Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice.

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases that represent ends of the spectrum of a single disease. The most common genetic cause of FTD and ALS is a hexanucleotide repeat expansion in the C9orf72 gene. Although epidemiological data suggest that traumatic brain injury (TBI) represents a risk factor for FTD and ALS, its role in exacerbating disease onset and course remains unclear. To explore the interplay between traumatic brain injury and genetic risk in the induction of FTD/ALS pathology we combined a mild repetitive traumatic brain injury paradigm with an established bacterial artificial chromosome transgenic C9orf72 (C9BAC) mouse model without an overt motor phenotype or neurodegeneration. We assessed 8-10 week-old littermate C9BACtg/tg (n = 21), C9BACtg/- (n = 20) and non-transgenic (n = 21) mice of both sexes for the presence of behavioural deficits and cerebral histopathology at 12 months after repetitive TBI. Repetitive TBI did not affect body weight gain, general neurological deficit severity, nor survival over the 12-month observation period and there was no difference in rotarod performance, object recognition, social interaction and acoustic characteristics of ultrasonic vocalizations of C9BAC mice subjected to repetitive TBI versus sham injury. However, we found that repetitive TBI increased the time to the return of the righting reflex, reduced grip force, altered sociability behaviours and attenuated ultrasonic call emissions during social interactions in C9BAC mice. Strikingly, we found that repetitive TBI caused widespread microglial activation and reduced neuronal density that was associated with loss of histological markers of axonal and synaptic integrity as well as profound neuronal transactive response DNA binding protein 43 kDa mislocalization in the cerebral cortex of C9BAC mice at 12 months; this was not observed in non-transgenic repetitive TBI and C9BAC sham mice. Our data indicate that repetitive TBI can be an environmental risk factor that is sufficient to trigger FTD/ALS-associated neuropathology and behavioural deficits, but not paralysis, in mice carrying a C9orf72 hexanucleotide repeat expansion.

Association between T wave morphology parameters and abnormal cardiac SPECT imaging.

BACKGROUND: T-wave morphology dispersion (TMD) described the electrocardiographic T-wave heterogeneity during a single cardiac cycle. Total cosine R-to-T (TCRT) is the average of the cosines of the angles between the QRS and T vectors on the ECG. We examine the predictive value of TMD and TCRT calculation to assess abnormal myocardial perfusion. METHODS: Retrospective single center cohort study including all patients referred for evaluation of ischemia by myocardial SPECT scanning with no known history of ischemic heart disease, from 1 January 2019 to 31 December 2019. Study endpoint was the correlation between the calculated TMD and TCRT values and detection of myocardial injury or ischemia by myocardial SPECT. RESULTS: Among 606 patients, calculated TCRT was 0.401 ± 0.53 for the normal group and 0.283 ± 0.62 for the abnormal group (p = 0.007). Measured TMD was 22.9 ± 16.6 degrees (p < 0.001) in the normal group, compared to 31.5 ± 22.8 degrees (p < 0.001) for the abnormal group. CONCLUSIONS: The results demonstrate a correlation between the decreased TCRT values and increase TMD and myocardial ischemia seen in SPECT results. The TCRT and TMD can be used as simple and non-invasive markers to predict abnormal SPECT results and ischemic heart disease in patients with no known cardiac history.

Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration.

Arf4 is proposed to be a critical regulator of membrane protein trafficking in early secretory pathway. More recently, Arf4 was also implicated in regulating ciliary trafficking, however, this has not been comprehensively tested in vivo. To directly address Arf4's role in ciliary transport, we deleted Arf4 specifically in either rod photoreceptor cells, kidney, or globally during the early postnatal period. Arf4 deletion in photoreceptors did not cause protein mislocalization or retinal degeneration, as expected if Arf4 played a role in protein transport to the ciliary outer segment. Likewise, Arf4 deletion in kidney did not cause cystic disease, as expected if Arf4 were involved in general ciliary trafficking. In contrast, global Arf4 deletion in the early postnatal period resulted in growth restriction, severe pancreatic degeneration and early death. These findings are consistent with Arf4 playing a critical role in endomembrane trafficking, particularly in the pancreas, but not in ciliary function.

Evaluation of the Best Method for Orthodontic Correction of Skeletal Deep Bites in Growing Patients: A Systematic Review.

This review aimed to evaluate the currently available evidence regarding the best method of correcting deep bites in growing patients. In September 2023, a search was conducted electronically across the following databases: PubMed®, Web of Science™, Scopus®, Embase®, Google™ Scholar, and Cochrane Library. In this systematic review, randomized control trials (RCTs), controlled clinical trials (CCTs), and cohort studies of growing patients with deep bite malocclusion who received treatment with the primary objective of treating the deep bite were included. Risk of bias of the included studies was assessed using two different tools; one tool was applied for RCTs and the other one for the CCTs and cohort studies. One RCT, one CCT, and one cohort study were included (85 patients). The flat fixed acrylic bite plane was superior in terms of duration of treatment when compared to the inclined fixed acrylic bite plane and the utility arch with posterior intermaxillary elastics. Limited evidence indicates that the inclined fixed acrylic bite plane causes a significant increase in the lower incisor inclination and a significant increase in the angle between the mandible and the anterior cranial base (SNB). However, limited evidence indicates that the utility arch with posterior intermaxillary elastics causes a significant decrease in the angle between the maxilla and the anterior cranial base (SNA). Regarding the vertical skeletal changes, it was found that the three methods were comparable; in each case, the vertical dimension of the face increased because of a significant increase in the lower first molar height. There is a need for further studies to strengthen the evidence of the treatment efficacy of the employed methods, with more RCTs to be conducted in this regard.

Patient-reported outcomes during accelerating the en-masse retraction of the upper anterior teeth using low-intensity electrical stimulation: a randomized controlled trial.

BACKGROUND: Low-intensity electrical stimulation (LIES) is considered a relatively recent technology that has received little attention in orthodontics as a method of acceleration. This study aimed to evaluate patient-reported outcome measures when LIES is used to accelerate the en-masse retraction of the upper anterior teeth. MATERIALS AND METHODS: The sample consisted of 40 patients (8 males, 32 females; mean age 21.1 ± 2.3 years), with Class II division I malocclusion who required extraction of the first premolars to retract upper anterior teeth. They were randomly assigned to the LIES group (n = 20) and the conventional en-masse retraction group (CER; n = 20). Patient responses regarding pain, discomfort, burning sensation, swelling, chewing difficulty, speech difficulty, and painkillers' consumption were recorded at these nine assessment times: 24 h (T1), 3 days (T2), and 7 days (T3) after force application, then in the second month after 24 h (T4), 3 days (T5), and 7 days (T6) of force re-activation, and finally after 24 h (T7), 3 days (T8), and 7 days (T9) of force re-activation in the third month. RESULTS: The mean values of pain perception were smaller in the LIES group than those in the CER group at all assessment times with no statistically significant differences between the two groups except during the second and third months (T5, T6, T8, and T9; P < 0.005). However, discomfort mean values were greater in the LIES group with significant differences compared to CER group during the first week of the follow-up only (T1, T2, and T3; P < 0.005). Burning sensation levels were very mild in the LIES group, with significant differences between the two groups at T1 and T2 only (P < 0.001). Speech difficulty was significantly greater in the LIES group compared to CER group at all studied times (P < 0.001). High levels of satisfaction and acceptance were reported in both groups, without any significant difference. CONCLUSION: Both the LIES-based acceleration of en-masse retraction of upper anterior teeth and the conventional retraction were accompanied by mild to moderate pain, discomfort, and chewing difficulty on the first day of retraction. These sensations gradually decreased and almost disappeared over a week after force application or re-activation. TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov, NCT05920525. Registered 17 June 2023 - retrospectively registered, http://clinicaltrials.gov/study/NCT05920525?term=NCT05920525&rank=1 .

Evaluation of the External Soft Tissue Changes Following the Correction of Class II Skeletal Malocclusion in the Adolescence Period Using Removable and Fixed Functional Appliances: A Systematic Review and Meta-Analysis.

In this systematic review, we aimed to assess the current evidence regarding the effectiveness of functional treatment with both removable and fixed appliances to normalize the external soft tissue for skeletal class II adolescent individuals. We performed a broad electronic search to retrieve relevant studies from nine databases to identify randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that investigated soft tissue changes following functional treatment and evaluated the changes using 2D lateral cephalometric radiographs and 3D-optical surface laser scanning. A total of three RCTs and eight CCTs were included. Ages ranged from 11 to 16 years with the fixed functional appliances, and from eight to 12 years with the removable ones, including 689 skeletal class II patients. Version 2 of Cochran's risk-of-bias (RoB2), and the risk of bias in non-randomized studies of interventions (ROBIN-I) were used to assess the risk of bias for the included papers. Of the 11 eligible studies, three studies were included in the meta-analysis to assess the upper and lower lip position in relation to the E-line (Ricketts's aesthetic line) in addition to the nasolabial angle. The meta-analysis showed that the upper lip retracted after functional treatment with Twin-block in relation to E-line (mean difference (MD) = -1.93; 95% CI: -2.37, -1.50; p < 0.00001; χ² = 5.43; p = 0.07; I2 = 63%), while the lower lip position did not change after functional treatment with Twin-block in relation to E-line (MD = 0.03; 95% CI: -0.56, 0.61; p = 0.92; χ² = 1.74; p = 0.42; I2 = 0%). The nasolabial angle increased after Twin-block treatment (MD = 5.75; 95% CI: 4.57, 6.93; p < 0.00001; χ² = 6.77; p = 0.03; I2 = 70%). The mentolabial angle and Z-angle also increased after functional therapy, where the facial convexity angle decreased, regardless of the functional devices used. On the other hand, using the 3D-optical surface laser scanning showed that the upper lip length and the commissural width did not change following therapy, but the lower lip increased in length, as well as the total face height. More high-quality RCTs are required to obtain accurate evidence in this field.

Evaluation of Three-Dimensional Digital Models Formulated From Direct Intra-oral Scanning of Dental Arches in Comparison With Extra-oral Scanning of Poured Dental Models in Terms of Dimensional Accuracy and Reliability.

BACKGROUND: The study's objective was to assess the dimensional accuracy and reliability of dental digital models prepared by direct intraoral scanning and indirect scanning of the plaster models compared to the plaster models as the gold standard. MATERIALS AND METHODS: This study included 20 patients. Nine had a class I malocclusion, seven had a class II malocclusion, and four had a class III malocclusion. Intraoral scanning was done for the upper and lower arches of all the patients enrolled in this study using an intraoral scanner (i700; Medit, Seoul, Korea). The next step was preparing the plaster model for the control group. Addition-silicone impressions were taken for each patient's arches. The impressions were poured according to American Board of Orthodontics (ABO) standards. Finally, the digital models of the indirect scanning group were prepared using a 3D desktop scanner (T710; Medit). In total, 26 measurements were made on the plaster and digital models. Paired t-tests were used to test for significant differences between the studied groups. The reliability of the studied techniques was tested using intraclass correlation coefficients (ICCs). Because of the multiple comparisons, the ɑ level was adjusted and set at 0.002. RESULTS: No significant differences were found between the intraoral scanning group (20 patients) and the plaster models group (20 patients; P>0.002). The ICCs ranged from 0.814 to 0.993, indicating excellent agreement between the direct digital and traditional plaster models. There were no significant differences between the digital and original plaster models (P>0.002). ICCs ranged from 0.834 to 0.995, indicating excellent agreement between the indirect digital and original plaster models. No significant differences were detected between the direct and indirect digital models (P>0.002). ICCs ranged between 0.813 and 0.999, indicating excellent agreement between direct and indirect digital models. CONCLUSION: Both direct and indirect scanning techniques are accurate and reliable for digital model preparation and can be considered an alternative to traditional plaster models used in clinical orthodontics diagnostic applications. The intraoral scanning technique can be considered a valid alternative for indirect scanning of the plaster models to prepare digital working models during the digital design and fabrication of orthodontic appliances such as clear aligners.

Estimating the unit costs of public hospitals and primary healthcare centers.

BACKGROUND: Many factors have affected the rise of health expenditures, such as high-cost medical technologies, changes in disease patterns and increasing demand for health services. All countries allocate a significant portion of resources to the health sector. In 2008, the gross domestic product of Palestine was estimated to be at $6.108bn (current price) or about $1697 per capita. Health expenditures are estimated at 15.6% of the gross domestic product, almost as much as those of Germany, Japan and other developed countries. The numbers of hospitals, hospital beds and primary healthcare centers in the country have all increased. The Ministry of Health (MOH) currently operates 27 of 76 hospitals, with a total of 3074 beds, which represent 61% of total beds of all hospitals in the Palestinian Authorities area. Also, the MOH is operating 453 of 706 Primary Health Care facilities. By 2007, about 40 000 people were employed in different sectors of the health system, with 33% employed by the MOH. AIM: This purpose of this study was to develop a financing strategy to help cover some or all of the costs involved in operating such institutions and to estimate the unit cost of primary and secondary programs and departments. METHODS: A retrospective study was carried out on data from government hospitals and primary healthcare centers to identify and analyze the costs and output (patient-related services) and to estimate the unit cost of health services provided by hospitals and PHCs during the year 2008. All operating costs are assigned and allocated to the departments at MOH hospitals and primary health care centers (PPHCs) and are identified as overhead departments, intermediate-service and final-service departments. Intermediate-service departments provide procedures and services to patients in the final-service departments. The costs of the overhead departments are distributed to the intermediate-service and final-service departments through a step-down method, according to allocation criteria devised to resemble as closely as possible the actual use of resources by each of the departments. The data were analyzed using spss. Data cleaning was carried out by cross-validating the results through conducting cross-tabulations between the hospital/center and section/program to identify errors from the data collection or entry process. Depreciation of assets and the consumption of capital costs are ignored in this study, as it is difficult to evaluate the MOH facilities owing to a lack of recording of depreciation of assets or other costs of servicing capital assets. RESULTS: Inpatient costs contributed about 75% of all costs, whereas outpatient services contributed the remaining 25% of total costs. The average cost per visit was $13.00 for outpatient departments, whereas the average cost per patient day for inpatient departments was $90.00. As for the unit cost for each department, intensive care unit and intermediate care unit services were the highest among all categories of daily hospital services ($208.00). This is in contrast to surgical operations ($124.00), specialized surgeries ($106.00), delivery department ($99.00), orthopedics ($98.50) and general surgery ($85.00). The lowest unit cost was found in the neonatology department ($72.00). In PHCs, the unit cost per visit was highest for psychiatry programs ($26.00), followed by other programs ($21.50), chronic diseases ($21.00), maternal and child health ($11.50), preventive programs ($9.00) and general medicine ($6.50). The exchange rate listed by The Wall Street Journal as of Wednesday August 25, 2010 is 1 US dollar = 3.82 new Israeli shekel (NIS). CONCLUSION: The findings have implications for policy and decision making in the health sector in Palestine concerning the cost of services provided by hospitals and PHCs. The availability of a standardized data set for cost assessment would greatly enhance and improve the quality of financial information as well as efficiency in the use of scarce resources.

Treatment Effectiveness of Clear Aligners in Correcting Complicated and Severe Malocclusion Cases Compared to Fixed Orthodontic Appliances: A Systematic Review.

This systematic review aimed to critically assess the available evidence regarding the effectiveness and efficiency of clear aligners in the comprehensive treatment of complex cases accompanied by premolars extraction. An electronic literature search by two reviewers was independently done on 27 February 2023 in the following databases without time and language limitations: Pubmed®, Scoups®, Google Scholar, Cochrane Library database, Web of Science™, and Proquest Database Open. Randomized controlled trials (RCTs) of any type, non-randomized clinical trials (CCT), cohort studies, and prospective, retrospective, and cross-sectional studies were reviewed. The risk of bias in included studies was assessed using the Risk of Bias (RoB 2.0) tool for randomized trials and the Risk of Bias in Non-randomized Studies (ROBINS-I) tool for non-randomized studies. After carefully searching the literature, six trials were included in this systematic review, three RCTs, two retrospective cohort studies, and one CCT. Two hundred eighty-three patients were included (186 females, 97 males). Three studies found that there were no differences between the clear aligners and fixed appliances when evaluations were done using the American Board of Orthodontists Objective Grading System (ABO-OGS) or the Peer Assessment Rating (PAR) index. Two studies found that there were some differences between predicted and achieved tooth movements when clear aligners were used in premolars extraction cases. Based on the included studies, the duration of treatment was shorter with fixed appliances than the clear aligners when applied to orthodontic extraction cases. Both clear aligners and fixed appliances were found effective in the orthodontic treatment of premolar extraction-based cases. Fixed appliances have the advantage of achieving better buccolingual inclination and occlusal contacts in a shorter treatment duration. Treatment with clear aligners might be associated with differences between predicted and achieved tooth movements. Therefore, the characteristics of these techniques should be considered when making a treatment decision.

Treatment effectiveness of young adults using clear aligners versus buccal fixed appliances in class I malocclusion with first premolar extraction using the ABO-Objective Grading System: A randomized controlled clinical trial.

OBJECTIVE: To compare the effectiveness of the clear aligners with the traditional fixed appliances in the treatment of premolars extraction complex cases using the American Board of Orthodontics Objective Grading System (ABO-OGS). MATERIAL AND METHODS: A single-centre, 2-parallel groups RCT with two arms. Forty severe crowding patients (14 males, 26 females; mean age: 21.40±2.42) who required four first premolars extraction were included and randomly allocated into two treatment groups: clear aligners therapy group (CAT), and fixed appliances therapy group (FAT). Cases complexities were measured on pre-treatment records using the Discrepancy index (DI). Post-treatment records were evaluated using the American Board of Orthodontics Objective Grading System (ABO-OGS). Two sample t-tests and Fisher's Exact tests were used to test for significant differences between the two groups. The statistical significance was set at P < 0.006 using Bonferroni's correction. RESULTS: For the DI, the mean scores were 32.25 (± 4.33) in the CAT group and 33 (± 7.92) in the FAT group. In the CAT group, the total OGS score ranged between 6-33 points with an average of 17.50(± 7.41), whereas the total score in the FAT group went between 4-30 points with an average of 12.89 (± 6.31) with no significant differences between the two groups (P=0.05). When comparison of the successful cases between the two groups was made, 11 cases received passing scores, and 9 cases received failing scores in the CAT group. Whereas in the FAT group, 17 cases received passing scores, and 3 received a failing score. No statistically significant differences were found in the passing rates between of the CAT and FAT groups (P = 0.421). CONCLUSIONS: According to the ABO-OGS total scores, there was no significant difference between the clear aligners and fixed appliances in the treatment of class I severe crowding cases with first premolars extraction in young adults. There were no differences between the two techniques in the OGS components scores except for the occlusal contacts, which were significantly better with the fixed appliances. When comparing the number of successful and failed cases between the two groups, no significant differences were noted, with the fixed appliances having a 30% higher success rate than the clear aligners, which must be considered clinically when choosing between these two techniques in the complex orthodontic cases treatment.

Effectiveness of Flapless Cortico-Alveolar Perforations Using Mechanical Drills Versus Traditional Corticotomy on the Retraction of Maxillary Canines in Class II Division 1 Malocclusion: A Three-Arm Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVES: Both invasive and minimally invasive surgical methods have recently gained popularity in accelerating orthodontic tooth movement. Traditional corticotomy (TC) was one of the first effective invasive surgical techniques in shortening orthodontic treatment time, whereas the flapless cortico-alveolar perforations (FCAPs) technique is a modern minimally invasive method that has recently shown good results in different types of orthodontic tooth movement. Therefore, this study aimed to compare the effectiveness of TC versus FCAPs in maxillary canine retraction when treating Class II division 1 malocclusion patients. MATERIALS AND METHODS: This was a single-blinded, single-center, three-arm randomized controlled trial. A total of 51 patients (22 males, 29 females, mean age 20.98 ± 1.95) whose treatment planning included the extraction of maxillary first premolars were enrolled and randomly divided into three groups: the TC group, the FCAPs group, and the control group. The assessed outcomes were the amount of canine retraction, anchorage loss, and canines' rotation, which was evaluated at five-time points till the completion of canine retraction. RESULTS: There were statistically significant differences in the amount of canine retraction between the three groups in the first two months (p < 0.001), with greater mean values in the TC group (p < 0.001) in the first month. However, the amount of canine retraction in the FCAPs group was significantly greater in the second month compared to the TC group (p = 0.003) and the control group (p < 0.001). In the first month of canine retraction, anchorage loss, and canine rotation were significantly lesser in the TC and FCAPs groups than in the control group (p < 0.001). On the contrary, the canines' rotation amount after the completion of retraction was greater in the TC group than in the other two groups (p < 0.001). CONCLUSION: TC and FCAPs are efficient adjunctive surgical methods for accelerating canine retraction. At the end of the first month, the TC accelerated canine retraction by 59.85% and FCAPs by 44% compared to the conventional retraction. At the end of the second month, the acceleration was less than recorded in the first month (35.44% and 50.20%, respectively). The acceleration effect of the surgical interventions appeared transient and did not last in the following observation period.

Evaluation of the Impact of Orthodontic Treatment on Patients' Self-Esteem: A Systematic Review.

Malocclusion may affect interpersonal relationships, self-esteem (SE), and psychological well-being, weakening patients' psychological and social activities. Several studies investigated the effect of orthodontic treatment on these social and psychological aspects, such as SE. However, the direct relationship between SE and orthodontic treatment has not yet been confirmed. This systematic review aimed to evaluate the existing evidence in the literature concerning the influences of orthodontic treatment on patients' SE systematically and critically. An electronic search in the following databases was done in September 2022: PubMed®, Web of Science™, Scopus®, Embase®, GoogleTM Scholar, Cochrane Library databases, Trip, and OpenGrey. Then, the reference list of each candidate study was checked for any potentially linked papers that the electronic search might not have turned up. Inclusion criteria were set according to the population/intervention/comparison/outcome/study design (PICOS) framework. For the data collection and analysis, two reviewers extracted data separately. The risk of bias 2 (RoB-2) and the risk of bias in non-randomized studies (ROBINS-I) tools were used to assess the risk of bias for randomized controlled trials (RCTs) and non-RCTs, respectively. The grading of recommendations assessment, development and evaluation (GRADE) approach was employed to evaluate the quality of the evidence for each finding. Sixteen studies (five RCTs, seven cohorts, and four cross-sectional) were included in this review. Unfortunately, the results could not be pooled into a meta-analysis. Only six studies have reported an increase in SE after orthodontic treatment (P<0.05 in these studies). No agreement between the included studies was observed regarding the influence of fixed orthodontic treatment, gender, or age on SE. The quality of evidence supporting these findings ranged from very low to low. There is low evidence indicating that fixed orthodontic treatment can improve patients' SE. In addition, unclear data are available about the influence of patients' gender and age on SE after orthodontic treatment. Therefore, high-quality RCTs are required to develop stronger evidence about this issue.

The Effectiveness of In-house Clear Aligners and Traditional Fixed Appliances in Achieving Good Occlusion in Complex Orthodontic Cases: A Randomized Control Clinical Trial.

OBJECTIVE: To compare the effectiveness and efficiency of the in-house clear aligners with the traditional fixed appliances in treating premolar-extraction-based complex cases. MATERIALS AND METHODS: A single-centered, 2-arm parallel-group randomized controlled clinical trial was conducted on thirty-six (12 males, 24 females; mean age: 21.24 ± 2.33) patients with severe crowding who required orthodontic treatment with four first premolars extraction. The patients were equally and randomly divided into two groups: The in-house clear aligners (CA) group and the fixed appliances (FA) group. All the measurements were made on the pre-and post-treatment dental cast models. The effectiveness was evaluated using Little's irregularity index (LII) and the Peer Assessment Rating index (PAR). The efficiency was evaluated by studying the treatment duration. Two sample t-tests and chi-square tests were used to test for significant differences between the two groups. Bonferroni correction was applied, and the adjusted alpha level was set at 0.006.  Results: Before treatment, there were no significant differences between the two groups regarding LII in the upper and lower jaws (p˃0.006). After treatment, the mean LII decreased in both groups, with no significant differences between the two studied groups (p˃0.006). There were no significant differences in all studied PAR domains between the two groups (p˃0.006). The mean score reduction in the CA group was 28.39 (±8.51) points, whereas it was 26.39 (±5.76) points in the FA group, with no significant differences between the two groups. All the patients in this study were improved. However, a great improvement was achieved in 88.9% of the patients in the CA group and 91.7% in the FA group, with no significant differences between them (p=0.674). The average treatment duration in the CA group was 23.27 (±5.28) months, whereas the average was 26.20 (±5.27) in the FA group, with no significant difference between the two groups. CONCLUSION: In-house clear aligners can be effective as fixed appliances in achieving good occlusion when treating complex orthodontic cases when suitable teeth movement protocol is used.

Evaluation of the efficacy of laser-assisted flapless corticotomy in accelerating canine retraction: a split-mouth randomized controlled clinical trial.

OBJECTIVE: To evaluate the efficacy of laser-assisted flapless corticotomy in the acceleration of canine retraction compared with the conventional technique and to evaluate patients' pain and discomfort levels after corticotomy. MATERIALS AND METHODS: A single-center randomized controlled trial was conducted on 18 class II division 1 patients (7 males, 11 females; age range: 16 to 24 years) who required the first-upper-premolar extraction followed by canine retraction. A split-mouth design was used in which the Er:YAG laser-assisted flapless corticotomy was randomly allocated to one side, whereas the other side served as the control side. The primary outcome measure was the canine retraction rate which was assessed immediately after laser application, 1, 2, 4, 8, and 12 weeks after laser application. Also, the levels of pain and discomfort during the first week following laser application were assessed. Paired t-tests or Wilcoxon matched-pairs signed-rank tests were used to detect significant differences. RESULTS: All of the selected eighteen patients entered the statistical analysis stage. Significant differences were observed (P < 0.001) in canine retraction rates between the experimental and control sides at the baseline to 1st-week, 1st- to 2nd-week, 2nd- to 4th-week, and 4th- to 8th-week intervals. No significant difference was found between the two sides at the 8th- to 12th-week interval. A significant reduction was seen in the mean score of pain during eating at all assessment times when compared to the baseline data (P = 0.002 at day 2, P < 0.001 at days 5 and 7). CONCLUSION: Er:YAG laser-assisted flapless corticotomy appears to be an effective treatment method for accelerating canine retraction and was accompanied by a mild degree of pain and discomfort. TRIAL REGISTRATION: ClinicalTrials.gov (No.: NCT04316403), retrospectively registered on the 20th of March 2020. URL: https://clinicaltrials.gov/ct2/show/NCT04316403.

The Effect of Treatment With Clear Aligners Versus Fixed Appliances on Oral Health-Related Quality of Life in Patients With Severe Crowding: A One-Year Follow-Up Randomized Controlled Clinical Trial.

Objective To compare the level of oral health-related quality of life (OHRQoL) between patients receiving clear aligners or fixed appliances within one year of follow-up using Oral Health Impact Profile 14 (OHIP-14), a validated self-administered questionnaire. Materials and methods A single-centered, two-arm parallel-group randomized controlled clinical trial was conducted on 36 adult patients (19 females, 17 males; age range: 18 to 25 years) who had severe crowding and require orthodontic treatment with first premolars extraction. The patients were equally and randomly divided into two groups: The clear aligners (CA) group and the fixed appliances (FA) group. OHRQoL was assessed using the OHIP-14 tool at various times during comprehensive orthodontic therapy: baseline (T0), one week (T1), two weeks (T2), one month (T3), 6 months (T4), and 12 months (T5) after starting the active orthodontic treatment. Mann-Whitney U test or Friedman test were used to detect significant differences. The level of significance was set at 5%.  Results All of the selected patients entered the statistical analysis stage. There were no significant differences between the CA and FA groups for the psychological discomfort, psychological disability, social disability, and handicap (P˃0.05) at almost all assessment times. For the functional limitation, physical pain, physical disability, and the overall score, there were significant differences between the studied groups (P˂0.05), with the FA group having higher mean scores than the CA group in all of the assessment times. Conclusion Patients' treatment with clear aligners has less impact on OHRQoL than those treated using conventional fixed appliances during the first year of treatment.

Evaluation of the fused deposition modeling and the digital light processing techniques in terms of dimensional accuracy of printing dental models used for the fabrication of clear aligners.

OBJECTIVE: The objective of this study was to assess the accuracy of physical reproductions of plaster orthodontic study casts fabricated by two different rapid prototyping techniques: Fused Deposition Modeling (FDM) and Digital Light Processing (DLP). MATERIALS AND METHODS: Twenty pairs of pretreatment plaster models were prepared from randomly selected patients at the Orthodontic Department, University of Damascus Dental School. Twenty-one reference points were placed on plaster models, followed by scanning and printing of these models using FDM and DLP techniques. Forty measurements were made on these models using a digital caliper. Paired t tests were used to detect significant differences in the measurements between the 3D printed replicas and the original plaster models (Gold Standard). Alpha level was adjusted due to the multiplicity of the tests. RESULTS: The intraclass correlation coefficients for all the comparisons made between the 3D replicas and the gold standard models were greater than 0.80 with ICCs ranging from 0.802 to 0.990 and from 0.853 to 0.990 for the FDM and DLP techniques, respectively. This indicated an excellent agreement. No statistically significant differences could be detected between the 3D-printed models and their corresponding plaster models. The overall mean difference was -0.11 mm and 0.00 ranging from -0.49 to 0.17 mm and from -0.42 to 0.50 mm, for the FDM and DLP techniques, respectively. CONCLUSION: The accuracy of the 3D models produced by the DLP and FDM techniques was acceptable. However, for the fabrication of clear aligners, the optimum fit of the produced plates in the patients' mouths is not completely guaranteed.

The determinants of hospital cost: a cost-volume-profit analysis of health services in the occupied territories: Palestine.

OBJECTIVE: The purpose of this study is to examine the unit costs of a multi-service hospital in Palestine for the period 2005-2007. We investigate the cost structure of the Rafidya Hospital located in Nablus city, for both inpatient and outpatient departments. METHODS: This study uses cost-volume-profit (CVP) analysis, also known as breakeven analysis. CVP analysis requires examining total costs, along with fixed and variable costs. CVP analysis illuminates how changes in assumptions about cost behaviour and the relevant range in which those assumptions are valid affect the relationships among revenues, variable costs and fixed costs at various production levels. KEY FINDINGS: For the hospital of interest, we find that fixed costs account for 70% of total costs, and variable costs were 30% of total costs. Inpatient departments accounted for 86% of total costs, and outpatient departments were 14% of total costs. Results of the breakeven analysis illustrate that several departments charge sufficient fees to cover all unit costs. CONCLUSIONS: Results provide useful information about unit cost based on four categories: (1) unit cost per admission of each department, (2) unit cost per patient day of each department, (3) unit cost per admission with annual capital cost of each department and (4) unit cost per patient day with annual capital cost. Our results provide hospital cost information that can be used by decision-makers to provide and expand healthcare services, in an effort to increase sustainability and profitability. The use of cost analysis by administrators and regulators will improve the quality of financial information, as well as enhance the efficient use of scarce resources.

Introduction of rotavirus vaccination in Palestine: An evaluation of the costs, impact, and cost-effectiveness of ROTARIX and ROTAVAC.

INTRODUCTION: The Palestinian Ministry of Health (MOH) started a routine rotavirus immunization program with ROTARIX in May 2016, with support for vaccine procurement and introduction provided through a global development organization. In 2018, financial responsibility for rotavirus vaccine procurement was transferred to the Palestinian government, which elected to shift to ROTAVAC vaccine because of its lower price per dose. This study aims to assess the cost, impact, and cost-effectiveness of rotavirus vaccination, specifically evaluating the economic implications of the change in vaccine product, accounting for the different characteristics of each rotavirus vaccine used. METHODS: We conducted primary and secondary data collection to assess the introduction, procurement, supply chain, and service delivery costs related to each vaccine. We used the UNIVAC model to project costs and benefits of rotavirus vaccination over a 10-year period comparing the use of ROTARIX versus no vaccination; ROTAVAC versus no vaccination; and ROTAVAC versus ROTARIX. We undertook scenario and probabilistic analyses to capture uncertainty in some of the study parameters. We used a 3% discount rate, and all costs are in 2018 US$. RESULTS: The cost to deliver one dose was lower for ROTAVAC than ROTARIX (US$2.36 versus $2.70), but the total cost per course, excluding vaccine cost, favored ROTARIX ($7.09 versus $5.39). Both vaccines had high probability of being cost-effective interventions in Palestine compared to no vaccine. Because of lower vaccination program costs for ROTAVAC, however, switching from ROTARIX to ROTAVAC was cost-saving. CONCLUSION: National decision-makers should consider systematically assessing multiple criteria beyond vaccine price when comparing the health and economic value of several products in order to fully account for all characteristics including product presentation, number of doses per course, cold chain volume, cost of delivery, and wastage.

A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system.

Sustained silencing of gene expression throughout the brain using small interfering RNAs (siRNAs) has not been achieved. Here we describe an siRNA architecture, divalent siRNA (di-siRNA), that supports potent, sustained gene silencing in the central nervous system (CNS) of mice and nonhuman primates following a single injection into the cerebrospinal fluid. Di-siRNAs are composed of two fully chemically modified, phosphorothioate-containing siRNAs connected by a linker. In mice, di-siRNAs induced the potent silencing of huntingtin, the causative gene in Huntington's disease, reducing messenger RNA and protein throughout the brain. Silencing persisted for at least 6 months, with the degree of gene silencing correlating to levels of guide strand tissue accumulation. In cynomolgus macaques, a bolus injection of di-siRNA showed substantial distribution and robust silencing throughout the brain and spinal cord without detectable toxicity and with minimal off-target effects. This siRNA design may enable RNA interference-based gene silencing in the CNS for the treatment of neurological disorders.

Skin reactions in a subset of patients with stage IV melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 monoclonal antibody as a single agent.

OBJECTIVE: To describe the clinical and histologic manifestations of skin reactions incidentally noted in patients with stage IV melanoma who were treated with up to 9 mg/kg of a humanized monoclonal antibody reactive against human cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) as a single agent every 3 weeks. SETTING: Single-institution prospective study. DESIGN: Patients treated with anti-CTLA-4 as a sole agent were prospectively referred for clinicopathologic characterization of skin reactions occurring during treatment. MAIN OUTCOME MEASURES: Specific clinicopathologic features were determined by means of a detailed history, a physical examination, conventional histologic analysis, antibody staining, and complete blood cell counts. RESULTS: Nine (14%) of 63 consecutive patients treated with anti-CTLA-4 as a sole agent developed skin eruptions that were attributed to anti-CTLA-4 in 8 of them. Skin lesions consisted primarily of discrete, pruritic, erythematous, minimally scaly papules that typically coalesced into thin plaques on the trunk and extensor surfaces of the extremities. Extensive alopecia was also noted in 1 patient. Histologically, a superficial, perivascular CD4+-predominant T-cell infiltrate with eosinophils in the dermis, rare dyskeratotic cells, and mild epidermal spongiosis were present. An increase (compared with pretreatment values) in the peripheral blood eosinophil frequency was observed in patients at the time of skin eruptions (P = .006). CONCLUSIONS: Specific features of the skin eruption dermatitis with increased tissue and peripheral blood eosinophil levels in a subset of treated patients. Specific features of skin eruption associated with anti-CTLA-4 resemble those described for maculopapular reactions to medications.