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Study Objective To study the safety of a degradable polymeric film (DPF) and its efficacy on reducing the risk of intrauterine-adhesion (IUA) formation in a rat model. Design A series of case-control studies relying on random allocation, where feasible. Setting University and good practice animal laboratories. Animals The animal models comprised female and male Oncins France Strain A and female Wistar rats. Intervention(s) and Measurements The Oncins France Strain A rats were used for in vivo evaluation of the impact of the DPF on endometrial thickness and its effect on fertility. For in vivo evaluation of the biologic response, 40 Wistar rats were randomly allocated to intervention and control groups, with matched sampling time after surgery. Finally, for the in vivo evaluation of the DPF's efficacy on IUA prevention, a total of 24 Wistar rats were divided into 3 groups: 1 treated with the DPF, 1 treated with hyaluronic acid gel, and a sham group. Main Results The DPF did not have a significant impact on endometrial thickness, and there were no significant differences in the number of conceived or prematurely terminated pregnancies, confirming its noninferiority to no treatment. The DPF did not induce irritation at 5 days and 28 days. Finally, the DPF significantly reduced the likelihood of complete IUA formation compared with hyaluronic acid gel– and sham-implanted animals, where only 27% of the animals had their uterine cavity obliterated compared with 80% and 100%, respectively. Conclusion The DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

Purpose Outcome differences driven by variation in Blacks' biologic response to treatment may contribute to persistent racial disparities in asthma morbidity and mortality. This review assessed systematic variation in β2 agonist treatment outcomes among Blacks compared to other groups. Methods We conducted a systematic review of studies reporting differential response to β2 agonists among Blacks, including studies identifying pharmacogenetic variants. Results Of 3158 papers, 20 compared safety or efficacy of β2 agonists among Blacks as compared with other subgroups. Six papers evaluating efficacy of short-acting β2 agonists (SABA) found similar or improved results among Blacks compared with other groups, while one small study found reduced response to SABA therapy among Blacks. Reports of safety and efficacy of long-acting β2 agonists (LABA) indicated similar results among Blacks in four papers, while four reports found reduced safety among Blacks, as compared with other groups. Four papers assessed genomic variation and relative treatment response in Blacks, with two finding significant effects of the p.Arg16Gly variant in ADRB2 on β2 agonist response and one finding significant gene-gene IL6/IL6R interaction effects on albuterol response. Conclusions Evidence suggests the potential for differences in β2 agonist outcomes among Blacks compared with other groups. This literature, however, remains small and significantly underpowered for substantive conclusions. There are notable opportunities for adequately-powered investigations exploring safety and efficacy of β2 agonists among Blacks, including pharmacogenomic modifiers of response.

There is a rising interest in use of big data approaches to personalize treatment of inflammatory bowel diseases (IBDs) and to predict and prevent outcomes such as disease flares and therapeutic nonresponse. Machine learning (ML) provides an avenue to identify and quantify features across vast quantities of data to produce novel insights in disease management. In this review, we cover current approaches in ML-driven predictive outcomes modeling for IBD and relate how advances in other fields of medicine may be applied to improve future IBD predictive models. Numerous studies have incorporated clinical, laboratory, or omics data to predict significant outcomes in IBD, including hospitalizations, outpatient corticosteroid use, biologic response, and refractory disease after colectomy, among others, with considerable health care dollars saved as a result. Encouraging results in other fields of medicine support efforts to use ML image analysis—including analysis of histopathology, endoscopy, and radiology—to further advance outcome predictions in IBD. Though obstacles to clinical implementation include technical barriers, bias within data sets, and incongruence between limited data sets preventing model validation in larger cohorts, ML-predictive analytics have the potential to transform the clinical management of IBD. Future directions include the development of models that synthesize all aforementioned approaches to produce more robust predictive metrics.

Response to biologic therapies in severe asthma is variable, with patients being either nonresponders, responders or super-responders. There is currently no explanation for this variation in response. If asthma-specific inflammatory pathways are part of a wider network of pathogenic mechanisms (including systemic inflammation), then the state of this wider network could either help or hinder the effect of the biologic. People with severe asthma are often polysymptomatic with a variable frequency of nonrespiratory symptoms. Application of existing network theory would predict that high systemic inflammation, measurable by the frequency of nonrespiratory symptoms, should decrease the effectiveness of biologics, a prediction consistent with the limited existing data. A detailed examination of the relationship between biologic response and the frequency or profile of nonrespiratory symptoms would provide a testable prediction of this hypothesis. The clinical presentation of super-responders is consistent with biologics sometimes having a positive effect on the pathology (level of dysregulation) in a network system. If that were the case, then network theory predicts the possibility of a short-term increase in nonrespiratory symptoms prior to the improvement reported by super-responders. If biologics lead to less network dysregulation in some patients, then this raises the possibility of new applications for this therapy and of an improved response to biologics if lifestyle improvement is started prior to biologic therapy.

On January 30, 2020, the World Health Organization (WHO) declared the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic a worldwide emergency. Worldwide there have been 170 million cases of the resulting disease coronavirus 2019 (COVID-19), of those, 3.53 million have resulted in death. The Food and Drug Administration (FDA) with Mayo Clinic as the lead institution authorized COVID-19 convalescent plasma (CCP) for treatment of SARS-CoV-2 infection. Effective therapeutic window for CCP administration had yet to be defined. We addressed this gap by characterizing longitudinal biologic response and clinical outcomes of COVID-19 patients treated with CCP. Primary outcome was discharged to home/home health.

Prosthetic inguinal hernia repair presents significant challenges. Some of these, such as mesh fixation and quality of the biologic response, are still debated among surgeons. For example, there is no strong consensus regarding a specific condition that characterizes the surgical procedure during herniorrhaphy. This issue concerns management of the hernia defect, which in conventional hernia repair with flat meshes remains patent. However, a critical analysis of typical postoperative complications after inguinal hernia repair reveals that some of these adverse events are related to patency of the hernial opening. Postoperative discomfort, pain with specific movements and even hernia recurrence can be caused by incomplete or defective management of the hernia defect. For this reason, a deeper understanding of this topic would be useful for improving postoperative outcomes. A recently updated concept for inguinal hernia repair takes this technical aspect into consideration. It is based on the use of a newly developed 3D scaffold—ProFlor™ (Insightra Medical, Inc., Clarksville, TN, USA)—that is intended to be deployed into the defect. This novel hernia repair device has interesting and original features, such as dynamic responsivity in compliance with inguinal movement, fixation-free mode and regenerative behavior that counteracts the degenerative effects of the disease. Another additional proprietary feature of this 3D scaffold is the full and permanent obliteration of the defect, which is a crucial aspect to improve outcomes by avoiding the typical adverse effects of this surgical procedure. Obliteration of the hernia defect with the 3D dynamic regenerative scaffold ProFlor™ appears to be superior to coverage by means of static (passive) flat meshes/plugs used in conventional hernia repair. This report highlights the principles of this procedural approach.

Nonoperative treatment on chronic ankle instability is based on understanding the biomechanics and stimulating the biologic response of the ankle complex. Mechanoreceptors play a central role in this issue.

Background Biologic agents are a highly useful class of medications for treating inflammatory bowel disease (IBD). Limited evidence exists to guide initiation of biologic therapy, especially in pediatric patients. It is unclear if disease severity is connected to biologic response. We hypothesized that the clinical, biochemical and radiographic characteristics of pediatric IBD at diagnosis were associated with subsequent initiation of biologic therapy. Methods We performed a retrospective analysis of the charts of all pediatric patients diagnosed with IBD at our centre over 14 years. Kaplan–Meier curves evaluated patient characteristics at diagnosis with time to initiation of biologic therapy. A Cox proportional hazards model was used for multivariate characteristic analysis. Results A total of 198 patients were included, 57.6% had Crohn’s disease, 27.8% had ulcerative colitis and 14.6% had IBD type unclassified. Mean follow-up time was 47.8 months. About 55.5% of the patients received a biologic medication, the mean time to biologic initiation was 21.5 months. Earlier initiation of biologic therapy was frequently associated with older age, higher disease activity index and lower serum albumin. Conclusions Older pediatric patients with more severely active disease and lower serum albumin levels at the time of IBD diagnosis were more likely to initiate biologic therapy when considering biologic initiation, even many years after diagnosis. Identification of these characteristics may help inform decisions to initiate biologic therapy earlier in the IBD disease course.

Biomechanical function, specifically implantation technique and immediate surgical fixation, of orthopaedic implants is the primary consideration during the development of orthopaedic implants. Biologic and material characteristics are additional factors to include in the design process because of the direct impact on short- and long-term implant performance. The body's initial interaction with implant materials can affect protein- and cell-based function, thereby either promoting or impeding osseointegration. An understanding and inclusion of the biologic response, material surface morphology, and material surface chemistry in implant design is crucial because these factors ultimately determine implant function and patient outcomes. Highlighting the biologic- and material-related advantages and inadequacies of current and potential implant materials as well as applications may guide further research and development of implant materials and designs.

BACKGROUND: Adult donor platelets (PLTs) are frequently transfused to prevent or stop bleeding in neonates with thrombocytopenia. There is evidence for PLT transfusion-related morbidity and mortality, leading to the hypothesis on immunomodulatory effects of transfusing adult PLTs into neonates. Candidate factors are biologic response modifiers (BRMs) that are expressed at higher rates in adult than in neonatal PLTs. This study investigated whether storage conditions or preparation methods impact on the release of those differentially expressed BRMs. STUDY DESIGN AND METHODS: Pooled PLT concentrates (PCs) and apheresis PCs (APCs) were stored under agitation for up to 7 days at room temperature (RT) or at 2 to 8 degrees C. The BRMs CCL5/RANTES, TGF beta 1, TSP1, and DKK1 were measured in PCs' supernatant, lysate, and corresponding plasma. PLT function was assessed by light transmission aggregometry. RESULTS: Concerning the preparation method, higher concentrations of DKK1 were found in pooled PCs compared to APCs. In supernatants, the concentrations of CCL5, TGF beta 1, TSP1, and DKK1 significantly increased, both over standard (��� 4 days) and over extended storage times (7 days). Each of the four BRMs showed an up to twofold increase in concentration after storage at RT compared to cold storage (CS). There was no difference in the aggregation capacity. CONCLUSION: This analysis shows that the release of adult-specific BRMs during storage is lowest in short- and CS APCs. Our study points to strategies for reducing the exposure of sick neonates to BRMs that can be specifically associated to PLT transfusion-related morbidity.

Introduction Orthodontic tooth movement results from increased inflammation and osteoclast activation. Since patients of all ages now routinely seek orthodontics treatment, we investigated whether age-dependent biologic responses to orthodontic force correlate with the rate of tooth movement. Methods We studied 18 healthy subjects, adolescents (11-14 years) and adults (21-45 years), with Class II Division 1 malocclusion requiring 4 first premolar extractions. Canines were retracted with a constant force of 50 cN. Gingival crevicular fluid was collected before orthodontic treatment and at days 1, 7, 14, and 28 after the canine retraction. Cytokine (IL-1β, CCL2, TNF-α) and osteoclast markers (RANKL and MMP-9) were measured using antibody-based protein assays. Pain and discomfort were monitored with a numeric rating scale. The canine retraction rate was measured from study models taken at days 28 and 56. Results Although the cytokine and osteoclast markers increased significantly in both age groups at days 1, 7, and 14, the increases were greater in adults than in adolescents. Interestingly, the rate of tooth movement in adults was significantly slower than in adolescents over the 56-day study period. Adults also reported significantly more discomfort and pain. Conclusions Age is a significant variable contributing to the biologic response to orthodontic tooth movement. Adults exhibited a significantly higher level of cytokine and osteoclasts activity but, counterintuitively, had a significantly slower rate of tooth movement.

Background Alternatives to room temperature storage of platelets (PLTs) are of interest to support blood banking logistics. The aim of this study was to compare the presence of biologic response modifiers (BRMs) in PLT concentrates stored under conventional room temperature conditions with refrigerated or cryopreserved PLTs. Study design and methods A three-arm pool-and-split study was carried out using buffy coat-derived PLTs stored in 30% plasma/70% SSP+. The three matched treatment arms were as follows: room temperature (20-24°C), cold (2-6°C), and cryopreserved (-80°C with DMSO). Liquid-stored PLTs were tested over a 21-day period, while cryopreserved PLTs were tested immediately after thawing and reconstitution in 30% plasma/70% SSP+ and after storage at room temperature. Results Coagulation factor activity was comparable between room temperature and cold PLTs, with the exception of protein S, while cryopreserved PLTs had reduced Factor (F)V and FVIII activity. Cold-stored PLTs retained α-granule proteins better than room temperature or cryopreserved PLTs. Cryopreservation resulted in 10-fold higher microparticle generation than cold-stored PLTs, but both groups contained significantly more microparticles than those stored at room temperature. The supernatant from both cold and cryopreserved PLTs initiated faster clot formation and thrombin generation than room temperature PLTs. Conclusion Cold storage and cryopreservation alter the composition of the soluble fraction of stored PLTs. These differences in coagulation proteins, cytokines, and microparticles likely influence both the hemostatic capacity of the components and the auxiliary functions.

International audience; Until now, the Draize test on rabbits has been the only test performed to anticipate ocular toxicity of pharmaceutical compounds, mainly irritation. The OECD is urging the scientific community to develop and validate alternative methods to reduce the need for animal testing. Since the models and tests used cannot reflect the entire biologic response, it is necessary to combine them into integrated approaches to testing and assessment (IATA) to obtain robust data. IATAs, along with adverse outcome pathways (AOP) that encompass molecular cascades and key events, require the best combinations of tests. This commentary manuscript describes these OECD tools and proposes original approaches for ocular surface AOP and an IATA for toxicity-induced dry eye (TIDE).

Total knee arthroplasty (TKA) is a well-established surgical procedure in the late stages of knee osteoarthritis. Nevertheless, this procedure is associated with a percentage of unsatisfactory results and biomechanical failures, with aseptic loosening being the most common cause of revision. Beside these problems, cutaneous and systemic hypersensitivity reactions to metals have arisen as an increasing concern after joint arthroplasties, even if allergies against implant materials are still a quite rare and not well-known problem. Ceramic composites have been recently used in prosthetic components, showing minimum wear and excellent long-term results in total hip replacement, due to their high resistance to scratching and their better wettability with respect to cobalt–chromium alloy. Furthermore, the biologic response to debris generated from these bearings is less aggressive. Knee joint simulator tests and clinical results demonstrate promising results of TKAs with ceramic components that should led to benefit for the patients.

Nastassja A Lewinski,1 Ivan Jimenez,1 Bridget T McInnes2 1Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA, 2Department of Computer Science, Virginia Commonwealth University, Richmond, VA, USA Abstract: A vast amount of data on nanomedicines is being generated and published, and natural language processing (NLP) approaches can automate the extraction of unstructured text-based data. Annotated corpora are a key resource for NLP and information extraction methods which employ machine learning. Although corpora are available for pharmaceuticals, resources for nanomedicines and nanotechnology are still limited. To foster nanotechnology text mining (NanoNLP) efforts, we have constructed a corpus of annotated drug product inserts taken from the US Food and Drug Administration’s Drugs@FDA online database. In this work, we present the development of the Engineered Nanomedicine Database corpus to support the evaluation of nanomedicine entity extraction. The data were manually annotated for 21 entity mentions consisting of nanomedicine physicochemical characterization, exposure, and biologic response information of 41 Food and Drug Administration-approved nanomedicines. We evaluate the reliability of the manual annotations and demonstrate the use of the corpus by evaluating two state-of-the-art named entity extraction systems, OpenNLP and Stanford NER. The annotated corpus is available open source and, based on these results, guidelines and suggestions for future development of additional nanomedicine corpora are provided. Keywords: nanotechnology, informatics, natural language processing, text mining, corpora

The field of biologic immune modulators is currently mushrooming at a dizzying pace. Although most of these biologics are tested and approved for one or a few indications, their unanticipated side effects and off-label use have contributed significantly to our understanding of basic immune mechanisms, the involvement of cytokines in several apparently nonimmunologic diseases, and the importance of compartmentalized immune responses. In this review we attempt to give a bird's-eye view of the major biologics and to highlight insights and implications derived from their secondary effects and adverse reactions.

Orthodontic tooth movement(OTM) is a complex process involving physiologic processes resulting in remodelling changes in the paradental tissues which are essential in orthodontic correction of tooth position. Medications have an influence on tooth movement and information on their consumption is essential to discuss treatment planning with patients. Various drugs either prescribed by the clinician or consumed by the patients enter the circulation and may be inhibitory, additive or synergise with the movement of teeth. Tooth movement through the remeodelling of bone is regulated by prostaglandins(PG) which play a direct role in bone resorption and is adversely affected by the use of NSAIDs(Non- Steroidal anti-inflammatory drugs) with research and clinical experience suggesting that their use slows down tooth movement due to a reduction in the number of osteoclastic cells. Since tooth movement is the key principle behind orthodontic treatment, any factor affecting the biologic response towards applied mechanical force is deemed to affect orthodontic treatment duration as well as efficacy. The purpose of this review article is to update the clinician on the roleof most commonly used pharmaceutical drugs capable of affecting bone metabolism and rate of orthodontic tooth movement so that best therapeutic strategy can be formulated for an individual.

Three-dimensional (3D) printing generates cellular architected metamaterials with complex geometries by introducing controlled porosity. Their ordered architecture, imitative from the hierarchical high-strength structure in nature, defines the mechanical properties that can be coupled with other properties such as the acoustic, thermal, or biologic response. Recent progress in the field of 3D architecture materials have advanced that enables for design of lightweight materials with high strength and stiffness at low densities. Applications of these materials have been identified in the fields of ultra-lightweight structures, thermal management, electrochemical devices, and high absorption capacity.

BACKGROUND Controversy exists regarding the ability of neoadjuvant chemoradiation (nCR) to diminish lymph node yield (LNY) and how that relationship is influenced by tumor response in patients undergoing proctectomy for locally advanced rectal cancer. MATERIALS AND METHODS The National Cancer Database was used to identify patients with rectal adenocarcinomas from 2004 to 2014. Patients that received nCR were compared with those that underwent surgery alone. LNY was stratified into

Pneumocystis jirovecii (previously carinii ) pneumonia (PCP) is rare in patients taking biologic response modifiers for rheumatic disease.[1][1]–[10][2] However, prophylaxis should be considered in patients who have granulomatosis with polyangiitis or underlying pulmonary disease, or who are

Purpose: To compile the current evidence on biomechanical, biologic, and clinical outcomes of undersized surgical preparation protocols in dental implant surgery. Materials and Methods: An electronic search using three different databases (PubMed, Web of Science, and Cochrane Library) and a manual hand search were performed including in vitro, animal, and clinical studies published prior to October 2015. Studies in which an undersized drilling protocol was compared with a nonundersized drilling protocol were included. Results: From an initial selection of 1,655 titles, 29 studies met the inclusion criteria, including 14 biomechanical, 7 biologic, 6 biologic and biomechanical, and 2 clinical. Due to methodologic variation, meta-analysis was not performed. Several studies showed that implants inserted with an undersized drilling approach reached a significantly higher insertion torque value than conventional drilling in low-density substrates, while this effect is less evident if a thick cortical layer is present. Similar results in terms of boneto- implant contact (BIC) were achieved in the longer term between implants inserted with undersized and nonundersized protocols. Results in the short term were inconclusive. Clinical studies did not show negative outcomes for undersized drilling, although clinical evidence was sparse. No data are available on marginal bone loss. Conclusion: From the biomechanical standpoint, an undersized drilling protocol is effective in increasing insertion torque in low-density bone. Biologic response in long-term healing after undersized implant placement is comparable to that in the nonundersized surgical drilling protocol. Clinical studies indicate that performing an undersized drilling protocol on low-density bone is a safe procedure; however, more extensive studies are needed to confirm these data.

Background: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic connective tissue diseases. Inadequate treatment of RA and AS results in health failure, disability and premature death. In recent years, development of immunology and genetic engineering techniques has started a new generation of drugs in the treatment of RA and AS, called biologic response modifiers or biologics. It is a very effective therapy of serious RA and AS. In many cases, they represent the only way to improve the quality of life, slowing or even arresting the development of these diseases. According to national statistics, the percentage of patients with rheumatic diseases treated with biologic treatment in Poland is less than 1.5%, and it is much lower than in Western European countries (20%).Purpose: The aim of the study was to evaluate the use of biological treatment in Lower Silesia in patients with RA and AS in the years 2006-2015, based on data obtained from the Lower Silesian Branch of the Polish National Health Fund.Results and conclusions: In the last 10 years the frequency of biological treatment of RA or AS in Lower Silesia was estimated as 2.06% of patients (in 2011) to 6.03% of patients (during the first 8 months of 2015). Biological treatment is more often used in Lower Silesia in comparison to national statistics and ranks at a similar level as in other countries of Central and Eastern Europe.

The assessment of plasma volume loss (∆PV) induced by exercise can be estimated from changes in hematocrit (Htc) and hemoglobin (Hb), and it is essential when investigating the metabolic or biologic response to exercise of circulating biomarkers. We aimed to ascertain whether the estimation of ∆PV may differ when Hb and Htc are determined by automated hematological analyzer (AHA) versus manual methods. Twenty-five healthy male subjects performed a maximal running incremental exercise. Blood samples were taken before exercise, immediately after exercise, and after a 30-min recovery. Hb and Htc (Htc-AHA) were determined by an AHA. Htc was also determined by microcentrifugation (Htc-M). The ∆PV immediately after exercise and after recovery was calculated. The serum concentrations of several specimens were determined and corrected for ∆PV derived from Htc-AHA (∆PVAHA) and from Htc-M (∆PVM). Htc-M was found to be higher than Htc-AHA at all time points (p 0.001). However, no differences were observed between ∆PVM and ∆PVAHA either post exercise (∆PVM -12.43% versus ∆PVAHA -12.41%, p = 0.929) or after recovery (∆PVM 1.47% versus ∆PVAHA 1.97%, p = 0.171). No significant differences were found between both ∆PV corrected concentrations of any biomarker (p ≥ 0.076). In conclusion, both AHA and the microcentrifuge may be reliably used to estimate ∆PV during exercise.

Purpose: To evaluate the mechanical properties and biologic response of single-phase Ti-Zr alloys cast in higher-purity casting conditions, with comprehensive compositions (from 10 to 90 mol% of Zr). Materials and Methods: The mechanical properties and in vitro biologic response with proportional increase of Zr to Ti-Zr alloy composition were assessed. Tensile strength, surface hardness, and Young's modulus were examined. The in vitro cell response of the alloys was also tested with mouse osteoblast cells. Results: Analyses of mechanical tests demonstrated improved strength and reduced Young's modulus on this binary alloy system. In vitro cell culture studies with osteogenic MCT3T-E1 cells exhibited the highest attachment rate with the largest and more mature cells on Ti10Zr, instead of commercially pure Ti, whereas a significantly lower cell attachment rate and delayed alkaline phosphatase-specific activity (ALP) differentiation were detected on Ti50Zr. Conclusion: The results revealed that the composition did have an impact on the in vitro biologic response. Ti-Zr alloys with 50-50 mol% composition had a decreased biologic response, although the mechanical properties improved. The overall highest strength was Ti with 30 mol% Zr without significant decrease of biologic response.

Juvenile idiopathic arthritis (JIA) is the most common childhood systemic disease associated with uveitis and significantly detracts from the child’s quality of life. Due to the high rate of ocular morbidities in JIA associated uveitis, the main treatment goal remains the complete elimination of active inflammation at all times. An aggressive ‘step-ladder’ approach starting with conventional immunotherapy is usually tried initially in order to control the ocular inflammation. For those who fail conventional therapy, biologic response modifiers have been shown to be effective in controlling the inflammation. Available data demonstrate the extensive and successful, yet off-label, use of biologic agents in the treatment of refractory JIA associated uveitis especially in cases that fail or deemed intolerant to conventional immunosuppressive therapy. In this review, we discuss different biologic response modifiers; their applications in the treatment of JIA associated uveitis and their safety profile i...

Background Static and fixated meshes to repair mobile structures like the groin may seem a procedural incongruence. Inguinal hernia is described as a degenerative disease. Therefore, the objective of disease treatment should be the regeneration of wasted tissue. The fibrotic scar plate, a typical biologic response of conventional static meshes, does not represent tissue regeneration but rather a foreign body reaction. These contrasting aspects seem to be related to high complication rates of inguinal herniorrhaphy. Recent studies concerning the pathophysiology of the groin have led to the development of new concepts for repairing inguinal protrusions. A proprietary designed 3D dynamic responsive implant showing regenerative biologic response is the result of this studies. Materials and methods A cohort of 389 individuals underwent open inguinal hernia repair with the 3D dynamic responsive implant following a specific surgical technique. Thanks to the inherent dynamic properties, all procedures were performed without need for fixation of the 3D prosthesis. Results The outcomes of the dynamic hernia repair procedure were reduced postoperative pain and minimized overall complication rates, also long term. Moreover, no patient discomfort or chronic pain was reported. Conclusions Inguinal hernia repair with the 3D dynamic responsive implant ProFlor seems to represent an effective concept change for the treatment of this widespread degenerative disease. Moving in synchrony with the groin, implanted without need of fixation and acting as a regenerative scaffold, ProFlor™ appears to possess all that is needed for a physiologic and pathogenetical consequent treatment of inguinal protrusions leading to a dramatic lessening of intra- and postoperative complications.

Decreasing the re-tear rate associated with rotator cuff repair has been a major focus of the orthopedic literature for the last two decades. While some of the literature has focused on improving the biologic milieu, much of the literature has been on improving the mechanics of the construct attaching the tendon to the bone. Much of this literature has focused on the time-zero strength of the attached tendon. More recently, the biologic response to these constructs, clinical outcomes, and re-tear rates for rotator cuff repair using these differing techniques has become available. This chapter highlights the results of this voluminous literature.

The exposome is a complement to the genome that includes non-genetic causes of disease. Multiple definitions are available, with salient points being global inclusion of exposures and behaviors, and cumulative integration of associated biologic responses. As such, the concept is both refreshingly simple and dauntingly complex. This article reviews high-resolution metabolomics (HRM) as an affordable approach to routinely analyze samples for a broad spectrum of environmental chemicals and biologic responses. HRM has been successfully used in multiple exposome research paradigms and is suitable to implement in a prototype universal exposure surveillance system. Development of such a structure for systematic monitoring of environmental exposures is an important step toward sequencing the exposome because it builds upon successes of exposure science, naturally connects external exposure to body burden and partitions the exposome into workable components. Practical results would be repositories of quantitative data on chemicals according to geography and biology. This would support new opportunities for environmental health analysis and predictive modeling. Complementary approaches to hasten development of exposome theory and associated biologic response networks could include experimental studies with model systems, analysis of archival samples from longitudinal studies with outcome data and study of relatively short-lived animals, such as household pets (dogs and cats) and non-human primates (common marmoset). International investment and cooperation to sequence the human exposome will advance scientific knowledge and also provide an important foundation to control adverse environmental exposures to sustain healthy living spaces and improve prediction and management of disease. Keywords: Mass spectrometry, Biomonitoring, Analytical chemistry, Metabolomics, Environmental surveillance

Fat plays multiple roles in determining the desirable physicochemical properties, sensory attributes, nutritional profile, and biologic response of food products. Overconsumption of fats is linked to chronic diseases, such as obesity, coronary heart disease, diabetes, and cancer. There is therefore a need to develop reduced-fat products with physicochemical properties and sensory profiles that match those of their full-fat counterparts. In addition, foods may be redesigned to increase the feelings of satiety and satiation, and thereby reduce overall food intake. The successful design of these types of functional foods requires a good understanding of the numerous roles that fat plays in determining food attributes and the development of effective strategies to replace these attributes. This article provides an overview of the current understanding of the influence of fat on the physicochemical and physiologic attributes of emulsion-based food products and highlights approaches to create high-quality foods with reduced-fat contents.

Mycosis fungoides and its leukemic variant, Sezary syndrome, are malignancies of skin-homing T-cells that represent the most common types of cutaneous T-cell lymphoma (CTCL). Treatments of CTCL reviewed are those current and emerging therapies for CTCL that modify the host biologic response and address the immune dysregulation that occurs in these patients.

The objective of this study was to explain the effect of the imagery relaxation technique on psychological acceptance and biologic response in school age (8-12 years) on the invasive procedure. The design used in this study was static group comparison. The population was the school age patient, around 8-12 years in Melati Room RSUP Dr. Soedono Madiun. Sample of this study were 20 respondent, recruited by using purposive sampling consisting of 10 respondents as the control group and 10 respondents as the experiment group, who met the inclusion criteria. The independent variable was the imagery relaxation technique and the dependent variable was the psychological and biological acceptance responses. Data were collected by using observation paper. The result showed that there were some differences between the control group and the experiment group in heart rate (p=0.000) and the respiratory rate (p=0.000), but there were no differences in the control group`s systole (p=0.476) and diastole (p=0.630). Conclusion: the imagery relaxation technique has significantly effect on the psychological acceptance response and the biological response (the respiratory rate and the heart rate).

Human tumors are characterized by an abnormal vascular network that develops because of unregulated angiogenesis. This contributes to abnormalities of the tumor microenvironment like hypoxia, acidosis and high interstitial fluid pressure that influence treatment response and patient survival. There is an important clinical need to develop new minimally invasive tools for characterizing the tumor microenvironment at diagnosis, and monitoring changes during treatment with radiotherapy,chemotherapy or new biologically targeted drugs. MR‐based imaging approaches offer exciting possibilities that have yet to be fully exploited. Dynamic contrast enhanced (DCE) MR allows the functional characteristics of the tumor vasculature to be interrogated serially over time. Studies in human cancers have shown substantial differences in DCE MR parameters between tumor and normal muscle in keeping with higher blood flow and vascular permeability. DCE MR has been shown to correlate with response to radiotherapy or drugs that specifically target the tumor vasculature. However, despite important advances, MR functional imaging has not been adopted in routine clinical practice, in part because of a lack of consensus on optimal imaging techniques, analysis methods and reporting metrics. Further refinement and standardization is required founded on interdisciplinary collaboration among clinicians, medicalimagers, biologists, physicists and mathematicians to make these techniques robust and clinically applicable. Learning Objectives: 1. Discuss the clinical use of MR functional imaging in patients receiving radiotherapy and the challenges to wide‐spread clinical utilization. 2. Discuss the value of MR functional imaging as a predictor of clinical outcome in patients receiving radiotherapy, and a means of monitoring biologic response over a course of fractionated treatment. 3. Understand the role of MR functional imaging in the evaluation of new treatment strategies comprised of radiotherapy and drugs that specifically target the tumor vasculature.

Overwhelming evidence supports the concept that wear particles are the primary initiator of aseptic loosening of orthopaedic implants. It is likely, however, that other factors modulate the biologic response to wear particles. This review focuses on three potential other factors: genetic susceptibility, Toll-like receptors (TLRs), and bacterial pathogen-associated molecular patterns (PAMPs). WHERE ARE WE NOW?: Considerable evidence is emerging that both genetic susceptibility and TLR activation are important factors that modulate the biologic response to wear particles, but it remains controversial whether bacterial PAMPs also do so. WHERE DO WE NEED TO GO?: Detailed understanding of the roles of these other factors may lead to identification of novel therapeutic targets for patients with aseptic loosening. HOW DO WE GET THERE?: Highest priority should be given to polymorphism replication studies with large numbers of patients and studies to replicate the reported correlation between bacterial biofilms and the severity of aseptic loosening.

Patients undergoing nuclear medicine procedures for cancer therapy are administered radiopharmaceuticals that emit various types of radiation. Because radiation has differential delivery to and uptake by cells in tissue, radiation exposures are often highly nonuniform. Some cell populations in a tissue may contain widely different amounts of radioactivity, whereas other cell populations in the same tissue may contain no radioactivity, referred to as labeled and unlabeled cells, respectively. Furthermore, the toxicity of the radiations emitted can depend on the location of the radioactive decay within the cell (e.g., nucleus vs. cytoplasm). Therefore, the response of a given cell depends on the absorbed dose received from radiations emitted by decays within the cell (self-dose) and emitted by decays in neighboring cells (cross-dose), among other factors. Taken together, these variables make it difficult to predict the response of cell populations to radiopharmaceuticals. Accordingly, to assist in designing treatment plans for therapeutic radiopharmaceuticals, an applet software application called MIRDcell was developed. This applet models the distribution of radiopharmaceuticals in tissues, calculates the distribution of radiation dose, models responses on a cell-by-cell basis, and predicts the surviving fraction of the labeled and unlabeled cell populations. MIRDcell can be accessed at http://mirdcell.njms.rutgers.edu/.

Appropriate use of local hemostatic agent is one of the important factors on the prognosis of endodontic microsurgery. However, most investigations to date focus on the hemostatic efficacy of the agents, whereas their biologic characteristics have not received enough attention. The purpose of this paper was to review the biologic response of local hemostatic agents, and to provide clinical guidelines on their use during endodontic microsurgery. Electronic database (PUBMED) was screened to search related studies from 1980 to 2013, and 8 clinical studies and 18 animal studies were identified. Among the materials used in these studies, most widely-investigated and used materials, epinephrine, ferric sulfate (FS) and calcium sulfate (CS), were thoroughly discussed. Influence of these materials on local tissue and systemic condition, such as inflammatory and foreign body reaction, local ischemia, dyspigmentation, delayed or enhanced bone and soft tissue healing, and potential cardiovascular complications were assessed. Additionally, biological property of their carrier materials, cotton pellet and absorbable collagen, were also discussed. Clinicians should be aware of the biologic properties of local hemostatic agents and their carrier materials, and should pay attention to the potential complications when using them in endodontic microsurgery.

Vemurafenib improves the management of advanced melanoma due to selective inhibition of the mutated BRAF V600E kinase. FDG-PET-CT is a tool for the evaluation of the biologic impact of inhibiting mutant BRAF. With vemurafenib at day 15, all the patients had at least partial metabolic response. Reductions in uptake correlate with longer progression free survival. In this case, incomplete information provided by the patient led to the performance of his third PET 85 hours after the introduction of vemurafenib. This early case of complete metabolic response suggests that FDG-PET-CT is a useful marker of early biologic response to vemurafenib.

Based on the available research on PEEK materials, to find that whether PEEK material has favourable properties and can enhance Osseointegration, so that they can be utilize as dental implant body/fixture. Appropriate selection of the implant biomaterial is a key factor for long term success of implants .The biologic environment does not accept completely any material so to optimize biological performance, implants should be selected to reduce the negative biologic response while maintaining adequate function. This review makes an effort to summarize peek implant bio material. Materials and Method: A literature review of English articles was conducted by using MEDLINE PubMed database restricted to 2010 - 2019 and constructed according PRISMA guidelines. Search terms included: “Dental Implants” [Mesh]) AND (“PEEK”), (“PEEK Dental Implant” [MeSH]) AND (“Osseointegration”), (“PEEK Dental Implant”). Results: Initially, the search resulted in 106 papers out of which 19 articles were excluded due to irrelevant titles and abstracts. Independent screenings of the abstracts were done to identify the articles related to the question in focus Eighty Seven studies were selected out of which 31 articles were further excluded dueto Articles and studies related to PEEK as Implant abutments,or implant restoration were excluded. Finally 21 articles were included in the review.

Background The goat is one of the most commonly used preclinical models for focal defect repair and regeneration. While the biomechanics of the human knee has been studied extensively, less is known about the biomechanics of the caprine knee. Differences between human and caprine knees have not been quantified and their significance is largely unknown. Methods We conducted a biomechanical analysis of the differences in goat and human knees to assess the validity of these preclinical in vivo models. Results CT and MRI scans revealed several differences in articular geometry: the caprine tibial plateaux were more convex and the menisci were significantly thicker and covered a larger proportion of the tibial articular surface. Caprine cartilage thickness was consistently thinner, while elastic modulus on indentation testing was consistently stiffer than human cartilage measured at eight different articular locations. Contact area and pressure were measured with electronic pressure sensors under loads normalized by multiples of body weight and at knee flexion angles reported for walking. The highest peaks in contact pressure were measured in the patellofemoral joint in goat and human knees. Peak contact pressure measured at 2 times body weight at the goat tibiofemoral joint at 70° flexion was significantly higher than for any other condition at the human tibiofemoral joint. Conclusion These differences in contact conditions might explain the lower quality of local repair reported for caprine femoral condylar defects relative to trochlear defects. Further comparative analysis, including biologic response, is necessary to determine the extent to which the goat knee reproduces clinical conditions.

PURPOSE To examine the biologic response to titanium implant surfaces treated with a neodymium:yttrium-aluminum-garnet laser. MATERIALS AND METHODS Sixty mini-implants made of grade 2 titanium were placed in the femora of 30 Wistar rats. Thirty implants had a machined surface and the other 30 had surfaces that were roughened by laser treatment. The animals were subdivided into three groups according to bone repair periods of 15, 30, and 60 days. The samples were observed under light and electron scanning microscopes and analyzed with the Student t test. RESULTS Formation of new bone trabeculae toward the surface was apparent for the laser-treated implants at 15 days. Thin layers of bone matrix in intimate contact with the surface in the area of the central screw threads were observed, indicating high biocompatibility. Similar results were seen with machined implants after 30 days. A significant difference in bone formation was observed between the implant types at 15 days. CONCLUSION Bone-to-implant contact was better on the surfaces subjected to laser treatment than on the machined titanium implants. The development of new laser treatments, which promote alterations in the surface energy as well as in the macro- and microstructures of titanium, may lead to improved bone-to-implant contact and thus better outcomes.