Significant Etiologic Factors Research Articles

TFEB signaling promotes autophagic degradation of NLRP3 to attenuate neuroinflammation in diabetic encephalopathy.

Diabetic encephalopathy (DE), a neurological complication of diabetes mellitus, has an unclear etiology. Shreds of evidence show that the Nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome-induced neuroinflammation and transcription factor EB (TFEB)-mediated autophagy impairment may take part in DE development. The crosstalk between these two pathways and their contribution to DE remains to be explored. A mouse model of type 2 diabetes mellitus (T2DM) exhibiting cognitive dysfunction was created, along with high glucose (HG) cultured BV2 cells. Following, 3-methyladenine (3-MA) and rapamycin were utilized to modulate autophagy. To evaluate the potential therapeutic benefits of TFEB in DE, we overexpressed and knocked down TFEB in both mice and cells. Autophagy impairment and NLRP3 inflammasome activation were noticed in T2DM mice and HG-cultured BV2 cells. The inflammatory response caused by NLRP3 inflammasome activation was decreased by rapamycin-induced autophagy enhancement, while 3-MA treatment further deteriorated it. Nuclear translocation and expression of TFEB were hampered in HG-cultured BV2 cells and T2DM mice. Exogenous TFEB overexpression boosted NLRP3 degradation via autophagy, which in turn alleviated microglial activation as well as ameliorated cognitive deficits and neuronal damage. Additionally, TFEB knockdown exacerbated neuroinflammation by decreasing autophagy-mediated NLRP3 degradation. Our findings have unraveled the pathogenesis of a previously underappreciated disease, implying that the activation of NLRP3 inflammasome and impairment of autophagy in microglia are significant etiological factors in the DE. The TFEB-mediated autophagy pathway can reduce neuroinflammation by enhancing NLRP3 degradation. This could potentially serve as a viable and innovative treatment approach for DE.

Polycaprolactone/gelatin-QAS/bioglass nanofibres accelerate diabetic chronic wound healing by improving dysfunction of fibroblasts

Worldwide, more than 25 % of patients with diabetes develop chronic diabetic wounds in their lifetime. Infection and dysfunctional fibroblasts represent two significant etiological factors contributing to impaired wound healing in patients with diabetes. It is therefore evident that the development of wound dressings with both anti-infective and DM fibroblast modulating functions has the potential for clinical applications. In this study, a PCL/gelatine-quaternary ammonium salts (QAS)/bioglass (BG) electrospun nanofibrous membrane was developed with physico-chemical and biological properties that not only meet the clinical requirements for wound dressings but also exhibit remarkable moisturising (water adsorption rate of 382.39 ± 4.36 %) and tear-resistance properties (a tear strength of ~5.5 MPa). The incorporation of QAS and BG has enhanced the biocompatibility and bioactivity of the nanofibres, while also imparting remarkable antimicrobial properties. The antibacterial efficacy of PGQ-BG against E. coli and S. aureus was found to be 92.8 ± 0.78 % and 99.3 ± 0.55 %, respectively. Moreover, it was demonstrated that PGQ-BG nanofibers exerted a promoting effect on the extracellular matrix (ECM) in dysfunctional fibroblasts and upregulated the expression level of α-smooth muscle actin (α-SMA), a marker of their differentiation to myofibroblasts in vitro and in vivo. Furthermore, the COL-III/COL-I ratio was significantly increased, indicating that PGQ-BG may also accelerate wound healing. The nanofibrous dressing reduced scar formation by increasing the COL-III/COL-I ratio. This is the first report of BG improving fibroblast dysfunction via COL-III and COL-I promotion in fibroblasts, both in vitro and in vivo. Therefore, this novel bioactive nanofibrous dressing represents an effective and safe therapeutic strategy for improving chronic wound healing in patients with diabetes.

Epidemiological characteristic of nails, skin of the feet and hands mycoses in the Perm region

Introduction. Mycoses of the skin and their derivatives are one of the most common groups of fungal infections. Lesion to the nails and skin of the feet and hands occupies a leading place in the structure of this pathology. These diseases are characterized by a long course and often ineffective therapy. Onychomycosis and fungal infections of the skin of the feet and hands are characterized by certain epidemiological features and have a diverse etiology.Aim. To study of the epidemiological characteristic of mycoses of the nails, skin of the feet and hands according to the data of the Regional Clinical Dermatovenerological Dispensary of Perm over a ten-year period to optimize the detection and further treatment of this pathologyMaterials and methods. For the study, statistical data from the Regional Clinical Dermatovenerological Dispensary in Perm were used. Data were analyzed for the period 2012–2021 to assess the dynamics of the prevalence of mycoses of the skin and nails of the feet and hands, their etiological structure. Cases recorded during direct patient contact were taken into account. For laboratory confirmation of mycoses, a culture method was used.Results and discussion. The number of cases of mycoses of the skin and nails of the feet and hands for the period from 2012 to 2021 was analyzed. It was established that the share of this pathology in the structure of superficial mycoses averaged 49.9%. There was no significant dynamics in the number of recorded cases of fungal infection of this location during the analyzed period. This pathology was more often observed in females than in males throughout the study period. The most significant etiological factors were representatives of Trichophyton spp., Candida spp., as well as molds. There has been a change in the etiological structure of mycoses of the nails, skin of the feet and hands over the observed period: there is a tendency towards a decrease in the proportion of dermatophytes and an increase in the proportion of yeast fungi.Conclusion. The relevance of the studied group of mycoses was confirmed using the example of the Perm region. The main cause of fungal infections of the nails and skin of the feet and hands were representatives of dermatophytes and Candida spp. It is recommended to focus on identifying this pathology in males during preventive examinations due to the low frequency of their visits to medical specialists.

Impact of weekly iron-folic acid supplementation on nutritional status and parasitic reinfection among school-age children and adolescents in Sub-Saharan Africa: a systematic review and meta-analysis.

Two significant etiological factors contributing to iron deficiency anemia, and undernutrition posing substantial public health challenges in Sub-Saharan Africa, are soil-transmitted helminths and malaria. This study carried out the effect of weekly iron-folic acid supplementation (WIFAS) on the nutrition and general health of school-age children and adolescents in Sub-Saharan Africa, a systematic review and meta-analysis have been conducted. To find pertinent publications for this study, a thorough search was carried out on May 20, 2023, across five databases: Pubmed (MEDLINE), Web of Science, Scopus, Cochrane Library, and Google Scholar. In addition, a search was conducted on August 23, 2023, to capture any new records. The inclusion criteria for the studies were based on school-age children and adolescent populations, randomized controlled trials, and investigations into the effects of WIFAS. The outcomes of interest were measured through anthropometric changes, malaria, and helminthic reinfection. A systematic review of 11 articles revealed that WIFAS significantly decreased the risk of schistosomiasis reinfection by 21% among adolescents (risk ratio = 0.79, 95%CI: 0.66, 0.97; heterogeneity I 2 = 0.00%, P = 0.02). However, no significant impact was observed on the risk of malaria reinfection (risk ratio = 1.02, 95%CI: 0.92, 1.13; heterogeneity I 2 = 0.00%, P = 0.67) or A. Lumbricoides reinfection (risk ratio = 0.95, 95%CI: 0.75, 1.19; heterogeneity I 2 = 0.00%, P = 0.65). Moreover, the analysis demonstrated that there is no significant effect of iron-folic acid supplementation in measured height and height for age Z-score (HAZ) of the school-age children (Hedge's g -0.05, 95%CI: -0.3, 0.2; test for heterogeneity I 2 = 0.00%, P = 0.7) and (Hedge's g 0.12, 95%CI: -0.13, 0.37; test for heterogeneity I 2 = 0.00%, P = 0.36) respectively. The effectiveness of WIFAS in reducing the risk of schistosomiasis reinfection in adolescents has been demonstrated to be greater than that of a placebo or no intervention. Additionally, the narrative synthesis of iron-folic acid supplementation has emerged as a potential public health intervention for promoting weight change. However, there was no significant association between WIFAS and Ascariasis, trichuriasis, and hookworm. Moreover, the certainty of the evidence for the effects of WIFAS on height and malaria is low and therefore inconclusive. Whereas, the certainty of the evidence for the effectiveness of WIFAS on Schistosomiasis is moderate. Even though the mechanisms need further research WIFAS may be implemented as part of a comprehensive public health strategy to address schistosomiasis in adolescents. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023397898, PROSPERO (CRD42023397898).

Hematological parameters, obesity, stress and oxidant - antioxidant indicators in patients with or without recurrent aphthous stomatitis: A case control study

IntroductionRecurrent Aphthous Stomatitis (RAS) is a frequent chronic disease of the oral cavity that affects 5–25 % of the population with a plethora of predisposing factors. Despite its equivocal etiology, immune alterations, hematologic deficiencies and oxidative stress has been reported to be significant etiologic factors. Stress and obesity are other environmental factors that have been studied to understand associations with RAS. ObjectivesThis study investigated the association of stress, hematologic parameters, oxidative indices and other selected salivary factors in a case control study on RAS Methods: Twenty-two participants each in both case and control groups were recruited with saliva and serum samples collected from them after a self-administered Recent Life Changing Questionnaire (RLCQ). OHI-S and salivary flow rate (SFR) were calculated with selected hematologic parameters and oxidative indices such as Total oxidant (TOS) and anti-oxidant (TAS) levels and their ratio - Oxidative Stress Index (OSI). Anti-oxidative indices of Ferric-Reducing Antioxidant Power (FRAP) and Glutathione Peroxidase Activity (GsPHx) were also estimated. Results: The RAS group had a significantly higher RLCQ scores at a median of 145 more than the control (57.5). There was no significant in their obesity indices, however there was a significant higher mean in the ESR (p< 0.0001) and Vit B12 (p = 0.0001); OHI-S was also significantly higher in the RAS group with a median of 1.65. Both the salivary and serum TOS were significantly higher in the RAS (10.0 ± 3.8, 15.4 ± 8.9) compared to the control group (7.92 ± 1.49, 9.56 ± 3.5). GsPHx activity was significantly higher in both the saliva and serum in the control group (0.08 ± 0.08, 0.19 ± 0.11) while nil significant difference was found in the FRAP activity. Regression showed most important variables to be the salivary GsPHx activity, followed by serum OSI and GsPHx activity. ConclusionThe oxidative indices of TOS, TAS and GsPHx can serve as significant biomarkers in detecting RAS. This further corroborates the role of immune dysregulation in the etiology and predisposition to RAS.

Etiological factors and pathophysiological mechanisms of the reparative process in various types of cephalohematoms and methods of their treatment

BACKGROUND: The evolutionarily formed biomechanism of childbirth in humans causes a high incidence of head injuries during the reproductive process. One of the indicators of cranial injury is cephalohematoma. Despite the presence of a number of protective and adaptive mechanisms on the part of the fetus, the frequency of subperiosteal hemorrhages remains high and does not tend to decrease. Modern knowledge about the etiology of cephalohematomas does not always fit into the framework of classical ideas about the causes of hemorrhage under the periosteum. The lack of a unified understanding of the pathomechanisms occurring in a long-term subperiosteal hemorrhage leads to a mismatch of tactical actions during their treatment and the development of complications.&#x0D; AIM: To assess the role of etiological factors in the formation of subperiosteal hemorrhage in newborns and to determine the main direction of the pathophysiological process during repair with various types of cephalohematomas and methods of treatment.&#x0D; MATERIALS AND METHODS: A study of 243 newborns with the presence of cephalohematomas of various localization for the period from 20182022 was carried out, an analysis of the etiological prerequisites, features of the reparative process with various volumes of hemorrhages and methods of treatment using descriptive statistics methods was carried out.&#x0D; RESULTS: The predominance of children with the presence of cephalohematomas with a history of the absence of hydraulic protection of the head due to early rupture of amniotic fluid was revealed in relation to other mechanical factors of intranatal damage. The greatest number of subperiosteal hemorrhages was noted in newborns from multiparous mothers. The main non-traumatic factor contributing to the formation of cephalohematomas was the factor of infectious effect on the fetus. The predominance of osteomalacic processes with medium and large volumes of cephalohematomas in relation to small-sized cephalohematomas, which had a tendency to early ossification, was noted. The effectiveness of therapeutic aspiration was noted in all cases of observation of newborns from the surgical subgroup.&#x0D; CONCLUSIONS: One of the most significant etiological factors for the occurrence of cephalohematomas in the observation group was the factor of intranatal mechanical trauma to the soft tissues of the head, due to the lack of hydraulic protection. The numerical predominance of newborns with subperiosteal hemorrhages from multiparous mothers contradicts the basic physiological canons of the biomechanism of labor and may be due to the high incidence of the infectious factor. The direction of the pathophysiological process in the course of repair in case of periosteal detachment may depend not only on microenvironmental factors, but also be determined by the amount of hemorrhage. The use of puncture treatment for cephalohematomas can significantly reduce the number of complications associated with long-term persistence of subperiosteal hemorrhage.

Immunotropic effects of including a combination of hepatoprotectors in the complex therapy of chronic pancreatitis combined with chronic viral hepatitis C

Among significant etiological factors contributing to chronic pancreatitis (CP), the infectious factor plays a role in 56.88% of patients and the hepatobiliary factor in 44.50%, which has drawn attention to the particular importance of these factors. Hepatitis C virus (HCV) is the most common and important viral agent that causes or worsens CP. HCV is not only a disease of the liver but also a systemic (generalized) infection that involves other organs, in particular the pancreas and the immune system.&#x0D; The aim is to study the state of the cellular and humoral immune systems of patients with CP against the background of treated chronic HCV (CHCV) under the influence of the proposed complex treatment with the additional inclusion of hepatotrophic drugs heparizine (HZ) and metadoxine (MD).&#x0D; Materials and methods. We examined 80 patients with a combined course of CP and CHCV. According to the methods of treatment, the patients were divided into 3 groups: group 1 (20 patients with CP and CHCV) received the generally accepted complex of protocol treatment (PT) for three months; group 2 (25 patients with CP and CHCV) received PT with the additional inclusion of the hepatotrophic agent Heparizine PLC 1 capsule 3 times a day after meals for 3 months; and group 3 (35 patients with CP and CVHC with CAGE ≥2.0) received PT with the additional inclusion of the hepatotrophic agent Heparizine PLC (one capsule) 3 times a day after meals for 3 months with the addition of MD (Liveria IS) 500 mg (one tablet) 2 times a day 15–30 min before meals for 3 months.&#x0D; Results and discussion. With the additional administration of HZ, a higher dynamics of cellular immunity indices was reached in relation to those in the PT group. When using a combination of HZ and MD, even better results were obtained in the dynamics of the following indices: an increase in the total population of T-lymphocytes by 5.2%, 22.9%, and 57.7% in groups 1–3, respectively; NK cells — by 13.1%, 23.0%, and 39.4%; T-helpers — by 10.7%, 22.8%, and 36.3%; T-suppressors — by 26.0%, 38.9%, and 45.3%; a decrease in the number of B-lymphocytes — by 10.4%, 18.9%, and 35.6%. An increase in the immunoregulatory index (CD4/CD8) was also achieved — by 11.5%, 17.7%, and 45.7%. The decrease in the levels of B-lymphocytes under the influence of treatment in all three groups was accompanied by a decrease in the activation of humoral factors in groups 1–3, respectively: a decrease in the content of IgG in blood serum by 8.7%, 15.5%, and 19.2%; IgA — by 21.8%, 70.2%, and 88.5%; and IgM — by 24.0%, 55.5%, and 84.9%; as well as a significant decrease in the levels of circulating immune complexes by 38.6%, 1.9 times and 2.9 times (p&lt;0.001).&#x0D; Conclusion. A positive immunocorrective effect of all three programs of complex treatment was proven, with a significantly higher level of those with the additional inclusion of HZ and especially the combination of HZ and MD in the complex therapy of patients with CP against the background of CHCV treated causally. Based on the results of correcting cellular and humoral immunity as an integral part of nutritional trophological status, it seems reasonable to include the proposed programs to eliminate nutritional and other disorders in people with CP and CHCV.

Cancer of tongue-our fixed entity

Background: Oral cancer ranks the top three of all cancers in India. This study aimed to determine etiologic factors for squamous cell carcinoma (SCC) of the tongue and its management. Methods: This longitudinal retrospective study was conducted with 30 patients of biopsy- proven SCC of tongue diagnosed in our hospital between the years of 2010-2022. Medical records, including history of abuse of alcohol, betel nuts, tobacco products and human papillomavirus (HPV) infection were recorded. The patients details including tumour size, location, node metastasis, grade, disease recurrence, other primary cancers, delay time until diagnosis, therapy course were noted. Patients were analyzed based on etiology and management undertaken. Results: Among 30 patients with SCC tongue, 25 (83.33%) were males, 5 (16.66%) were females. Smoking was significantly higher in males (20 patients), in those 5 alcoholics. Chronic mechanical trauma was observed in 5 patients. HPV infection was observed in 2 males, 3 females had betel nut chewing habit and use of smokeless tobacco. Among 30 cases alcohol abuse, smoking, chronic mechanical traumas, HPV infection and betel nut chewing appeared as significant etiologic factors of which smoking was the most common etiology (50%). Surgical excision with neck dissection followed by radiotherapy was treatment undertaken in our study patients based on SCC tongue stage. Conclusions: our study concluded that smoking is the most common etiology of SCC tongue, the definitive treatment is surgery combined with radiotherapy based on TNM staging.

Surgical Management of Cervical Myelopathy: Current Algorithm

Cervical myelopathy (CM) is a progressive disorder associated with a varied spectrum of etiological factors. Cervical spondylotic myelopathy (CSM) encompasses two-thirds of the cases of CM, while ossified posterior longitudinal ligament (OPLL) and ossified ligamentum flavum (OLF) are significant regional etiological factors. Microvascular disruption, resulting from repetitive dynamic compression or static pressure to the spinal cord, is attributed as a primary pathophysiological mechanism for CM. Magnetic resonance imaging (MRI) is the investigation of choice to assess the spinal cord. Lateral cervical radiographs are crucial for lordosis assessment, and tomographic scans (CT) can delineate the extent of OPLL and OLF. Non-surgical treatment is usually not successful once the patient develops progressive myelopathy. Anterior cervical procedures are ideal for one or two level disc-osteophytes complexes or in patients with kyphotic cervical alignment. Laminoplasty is an effective motion-preserving option in patients with adequate cervical lordosis. Laminectomy or laminoplasty and fusion are optimal for patients with significant preoperative neck pain. Posterior surgery is preferred over anterior surgery for CM involving three or more levels. Older age at presentation, longer duration of symptoms, and severity of pre-operative symptoms are adverse prognostic factors. Progressive cervical myelopathy is a surgical disease, and early intervention is rewarded with better outcomes. Keywords: Cervical myelopathy, Cervical spondylotic myelopathy, OPLL, OLF, Laminoplasty, Laminectomy, ACDF, Cervical corpectomy.

Incidence and Clinical Presentation of Temporo-Mandibular Joint Disorders and their Association with Psychological Distress and Para-Functional Habits in a Non-Patient Population.

The study aims at finding the incidence of temporo-mandibular joint disorders (TMDs) in a non-patient population and relates their association with psychological distress and parafunctional habits. A DC/TMD questionnaire and DASS-21 scale survey were completed by selected participants followed by clinical examination of TMDs symptoms in sample population. A study sample of 855 participants revealed 36.65% population with various TMDs symptoms, while 63.5% population had no TMDs symptoms. 50.8% study participants were men, and 49.2% were women. Of all affected population, 16.2% had pain-related TMDs, 12.39% had intra-articular TMDs symptoms, and 8.07% had TMJ pain associated with pain or dysfunction. For all TMDs symptoms groups, the strongest correlations were for depression, while no significant associations were observed with parafunctional habits in all groups. Overall psychological distress and anxiety increased the prospects of TMDs symptoms. Clinical factors like muscle tenderness, crossbite and deep vertical overlap seem to be significant etiological factors, while angle molar relationship and parafunctional habits do not seem to be significant etiologic factors in TMDs.

Tooth root resorption: A review.

Tooth root resorption is multifactorial, leading to progressive destruction and eventual loss of tooth root dentin and cement. There are internal and external types of root resorption, each having its variety. The etiology and pathogenesis of tooth root resorption are poorly understood, and the most significant etiological factors are trauma, pulpal infection, tooth bleaching, and orthodontic treatment. Tooth root resorption is primarily asymptomatic; thus, it is revealed accidentally by radiographic examination. Progressive clinical manifestations are pain, tooth discoloration, tooth mobility, and other conditions. Awareness of the causes and risk factors allowing tooth root resorption, and regular radiographic examination, in case of necessity, make it possible to reveal resorption at an early stage and to prevent its further development. Thus, the aim of this study is to present etiopathogenesis, a clinical course, and diagnostic peculiarities of internal and external types of tooth root resorption, enabling practicing dentists to timely diagnose root resorption and take appropriate measures to avoid further complications. Within the limitation of this review, even though the etiopathogenesis of tooth root resorption is yet not fully understood, it is suggested that the etiological factors fall into two groups (endogenic and exogenic) to enhance further understanding of the possible causes and mechanisms of root resorption and allow practitioners to monitor high-risk patients and make timely diagnoses. Moreover, radiographic examination and CBCT are indispensable for the diagnosis of root resorption.

Efficacy of Radiation Treatement in Ocular Adnexa Mucosa-Associated Lymphoid Tissue Lymphoma: A Retrospective Evaluation in a Single Center Experience

BACKGROUNDThe ocular adnexa mucosa-associated lymphoid tissue lymphoma (OAML or MALT lymphoma) is the most common form of ophthalmic Non-Hodgkin's Lymphoma (NHL) and accounts for approximately 1-2% of all lymphomas. The great majority of ophthalmic NHL is of B-cell origin and involves ocular adnexal regions, which include orbit, conjunctiva, lacrimal gland or eyelid. OAML is a disease of the elderly population (median age 65 years) with greater prevalence among females. Several studies have shown a correlation between autoimmune and inflammatory disorders and ocular adnexa MALT lymphoma. In fact, patients with Sjögren disease or thyrotoxicosis with/without thyroid orbitopathy are at much greater risk for developing OAML. Similarly, inflammatory disorders such as chronic conjunctivitis are significant etiological factors. Recently, Chlamydia psittaci (Cp) infection has been identified as a risk factor of OAML development. Morphologically, adnexa MALT lymphoma is characterized by heterogenous cell population with CD20+, CD10−, CD23−, BCL6−, Cyclin D1−. Treatment options include surgery, (immuno)chemotherapy and radiotherapy, but some new approaches have been introduced, such as Cp eradication antibiotic therapy or radioimmunotherapy. PATIENTS AND METHODSWe performed a retrospective analysis on 82 patients (42 females and 40 males, mean age 62.96 ± 15,03) with OAML treated with radiotherapy from January 1986 to December 2017 at Veneto Institute of Oncology-IRCCS. All patients had stage IE at the diagnosis and didn't present systemic symptoms, while the most common local symptoms were eye swelling (45 pts, 55%), conjunctivitis (14 pts, 17%) and exophthalmos (12 pts, 14%). The desease was localized in the left eye in 42 patients (51%), in the right eye in 33 (40%) and bilaterally in 7 patients (9%). The diagnosis was obtained by pathological or cytological examination whereas the staging was performed with haematological tests, total body computer tomography (TBCT), magnetic resonance imaging (MRI) and bone marrow biopsy. Since 2008, the staging was obtained also by using positron emission tomography (PET). All patients were treated with 3D-conformal radiotherapy (RT); CO60 ɣ rays were used in 7 patients (8,5%) and 6 MV photons in the rest of the 75 pts (91,5%). The median dose was 30,6 Gy (range 30-40 Gy) with a standard fractioning (1,8 Gy per day). RESULTSThe median follow up was 8,4 years. Complete response (CR) was obtained in all 82 patients (pts). Local relapse was observed in 2 patients (2,5%), both in contralateral eye, and systemic in 10 (12%). Of these, Rituximab monotherapy was administered in 4 patients, Rituximab and Chlorambucil in 2, R CVP in 1 patients, R CHOP in 2 and the regimen MVP-BV in 1 patient. The cumulative progression free survival (PFS) was 88%. Twenty-two patients (27%) died, all for non-oncological reasons. The radiotherapy was well tolerated with grade toxicity, according RTOG scale, ranging from G1 (36 pts) to G2 (20 pts). Most frequent acute side effects were conjunctivitis (23 pts, 28%), erythema (22 pts, 27%) and edema (11 pts, 13.5%), whereas the most common late toxicities were cataract (33 pts) and xerophthalmia (8 pts). Total dose > 30,6 Gy resulted significantly associated with cataract (p>0,005). Fifty percent of the patients had no late toxicity. CONCLUSIONSIn patients with ocular adnexa MALT lymphoma, 3D conformal radiotherapy is an effective treatment with PFS of 88%. Such therapy is well-tolerated in terms of acute and late toxicities and with eyesight well preserved. Cataract represents the most common late side effect and it seems to be associated with a total dose > 30,6 Gy. DisclosuresNo relevant conflicts of interest to declare.

Etiological role of opportunistic microflora in the pathogenesis of implant-associated inflammation after primary total knee replacement

Objective: to investigate etiological role of opportunistic microflora in the pathogenesis of implant-associated inflammation in patients after primary knee replacement and antibiotic resistance of major infectious agent groups. Material and Methods. We conducted the retrospective analysis of microbiological samples from 383 patients with postoperative implant-associated inflammation after the primary total knee arthroplasty. Results. Gram-positive cocci (63.5%) are the leading agents of implant-associated inflammation. We also noted an increase in the etiological role of coagulase-positive staphylococci. Among the Gram-negative group, Enterobacteriaceae and non-fermenting bacteria were major agents. We revealed high resistance of Staphylococcus spp. to antibiotics of various groups, among which oxazolidinones and glycylcyclines were the most active. Gram-negative bacteria exhibited high resistance to cephalosporine and macrolides, whereas carbapenems and fluoroquinolones worked best. Conclusion. Gram-negative Enterobacteriaceae, non-fermenters, and Gram-positive cocci are the most significant etiological factors in the pathogenesis of implant-associated inflammation in patients after primary total knee arthroplasty.

Molecular factors associated with regression of liver fibrosis of alcoholic etiology

Liver fibrosis develops as a result of chronic liver damage of various etiologies, is characterized by excessive synthesis of connective tissue by activated stellate liver cells. The toxic effect of alcohol is one of the most significant and common etiological factors worldwide. Stellate cell activation results from the interaction of multiple molecular fibrogenic pathways triggered by intracellular and extracellular, hepatic and extrahepatic stimuli. Data analysis showed that knowledge about these abnormal pathways and biomolecular processes may further contribute to the improvement of approaches to assessment of disease prognosis and treatment of alcoholic liver disease.

Abstract SY27-01: The changing etiology of liver cancer

Abstract Collectively liver cancer accounts for nearly 9% of all reported cancer deaths and is one of the most common causes of cancer mortality worldwide http://gco.iarc.fr/ (1). The incidence of liver cancer varies enormously globally and unfortunately the burden of this nearly always fatal disease is much greater in the less economically developed countries of Asia and sub-Saharan Africa (2). HCC is also the most rapidly rising solid tumor in the US and Central America and is overrepresented in minority communities, including African-Americans, Hispanic/Latino-Americans and Asian-Americans (1,3,4). Overall, there are more than 850,000 new cases each year and more than 300,000 deaths annually in the People’s Republic of China (P.R.C.) alone (2). In contrast with most common cancers in the economically developed world where over 90% of cases are diagnosed after the age of 45, in high-risk regions for liver cancer onset begins to occur in both men and women by 20 years of age and peaks between 40-49 years of age in men and between 50-59 years of age in women (5-7). Gender differences in liver cancer incidence have also been well described and worldwide the number of cases among men were 554,000 and 228,000 among women in 2012 (8)(9). To date, the significant etiological factors associated with development of HCC have been defined by biomarker studies and they are infection in early life with hepatitis B virus (HBV) and lifetime exposure to high levels of aflatoxin B1 (AFB1) in the diet (10,11). Over the past 25 years, an appreciation for the role of the hepatitis C virus (HCV) has also emerged. HCV is contributing to HCC being the most rapidly rising solid tumor in the US and Japan (12). Detailed knowledge of the etiology of HCC has spurred many mechanistic studies to understand the pathogenesis of this nearly always-fatal disease (10,13,14). Fortunately, the successful development and deployment of some highly effective new drugs that cure HCV infection is a major advance and will hopefully diminish the role of this virus in liver cancer (15,16). Alcohol is a recognized human carcinogen and alcoholic cirrhosis and heavy alcohol use have been repeatedly associated with an increase in HCC risk (23). However, it is unclear if alcohol use in the absence of cirrhosis influences HCC development (24). Several studies have demonstrated an increased risk of HCC up to 5-fold with consumption of more than 80g of alcohol per day or approximately 6-7 drinks per day (23). The risk of HCC ranges from borderline significant to doubled with chronic alcohol consumption of less than 80g/day (23). A synergism between alcohol and HBV and HCV infections has also been described (23,25). In economically developed countries the dramatic rise in overweight and nonalcoholic fatty liver disease has also been related to increased HCC (26-28). Of major concern for the future are the role that obesity, diabetes and general underlying fatty liver disease will play in the development of liver cancer (29-31). Both therapeutic and pre-disease interventions will need to be deployed now to blunt the impact of these risk factors in the decades to come. Collectively, the development and validation of a new generation of biomarkers reflecting complex processes such as inflammation will need to be deployed.

Is IL-1β Further Evidence for the Role of Propionibacterium acnes in Degenerative Disc Disease? Lessons From the Study of the Inflammatory Skin Condition Acne Vulgaris.

The pathogenesis of degenerative disc disease is a complex and multifactorial process in which genetics, mechanical trauma, altered loading and nutrition present significant etiological factors. Infection of the intervertebral disc with the anaerobic bacterium Propionibacterium acnes is now also emerging as a potentially new etiological factor. This human commensal bacterium is well known for its long association with the inflammatory skin condition acne vulgaris. A key component of inflammatory responses to P. acnes in acne appears to be interleukin (IL)-1β. Similarly, in degenerative disc disease (DDD) there is compelling evidence for the fundamental roles of IL-1β in its pathology. We therefore propose that P. acnes involvement in DDD is biologically very plausible, and that IL-1β is the key inflammatory mechanism driving the host response to P. acnes infection. Since there is a solid theoretical basis for this phenomenon, we further propose that the relationship between P. acnes infection and DDD is causal.

A 2-Year Prospective Cohort Study of Overuse Running Injuries: The Runners and Injury Longitudinal Study (TRAILS)

Background: The National Center for Injury Prevention and Control, noting flaws in previous running injury research, called for more rigorous prospective designs and comprehensive analyses to define the origin of running injuries. Purpose: To determine the risk factors that differentiate recreational runners who remain uninjured from those diagnosed with an overuse running injury during a 2-year observational period. Study Design: Cohort study; Level of evidence, 2. Methods: Inclusion criteria were running a minimum of 5 miles per week and being injury free for at least the past 6 months. Data were collected at baseline on training, medical and injury histories, demographics, anthropometrics, strength, gait biomechanics, and psychosocial variables. Injuries occurring over the 2-year observation period were diagnosed by an orthopaedic surgeon on the basis of predetermined definitions. Results: Of the 300 runners who entered the study, 199 (66%) sustained at least 1 injury, including 73% of women and 62% of men. Of the injured runners, 111 (56%) sustained injuries more than once. In bivariate analyses, significant (P ≤ .05) factors at baseline that predicted injury were as follows: Short Form Health Survey–12 mental component score (lower mental health–related quality of life), Positive and Negative Affect Scale negative affect score (more negative emotions), sex (higher percentage of women were injured), and knee stiffness (greater stiffness was associated with injury); subsequently, knee stiffness was the lone significant predictor of injury (odds ratio = 1.18) in a multivariable analysis. Flexibility, quadriceps angle, arch height, rearfoot motion, strength, footwear, and previous injury were not significant risk factors for injury. Conclusion: The results of this study indicate the following: (1) among recreational runners, women sustain injuries at a higher rate than men; (2) greater knee stiffness, more common in runners with higher body weights (≥80 kg), significantly increases the odds of sustaining an overuse running injury; and (3) contrary to several long-held beliefs, flexibility, arch height, quadriceps angle, rearfoot motion, lower extremity strength, weekly mileage, footwear, and previous injury are not significant etiologic factors across all overuse running injuries.

Prematurity: Epidemiology and Etiological Factors in a Maternity Ward in Dakar (Senegal)

Background: Prematurity is the leading cause of neonatal mortality and morbidity in the world. Several etiological factors contribute to its occurrence requiring identification for effective prevention. The objective of this work was to study the epidemiological and etiological factors of prematurity in the maternity ward of the Grand YOFF General Hospital (GYGH) in Dakar. Methods: This was a prospective study including all live and viable newborns conducted during January 1st to August 31st. They were divided into 2 groups: premature infants (22 WA-36 WA+6 days) and term infants (over 37 WA). Statistical comparisons were based on percentages for the chi-square test or Fisher's exact small sample test. Results: During the study, 501 newborns were collected including 360 term neonates (71.9%) and 141 premature babies (28.1%). The sex ratio was 1.07. Of the premature babies, 48.2% were hypotrophic. There were 13 cases of premature death (9.22%). The occurrence of prematurity was significantly related to educational level, geographic origin and body mass index (BMI). The number of prenatal consultations (PNC) less than 3 was related to a risk of prematurity (p=0.001). Genitourinary infections (p=0.059), high blood pressure (p=0.047), pre-eclampsia (p=0.009), isolated anaemia (p=0.0001) and isolated bleeding (p=0.015) were found as significant etiological factors. Conclusion: In our study, several etiological factors associated with prematurity were identified. Combating these factors is an effective way to prevent prematurity in our low-income countries.

Neonatal Necrotizing Enterocolitis

Neonatal Necrotizing Enterocolitis (NEC) is a highly lethal disease of the newborn infant, which has aroused great interest in the past decades. It is characterized by ischemic necrosis of the intestinal wall, frequently leading to perforation and death. Unlike most neonatal emergencies, it is acquired and can be successfully treated without operation in most cases.The etiology is still obscure and is considered to be multifactorial. Intesti11al ischemia, infections, cow's milk, and hyperosmolar feeding are among the important factors associated with the pathogenesis of NEC in the newborn Many other factors are also related to the occurrence of this disease but some of them are still controversial.The general opinion is that requiring a background of mucosal ischemia and damage; the presence of both intestinal bacteria and enteric feedings appear to be of significant etiologic factors. The important pathologic lesion is the mucosal damage and necrosis involving mostly the ileum and colon exdept the duodenum. Perforations usually occur in the ileocecal region where the intestinal wall is extremely thin.

Lekarz dentysta i lekarz pediatra – współdziałanie w zapobieganiu i wczesnym diagnozowaniu problemów zdrowotnych narządu żucia

The paper points out that in polish population dental and orthodontic prophylaxis is not widely propagated. It indicates the role of pediatricians in parents education of oral health prophylaxis and shows the role of primary health professionals in early detection and prevention of malocclusions and oral defects. In this paper the overall knowledge on dental prophylaxis was systemized. Dental caries and malocclusions are the particular problems concerning small patients. Epidemiological studies showed that the prevalence of malocclusions among polish children and adolescents is around 61.8%. Parafunctions together with dysfunctions and milk tooth early loss are the most common and significant etiological factors of acquired malocclusions. Pediatricians are able to detect many of that bad habits during out patients visits. Prevention is particularly important at the early stage of growing, because this is the time when stomatognatic system is the most susceptible for deformations. Thus, it is worth to remember that oral health is strongly related to general child’s health.