Vacuum-assisted access sheath in supine mini-percutaneous nephrolithotomy (mini-PCNL).

INTRODUCTION: The vacuum-assisted access sheath is a new device for the treatment of kidney stones with percutaneous nephrolithotomy (PCNL). OBJECTIVE: Our aim was to compare the stone-free rate (SFR) and complications between standard mini percutaneous nephrolithotomy (Mini-PCNL) and vacuum-assisted PCNL (Va-PCNL). METHODS: Retrospective study of patients undergoing Mini-PCNL and Va-PCNL from January 2018 to June 2022. Va-PCNL was performed with a disposable sheath (ClearPetra®) with continuous high-flow irrigation and vacuum fluid dynamics for easier stone fragment removal. Baseline patient characteristics, surgical outcomes, perioperative and postoperative data were collected. We compared SFR and complications. RESULTS: A total of 136 patients were identified, 57 (41,9%) underwent Va-PCNL and 79 (58,15%) Mini-PCNL. Mean operative time was significantly shorter in the Va-PCNL group (95 min.) than in Mini-PCNL (146 min; P = ,001) group. The tubeless technique was performed more frequently in Va-PCNL group (61,4% vs. 34,2%; P = ,002). We did not observe any differences in postoperative complications. The mean hospital stay was significantly lower in Va-PCNL with 1,7 ± 1,9 days per patient compared with 2,7 ± 1,5 days in the Mini-PCNL group (P = ,001). There were no differences in SFR at 3 months between Va-PCNL (71,9%) and Mini-PCNL (71,8%; P =v ,848). CONCLUSION: Patients treated with Va-PCNL had comparable results to Mini-PCNL, showing equal SFR with similar infectious complications rates. Potential benefits of Va-PCNL include shorter operative time and postoperative stay.

Cell-specific expression of insulin/insulin-like growth factor-I receptor hybrids in the mouse brain.

Insulin (IR) and insulin-like growth factor I (IGF-IR) receptors share structural homology and can form hybrid heterodimers. While different observations suggest that hybrid receptors are important in physiology and pathology, little is known about their function in the brain. To gain further insight into the role of IR/IGF-IR hybrids in this organ, we analyzed their cellular distribution in the mouse brain. We combined proximity ligation assays (PLA) for IR and IGF-IR, a technique that detects close protein-protein interactions, with immunocytochemistry for brain cell markers to identify IR/IGF-IR hybrids in the major types of brain cells. Intriguingly, while all the types of brain cells analyzed co-express both receptors, only neurons, astroglia, and microglia show readily detectable IR/IGF-IR hybrids. Hybrid PLA signal was negligible in brain endothelial cells and was absent in oligodendrocytes. Hybrids were comparatively more abundant in neurons and peaked after brain development was completed. Cell-specific expression and greater abundance in the adult brain suggests specialized actions of IR/IGF-IR hybrids in this organ, particularly in neurons.

Hippocampal sclerosis induced in mice by a Taenia crassiceps metacestode factor.

An experimental Taenia crassiceps mouse model was used to assess the role of Taenia solium metacestode factor (Fac) in human neurocysticercosis. Intraperitoneal infection with T. crassiceps metacestodes or subcutaneous inoculation with a T. crassiceps metacestode factor (Fac) produced significant impairment of performance (learning) in the Barnes maze and induced bilateral hippocampal sclerosis in mice. Several staining techniques revealed important cell dispersion, extensive apoptosis and cell loss in the dentate gyrus, hilus and CA1-CA3 regions of both hippocampi, as well as intense deterioration of the adjacent cortex. An outstanding disruption of its histoarchitecture in the surrounding tissue of all these regions and apoptosis of the endothelial cells were also observed.

Simultaneous determination of 20 drugs of abuse in oral fluid using ultrasound-assisted dispersive liquid-liquid microextraction.

Drugs of abuse and new psychoactive substances (NPS) for recreational purposes are in constant evolution, and their consumption constitutes a significant risk to public health and road safety. The development of an analytical methodology to confirm the intake of illicit drugs in biological fluids is required for an effective control of these substances. An ultra-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) was developed for simultaneous determination of 10 synthetic cathinones and 10 illicit drugs in oral fluid easily sampled through non-invasive maneuvers. The UPLC-MS/MS method was coupled to an ultrasound-assisted dispersive liquid-liquid microextraction (US-DLLME), which is a miniaturized and inexpensive technique that uses reduced volumes of solvents and samples. The US-DLLME was optimized by using a 213441//18 asymmetric screening design and a Doehlert design. Sample volume, dispersion and extraction solvent volumes, pH, US time, and amount of sodium chloride were evaluated. The US-DLLME-UPLC-MS/MS method was validated according to international guidelines. Limits of quantitation (LOQs) ranged from 0.25 to 5 ng mL-1, and the linear range spanned from LOQ to 500 ng mL-1 with R2 higher than 0.9907, for most of the target drugs. Precision ranged from 1.7 to 14.8 %RSD. Accuracy, i.e., extraction recovery, ranged from 74 to 129%. The proposed method was successfully applied to the analysis of 15 samples from patients on a drug detoxification program.

Insulin Peptides as Mediators of the Impact of Life Style in Alzheimer's disease.

The search for the cause of Alzheimer's disease (AD), that affects millions of people worldwide, is currently one of the most important scientific endeavors from a clinical perspective. There are so many mechanisms proposed, and so disparate changes observed, that it is becoming a challenging task to provide a comprehensive view of possible pathogenic processes in AD. Tauopathy (intracellular neurofibrillary tangles) and amyloidosis (extracellular amyloid plaques) are the anatomical hallmarks of the disease, and the formation of these proteinaceous aggregates in specific brain areas is widely held as the ultimate pathogenic mechanism. However, the triggers of this dysproteostasis process remain unknown. Further, neurofibrillary tangles and plaques may only constitute the last stages of a process of still uncertain origin. Thus, without an established knowledge of its etiology, and no cure in the horizon, prevention - or merely delaying its development, has become a last-resort goal in AD research. As with other success stories in preventive medicine, epidemiological studies have provided basic knowledge of risk factors in AD that may contribute to understand its etiology. Disregarding old age, gender, and ApoE4 genotype as non preventable risk factors, there are diverse life-style traits - many of them closely related to cardiovascular health, that have been associated to AD risk. Most prominent among them are diet, physical and mental activity, exposure to stress, and sleep/wake patterns. We argue that all these life-style factors engage insulinergic pathways that affect brain function, providing a potentially unifying thread for life-style and AD risk. Although further studies are needed to firmly establish a link between faulty insulinergic function and AD, we herein summarize the evidence that this link should be thoroughly considered.

A description of hydroquinone clathrates using molecular dynamics: Molecular model and crystalline structures for CH4 and CO2 guests.

The crystalline structure of hydroquinone clathrates has been studied using molecular dynamics. A flexible non-polarizable all-atom molecular model, based on the original Optimized Potentials for Liquid Simulations force field with recalculated point electric charges, has been used to describe the hydroquinone molecule, and the crystalline solid structure of the α native phase has been analyzed. Then, the ß clathrates have been studied, considering CO2 and CH4 as guest molecules, and also the empty clathrate structure. In all cases, the lattice parameters obtained through molecular simulation show excellent agreement with reported experimental values, showing that the molecular model selected is able to reproduce both the native crystalline phase and also the clathrate structures. In addition, the process of clathrate guest molecule release upon heating has been characterized, and the simulations show a good correspondence with the very recent experimental trends observed for both guest molecules analyzed.

Natural organic matter contained in clay rock pore water: Direct quantification at the molecular level using electrospray ionization mass spectrometry.

RATIONALE: Natural organic matter (NOM) is present in the environment and could influence the migration of heavy metals/radionuclides. The dissolved fraction of NOM (DOM) is usually quantified using total organic carbon analysis or UV-visible spectrometry. Nonetheless, analysis using pattern recognition cannot provide the full spectrum of organic molecules contained in waters, especially low-molecular-weight compounds. In the context of nuclear performance assessment studies, ground waters may contain DOM and a key aspect is to quantify different categories of NOM types in order to further evaluate the transport and fate of radionuclides in the environment. METHODS: Thus, a method for the quantification of DOM at the molecular level was developed, based on electrospray ionization mass spectrometry (ESI-MS). This method simultaneously gives structural information on DOM and the individual concentrations of these low-molecular-weight compounds without pretreatment and/or preconcentration of the samples. RESULTS: Several methods of quantification (internal calibration, calibrated addition of external standard, sequential tandem mass spectrometry) have been optimized and successfully applied to real natural samples. They are discussed in this paper with a focus on acidic compounds, which are the compounds that most probably could influence the migration of heavy metals and radionuclides in the clay rock pore water from the French Callovo-Oxfordian (COx) nuclear repository site. CONCLUSIONS: Quantification of in situ dissolved NOM from the COx has been performed using ESI-MS. For the first time to our knowledge, it was possible to give a quite exhaustive and quantitative inventory of the small organic compounds present without proceeding to any chemical treatment or sample crushing and for naturally occurring concentrations.

Late complications of percutaneous tracheostomy using the balloon dilation technique. / Complicaciones tardías de la traqueotomía percutánea con la modalidad de dilatación con balón.

OBJECTIVE: The purpose of this study was to determine the late complications in critically ill patients requiring percutaneous tracheostomy (PT) using the balloon dilation technique. DESIGN: A prospective, observational cohort study was carried out. SCOPE: Two medical-surgical intensive care units (ICU). PATIENTS: All mechanically ventilated adult patients consecutively admitted to the ICU with an indication of tracheostomy. INTERVENTIONS: All patients underwent PT according to the Ciaglia Blue Dolphin® method, with endoscopic guidance. Survivors were interviewed and evaluated by fiberoptic laryngotracheoscopy and tracheal computed tomography at least 6 months after decannulation. VARIABLES: Intraoperative, postoperative and long-term complications and mortality (in-ICU, in-hospital) were recorded. RESULTS: A total of 114 patients were included. The most frequent perioperative complication was minor bleeding (n=20) and difficult cannula insertion (n=19). Two patients had severe perioperative complications (1.7%) (major bleeding and inability to complete de procedure in one case and false passage and desaturation in the other). All survivors (n=52) were evaluated 211±28 days after decannulation. None of the patients had symptoms. Fiberoptic laryngotracheoscopy and computed tomography showed severe tracheal stenosis (>50%) in 2patients (3.7%), both with a cannulation period of over 100 days. CONCLUSIONS: Percutaneous tracheostomy using the Ciaglia Blue Dolphin® technique with an endoscopic guide is a safe procedure. Severe tracheal stenosis is a late complication which although infrequent, must be taken into account due to its lack of clinical expressiveness. Evaluation should be considered in those tracheostomized critical patients who have been cannulated for a long time.

A fast bioanalytical method based on microextraction by packed sorbent and UPLC-MS/MS for determining new psychoactive substances in oral fluid.

The emergence in recent years of potentially dangerous new psychoactive substances (NPS) that are not under international control has led to the development of multi-analyte procedures for their unequivocal quantification. A fast ultra-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS), in combination with a sample pretreatment based on microextraction by packed sorbent (MEPS), was for the first time used in this work for the simultaneous determination of NPS in oral fluid. This matrix is an effective alternative to typical biological samples for drug control in substitution therapy programs, and also for the prevention and reduction of traffic accidents. The proposed method allowed the separation and quantification of eleven synthetic cathinones, six opiates, scopolamine, cocaine and two metabolites in less than 3.0min by using appropriate isotope-labelled internal standards. The MEPS procedure, which is a miniaturized version of the SPE technique, is completed within 15min. The influence of variables such as the washing solution and eluent volumes, phase type, number of aspirate-dispense cycles and pH was investigated by using a 3441//16 asymmetric screening design and a response surface methodology based on a Doehlert design. The MEPS process performed optimally with a mixed-mode C8/SCX sorbent and a sample pH of 9. The proposed method was validated according to major guidelines and found to span the linear concentration range 0.5-500ngmL-1 (R2 ≥ 0.9903), and to be selective and precise (within- and between-day precision as %RSD were both lower than 13.7%). The accuracy, in terms of analyte extraction recovery, ranged from 75% to 125% for most of the analytes. The MEPS-UPLC-MS/MS method was successfully used to analyse twelve real samples from patients on a drug detoxification programme and proved an effective tool for drug monitoring.

A role for astrocytes in cerebellar deficits in frataxin deficiency: Protection by insulin-like growth factor I.

Inherited neurodegenerative diseases such as Friedreich's ataxia (FRDA), produced by deficiency of the mitochondrial chaperone frataxin (Fxn), shows specific neurological deficits involving different subset of neurons even though deficiency of Fxn is ubiquitous. Because astrocytes are involved in neurodegeneration, we analyzed whether they are also affected by frataxin deficiency and contribute to the disease. We also tested whether insulin-like growth factor I (IGF-I), that has proven effective in increasing frataxin levels both in neurons and in astrocytes, also exerts in vivo protective actions. Using the GFAP promoter expressed by multipotential stem cells during development and mostly by astrocytes in the adult, we ablated Fxn in a time-dependent manner in mice (FGKO mice) and found severe ataxia and early death when Fxn was eliminated during development, but not when deleted in the adult. Analysis of underlying mechanisms revealed that Fxn deficiency elicited growth and survival impairments in developing cerebellar astrocytes, whereas forebrain astrocytes grew normally. A similar time-dependent effect of frataxin deficiency in astrocytes was observed in a fly model. In addition, treatment of FGKO mice with IGF-I improved their motor performance, reduced cerebellar atrophy, and increased survival. These observations indicate that a greater vulnerability of developing cerebellar astrocytes to Fxn deficiency may contribute to cerebellar deficits in this inherited disease. Our data also confirm a therapeutic benefit of IGF-I in early FRDA deficiency.

Analysis of drugs of abuse in human plasma using microextraction by packed sorbents and ultra-high-performance liquid chromatography.

A miniaturized and simple method based on digitally programmed microextraction by packed sorbent (eVol®-MEPS) coupled to ultra-performance liquid chromatography (UPLC) has been developed for quantitative determination of three synthetic cathinones and seven conventional drugs of abuse and metabolites. The influence of several extraction parameters, such as washing and elution solvents were tested. In addition important variables affecting MEPS performance, namely sample volume, sorbent drying time, washing solvent volume, elution volume, number of extraction cycles, sorbent phase and pH, were evaluated using an asymmetrical screening design. The optimal experimental conditions involved 300µL of plasma, loading 10×100µL of sample through a C8/SCX sorbent in a MEPS syringe placed in the semi-automatic eVol® system, washing using 150µL H2O:MeOH (90:10, v/v), drying for 0.5min and elution using 200µL dichloromethane:2-propanol:ammonium hydroxide (78:20:2, v/v/v). The drugs separation was achieved using an ACQUITY BEH Shield RP18 column (2.1mm×100mm×1.7µm) in 3min. Under optimized conditions the proposed method was validated in terms of selectivity, linearity, limits of detection (LOD) and quantitation (LOQ), precision and matrix effect, using standard addition calibration. The combination of MEPS and UPLC provides a method for the primary screening of the analytes in 18min with excellent recoveries at three concentration levels, ranging between 80 and 104% (relative standard deviation <11%). The developed methodology has been successfully applied to plasma samples from polydrug abusers.

Circulating Insulin-Like Growth Factor I Regulates Its Receptor in the Brain of Male Mice.

The role of IGF-1 and its receptor (IGF-1R) in brain pathology is still unclear. Thus, either reduction of IGF-IR or treatment with IGF-1, two apparently opposite actions, has proven beneficial in brain diseases such as Alzheimer's dementia. A possible explanation of this discrepancy is that IGF-1 down-regulates brain IGF-1R levels, as previously seen in a mouse Alzheimer's dementia model. We now explored whether under normal conditions IGF-1 modulates its receptor. We first observed that in vitro, IGF-1 reduced IGF-1R mRNA levels in all types of brain cells including neurons, astrocytes, microglia, endothelial cells, and oligodendrocytes. IGF-1 also inhibited its own expression in neurons and brain endothelium. Next, we analyzed the in vivo actions of IGF-1. Because serum IGF-1 can enter the brain, we injected mice with IGF-1 ip. As soon as 1 hour after the injection, decreased hippocampal IGF-1 levels were observed, followed by increased IGF-1 and IGF-1R mRNAs 6 hours later. Because environmental enrichment (EE) stimulates the entrance of serum IGF-1 into the brain, we analyzed whether a physiological entrance of IGF-1 also produced changes in brain IGF-1R. Stimulation of IGF-1R by EE triggered a gradual decrease in hippocampal IGF-1 levels. After 6 hours of EE exposure, IGF-1 levels reached a significant decrease in parallel with increased IGF-1R expression. After longer times, IGF-1R mRNA levels returned to baseline. Thus, under nonpathological conditions, IGF-1 regulates brain IGF-1R. Because baseline IGF-1R levels are rapidly restored, a tight control of brain IGF-1R expression seems to operate under physiological conditions.

Apoptosis of mouse hippocampal cells induced by Taenia crassiceps metacestode factor.

Seizures, headache, depression and neurological deficits are the signs and symptoms most frequently reported in human neurocysticercosis. However, the cause of the associated learning and memory deficits is unknown. Here, we used Taenia crassiceps infection in mice as a model of human cysticercosis. The effects of T. crassiceps metacestode infection or T. crassiceps metacestode factor (MF) treatment on mouse hippocampal cells were studied; control mice were included. At 45 days after infection or treatment of the mice with MF, all mice were anaesthetized and perfused transcardially with saline followed by phosphate-buffered 10% formalin. Then the brains were carefully removed. Coronal sections stained using several techniques were analysed. Extensive and significant apoptosis was found in the experimental animals, mainly in the dentate gyrus, CA1, CA2, CA3 and neighbouring regions, in comparison with the apparently intact cells from control mice (P < 0.01). These results suggest that neurological deficits, especially the learning and memory deficits, may be generated by extensive apoptosis of hippocampal cells.

A Taenia crassiceps factor induces apoptosis of spleen CD4+T cells and TFG-ß and Foxp3 gene expression in mice.

This study was undertaken to determine whether a parasite substance produces structural pathology in the mouse spleen. A low-molecular-weight Taenia crassiceps metacestode factor (MF) isolated from the peritoneal fluid of female mice infected with T. crassiceps metacestodes induced pathological and immunological changes in mouse spleen cells in vivo. Electron microscopy and confocal microscopy revealed severe changes in the spleen histoarchitecture of T. crassiceps-infected and MF-treated mice. Apoptotic degenerated spleen cells were observed in the white and red pulps and were more conspicuous in the white pulp of the spleen from the T. crassiceps-infected mice than in that of the MF-treated mice. Flow cytometry analysis revealed that the numbers of spleen CD4+T cells were significantly lower in both experimental groups than in control mice. The ex vivo expression of transforming growth factor (TGF)-ß and factor Foxp3 were significantly higher in splenocytes of the experimental mice than the basal expression observed in the control cells. These findings may have potential applications for a better understanding of the host-parasite relationship in human neurocysticercosis.

A Taenia crassiceps metacestode factor enhances ovarian follicle atresia and oocyte degeneration in female mice.

The histopathological effects of Taenia crassiceps infection or T. crassiceps metacestode factor inoculation on the mouse ovary were determined using six female mice in three groups: infected mice, mice inoculated with the metacestode factor and control mice. The control group was subcutaneously inoculated with healthy peritoneal fluid. The infected group was intraperitoneally inoculated with 40 T. crassiceps metacestodes, and the metacestode factor group was subcutaneously inoculated with T. crassiceps metacestode factor (MF). Light and electron microscopy and TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling) assays revealed a significant increase in ovarian follicular atresia (predominantly in antral/preovulatory stages of development), oocyte degeneration (P< 0.05), and a decrease in the amount of corpus luteum in follicles of mice infected and inoculated with MF compared with the control group. Significant abnormalities of the granulosa cells and oocytes of the primordial, primary and secondary ovarian follicles occurred in both treated mouse groups (P< 0.05) compared with no degeneration in the control group. These pathological changes in female mice either infected with T. crassiceps metacestodes or inoculated with T. crassiceps MF may have consequences for ovulation and fertility.

Analysis of drugs of abuse in human plasma by dispersive liquid-liquid microextraction and high-performance liquid chromatography.

Opioids and cocaine are widely used at present, both for recreational purposes and as drugs of abuse. This raises the need to develop new analytical methods specifically designed for the simultaneous detection of several drugs of abuse in biological samples. In this work, dispersive liquid-liquid microextraction (DLLME) was assessed as a new sample treatment for the simultaneous extraction of morphine (MOR), 6-acetylmorphine (6AM), cocaine (COC), benzoylecgonine (BZE) and methadone (MET) from human plasma. Preliminary assays were done before developing an experimental design based on a Uniform Network Doehlert which allowed the optimum extraction conditions to be identified, namely: a volume of extractant solvent (chloroform) and dispersant solvent (acetonitrile) of 220 µl and 3.2 ml, respectively; 0.2 g of NaCl as a salting-out additive; pH 10.6 and ultrasound stirring for 3.5 min. The resulting extracts were analyzed by high-performance liquid chromatography with photodiode array detection (HPLC-PDA), using an XBridge® RP18 column (250 × 4.6 mm i.d., 5 µm particle size). Calibration graphs were linear over the concentration range 0.1-10 µg ml⁻¹, and detection limits ranged from 13.9 to 28.5 ng ml⁻¹. Precision calculated at three different concentration levels in plasma was included in the range 0.1-6.8% RSD. Recoveries of the five drugs were all higher than 84% on average. Finally the proposed method was successfully applied to 22 plasma samples from heroin, cocaine and/or methadone users, and the most frequently detected drug was benzoylecgonine, followed by methadone, cocaine and morphine.

[Percutaneous tracheostomy through dilatation with the Ciaglia Blue Dolphin(®) method]. / Traqueotomía percutánea por dilatación con el método Ciaglia Blue Dolphin(®)

OBJECTIVE: To describe the perioperative and postoperative complications in critically ill patients requiring percutaneous tracheostomy using the Ciaglia Blue Dolphin(®) technique. DESIGN: A prospective, observational, cohort study was carried out. SCOPE: Two medical-surgical Intensive Care Units. PATIENTS: Adult patients subjected to prolonged mechanical ventilation. INTERVENTION: Percutaneous tracheostomy using Ciaglia Blue Dolphin(®) with an endoscopic guide. VARIABLES: Demographic variables, intraoperative and postoperative complications, and Intensive Care Unit and ward mortality were recorded. RESULTS: Seventy patients were included. Age: 68.6 ± 12 years (68.6% males). APACHE II score: 23.5±8.7. Duration of mechanical ventilation prior to percutaneous tracheostomy: 14.3 ± 5.5 days. Perioperative complications were recorded in 25 patients. In 23 of them the complications were mild: difficulty inserting the tracheostomy cannula (n=10), mild bleeding (n=7), partial atelectasis (n=3), cuff leak (n=2), and technical inability to complete the procedure (switch to Ciaglia Blue Rhino(®)) (n=1). Severe complications were recorded in 2 patients: severe bleeding that forced completion of the procedure via surgical tracheostomy (n=1), and false passage with desaturation (n=1). None of the complications proved life-threatening. Eleven complications occurred in the learning curve. As postoperative complications, mild peri-cannula bleeding was seen in 2 patients. CONCLUSIONS: Percutaneous tracheostomy using the Ciaglia Blue Dolphin(®) technique with an endoscopic guide is a safe procedure. As with other procedures, the learning curve contributes to increase the incidence of complications. Potential benefits versus other percutaneous tracheostomy techniques should be explored by randomized trials.

Effect of ageing time on suckling lamb meat quality resulting from different carcass chilling regimes.

The effect of ageing on suckling lamb carcasses subjected to three chilling treatments was studied: Conventional (2 °C for 24h), ultra-fast (-20 °C for 3.5h then 2 °C until 24h post mortem) and slow chilling (12 °C for 7h then 2 °C until 24h post mortem) treatments. Meat quality measurements were carried out in carcasses at 24h post mortem and also after 5 days of ageing. Carcass chilling losses were not affected by a chilling regime. Aged meat showed higher cooking losses than non-aged meat (p<0.05). Sarcomere length of ultra-fast t was shorter (p<0.05) than conventional and conventional was shorter than slow chilling treatment (p<0.05), at 24h and after 5 days of ageing. Conventional and ultra-fast chilling treatments resulted in higher shear force values at 24h post mortem (p<0.05) compared to slow treatment. All treatments improved sensory scores with ageing (p<0.05), but ultra-fast chilling treatment did not attain higher values as the other two treatments.

Osteopontin gene SNPs (rs9138, rs11730582) mediate susceptibility to external root resorption in orthodontic patients.

OBJECTIVE: External apical root resorption (EARR) is a frequent iatrogenic effect of orthodontic treatment. Substantial variability in responses to postorthodontic EARR has been observed among patients even when similar treatment protocols were used. This observation suggests that environmental and/or genetic variations between individuals may confer susceptibility or resistance to developing EARR. The objective of this study is to determine whether variants in the osteopontin gene, an essential mediator in the odontoclast fusion and attachment process, are positively/negatively associated with postorthodontic EARR. MATERIALS AND METHODS: Genetic screening of eighty-seven orthodontic patients was performed for two polymorphisms in the osteopontin gene cluster (rs9138 and rs11730582). Subjects were divided into groups, according to the presence or absence of EARR (>2 mm). Genotype distributions and allelic frequencies were calculated using the chi-square test. Logistic regression analysis was used to assess the extent to which clinical-related parameters interfered with the EARR. Odds ratios (OR) and 95% confidence intervals were also calculated. RESULTS: Data from this study show that subjects heterozygous and homozygous for the most frequent allele of the osteopontin gene at position 89261521 [OR: 0.035 (P = 0.035*) (allele A)] and 89253600 [OR: 0.20 (P = 0.025*) (allele T)], respectively, are protected against postorthodontic EARR. Nevertheless, a highly significant association was found in the comparative analysis of homozygous subjects [2/2 (CC)] for the osteopontin gene (rs9138), resulting in an increased risk of suffering postorthodontic EARR[OR: 4.10; P = 0.045*; CI: 95%]. Subjects who were homozygous [2/2 (CC)] for the osteopontin gene (rs11730582) were more likely, and to a greater extent, to be affected with EARR [OR: 11.68; P < 0.039*; CI: 95%] compared with other genotypes. CONCLUSION: Variations in the osteopontin gene (rs9138 and rs11730582) are determinants of a genetic predisposition to suffer EARR secondary to orthodontic treatment.