Effects of antibiotics on the developing enamel in neonatal mice

Purpose Identifying factors causing Molar-Incisor Hypomineralization (MIH) is an ongoing challenge. Preterm infants, routinely treated with antibiotics in cases of suspected sepsis, are more commonly afected by dental developmental defects. This study aimed to investigate the efects of gentamycin and ampicillin on the developing enamel in neonatal CD-1 mice in vivo. Methods Neonatal mice were randomized into a study (n=36) and a control (n=35) group. Antibiotics were injected intravenously for 4 days. All mice were sacrifced after 15–18 days. Micro-CT was used to analyse the mineral density (MD) of the enamel and the proportion of the enamel object volume (vol%) in frst molars and incisors. Results We demonstrated a signifcantly lower vol% enamel in the maxillary (30.9% vs. 32.7%; p=0.004) and mandibular (32.5% vs. 34.6%; p=0.015) molars in the study group than in the controls. The incisors were divided into segments upon analysis. We demonstrated both lower vol% and lower MD of the enamel in most segments in treated individuals compared to controls (p Conclusion The reduced MD and vol% in the molars and incisors are likely to have been caused by the antibiotics given during tooth development. The presented analysis of teeth in neonatal mice with micro-CT could be a valid model for further research on dental developmental defects

LEAN concept – possibilities of implementation and improvement of business processes in public healthcare organizations

Uvod: Osnovni je postulat lean koncepta da se veća efikasnost procesa rada može postići kroz proces kontinuiranog poboljšanja. To znači eliminiranje otpada i maksimiziranje aktivnosti koje dodaju vrijednost. Zdravstveni sustavi u Nizozemskoj, Velikoj Britaniji, Italiji i Sjedinjenim Američkim Državama implementirali su lean koncept. Cilj rada: Ispitati mišljenje zdravstvenih radnika javne bolnice na području Sarajeva o mogućnostima unaprjeđenja poslovnih procesa implementacijom lean koncepta. Metoda: Istraživanje je provedeno kao presječna studija u javnoj bolnici na području Sarajeva. Upitnik je poslane-poštom zdravstvenim radnicima. Obuhvaćen je 91 ispitanik oba spola (doktori medicine, specijalizanti, diplomirane medicinske sestre, medicinske sestre i administrativno osoblje). Rezultati: Utvrđena je pozitivna korelacija stavova o efektivnosti i efikasnosti poslovnih procesa. Prema mišljenju ispitanika, veća efektivnost poslovnih procesa pridonosi većoj efikasnosti (r = 0,846; p < 0,05). Spearmanov koeficijent rs = 0,81 pokazuje jaku povezanost efektivnosti i efikasnosti poslovnih procesa. Zaključak: Istraživanje je pokazalo da postoji pozitivan stav o utjecaju lean koncepta na poboljšanje učinkovitosti poslovnih procesa. Očekivani pozitivni učinciimplementacije lean koncepta manifestiraju se kroz: brže pružanje usluge pacijentima, smanjivanje vremena čekanja usluge i generalno poboljšanje poslovnih procesa.Introduction: The basic postulate of the lean concept is that greater efficiency of the work process can be achieved through a process of continuous improvement, which aims to eliminate waste and maximize activities that add value.The Netherlands, Great Britain, Italy and the United States were examples of healthcare systems that implemented the lean concept. Aim: To examine the opinion of health workers of a public hospitals in the Sarajevo area about the possibilities of improving business processes by implementing the lean concept. Method: The cross-sectional study was conducted using a questionnaire. The questionnaire was sent to the e-mail addresses of health workers of public health organizations. 91 respondents of both sexes (doctors of medicine, residents, registered nurses, nurses and administrative staff) were included. Results: A positive correlation was establishedin the attitude toward the effectiveness and efficiency of business processes. According to the participant’s opinion, the greater effectiveness of business processes contributes to greater efficiency (r=0.846; p<0,05). Spearman’s coefficient rs=0.81 shows a strong connection between the effectiveness and efficiency of business processes. Conclusion: The study showed that there is a positive attitude towards the impact of the lean concept on improving the efficiency of business processes. The reducexpected positive effects of the implementation of the lean concept are manifested through faster provision of services to patients, reduction of service waiting times and general improvement of business processes

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The Three Paralogous MicroRNA Clusters in Development and Disease - miR-17-92, miR-106a-363, and miR-106b-25

MicroRNAs (miRNAs) form a class of noncoding RNA genes whose products are small single-stranded RNAs that are involved in the regulation of translation and degradation of mRNAs. There is a fine balance between deregulation of normal developmental programs and tumor genesis. An increasing body of evidence suggests that altered expression of miRNAs is entailed in the pathogenesis of human cancers. Studies in mouse and human cells have identified the miR-17-92 cluster as a potential oncogene. The miR-17-92 cluster is often amplified or overexpressed in human cancers and has recently emerged as the prototypical oncogenic polycistron miRNA. The functional analysis of miR-17-92 is intricate by the existence of two paralogues: miR-106a-363 and miR-106b-25. During early evolution of vertebrates, it is likely that the three clusters commenced via a series of duplication and deletion occurrences. As miR-106a-363 and miR-106b-25 contain miRNAs that are very similar, and in some cases identical, to those encoded by miR-17-92, it is feasible that they regulate a similar set of genes and have overlapping functions. Further understanding of these three clusters and their functions will increase our knowledge about cancer progression. The present review discusses the characteristics and functions of these three miRNA cluster

Pre-Clinical Cell-Based Therapy for Limbal Stem Cell Deficiency

The cornea is essential for normal vision by maintaining transparency for light transmission. Limbal stem cells, which reside in the corneal periphery, contribute to the homeostasis of the corneal epithelium. Any damage or disease affecting the function of these cells may result in limbal stem cell deficiency (LSCD). The condition may result in both severe pain and blindness. Transplantation of ex vivo cultured cells onto the cornea is most often an effective therapeutic strategy for LSCD. The use of ex vivo cultured limbal epithelial cells (LEC), oral mucosal epithelial cells, and conjunctival epithelial cells to treat LSCD has been explored in humans. The present review focuses on the current state of knowledge of the many other cell-based therapies of LSCD that have so far exclusively been explored in animal models as there is currently no consensus on the best cell type for treating LSCD. Major findings of all these studies with special emphasis on substrates for culture and transplantation are systematically presented and discussed. Among the many potential cell types that still have not been used clinically, we conclude that two easily accessible autologous sources, epidermal stem cells and hair follicle-derived stem cells, are particularly strong candidates for future clinical trials

Therapeutic Strategies for Dry Mouth Management with Emphasis on Electrostimulation as a Treatment Option

Objectives. Xerostomia is a subjective sensation of dry mouth. It is commonly associated with salivary gland hypofunction. Both changes in the composition of the saliva and a reduction in the quantity secreted may be an objective finding of dry mouth. Although there are no currently available cures for the conditions resulting in dry mouth, there are several treatment options that give hope for patients who suffer from xerostomia. Individuals with some residual salivary gland function, which are contraindicated to pharmacological therapies, would benefit the most from identifying novel, alternative effective methods for stimulating production of saliva. The aim of this study was to give an overview of the latest and most relevant data related to treatment modalities for the management of dry mouth conditions. Data Resources and Study Selection. The present review was prepared by searching the National Library of Medicine database using the relevant medical terms and their combinations. A total of thirty-three studies met the inclusion criteria. Data were extracted by one author and verified by another. Conclusion. A number of patients showed positive treatment outcomes, and the adverse effects of both electrical stimulation (ES) and acupuncture have been reported as mild and transient. In patients who have undergone radiotherapy, acupuncture is shown to increase salivation. However, in patients with Sjogren’s syndrome, the effects of ES devices seem to be elusive. Moreover, due to the instability of the findings in relation to longevity of clinical effect, patient satisfaction, quality of life, and clinical effectiveness of such treatments, the results remain vague

Culture of Oral Mucosal Epithelial Cells for the Purpose of Treating Limbal Stem Cell Deficiency

The cornea is critical for normal vision as it allows allowing light transmission to the retina. The corneal epithelium is renewed by limbal epithelial cells (LEC), which are located in the periphery of the cornea, the limbus. Damage or disease involving LEC may lead to various clinical presentations of limbal stem cell deficiency (LSCD). Both severe pain and blindness may result. Transplantation of cultured autologous oral mucosal epithelial cell sheet (CAOMECS) represents the first use of a cultured non-limbal autologous cell type to treat this disease. Among non-limbal cell types, CAOMECS and conjunctival epithelial cells are the only laboratory cultured cell sources that have been explored in humans. Thus far, the expression of p63 is the only predictor of clinical outcome following transplantation to correct LSCD. The optimal culture method and substrate for CAOMECS is not established. The present review focuses on cell culture methods, with particular emphasis on substrates. Most culture protocols for CAOMECS used amniotic membrane as a substrate and included the xenogeneic components fetal bovine serum and murine 3T3 fibroblasts. However, it has been demonstrated that tissue-engineered epithelial cell sheet grafts can be successfully fabricated using temperature-responsive culture surfaces and autologous serum. In the studies using different substrates for culture of CAOMECS, the quantitative expression of p63 was generally poorly reported; thus, more research is warranted with quantification of phenotypic data. Further research is required to develop a culture system for CAOMECS that mimics the natural environment of oral/limbal/corneal epithelial cells without the need for undefined foreign materials such as serum and feeder cells

Genetic Aspects of Dental Erosive Wear and Dental Caries

Objectives. The present review aims to give an overview of the literature focusing on novel genetic aspects of dental erosion and dental caries. Once the tooth erupts into the oral cavity, the regenerative capability of enamel is fundamentally limited due to the loss of dental epithelium during eruption. The susceptibility or resistance to dental erosion and caries is presumably a result of environmental, phenotypic, and/or genetic influence. Even though it is evident that individuals frequently exposing their teeth to acid and sugar are at high risk of developing dental erosion and caries, the findings exclusively based on these factors are elusive. Data resources and study selection. The present review was based on data collected from the National Library of Medicine database with different combinations of the following terms: “tooth,” “dental,” “dentin,” “enamel,” “erosion,” “erosive wear,” “caries,” “decay,” “gene,” and “genetic.” A total of forty-six studies met the inclusion criteria. Data were extracted by one reviewer and verified by another. Conclusion. The high prevalence of erosion and caries among certain groups, and observations that not all individuals appearing to be at risk develop these lesions, has sparked research on identifying genetic effects to these conditions. A connection of genome-wide and candidate gene studies has increased considerably in the literature. This review reveals largely varying success among studies, demonstrating the difficulties of developing the study with adequate sample sizes and durable phenotype definitions that permit enough statistical power to identify genetic contributors

Five-minute Apgar score ≤ 5 and molar incisor hypomineralisation (MIH) - a case control study

Background: The aetiology of molar incisor hypomineralisation (MIH) is unclear. The asymmetric distribution of MIH in the dentition may indicate that an insult of short duration that affects ameloblasts at a vulnerable stage could be a causative factor. Apgar ≤ 5 at 5 min may indicate asphyxia (hypoxic-ischemic insult) during birth. It was hypnotised that low Apgar score during birth may cause MIH. The present study aimed to examine a possible association between Apgar ≤ 5 at 5 min and the occurrence of MIH. Method: Two study groups were selected for examination. The cases comprised 67 children aged 8–10 years born with Apgar score equal to or below 5 after 5 min. The control group comprised 157 age-matched healthy children. First permanent molars, second primary molars and all permanent incisors were examined in all children. Clinical examination was undertaken by two calibrated examiners and intraoral close-up photographs of the teeth were later evaluated by three calibrated and blinded clinicians. Demarcated opacities, post-eruptive breakdown, atypical restorations and extractions due to MIH, according to the criteria of the European Association of Paediatric Dentistry, were assessed. Results: The prevalence of MIH did not differ between the two groups. A chi-square test failed to confirm any statistically significant relationship between 5-min Apgar scores and MIH occurrence. In addition, there was no statistically significant relationship between the number of affected first permanent molars in cases and controls. Conclusion: There was no association between Apgar ≤ 5 at 5 min and the occurrence of MIH