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PurposeIn a combined in vitro/in vivo approach, tunnel vs. box-only resin composite restorations should be evaluated using thermomechanical loading (TML) in vitro and a restrospective clinical trial in vivo.Materials and methodsFor the in vitro part, box-only and tunnel cavities were prepared in 32 extracted human third molars under simulated intraoral conditions in a phantom head. Specimens were randomly assigned to four groups (n= 8; 16 box-only/16 tunnel) and received bonded resin composite restorations with Amelogen Plus (box A/tunnel A) or lining with Ultraseal and Amelogen plus (box B/tunnel B) both bonded using PQ1 (all Ultradent). Specimens were subjected to a standardized aging protocol, 1-year water storage (WS) followed by TML (100,000 × 50 N; 2500 × + 5/+ 55 °C). Initially and after aging, marginal qualities were evaluated using replicas at × 200 magnification (SEM). For the corresponding in vivo observational study, 229 patients received 673 proximal resin composite restorations. From 371 tunnel restorations, 205 cavities were filled without flowable lining (tunnel A), and 166 tunnels were restored using UltraSeal as lining (tunnel B). A total of 302 teeth received conventional box-only fillings. Restorations were examined according to modified USPHS criteria during routine recalls up to 5 years of clinical service.ResultsIn vitro, all initial results showed 100% gap-free margins when a flowable lining was used. Tunnels without lining exhibited some proximal shortcomings already before TML and even more pronounced after TML (p< 0.05). After TML, percentages of gap-free margins dropped to 87–90% in enamel with lining and 70–79% without lining (p< 0.05). In vivo, annual failure rates for box-only were 2.2%, for tunnel A 6.1%, and for tunnel B 1.8%, respectively (p< 0.05). Tunnels had significantly more sufficient proximal contact points than box-only restorations (p< 0.05). Flowable lining was highly beneficial for clinical outcome of tunnel-restorations (p< 0.05).ConclusionsWith a flowable lining, tunnel restorations proved to be a good alternative to box-only resin composite restorations.Clinical relevanceClass II tunnel restorations showed to be a viable alternative for box-only restorations, however, only when flowable resin composite was used as adaptation promotor for areas being difficult to access.

Parkinson's disease is a highly disabling, progressive neurodegenerative disease that manifests as a mix of motor and non‐motor signs. Although we are equipped with some symptomatic treatments, especially for the motor signs of the disease, there are still no established disease‐modifying drugs so the disease progresses unchecked. Standard drug discovery programs for disease‐modifying therapies have provided key insights into the pathogenesis of Parkinson's disease but, of the many positive candidates identified in pre‐clinical studies, none has yet translated into a successful clinically efficacious drug. Given the huge cost of drug discovery programs, it is not surprising that much attention has turned toward repurposing strategies. The trialing of an established therapeutic has the advantage of bypassing the need for preclinical safety testing and formulation optimization, thereby cutting both time and costs involved in getting a treatment to the clinic. Additional reduced failure rates for repurposed drugs are also a potential bonus. Many different strategies for drug repurposing are open to researchers in the Parkinson's disease field. Some of these have already proven effective in identifying suitable drugs for clinical trials, lending support to such approaches. In this review, we present a summary of the different strategies for drug repurposing, from large‐scale epidemiological correlation analysis through to single‐gene transcriptional approaches. We provide examples of past or ongoing studies adopting each strategy, where these exist. For strategies that have yet to be applied to Parkinson's disease, their utility is illustrated using examples taken from other disorders., The journey of exenatide shows the potential that repurposing strategies based upon initial epidemiological observations offer for identifying new disease‐modifying therapies for Parkinson's disease.

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Aims and objectives: To evaluate whether implementing the Modified Early Warning Scoring system impacts nurses’ free text notes related to Airway, Breathing, Circulation and Pain in general ward medical and surgical patients. Background: The quality of nursing documentation in patient health records is important to secure patient safety, but faces multiple challenges whether being paper-based or electronic. Nurses’ ability to draw a complete picture of the patient situation is thereby compromised. Structured use of the Modified Early Warning Score, found to reduce unexpected death, might affect nurses’ free text documentation of clinical observations. Design: A prospective, pre- and postinterventional, nonrandomised study adhering to the EQUATOR guideline TREND. Methods: Data on nurses’ free text notes were obtained in 1,497 patient records during one preinterventional (March–June 2009) and two postinterventional study periods (September–December 2010 and March–June 2011) in a Danish university hospital. Data were organised by the Airway, Breathing and Circulation principles and by nurses’ working shifts in the 56 hr surrounding the first recording of deviating vital parameters or a Modified Early Warning Score ≥ 2. Preinterventional free text notes were compared with notes from the two postinterventional periods, respectively. Results: In the 8-hr working shift where deviations in vital parameters were recorded for the first time, nurses’ free text notes related to patients’ breathing (B) increased significantly, comparing 2009 with 2010 and 2011, respectively. In the 24 hr following initial deviations in vital parameters, a significant increase in free text notes was identified concerning Airway, Breathing and Circulation-related symptoms or problems. Conclusion: Mandatory use of the Modified Early Warning Score and related implementation activities significantly impacts nursing documentation of free text notes. Relevance to clinical practice: Nurses’ practice of communicating observed clinical symptoms by documenting free text notes should be supported through measures to enhance situation awareness.

Skin healing defects severely impair the quality of life of millions of people and burden healthcare systems globally. The therapeutic approach to these pathologies still represents a challenge. Novel scaffolds, used as dermal substitutes, possibly represent a promising strategy in complex wound management. Integra Flowable Wound Matrix (IFWM) is composed of a lyophilised, micronised form of collagen/chondroitin sulphate matrix, already used in regenerative medicine and endorsed in the therapy of diabetic foot lesions. In this paper, IFWM was applied to a tunnelling hard-to-heal skin lesion in order to restore tissue integrity. Although the different phases of skin wound healing are well established, the molecular mechanism underpinning IFWM-induced tissue repair are almost unknown. Here, we report, for the first time, the comparative analysis of molecular, histological and clinical observations of the healing process of a hard-to-heal tunnelling skin wound. The therapeutic success of this clinical case allowed us to recommend the use of IFWM as a tissue substitute in this rare type of hard-to-heal wound in which the high inflammatory status hampered the natural healing process. Declaration of interest: The authors have no conflicts of interest.

The article describes four clinical observations of patients with babesiosis detected in the European part of the Russian Federation, two of whom were under the direct supervision of the authors. The analysis of epidemiological data, clinical picture, results of laboratory studies in the dynamics of the disease. Differential diagnosis and treatment are discussed.В статье приводится описание четырех клинических наблюдений за больными с бабезиозом, выявленных в европейской части Российской Федерации, из которых двое находились под непосредственным наблюдением авторов. Дается анализ эпидемиологических данных, клинической картины, результатов лабораторных исследований в динамике заболевания. Обсуждаются вопросы дифференциальной диагностики и лечения.

Intestinal lymphangiectasia is a very rare pathology, characterized by the presence of enlarged lymphatic vessels in all layers of the intestinal wall and in the mesentery. As a result, "lymphatic lakes" are formed, through which lymph exudates into the lumen of the intestine. The main manifestation is hypoproteinemic edema. Diagnosis of the disease is based on laboratory-instrumental methods of investigation, including by determining in the stool α-1 antitrypsin as a screening test. Treatment includes: a diet rich in calcium, trace elements, be sure to use medicinal foods enriched with medium chain triglycerides, substitution and symptomatic therapy.

Background: Diabetes mellitus (DM) remains a major health problem worldwide. Several clinical trials have shown the superiority of the Traditional Chinese Medicine in delaying or reversing the development and progression of DM. This study aimed to evaluate the efficacy of Jinlida (JLD) granule, a Chinese herbal recipe, in the treatment of impaired glucose tolerance (IGT) and its effect on the prevention of DM. Methods: Sixty-five IGT patients were randomized to receive one bag of JLD granules three times daily (JLD group, n = 34) or no drug intervention (control group, n = 31) for 12 weeks. Oral glucose tolerance test, glycated hemoglobin A1c (HbA1c), body mass index, blood lipids levels, fasting insulin, and insulin resistance calculated using homeostatic model assessment (HOMA-IR) of all the patients were observed and compared before and after the treatment. Results: Sixty-one participants completed the trial (32 in JLD group and 29 in the control group). There were statistically significant decreases in HbA1c (P < 0.001), 2-h plasma glucose (P < 0.001), and HOMA-IR (P = 0.029) in JLD group compared with the control group after 12 weeks of treatment. After 12 weeks of treatment, two (6.9%) patients returned to normal blood glucose, and five (17.2%) patients turned into DM in control group, while in the JLD group, 14 (43.8%) returned to normal blood glucose and 2 (6.2%) turned into DM. There was a significant difference in the number of subjects who had normal glucose at the end of the study between two groups (P = 0.001). Conclusions: JLD granule effectively improved glucose control, increased the conversion of IGT to normal glucose, and improved the insulin resistance in patients with IGT. This Chinese herbal medicine may have a clinical value for IGT.

To explore the relationship between mouse double minute 2 binding protein (MTBP) and the prognosis of cancer patients, a databank-based reanalysis was conducted and a clinical observation about lung adenocarcinoma was taken to verify the result of data analysis. We reanalyzed all the downloaded data in order to make a conclusion about the relationship between MTBP and the prognosis of cancer patients. At last, we collected 112 lung cancer patients with MTBP information to verify the results of data analysis (GSE30219). The overall Kaplan–Meier curve results of 6 eligible data groups were shown in Fig. 1. The Kaplan–Meier curve result of GSE16011 was shown in Fig. 1A (concordance index = 59.48, Log-Rank Equal Curves [P = 5.942e−05], R2 = 0.045/1, risk groups hazard ratio = 1.69 [conf. int. 1.3–2.9], P = 7.344e−05), while the stratification results were displayed independently in Figs. 2 and 3. The similar results could be seen in other 5 data groups. The tissue sections of 112 patients with lung adenocarcinoma were collected and immunohistochemically stained. The hyper expression rate of MTBP in adenocarcinoma was 23.21% (26/112). The results showed that patients with hyper expression of MTBP had significantly worse prognosis than the control group, and the survival curves were clearly separated from each other (Fig. 4B, P = .000). Hyper expression of MTBP maybe an adverse event for the survival of some cancer patients, especially in glioblastoma, kidney cancer, and lung cancer patients, which has been verified in 112 lung cancer patients with MTBP status.

Background Clinical observation of aberrant movement patterns during active forward bending is one criterion used to identify patients with non-specific low back pain suspected to have movement coordination impairment. The purpose of this study was to describe and quantify kinematic patterns of the pelvis and trunk using a dynamics systems approach, and determine agreement between clinical observation and kinematic classification. Method Ninety-eight subjects performed repeated forward bending with clinical observation and kinematic data simultaneously collected. Kinematic data were plotted using angle-angle, coupling-angle, and phase-plane diagrams. Accuracy statistics in conjunction with receiver operating characteristic curves were used to determine agreement between clinical observation and kinematic patterns. Results Kinematic patterns were consistent with clinical observation and definitions of typical and aberrant movement patterns with moderate agreement (kappa = 0.46–0.50; PABAK = 0.49–0.73). Early pelvic motion dominance in lumbopelvic coupling-angle diagram ≥59° within the first 38% of the movement represent observed altered lumbopelvic rhythm. Frequent disruptions in lumbar spine velocity represented by phase-plane diagrams with local minimum occurrences ≥6 and sudden decoupling in lumbopelvic coupling-angle diagrams with sum of local minimum and maximum occurrences ≥15 represent observed judder. Conclusion These findings further define observations of movement coordination between the pelvis and lumbar spine for the presence of altered lumbopelvic rhythm and judder. Movement quality of the lumbar spine segment is key to identifying judder. This information will help clinicians better understand and identify aberrant movement patterns in patients with non-specific low back pain.

Proton therapy (PT) is a highly conformal type of radiation therapy that can target the tumor while sparing dose to surrounding normal tissues. This study reviews a single institution's experience managing patients with non-Hodgkin lymphoma (NHL) treated with PT. Eleven patients with NHL were treated with PT from January 2008 to January 2014 on an institutional review board-approved outcomes tracking protocol, and included patients with indolent orbital lymphoma (n = 4), primary mediastinal B-cell lymphoma (n = 3), plasmablastic lymphoma (n = 2) and natural killer (NK) T-cell lymphoma (n = 2). The median follow-up was 38 months. The 2-year rate of local control was 91%, with one patient with NK T-cell lymphoma having recurrence in-field. Toxicities were limited to grade 2 at highest, during follow-up. PT is a feasible and effective treatment for NHL. Early outcomes are favorable. Longer follow-up and more patients are needed to confirm our findings.