. Demographic factors and risk factors for nonunion were recorded. The nonunion rate for each joint (ankle, subtalar, talonavicular, calcaneocuboid, navicular cuneiform and tarsometatarsal joints) was determined. The mean age of the patients was 56, BMI 27.83, 32% were male, diabetes was present in 8.9%, smoking present in 10.9%, rheumatoid arthritis present in 10%. No graft was used in 1249 fusions, Autograft in 644, PDGF with TCP (regular) in 113, and PDGF injectable (TCP and collagen) formula in 110. Combinations were used in 159 patients. Odds ratios were used with 95% confidence intervals and p values.

Results:

No graft was used in 1249 fusions with 34 revisions for nonunion (2.7%) and graft was used in 1052 patients with 59 non unions (5.6%). The odds ratio for nonunion with graft was 2.2x, and was not significant. The odds ratio for PDGF with TCP for nonunion was higher than the PDGF injection, at 5 x versus 1 x. However the difference was not significant. The demographics of patients receiving graft were different than those not receiving graft, and were more likely to be older, male, have a higher BMI, be smokers and have diabetes. The appended figure shows the odds ratios for risk factors for receiving graft.

Conclusion:

Bone graft substitute and bone grafts result in a similar union rate for patients undergoing foot and ankle fusions. However patients receiving graft have higher risk factors for nonunion compared to those not receiving graft. This paper demonstrates that the concept of using graft for at risk patients is merited, with similar fusion rates being achieved. Larger patient numbers would be required to reach statistical conclusions.
Rates of Nonunion for Different Joints after Foot And Ankle Surgery: A Review of 2301 Fusions
Authors: Younger Alastair S.E. , Veljkovic Andrea , Wing Kevin , Penner Murray J. , Qian Hong , Wong Hubert
Published: October 2019

Category:

Ankle, Ankle Arthritis, Hindfoot, Midfoot/Forefoot

Introduction/Purpose:

Nonunion after fusion results in ongoing pain and a request for repeat surgery in many patients. Nonunion is therefore a failure of the primary surgery. Patients undergoing fusion surgery need to understand the risk for nonunion and the risk for repeat surgery. This is a review of fusions performed at a single institution by 4 foot and ankle surgeons to outline the nonunion rate after foot and ankle fusion for different joints.

Methods:

Data on fusions performed between January 1, 2010 to July 31, 2006 were retrospectively extracted from database. The records were reviewed to determine the union status of each fusion. Demographic and clinic risk factors of nonunion were recorded. The nonunion rate for each joint (ankle, subtalar, talonavicular, calcaneocuboid, navicular cuneiform, tarsometatarsal and metatssophalengeal joints) was estimated. Due to multiple surgeries performed on individual patient and fusions in the same surgery, random effects logistic regression models were conducted to assess the impact of risk factor on nonunion. The study include 2301 fusions preformed on 1320 patients. The minimum follow up was two years. The majority of patients were female (70%), with mean age of 57 years old and mean body mass index (BMI) of 28. There were 9% of patients with diabetes, 11% being smokers, 18% having lung disease, 8% with renal disease, and 29% with high blood pressure.

Results:

The risk of nonunion by joint is outlined in figure 1. The ankle showed the highest nonunion rate at 8%, and the calcaneocuboid joint had the lowest rate at 2%. Comparing to ankle, the nonunion rate was significantly lower at Talocalcaneal (Subtalar) joint (Odd ratio [OR]=0.05, p-value= 0.02) and Tarsometatarsal (OR=0.03, p-value=0.01). Across all joints the nonunion rate was higher in males, smokers, having a higher BMI and diabetes Age had a minimal effect.

Conclusion:

Union rate varied among fusion sites. Patient’s demographic and clinic characteristics might be potential risk factors for nonunion. This paper assists surgeons in determining the risk factors for nonunion after foot and ankle fusions. The ankle joint is at highest risk for nonunion, and the tarsometatarsal joint and the subtalar joints the lowest risk.
Results of a Prospective Randomized Study Following Osteosynthesis Using 1/3 Tubular Plate in AO Technique vs Osteosynthesis Using Polyaxial Locking Plates in Distal Fibula Fracture
Authors: Zyskowski Michael , Pesch Sebastian , Greve Frederik , Matthey Francesca von , Wurm Markus , Kirchhoff Chlodwig
Published: October 2019

Category:

Ankle, Trauma

Introduction/Purpose:

In modern economies health care comprising treatment and disability after trauma is a financial burden. In this context techniques of ORIF that allow for early full weight bearing might not only improve the clinical outcome but also shorten the period of working disability. The aim of the study is to analyze whether ORIF of ankle fractures using a new polyaxial locking or a standard tubular plate allow for a better outcome and reduction of complications.

Methods:

In this prospective study, all patients with a distal fibula fracture (AO 44 B1.1, B1.2, B1.3), who met the criteria for surgical treatment were included. Patients were randomized to either the group A (tubular plate, Depuy Synthes) or group B (polyaxial locking plate, NEWCLIP TECHNICS, Active Ankle®). First outcome parameter was functionality of the ankle joint, assessed by the Olerud and FAOS score. Secondary outcome parameter were postoperative complications. These were divided into minor complications: Superficial wound infection, delayed wound healing, mechanically prominent implant, skin irritations and major complications requiring surgical revision: Deep wound infection, material loosening, loss of reduction. Clinical and radiological controls were performed 6 weeks, 12 weeks, 6 months and 1 year postoperatively.

Results:

52 patients (31W/21 M) with an age of 43y (range 22-64) have been included. 7 Patients (13.5%) dropped out. 45 patients were available for follow up. 20 patients were treated with polyaxial locking plates (44.4%), 25 patients by 1/3 tubular plate in AO technique (55.6%). Two minor complications (16%) occurred in the Active Ankle® group, four minor complications (16%) in the AO arm. At the first two control stages after six and 12 weeks a significant distinctions in the Olerud and FAOS score could be obtained in between the two study arms. Mean Olerud score after 6 weeks AA 56,05/AO 45,22 p=0,02, after 12 weeks AA 69,47/AO 59,79 p=0,04. Mean FAOS in week 6 AA 66,7/AO 56,08 p=0,02, in week 12 AA 75,1/AO 66,12 p=0,03.

Conclusion:

Our results are quite positive. We could demonstrate that a significant better clinical function during the early postoperative stages, after 6 weeks and 12 weeks, presented in the group treated with polyaxial locking plates. Further we proved that ORIF with polyaxial locking plates is a safe and stabile osteosyntheses and could promote an early weight bearing postoperative regime. That has the consequence that we could shorten the absence from work, the patient’s mobility can be restored faster and the costs for the health care system decrease significantly.
How I treat sickle cell disease with hematopoietic cell transplantation
Authors: Stenger Elizabeth O. , Shenoy Shalini , Krishnamurti Lakshmanan
Published: October 2019

Hematopoietic stem cell transplantation can be curative for sickle cell disease, but decision-making is often complex. This How I Treat provides a perspective on how to negotiate this process for an individual patient.
Targeting cyclooxygenase by indomethacin decelerates progression of acute lymphoblastic leukemia in a xenograft model
Authors: Richartz Nina , Duthil Eva , Ford Anthony , Naderi Elin Hallan , Bhagwat Sampada , Gilljam Karin M. , Burman Marta Maria , Ruud Ellen , Blomhoff Heidi Kiil , Skah Seham
Published: October 2019

Key Points

The COX inhibitor indomethacin delays progression of ALL in a human xenograft mouse model. The xenograft-derived ALL cells treated with indomethacin express elevated levels of p53.
Second primary malignancies in ruxolitinib-treated myelofibrosis: real-world evidence from 219 consecutive patients
Authors: Maffioli Margherita , Giorgino Toni , Mora Barbara , Iurlo Alessandra , Elli Elena , Finazzi Maria Chiara , Caramella Marianna , Rumi Elisa , Carraro Maria Cristina , Polverelli Nicola , D’Adda Mariella , Malato Simona , Rossi Marianna , Molteni Alfredo , Vismara Alessandro , Sissa Cinzia , Spina Francesco , Anghilieri Michela , Cattaneo Daniele , Renso Rossella , Bellini Marta , Pioltelli Maria Luisa , Cavalloni Chiara , Barraco Daniela , Accetta Raffaella , Bertù Lorenza , Della Porta Matteo Giovanni , Passamonti Francesco
Published: October 2019

Key Points

We present real-world data on all ruxolitinib-treated myelofibrosis patients in a 10-million-resident region, with a follow-up of 2 years. We found no evidence of an increased risk of developing lymphomas.
Plasma-Enhanced Chemical Vapor Deposition of Acetylene on Codeposited Bimetal Catalysts Increasing Graphene Sheet Continuity Under Low-Temperature Growth Conditions
Authors: Tracy Joshua , Zietz Otto , Olson Samuel , Jiao Jun
Published: October 2019

Here, we report a novel method for low-temperature synthesis of monolayer graphene at 450 °C on a polycrystalline bimetal Ni-Au catalyst. In this study, low-temperature chemical vapor deposition synthesis of graphene was performed at 450 °C on codeposited Ni-Au which shows successful monolayer graphene formation without an extra annealing process. The experimental results suggest that electron beam codeposition of bimetal catalyst is the key procedure that enables the elimination of the pre-growth high-temperature annealing of the catalyst prior to graphene synthesis, an indispensable process, used in previous reports. The formation was further improved by plasma-assisted growth in which the inductively coupled plasma ionizes the carbon precursors that interact with codeposited Ni-Au catalyst of 50 nm in thickness at 450 °C. These combined growth conditions drastically increase the graphene’s sheet uniformity and area connectivity from 11.6% to 99%. These fabrication parameters enable the graphene formation that shifts from a bulk diffusion-based growth model towards a surface based reaction. The technique reported here opens the opportunity for the low-temperature growth of graphene for potential use in future CMOS applications.
Domainoid: domain-oriented orthology inference
Authors: Persson Emma , Kaduk Mateusz , Forslund Sofia K. , Sonnhammer Erik L. L.
Published: October 2019

Background

Orthology inference is normally based on full-length protein sequences. However, most proteins contain independently folding and recurring regions, domains. The domain architecture of a protein is vital for its function, and recombination events mean individual domains can have different evolutionary histories. It has previously been shown that orthologous proteins may differ in domain architecture, creating challenges for orthology inference methods operating on full-length sequences. We have developed Domainoid, a new tool aiming to overcome these challenges faced by full-length orthology methods by inferring orthology on the domain level. It employs the InParanoid algorithm on single domains separately, to infer groups of orthologous domains.

Results

This domain-oriented approach allows detection of discordant domain orthologs, cases where different domains on the same protein have different evolutionary histories. In addition to domain level analysis, protein level orthology based on the fraction of domains that are orthologous can be inferred. Domainoid orthology assignments were compared to those yielded by the conventional full-length approach InParanoid, and were validated in a standard benchmark.

Conclusions

Our results show that domain-based orthology inference can reveal many orthologous relationships that are not found by full-length sequence approaches.

Availability

https://bitbucket.org/sonnhammergroup/domainoid/
Adverse events associated with continuous interscalene block administered using the catheter-over-needle method: a retrospective analysis
Authors: Tanijima Meishu , Takechi Kenichi , Nakanishi Kazuo , Yorozuya Toshihiro
Published: October 2019

Background

Continuous interscalene block is widely used for pain management in shoulder surgery. However, continuous interscalene block performed using the catheter-through-needle method is reportedly associated with adverse events such as pericatheter leakage of the local anesthetic, phrenic nerve paralysis, and hoarseness. Because we expected that the catheter-over-needle method would reduce these adverse events, we examined cases in which continuous interscalene block was performed using the catheter-over-needle method to determine what adverse events occurred and when.

Methods

We retrospectively reviewed the anesthesia and medical records of adult patients who underwent catheter insertion to receive a continuous interscalene block performed using the catheter-over-needle method at our hospital from July 2015 to July 2017.

Results

During the surveillance period, 122 adult patients underwent catheter insertion to receive a continuous interscalene block administered using the catheter-over-needle method. No case of pericatheter local anesthetic leakage was observed. Adverse events, such as dyspnea, hoarseness, insufficient anesthetic effect, dizziness, cough reflex during drinking, or ptosis, were observed in 42 patients (34.4%; 95% confidence interval 26–42.7). Most of the adverse events occurred on postoperative day 2. The median time between surgery and the onset of adverse events was 28.5 h.

Conclusions

The catheter-over-needle method may prevent the pericatheter leakage of the local anesthetic. However, adverse events occurred in more than one-third of the patients. During continuous interscalene block, patients must be carefully observed for adverse events, especially on postoperative day 2.

Trial registration

This study was registered at the UMIN Clinical Trials Registry on August 13th, 2019 (UMIN000037673).
Changes in waist circumference and risk of all-cause and CVD mortality: results from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study
Authors: Mulligan Angela A. , Lentjes Marleen A. H. , Luben Robert N. , Wareham Nicholas J. , Khaw Kay-Tee
Published: October 2019

Background

Measures of abdominal adiposity are strongly associated with all-cause mortality and cardiovascular disease (CVD). However, data are limited and conflicting regarding the consequences of changes in body fat distribution. The main aims of this paper are to investigate the association between changes in waist circumference (WC) and all-cause and CVD mortality and to examine these changes in relation to concurrent changes in weight.

Methods

The European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study recruited 25,639 participants between 1993 and 1997, aged 39–79, a number of whom also attended a second examination (1998–2000), and were followed up to 2016 for mortality. Participants were eligible for inclusion if they had WC, weight and height measurements at both time-points; those with a self-reported history of CVD or cancer, body mass index < 18.5 kg/m2 or missing data on covariates were excluded, leaving 12,337 participants for analyses. The median (IQR) follow-up time was 16.4 (15.7, 17.2) years. Hazard Ratios (HRs) for all-cause (2866 deaths) and CVD mortality (822 deaths), by categories of WC change, were determined using Cox proportional hazards analyses.

Results

After multivariable adjustment, the HRs (95% CIs) for all-cause mortality for men and women with a WC gain (WCG) >  5 cm were 1.51 (1.29–1.75) and 1.25 (1.06–1.46) respectively. For CVD mortality in men and women with a WCG >  5 cm, the HRs were 1.84 (1.39–2.43) and 1.15 (0.85–1.55) respectively. In analyses of concurrent changes in WC and weight, the greatest risk (HRs) (95% CIs) in men occurred with weight loss and WCG: 1.80 (1.13–2.86) for all-cause and 2.22 (1.03–4.82) for CVD mortality. In women, the greatest risk for both all-cause (HR 1.50 (1.16–1.95)) and CVD mortality (HR 1.81 (1.15–2.85)) was observed in those with weight loss and maintenance of WC (WCM).

Conclusions

Objectively measured WCG > 5 cm, was associated with subsequent higher total mortality risk and higher CVD mortality risk in men. Interventions focusing on preventing increase in central adiposity rather than lowering weight per se in later life may potentially have greater health benefits.
Impact on core values of family medicine from a 2-year Master’s programme in Gezira, Sudan: observational study
Authors: Mohamed Khalid Gaffer , Hunskaar Steinar , Abdelrahman Samira Hamid , Malik Elfatih Mohamed
Published: October 2019

Background

Training of family physicians should include not only clinical and procedural skills, but also core values as comprehensive care, continuity of care, leadership and patient-centeredness. The Gezira Family Medicine Project (GFMP) is a 2 years Master’s programme in family medicine in Sudan. We assessed the impact of GFMP on the candidates’ adherence to some core values of family medicine.

Methods

This is a prospective study with before-after design based on repeated surveys. We used Patient-Practitioner Orientation Scale (PPOS) to assess physicians’ attitude towards patient-centeredness. Practice based data from individual patients’ consultations and self-assessment methods were used to assess physicians’ adherence to core values.

Results

At the end of the programme the candidates (N = 110) were significantly more active in community health promotion (p <  0.001), more confident as a team leader (p = 0.008), and showed increased adherence to national guidelines for managing diabetes (p = 0.017) and hypertension (p = 0.003). The responding candidates had more knowledge about patients’ medical history (p <  0.001), family history (p < 0.001) and family situation (p < 0.001). There were more planned follow up consultations (p < 0.001) and more referrals (p = 0.040). In contrast, results from PPOS showed slightly less orientation towards patient-centeredness (p = 0.007).

Conclusions

The GFMP Master’s programme induced a positive change in adherence to several core values of family medicine. The candidates became less patient-centered.
Exploring Leishmania infantum cathepsin as a new molecular marker for phylogenetic relationships and visceral leishmaniasis diagnosis
Authors: da Silva Ryan Emiliano , Sampaio Bruna Matarucco , Tonhosolo Renata , da Costa Andrea Perei ra , da Silva Costa Luiz Eduardo , Nieri-Bastos Fernanda Ap. , Sperança Márcia Aparecida , Marcili Arlei
Published: October 2019

Background

Leishmania infantum, the etiological agent of visceral leishmaniasis, is a neglected zoonosis that requires validation and standardization of satisfactory diagnostic methodologies. Thus, the aim of the present study was to evaluate the effectiveness of cathepsin L-like protease as a target for making molecular diagnoses and as a phylogenetic marker enabling to understand the intraspecies variations and evolutionary history of L. infantum in Brazil.

Methods

We used 44 isolates of L. infantum. The cathepsin L-like gene fragments were amplified, sequenced, manually aligned and analyzed using inference methods. The sequences generated were used to search and design oligonucleotide primers to be used in reactions specific to the target parasite.

Results

The cathepsin L-like gene did not show any intraspecies variability among the isolates analyzed. The pair of primers proposed amplified the target deoxyribonucleic acid (DNA) of L. infantum isolates and were effective for DNA amplification at concentrations of as low as 10− 11 ng/μl. The proposed marker did not present cross-reactions with other hemoparasites. When used for making the diagnosis in a panel of clinical samples from dogs, a positivity rate of 49.03% (102/208) was obtained, versus 14.42% (30/208) for a ribosomal internal transcribed spacer (ITS) marker. In samples from sandflies, the rate was 6.25% and from humans, 14.28%.

Conclusions

The results described in this work allow us to infer that CatLeish-PCR is a sensitive and specific marker for use in diagnostic trials of L. infantum and in clinical and epidemiological surveys.
Chromosomal and plasmid-mediated fluoroquinolone resistance in human Salmonella enterica infection in Ghana
Authors: Acheampong Godfred , Owusu Michael , Owusu-Ofori Alex , Osei Isaac , Sarpong Nimako , Sylverken Augustina , Kung Hung-Jui , Cho Shu-Ting , Kuo Chih-Horng , Park Se Eun , Marks Florian , Adu-Sarkodie Yaw , Owusu-Dabo Ellis
Published: October 2019

Background

Salmonella infection poses significant public health threat globally, especially in resource-limited countries. Emergence and spread of antibiotic resistant strains to fluoroquinolones have led to treatment failures and increased mortality in Salmonella infection. However, there is dearth of information regarding mechanisms of resistance to fluoroquinolones in Ghana. This study therefore sought to identify chromosomal mutations and plasmid-mediated resistance as possible mechanisms of fluoroquinolone resistance from clinical isolates in Ghana.

Methods

This was a retrospective study of archived isolates biobanked at Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana. Isolates were obtained from blood, stool and oropharynx samples at two hospitals, between May, 2016 and January, 2018. Salmonella identification was done using standard microbiological protocols and antibiotic susceptibility testing performed by Kirby-Bauer disc diffusion method. Isolates with intermediate susceptibility and/or resistance to nalidixic acid and/or ciprofloxacin were selected and examined for chromosomal mutations by Sanger sequencing and plasmid-mediated resistance by PCR.

Results

Of 133 biobanked isolates cultured, 68 (51.1%) and 16 (12%) were identified as Salmonella Typhi and non-typhoidal Salmonella (NTS), respectively. Sequence analysis of gyrA gene revealed the presence of 5 different nonsynonymous mutations, with the most frequent mutation (Ile203Ser) occurring in 12 out of 13 isolates tested. Gyrase B (gyrB) gene had 1 nonsynonymous mutation in 3 out of 13 isolates, substituting phenylalanine with leucine at codon 601 (Phe601Leu). No mutation was observed in parC and parE genes. Two NTS isolates were found to harbour qnrS plasmid-mediated resistant gene of molecular size 550 bp with high ciprofloxacin MIC of 0.5 μg/ml.

Conclusion

This study reports for the first time in Ghana plasmid-mediated fluoroquinolone resistant gene qnrS in Salmonella clinical isolates. Nonsynonymous mutations of gyrA and gyrB genes likely to confer Salmonella reduced susceptibility to ciprofloxacin were also reported.
Arg913Gln variation of SLC12A3 gene is associated with diabetic nephropathy in type 2 diabetes and Gitelman syndrome: a systematic review
Authors: De la Cruz-Cano Eduardo , Jiménez-González Cristina del C. , Morales-García Vicente , Pineda-Pérez Conny , Tejas-Juárez Juan G. , Rendón-Gandarilla Francisco J. , Jiménez-Morales Silvia , Díaz-Gandarilla José A.
Published: October 2019

Background

Diabetic nephropathy is a global common cause of chronic kidney disease and end-stage renal disease. A lot of research has been conducted in biomedical sciences, which has enhanced understanding of the pathophysiology of diabetic nephropathy and has expanded the potential available therapies. An increasing number of evidence suggests that genetic alterations play a major role in development and progression of diabetic nephropathy. This systematic review was focused on searching an association between Arg913Gln variation in SLC12A3 gene with diabetic nephropathy in individuals with Type 2 Diabetes and Gitelman Syndrome.

Methods

An extensive systematic review of the literature was completed using PubMed, EBSCO and Cochrane Library, from their inception to January 2018. The PRISMA guidelines were followed and the search strategy ensured that all possible studies were identified to compile the review. Inclusion criteria for this review were: 1) Studies that analyzed the SLC12A3 gene in individuals with Type 2 Diabetes and Gitelman Syndrome. 2) Use of at least one analysis investigating the association between the Arg913Gln variation of SLC12A3 gene with diabetic nephropathy. 3) Use of a case–control or follow-up design. 4) Investigation of type 2 diabetes mellitus in individuals with Gitelman’s syndrome, with a history of diabetic nephropathy.

Results

The included studies comprised 2106 individuals with diabetic nephropathy. This review shows a significant genetic association in most studies in the Arg913Gln variation of SLC12A3 gene with the diabetic nephropathy, pointing out that the mutations of this gene could be a key predictor of end-stage renal disease.

Conclusions

The results showed in this systematic review contribute to better understanding of the association between the Arg913Gln variation of SLC12A3 gene with the pathogenesis of diabetic nephropathy in individuals with T2DM and GS.
Psychological and social consequences of non-invasive prenatal testing (NIPT): a scoping review
Authors: Labonté Valérie , Alsaid Dima , Lang Britta , Meerpohl Joerg J.
Published: October 2019

Background

Genomics-based noninvasive prenatal tests (NIPT) allow screening for chromosomal anomalies such as Down syndrome (trisomy 21). The technique uses cell-free fetal DNA (cffDNA) that circulates in the maternal blood and is detectable from 5 weeks of gestation onwards. Parents who choose to undergo this relatively new test (introduced in 2011) might be aware of its positive features (i.e. clinical safety and ease of use); however, they might be less aware of the required decisions and accompanying internal conflicts following a potential positive test result. To show the evidence on psychological and social consequences of the use of NIPT, we conducted a scoping review.

Methods

We systematically searched four electronic databases (MEDLINE (Ovid), Cochrane Library (Wiley), CINAHL (EBSCO) and PsychINFO (EBSCO)) for studies that investigated the psychological or social consequences of the use of NIPT by pregnant women or expecting parents. The search was limited to studies published between 2011 and August 8, 2018. We identified 2488 studies and, after removal of duplicates, screened 2007 titles and abstracts, and then assessed 99 articles in full text (both screenings were done independently in duplicate). We included 7 studies in our analysis.

Results

Five studies assessed anxiety, psychological distress and/or decisional regret among women with validated psychological tests like the Spielberger State Trait-Anxiety Inventory (STAI), the Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R), the Kessler Psychological Distress Scale (K6) or the Decisional Regret Scale (DRS). Two studies assessed women’s experiences with and feelings after NIPT in interviews or focus groups. The included studies were heterogeneous in location, study setting, inclusion criteria, outcome assessment, and other characteristics.

Conclusions

Only few studies on psychological consequences of NIPT have been identified. The studies assessed only short-term psychological consequences of NIPT at baseline and/or after receiving the results or after giving birth. Studies show that short term anxiety decreased when women received negative NIPT results and that decisional regret was generally low. We could not identify studies on long term consequences of NIPT, as well as studies on women’s partners’ short and long term outcomes, nor on social consequences of NIPT.
Adverse childhood experiences and poor birth outcomes in a diverse, low-income sample
Authors: Mersky Joshua P. , Lee ChienTi Plummer
Published: October 2019

Background

Adverse childhood experiences (ACE) are associated with an array of health consequences in later life, but few studies have examined the effects of ACEs on women’s birth outcomes.

Methods

We analyzed data gathered from a sample of 1848 low-income women who received services from home visiting programs in Wisconsin. Archival program records from a public health database were used to create three birth outcomes reflecting each participant’s reproductive health history: any pregnancy loss; any preterm birth; any low birthweight. Multivariate logistic regressions were performed to test the linear and non-linear effects of ACEs on birth outcomes, controlling for age, race/ethnicity, and education.

Results

Descriptive analyses showed that 84.4% of women had at least one ACE, and that 68.2% reported multiple ACEs. Multivariate logistic regression analyses showed that cumulative ACE scores were associated with an increased likelihood of pregnancy loss (OR = 1.12; 95% CI = 1.08–1.17), preterm birth (OR = 1.07; 95% CI = 1.01–1.12), and low birthweight (OR = 1.08; 95% CI = 1.03–1.15). Additional analyses revealed that the ACE-birthweight association deviated from a linear, dose-response pattern.

Conclusions

Findings confirmed that high levels of childhood adversity are associated with poor birth outcomes. Alongside additive risk models, future ACE research should test interactive risk models and causal mechanisms through which childhood adversity compromises reproductive health.