Increase In SNA Research Articles

Does Upper Incisors Procline following Rapid Maxillary Expansion Facemask Therapy?

Background: The present study is intended to evaluate the changes in upper incisor angulation, skeletal and dental parameters, soft-tissue and airway dimensions following rapid palatal expansion and maxillary protraction. Materials and Methods: Twenty class III subjects (mean age 11.3 years) were given bonded rapid maxillary expansion (RME) and facemask (FM) for 6 months. Pre- and posttreatment cephalogram were compared and dental, skeletal, soft-tissue, and airway changes were quantified. Results: The mean increase in SNA was 1.85° (P < 0.001) while SNB decreased by 1.85° (P < 0.001). Upper and lower face height increased (UFH 1.1 mm, P < 0.05; LFH 2.92 mm, P < 0.001). Upper lip moved forward (E line U/lip 1.27 mm, P < 0.001; S line U/lip 1.3 mm, P < 0.01). 1-SN decreased by 4.35° and 1-NA decreased by 4.50° with P < 0.01. Overjet improved by 3.07 mm (P < 0.001). Conclusion: RME and FM therapy resulted in maxillary forward movement; mandible rotated downward and backward; UFH and LFH increased. The upper lip exhibited forward movement, resulting in a less concave profile. Upper incisor retroclined and there was increase in overjet and no changes in airway dimensions. The upper incisors following RME and FM does not always procline; it is decided by the interaction of four factors – mesial dental movement, rotation of maxillary/occlusal plane, amount of expansion with RME (expansion effect), and reverse twin block if incorporated with FM.

Maxillary anterior segmental distraction osteogenesis to correct maxillary hypoplasia and dental crowding in cleft palate patients: a preliminary study

BackgroundThe aim of this study was to present comprehensive skeletal, dental and facial aesthetic outcomes and long-term stability of maxillary anterior segmental distraction osteogenesis (MASDO) for the treatment of maxillary hypoplasia in CLP.Materials and methodsSix patients with maxillary hypoplasia treated with MASDO by a miniscrew assisted intraoral tooth-borne distractor were included. Cephalometric radiographs were obtained before distraction (T1), after the consolidation period (T2) and after orthodontic treatment or before orthognathic surgery (T3). Thirty-one cephalometric variables (12 skeletal, 9 dental, and 10 soft tissue variables) were used to evaluate changes in the dentofacial structures and the soft tissue profile. Friedman and Wilcoxon tests were applied to identify significant differences in hard and soft tissue changes during the T1–T2, T2–T3, and T1–T3 periods.ResultsAll patients successfully underwent MASDO without serious complications. From T1 to T2, forward movements of ANS and A (FH ⊥ N–A, VRL–ANS and VRL–A) were significant (p < 0.05). Significant increases in SNA and ANB were noted. Significant upward movement of points ANS (CFH–ANS) and A (CFH–A) was observed (p < 0.05). After distraction, a significant decrease in overjet and an increase in overbite were obtained (p < 0.05). Anterior tipping of the upper incisors (U1/ANS–PNS and U1/SN) was observed (p < 0.05). The soft tissue points of Pn, Sn, Ss, and ls showed significant anterior movement (p < 0.05). In addition, a significant increase in the nasolabial angle was measured (p < 0.05). All of the above data showed no statistically significant changes between T2 and T3 (p > 0.05).ConclusionMASDO using a miniscrew assisted tooth-borne distractor presented significant maxillary advancement and favorable long-term stability in treating CLP patients with maxillary hypoplasia.

The effect of tooth borne versus skeletally anchored Alt-RAMEC protocol in early treatment of Class III malocclusion: a single-centre randomized clinical trial.

This was a randomized, controlled trial designed to compare outcomes between the use of dental and skeletal anchorage, using the Face mask/Alternate Rapid Maxillary Expansion and Contraction (FM/Alt-RAMEC) protocol. The study was carried out at Mater Dei Hospital, Malta and included prepubertal skeletal Class III malocclusion patients where the aetiology was primarily maxillary hypoplasia. Two groups were assigned. Group I was treated with FM/Alt-RAMEC and group II was treated with skeletally anchored FM/Alt-RAMEC. Wear-time (WT) of the FM was monitored using TheraMon microsensors. Patients were instructed to wear the FM for 12-14 hours/day for 9 months. Changes were evaluated with lateral cephalograms and analysed with Wilcoxon and Mann-Whitney U tests. ANOVA was used to analyse the effect of gender on compliance parameters. Spearman's correlation coefficient was used to assess the correlation between compliance and skeletal changes. To compare the skeletal and dentoalveolar changes in patients treated with these two protocols. The primary outcome was to assess skeletal and dentoalveolar outcomes in patients treated with skeletally anchored FM/RME and tooth-borne FM/RME; utilizing Alt-RAMEC protocol. The secondary outcome was compliance rate and adherence to FM wear among patients. Randomizer software and the sealed envelope technique were used to randomly allocate patients 1:1 into either group I (tooth-borne FM/Alt-RAMEC) or group II (skeletally anchored FM/Alt-RAMEC). It was not possible to blind to treatment allocation, but blinding was used when assessing the outcomes. Numbers randomized and analysed. Thirty-five patients were allocated. Group I consisted of 18 subjects and group II consisted of 17 subjects. One patient in group I dropped out due to illness, so 17 subjects in each group completed the study. Post-treatment changes in group I showed significant increases in SNA (2.10°), ANB (3.90°), Wits (4.70 mm), and overjet (5.40 mm). Group II showed significant increases in ANB (3.10°), Wits (3.20 mm), and overjet (4.50 mm). Wearing time for group I patients was 7.87 ± 2.88 hours/day and for group II was 6.98 ± 2.68 hours/day, with no significant difference between the groups. Lack of long-term follow-up post-treatment, making the conclusion applicable only in the short term. No harm was observed in both groups. Despite the large difference between the measured and the patient-reported daily WT, both tooth-borne and skeletally anchored FM/Alt-RAMEC showed positive, similar, skeletal and dental effects. ISRCTN12197405.

PO-455617-6 FUNCTIONAL CONSEQUENCES OF SYMPATHETIC NEURAL REMODELING IN PREMATURE VENTRICULAR CONTRACTION-INDUCED CARDIOMYOPATHY REVEALED BY DUAL STRESSOR PVC AND EXERCISE CHALLENGE

A common presentation of PVC-induced cardiomyopathy (PVC-CM) is exertional fatigue and dyspnea without overt heart failure. The sympathetic nervous system is an adaptive mechanism that augments the cardiac response to an external stressor such as PVCs. We hypothesize that one mechanism of exercise intolerance in PVC-CM is due to the inability of the remodeled sympathetic nervous system maximally recruited from chronic frequent PVC exposure to further augment in response to exercise challenge. To assess the sympathetic neural response to exercise in the presence or absence of PVCs, during baseline state and after development of PVC-CM. In 8 canines, we implanted pacemakers to administer bigeminal PVCs at 200ms coupling for 12-weeks to induce PVC-CM and radio-telemetry device to record ambulatory ECG and nerve activity from the left stellate ganglion nerve (SNA). In order to assess the sympathetic nerve response to exercise (exercise - rest SNA), we subjected animals to the “dual stressor” of a 9-minute exercise tolerance test (ETT, 1.1-3.3mph) in SR and in the presence of bigeminal PVCs (200ms coupling), at baseline (before 12-week PVC exposure) and after development of PVC-CM (after 12-week PVC exposure). SNA (Figure 1A) was significantly increased during exercise compared with rest in all groups except when exercise was performed in presence of PVCs in PVC-CM (CMPVC). The absolute increase in SNA with exercise (exercise-rest SNA) (Figure 1B) was significantly greater in the presence of PVCs compared with SR at baseline but this was reversed in PVC-CM, i.e., significantly less in the presence of PVCs compared with SR. In PVC-CM, the % increase in SNA with exercise (Figure 1C) was less than at baseline, particularly in the presence of PVCs. In PVC-CM, there is generalized sympathetic upregulation but also a failure to further augment the sympathetic response response to exercise, most likely because of maximally recruited nerve endings from chronic frequent PVC perturbation. This data could explain exercise intolerance observed in patients with PVC-CM and suggest that exercise testing could be a useful tool in the clinical assesment of patients with PVC-CM.

Maxillomandibular Advancement for OSA: A 25-year perspective

The aim of this study was to evaluate the result of maxillomandibular advancement (MMA) for the treatment of obstructive sleep apnea (OSA) by a single surgeon. Patients that underwent MMA for the treatment of OSA over a 25-year period were included in the study. Patients who initially presented for revision MMA surgery were excluded. Demographics (e.g., age, gender, pre- and post-MMA body mass index [BMI]), pre- and post-MMA cephalometrics (e.g., sella-nasion-point A angle [SNA], sella-nasion-point B angle [SNB], posterior airway space base of tongue [PAS]) and pre- and post-MMA sleep study metrics (e.g., respiratory disturbance index [RDI], lowest desaturation [SpO2-nadir], oxygen desaturation index [ODI], total sleep time [TST],% TST Stage N3 sleep,% TST rapid eye movement [REM] sleep) were abstracted. MMA surgical success was defined as a ≥ 50% reduction in RDI (or ODI) and post-MMA RDI (or ODI) < 20 events/hour. MMA surgical cure was defined as a post-MMA RDI (or ODI) < 5 events/hour. A total of 1010 patients underwent MMA for the treatment of OSA. The mean age was 39.6 ± 14.3 years, and the majority were male (77%). Nine hundred forty-one patients with complete pre- and postoperative PSG data were analyzed. The mean ODI and RDI improved from 32.6 ± 27.4 to 7.7 ± 15.5 and 39.1 ± 24.2 to 13.6 ± 14.6 events per hour, respectively. The overall surgical success and surgical cure based on ODI was 79.4% and 71.9%, respectively. The overall surgical success and surgical cure based on RDI was 73.1% and 20.7%, respectively. Stratified by preoperative RDI showed older age, greater BMI were associated with greater preoperative RDI. Bivariate predictors of greater RDI reduction include younger age, female gender, lower preoperative BMI, higher preoperative RDI, greater BMI reduction postoperatively and greater change in SNA and PAS. Bivariate predictors of surgical cure based on RDI (RDI < 5) include younger age, female gender, lower preoperative RDI, and greater change in SNA and PAS. Bivariate predictor of RDI success (RDI < 20) include younger age, female gender, lower preoperative BMI, lower preoperative RDI, greater BMI reduction, greater increase in SNA, SNB and PAS postoperatively. Comparison of the first 500 patients and the later 510 patients demonstrate patients undergoing MMA have become younger, having lower RDI while achieving a better surgical outcome. Linear multivariate associations of greater percentage RDI reduction include younger age, greater percent change of SNA, greater preoperative SNA, lower preoperative BMI and higher preoperative RDI. MMA is an effective treatment to improve OSA, but the result can vary. Patient selection based on favorable prognostic factors and maximizing the advancement distance can improve outcomes.

A retrospective comparison of two protocols for correction of skeletal Class III malocclusion in prepubertal children: hybrid hyrax expander with mandibular miniplates and rapid maxillary expansion with face mask

BackgroundThis study compared the skeletal and dental effects of a hybrid maxillary expander with mandibular miniplates (HE-MP) and Class III elastics to conventional tooth-borne rapid maxillary expander and face mask (RME–FM) in skeletal Class III treatment.MethodsThis retrospective study included 36 skeletal Class III patients. Eighteen patients (mean age 10.24 ± 1.31 years) were treated with a hybrid expander, two mandibular L-shaped miniplates and full-time Class III elastics (HE-MP group). Their results were compared to a group of patients treated with conventional RME–FM (n = 18; mean age 10.56 ± 1.41 year). Radiographs were taken before (T1) and after treatment (T2). All patients were in cervical maturation stages CS1–CS3 at T1. The measured outcomes were the changes in sagittal and vertical skeletal and dental cephalometric measurements.ResultsTreatment time was approximately 15.5 ± 2.8 months with the HE-MP and 11.85 ± 3.41 months for the RME–FM. The Class III malocclusion was corrected in both groups with significant changes. The maxilla advanced more in the HE-MP group, with an increase in SNA of 4.26° ± 2.15° compared to 1.14 ± 0.93 in the RME–FM group (p < 0.001). The effect on the mandible was similar in both groups, while the overall skeletal change was significantly greater with HE-MP, with an increase in the ANB of 5.25° ± 2.03° and a Wits appraisal increase of 6.03 ± 3.13 mm, as opposed to 2.04° ± 1.07° and 2.94 ± 1.75 mm with the RME–FM (p < 0.001). Dental changes were significantly higher with RME–FM, with an increase in incisor inclination (U1-SN) of 5.02° ± 3.93° (p < 0.001), with no significant changes in the HE-MP group. The mandibular incisors retroclined by 5.29° ± 3.57° at L1-MP with the RME–FM, while they advanced slightly with the HE-MP by 2.87° ± 5.37° (p < 0.001).ConclusionThe use of skeletal anchorage for maxillary expansion and protraction significantly increases skeletal effects and reduces dental side effects compared to tooth-borne maxillary expansion and protraction. These results need to be investigated in the long term.

Maxillomandibular Advancement for OSA: A 25-year perspective

The aim of this study was to evaluate the result of maxillomandibular advancement (MMA) for the treatment of obstructive sleep apnea (OSA) by a single surgeon. Patients that underwent MMA for the treatment of OSA over a 25-year period were included in the study. Patients who initially presented for revision MMA surgery were excluded. Demographics (e.g., age, gender, pre- and post-MMA body mass index [BMI]), pre- and post-MMA cephalometrics (e.g., sella-nasion-point A angle [SNA], sella-nasion-point B angle [SNB], posterior airway space base of tongue [PAS]) and pre- and post-MMA sleep study metrics (e.g., respiratory disturbance index [RDI], lowest desaturation [SpO2-nadir], oxygen desaturation index [ODI], total sleep time [TST],% TST Stage N3 sleep,% TST rapid eye movement [REM] sleep) were abstracted. MMA surgical success was defined as a ≥ 50% reduction in RDI (or ODI) and post-MMA RDI (or ODI) < 20 events/hour. MMA surgical cure was defined as a post-MMA RDI (or ODI) < 5 events/hour. A total of 1010 patients underwent MMA for the treatment of OSA. The mean age was 39.6 ± 14.3 years, and the majority were male (77%). Nine hundred forty-one patients with complete pre- and postoperative PSG data were analyzed. The mean ODI and RDI improved from 32.6 ± 27.4 to 7.7 ± 15.5 and 39.1 ± 24.2 to 13.6 ± 14.6 events per hour, respectively. The overall surgical success and surgical cure based on ODI was 79.4% and 71.9%, respectively. The overall surgical success and surgical cure based on RDI was 73.1% and 20.7%, respectively. Stratified by preoperative RDI showed older age, greater BMI were associated with greater preoperative RDI. Bivariate predictors of greater RDI reduction include younger age, female gender, lower preoperative BMI, higher preoperative RDI, greater BMI reduction postoperatively and greater change in SNA and PAS. Bivariate predictors of surgical cure based on RDI (RDI < 5) include younger age, female gender, lower preoperative RDI, and greater change in SNA and PAS. Bivariate predictor of RDI success (RDI < 20) include younger age, female gender, lower preoperative BMI, lower preoperative RDI, greater BMI reduction, greater increase in SNA, SNB and PAS postoperatively. Comparison of the first 500 patients and the later 510 patients demonstrate patients undergoing MMA have become younger, having lower RDI while achieving a better surgical outcome. Linear multivariate associations of greater percentage RDI reduction include younger age, greater percent change of SNA, greater preoperative SNA, lower preoperative BMI and higher preoperative RDI. MMA is an effective treatment to improve OSA, but the result can vary. Patient selection based on favorable prognostic factors and maximizing the advancement distance can improve outcomes.

Comparable Skeletal and Dental Movements Achieved Using Conventional and Surgery-First Techniques in Class III Patients

The surgery-first (SF) approach to orthognathic surgery has been proposed as a more efficient method to correct the dentofacial deformity. This study aimed to evaluate if the magnitude of skeletal and dental changes achieved in Class III patients treated with either conventional orthognathic surgery (COS) or SF techniques differ. A retrospective cohort study of Class III orthognathic surgery patients between January 2006 and May 2020 with available pre- and post-treatment lateral cephalograms was conducted at an academic institution. The primary predictor variable was surgery technique: COS or SF. Assessed outcome variables included cephalometric skeletal parameters: SNA, SNB, ANB, Wits Appraisal, Sn-GoGn, and FMA; and dental parameters: U1-SN, U1-NA (°), U1-NA (mm), L1-NB (°), L1-NB (mm), and overjet. Within-group posttreatment parameters were analyzed with paired t tests. Pretreatment, posttreatment, and between-group parameter changes were analyzed by 2-sided 2-sample independent t tests. Potential covariates, including gender, surgical procedure, previous conventional treatment, extractions (excluding 3rd molars), crowding, and midline discrepancy, were analyzed using Fisher exact tests. Thirty-nine subjects were included in this study: 1) 21 COS (age: 20.9±8.7years) and 2) 18 SF (age: 19.6±5.0years). Cohorts were comparable (P>.05) for all analyzed covariates. COS showed statistically significant increases in L1-GoGn (3.31±6.23°; P=.024), overjet (4.26±3.99mm; P<.001), ANB (3.5±2.79°; P<.001), SNA (3.5±1.85°; P<.001), and Wits Appraisal (3.78±4.97mm; P=.002). SF showed statistically significant increases in L1-GoGn (4.19±4.85°; P=.002), L1-NB (3.08±4.13°; P=.006), L1-NB (0.79±1.35mm; P=.023), overjet (5.82±2.96mm; P<.001), ANB (5.51±3°; P<.001), SNA (4.13±2.38°; P<.001), and Wits Appraisal (5.92±3.42mm; P<.001) and statistically significant decreases in U1-NA (-3.69±7.35°; P=.048) and SNB (-1.38±2.14°; P=.014). There were no statistically significant differences in skeletal or dental parameters between groups when adjusted for pretreatment levels of that parameter. The mean treatment duration was 38months (standard deviation=12.7) in COS and 17.6months (standard deviation=5.2) in SF. The results show that skeletal and dental changes between groups were not statistically different, despite an average 20-month difference in treatment duration. This suggests that either technique can be used to achieve comparable degrees of skeletal and dental movement in Class III patients.

A Foundation for the Neural Control of Viral Fever

Fever, an acute‐phase neurally‐regulated increase in body temperature, is thought to be an adaptive response to optimize host defenses against invading pathogens. However, fever can be an unpleasant symptom of infection and excessive fever (&gt;41oC) can cause irreversible protein denaturation and result in tissue damage, seizure, coma and death. Common therapeutic approaches to fever include the use of non‐steroidal anti‐inflammatory drugs and cyclooxygenase inhibitors, however these approaches are ineffective for reducing prostaglandin‐independent fevers, can interfere with adaptive and innate immune defenses and are contraindicated for use in some viral infections, including SARS‐CoV2. Although research over the past couple of decades has defined the fundamental central nervous system (CNS) pathways necessary for the lipopolysaccharide model of bacterial fever, the CNS circuits mediating viral fevers are almost completely unknown. Double‐stranded RNA is an intermediary in viral replication and serves as a pathogen‐associated molecular pattern that elicits the acute phase responses to viral infection. Systemic administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic double stranded RNA, mimics the acute phase responses to viral infection. Neurons in the rostral raphe pallidus area (rRPa) and the dorsomedial hypothalamus play important roles in the control of the sympathetic outflow to thermoeffectors, therefore we hypothesized that neurons in these areas would be essential for fever elicited by a model of viral fever, intravenous (iv) poly I:C. Female and male Sprague Dawley rats anesthetized with urethane and α‐chloralose (for BAT sympathetic nerve recording, n=3) or isoflurane (for cutaneous vasoconstriction experiments, n=3) received iv poly I:C (1mg/kg for experiments with sympathetic nerve recording, or 500μg/kg for experiments for cutaneous vasoconstriction). Systemically administered poly I:C increased BAT SNA (+601 ± 161% baseline), BAT temperature (TBAT; +3.1 ± 0.8°C), and expired CO2 (+0.9 ± 0.2%). Poly I:C also elicited CVC, as observed by reductions in paw or tail skin temperature (TPAW/TTail) (‐2.6 ± 1.2°C). A nanoinjection of the ionotropic glutamate receptor antagonists, AP5 and CNQX in the rRPa reversed poly I:C‐evoked increases in BAT SNA (‐596 ± 128% baseline), TBAT (‐1.3 ± 0.2°C), and expired CO2 (‐0.5 ± 0.1%). Nanoinjection of AP5 and CNQX into the DMH reversed the polyI:C‐evoked reduction in TPAW/TTail (+2.8 ± 1.1°C). These data suggest that the activity of neurons in the rRPa and the DMH are necessary for poly I:C‐induced activation of BAT thermogenesis and cutaneous vasoconstriction. These data define critical components of the neural circuits for poly I:C‐induced fever, highlight differences between the neural circuitry mediating bacterial fever and viral fever, and provide a foundation for elucidating additional brain mechanisms responsible for viral fever.

Comparison of Pre-operative and Postoperative Skeletal and Dental Movements in Class III Patients Treated with Conventional and Surgery-first Techniques

The conventional orthognathic-surgery technique involves lengthy pre-surgical orthodontic interventions, while invoking a surgery-first technique eliminates this necessity. Previous studies have reported the degree of skeletal and dental movements achieved using the conventional approach compared to orthodontic camouflage. However, none has directly compared the conventional orthognathic-surgery and surgery-first techniques. The objective of this study was to determine the magnitude of skeletal and dental changes achieved in class III patients with conventional orthognathic surgery (COS) and surgery-first (SF) techniques.In total, 82 lateral cephalograms for class III patients (n = 41) were analyzed for 2 groups: 1) COS (20.9±8.7 years) and 2) SF (20.7±6.6 years). Skeletal parameters such as SNA, SNB, ANB, Wits Analysis, Sn-GoGn, FMA, and lower anterior facial height and dental parameters such as U1-SN, U1-NA (°), U1-NA (mm), L1-NB (°), L1-NB (mm), and overjet were analyzed. Paired T-test analyses were performed to analyze the changes between pre-treatment and post-treatment parameters within the 2 groups, and 2-sample T-tests were used to compare the pre-treatment and post-treatment changes between the 2 groups.COS showed significant increase in L1-GoGn, overjet, ANB, SNA, and Wits analysis. SF showed significant increase in L1-GoGn, L1-NB (°), L1-NB (mm), overjet, ANB, SNA, and Wits analysis and significant decrease in U1-NA (°) and U1-NA (mm). The comparison between COS and SF showed that there was no statistically significant difference in the skeletal and dental parameters between the 2 groups.The results indicate that orthognathic surgery in class III patients with conventional orthognathic-surgery and surgery-first techniques does not produce a difference in results among the skeletal and dental parameters, suggesting that either technique can be used to achieve similar results with a comparable degree of skeletal and dental movement in patients with class III malocclusion.

Regulation of Coronary Blood Flow by the Carotid Body Chemoreceptors in Ovine Heart Failure.

Carotid bodies (CBs) are peripheral chemoreceptors, which are primary sensors of systemic hypoxia and their activation produces respiratory, autonomic, and cardiovascular adjustments critical for body homeostasis. We have previously shown that carotid chemoreceptor stimulation increases directly recorded cardiac sympathetic nerve activity (cardiac SNA) which increases coronary blood flow (CoBF) in conscious normal sheep. Previous studies have shown that chemoreflex sensitivity is augmented in heart failure (HF). We hypothesized that carotid chemoreceptor stimulation would increase CoBF to a greater extent in HF than control sheep. Experiments were conducted in conscious HF sheep and control sheep (n = 6/group) implanted with electrodes to record diaphragmatic electromyography (dEMG), flow probes to record CoBF as well as arterial pressure. There was a significant increase in mean arterial pressure (MAP), CoBF and coronary vascular conductance (CVC) in response to potassium cyanide (KCN) in both groups of sheep. To eliminate the effects of metabolic vasodilation, the KCN was repeated while the heart was paced at a constant level. In this paradigm, the increase in CoBF and CVC was augmented in the HF group compared to the control group. Pre-treatment with propranolol did not alter the CoBF or the CVC increase in the HF group indicating this was not mediated by an increase in cardiac sympathetic drive. The pressor response to CB activation was abolished by pre-treatment with intravenous atropine in both groups, but there was no change in the CoBF and vascular conductance responses. Our data suggest that in an ovine model of HF, carotid body (CB) mediated increases in CoBF and CVC are augmented compared to control animals. This increase in CoBF is mediated by an increase in cardiac SNA in the control group but not the HF group.

Activation of the Rostral Ventrolateral Medulla Reveals Specialized Control of Sympathetic Nerves Involved in Regulation of Blood Glucose and Blood Pressure

BACKGROUND The sympathetic nervous system mediates the “fight-or-flight” response, including stimulation of the adrenal glands to secrete epinephrine. Epinephrine increases heart rate and contractility and increases blood glucose. Sympathetic nerve activity to functionally distinct targets is regulated differentially by the rostral ventrolateral medulla (RVLM). Therefore, it is important to recognize the numerous roles of the RVLM in control of both blood pressure and blood glucose. Anatomical evidence suggests that innervation of the adrenal gland is from ipsilateral spinal sympathetic neurons and, in turn by RVLM neurons primarily from the ipsilateral side; however, the functional implications of lateralized innervation are lacking. Functional evidence also suggests that withdrawal of tonic GABAergic inhibition in the RVLM during decreases in blood pressure is an important regulatory mechanism in the excitation of sympathetic vasoconstrictor nerves (e.g., splanchnic SNA). We were interested in whether similar neurotransmitter mechanisms mediate hypotension-induced increases in adrenal SNA (AdSNA). Thus, the goals of the present study were to 1) compare effects of contralateral vs. ipsilateral RVLM activation on sSNA and AdSNA, 2) determine the role of RVLM GABAA receptors in hypotension-induced increases in sSNA and AdSNA and 3) investigate functional outcomes in a physiologically relevant model of altered glucose regulation. We hypothesized that activation of the RVLM produces differential increases in sSNA versus AdSNA, given the unique functional role of AdSNA in glucose regulation. METHODS We measured AdSNA and sSNA in male Sprague-Dawley rats during ipsilateral or contralateral glutamatergic activation of the RVLM. We produced decreases in blood pressure (sodium nitroprusside, i.v.) before and after bilateral GABAA receptor blockade (bicuculline, 5mM 90nL). In related experiments, blood glucose was also recorded before and after 2-deoxyglucose (2-DG, i.v.). Lastly, adrenal glands from active (12 wk running wheels) and sedentary animals were analyzed to measure adrenal medulla size. RESULTS Our results indicated that glutamate (100 mM, 30nL) injected into the left RVLM produced increases in ipsilateral AdSNA that were more than twice that of increases following right RVLM (contralateral) injections (p<0.05; n=6). In contrast, sSNA responses were equivalent to glutamate injections on either side of the RVLM. In response to hypotension, both sSNA and AdSNA increased; however, increases in sSNA but not AdSNA were eliminated by bicuculline (p<0.05; n=4). In preliminary experiments, sedentary animals demonstrated potentially greater increases in glucose in response to 2-DG stimulation (p=0.21, n=4) and possibly smaller adrenal medulla size (p=0.142, n=3). CONCLUSION The results confirm previous anatomical findings that the RVLM has predominantly ipsilateral innervation of adrenal nerves. Baroreflex-mediated increases in sSNA but not AdSNA are mediated by GABAA receptors in the RVLM. A deeper understanding of neural control of adrenal function provides insight into comorbidities between cardiovascular and metabolic disease pathologies.

Clinical Experience of the Efficacy and Safety of Low-dose Tolvaptan Therapy in a UK Tertiary Oncology Setting.

In patients with cancer, hyponatremia is associated with increased morbidity and mortality and can delay systemic therapy. To assess the safety and efficacy of low-dose tolvaptan (7.5 mg) for hospitalized, adult patients with hyponatremia due to syndrome of inappropriate antidiuresis (SIAD), and coexisting malignancy. Retrospective evaluation in a tertiary cancer center. Fifty-five patients with mean baseline serum sodium (sNa) 117.9 ± 4.6 mmol/L were included. In total, 90.9% had severe hyponatremia (sNa < 125 mmol/L). Mean age was 65.1 ± 9.3 years. Following an initial dose of tolvaptan 7.5 mg, median (range) increase in sNa observed at 24 hours was 9 (1-19) mmol/L. Within 1 week, 39 patients (70.9%) reached sNa ≥ 130 mmol/L and 48 (87.3%) had sNa rise of ≥5 mmol/L within 48 hours. No severe adverse events were reported. Thirty-three (60%) and 17 (30.9%) patients experienced sNa rise of ≥8 and ≥12 mmol/L/24 hours, respectively. The rate of sNa correction in the first 24 hours was significantly higher among participants that continued fluid restriction after tolvaptan administration (median [quantiles]: 14 [9-16] versus 8 [5-11] mmol/L, P = .036). Moreover, in the over-rapid correction cohort (≥12 mmol/L/24 hours) demeclocycline was appropriately discontinued only in 60% compared with 91.7% of the remaining participants (P = .047). Lower creatinine was predictive of higher sNa correction rate within 24 hours (P = .01). In the largest series to date, although low-dose tolvaptan was demonstrated to be effective in correcting hyponatremia due to SIAD in cancer patients, a significant proportion experienced over-rapid correction. Concurrent administration of demeclocycline and/or fluid restriction must be avoided due to the increased risk of over-rapid correction.

Dental developmental stage affects the treatment outcome of maxillary protraction in skeletal Class III children: A systematic review and meta-analysis

Abstract Background: The aim of this study was to investigate the effect of the stage of dental development on the treatment outcome of maxillary protraction in skeletal Class III children. Materials and methods: The Medline, Web of Science, Embase, Cochrane Library, CMB and CNKI database were searched to identify all of the relevant articles published prior to 30 August 2019. The grey literature was also searched. Human controlled clinical trials in which patients with a skeletal Class III malocclusion were treated by maxillary protraction (facemask with or without rapid maxillary expansion) were considered. The quality of the included studies was assessed using ROBINS-I. Meta-analysis was performed using RevMan 5.3. Results: A total of 19 trials were included in the systematic review and 16 trials were included in the meta-analysis, of which three studies were assessed as low risk of bias (high quality), eight were assessed as having a moderate risk of bias, and five were assessed as a high risk of bias. The treatment effect of maxillary protraction in skeletal Class III children was greater in the primary dentition than that in the early mixed dentition with respect to an increase in SNA, ANB and SN/GoGn. The treatment effect was greater in the early mixed dentition than in the late mixed dentition, with an evident decrease in SNB. The treatment effect was greater in the early mixed dentition than that which occurred in the early permanent dentition, with an increase in SNA and ANB. The treatment effect was not significantly different, either between the primary dentition and late mixed dentition, or between the late mixed dentition and early permanent dentition. No study compared the treatment effect between the primary dentition and early permanent dentition. Conclusion: The dental developmental stage affects the treatment effect of maxillary protraction in skeletal Class III children. The treatment effect at an early dentition stage may be more effective than that at a late dentition stage in improving a skeletal Class III relationship. Although the variations in effectiveness between the various dental stage groups were generally statistically significant, most variations were small, with unclear clinical significance.

Comparison of dentofacial morphology between parents of children with and without craniofacial anomalies using cephalogram imaging.

To compare cephalometric parameters in parents of children with bilateral cleft lip and palate (BCLP) and parents of children without any craniofacial anomaly. A sample of 100 sets of parents were segregated into two groups of 50 parents each. The two groups included parents of children with BCLP and the parents of children with no craniofacial anomaly. Lateral cephalograms and postero-anterior (PA) cephalograms were examined for 100 parents of both the BCLP and control group, respectively. Tracings were scrutinized for 34 linear and angular parameters of dentocraniofacial skeleton. Data were analysed using unpaired Student's t-test. Result: Evaluated lateral cephalograms revealed 15 significant parameters in parents of children with BCLP including a significant increase in Ptm-S, maxillary length, SNA, articular angle and gonial angle. A significant decrease was noted in SN length, cranial base flexion, mandibular length, mandibular body length, total facial height, upper facial height, posterior facial height, Y-axis length and soft tissue total anterior facial height. Upon evaluation of PA cephalograms, four significant parameters were found in parents of children with BCLP. Cranial width, bizygomatic width, maxillary width and lateral interorbital width were significantly decreased in the parents of children with BCLP. Distinct dentocraniofacial morphological features have been found in parents of children with BCLP. Evaluation of these features might be the key to predicting the occurrence of clefts in their children and also planning for future linkage analysis studies amongst them.

Maxillary protraction in patients with unilateral cleft lip and palate : Evaluation of soft and hard tissues using the Alt-RAMEC protocol.

The aim of this study was to evaluate the hard and soft tissue effects and differences of the Alt-RAMEC protocol to the facemask and conventional facemask protocols in patients with unilateral cleft lip and palate. This prospective study was carried out with 30patients with unilateral cleft lip and palate with skeletal and dental classIII malocclusions who were referred to a university department of orthodontics. The patients were evaluated with the cervical vertebral maturation method and divided into two groups, each consisting of 15patients. The patients in groupI (mean age 10.00 ± 0.73 years) were treated according to conventional facemask protocol, and the patients in groupII (mean age 10.07 ± 2.43 years) were treated according to the Alt-RAMEC protocol before facemask application. Lateral cephalometric radiographs were evaluated by using the Dolphin Imaging Software version 11.7. The skeletal, dentoalveolar and soft tissue differences and treatment times were evaluated. GroupII demonstrated a5.73° increase in SNA, which was statistically significant, while this increase was 3.13° in groupI (p < 0.001). Results for Co‑A and A‑PTV showed asignificant increase for groupII only (groupI: 1.02 mm, 1.06 mm, groupII: 3.02 mm, 2.21 mm; p < 0.05 and p < 0.01, respectively). In addition, groupII presented significant increase for the values of ANB, N‑A-Pg, SN/MP, Wits, U1-SN, U1-L1, U1-PTV, U1-FHP, U6-PTV, U6-FHP, overjet, Ss-PTV, UL-PTV and UL‑S line (p < 0.001). The treatment mean times were 7.3months in groupI and 4.7months in groupII (p < 0.01). Applying the facemask after having followed the Alt-RAMEC protocol induced more skeletal, dentoalveolar and soft tissue changes in comparison to the conventional facemask protocol in patients with unilateral cleft lip and palate.

Osmotic demyelination syndrome: are patients with end-stage liver disease a special risk group?

The osmotic demyelination syndrome (ODS) is a serious neurological complication associated with the rapid correction of chronic hyponatremia and is associated with high morbidity and mortality. The incidence of ODS after liver transplantation (LT) is 0.8% to 1.4% and is higher than in the general population. Patients with end stage liver disease (ESLD) are very susceptible to ODS primarily because chronic hyponatremia is the most common electrolyte disorder in these patients. Impaired liver function also leads to disruption of astrocyte metabolism resulting in abnormalities of blood-brain barrier function and a decreased ability to generate new intracellular osmotically active compounds (osmolytes) in response to osmotic changes. LT is the only definitive treatment for hyponatremia in ESLD. Massive fluid shifts that occur intraoperatively can change serum sodium concentration (sNa) significantly. The severity of preoperative chronic hyponatremia is an important risk factor for ODS after LT. ODS after LT is most likely due to unintentional sodium administration intraoperatively. Measures to prevent ODS should cover the entire perioperative period. Chronic symptomatic hyponatremia should be carefully treated if LT is imminent. An intraoperative management strategy to minimize increases in sNa is vital and includes limiting fresh frozen plasma and cryoprecipitate administration by using concentrated clotting factors, administering hypotonic intravenous fluids and sodium-free buffering solutions, as well as using low-sodium continuous renal replacement therapy. sNa levels and urine output should be monitored frequently intraoperatively as well as postoperatively. Neurological symptoms are common after LT, and a high index of suspicion must be maintained to diagnose ODS.

Rigid External Le Fort I Distraction Followed by Secondary Bone Grafting for Maxillary Advancements in Patients With Cleft Lip and Palate.

Maxillary hypoplasia after cleft lip and palate (CLP) repair can result in significant functional and aesthetic impairments. Le Fort I osteotomy & advancement and Le Fort I distraction osteogenesis are standard treatment options for individuals with CLP-associated midface retrusion. However, both of these modalities continue to be associated with a high relapse rate. This study describes surgical outcomes of a 2-stage technique utilizing distraction osteogenesis combined with bone grafting and rigid fixation, which may optimize skeletal stability by reducing relapse. A retrospective review of CLP patients with severe maxillary hypoplasia evaluated by a single surgeon from 2003 to 2014 was performed. Twenty-one subjects were identified that underwent maxillary advancement via a 2-stage technique: (1) Le Fort I external rigid distraction using a HALO device, followed by (2) autologous iliac crest bone graft application and plate-fixation. Post-operative cephalograms were taken on average 1-year following surgery. Twelve subjects met the inclusion/exclusion criteria. A distraction rate of 1 mm/day was achieved with an average of 14 mm of maxillary advancement. Average increase in SNA was +9.03°, with an increase from 71.84° to 80.88° (normal = 82.0°, P value <0.0001), with no significant change in SNB, and a +9.63° change in ANB from -7.76° to 1.88° (normal = 1.6°, P value <0.0001). The described 2-step procedure had similar cephalometric improvements as compared to distraction osteogenesis alone. However, successive bone grafting and rigid fixation as a second procedure may help ameliorate relapse risk and optimize the correction of maxillary hypoplasia in susceptible populations.

Effects of orthopedic skeletal Class III correction in growing subjects using skeletal anchorage and Class III elastics

Aim of the study: The objective of this study was to evaluate the skeletal and dental effects of intermaxillary Class III elastics using bone anchored miniplates compared to an untreated Class III control group.Subjects and methods: 24 subjects (14 females and 10 males) having skeletal Class III malocclusion with maxillary deficiency with an age range of 8-11 years old were divided into two groups 12 patients each (n=12). Group A constituted treatment with Class III elastics anchored to 4 titanium miniplates, 2 anchored in the zygomatic buttress of the maxilla and 2 miniplates anchored in the symphyseal region of the mandible at the lateral/canine region. Group B (n=12) constituted untreated skeletal Class III cases (control group). The treatment and observation periods for both groups were 8 months. Lateral cephalometric radiographs were taken for the patients at start of treatment (T1) and at the end of the treatment/observation periods (T2). The radiographs were analyzed by performing lateral cephalometric analysis. Independent student t test was done to compare variables between the two groups.Results: There was correction of the skeletal Class III in the miniplates group with statistically significant increase in angle SNA (mean 3.50° ± 0.68), A-Nperp (mean 4.04mm ± 1.20), ANB (mean 4.06◦±0.95) and Witts appraisal (mean 4.91mm ± 1.76) .Slight mandibular retrusion occurred with a reduction in angle SNB (mean -0.56◦ ±0.57). Changes in B-Nperp were (-1.85mm±1.36).Overjet correction was obtained and no significant changes in the maxillary incisor angulation was observed. There was proclination of mandibular incisors by (mean 6.43◦±2.11).Conclusions: The use of intermaxillary Class III elastics and miniplates in the orthopedic treatment of skeletal Class III is a successful technique with more skeletal than dental effects.

Neurons in the rat ventral lateral preoptic area are essential for the warm-evoked inhibition of brown adipose tissue and shivering thermogenesis.

To determine the role of neurons in the ventral part of the lateral preoptic area (vLPO) in CNS thermoregulation. In vivo electrophysiological and neuropharmacological were used toevaluate the contribution of neurons in the vLPO to the regulation of brown adipose tissue (BAT) thermogenesis and muscle shivering in urethane/chloralose-anaesthetized rats. Nanoinjections of NMDA targeting the medial preoptic area (MPA) and the vLPO suppressed the cold-evoked BAT sympathetic activity (SNA), reduced the BAT temperature (TBAT ), expired CO2 , mean arterial pressure (MAP), and heart rate. Inhibition of vLPO neurons with muscimol or AP5/CNQX elicited increases in BAT SNA, TBAT , tachycardia, and small elevations in MAP. The BAT thermogenesis evoked by AP5/CNQX in vLPO was inhibited by the activation of MPA neurons. The inhibition of BAT SNA by vLPO neurons does not require a GABAergic input to dorsomedial hypothalamus (DMH), but MPA provides a GABAergic input to DMH. The activation of vLPO neurons inhibits the BAT thermogenesis evoked by NMDA in the rostral raphe pallidus (rRPa), but not that after bicuculline in rRPa. The BAT thermogenesis elicited by vLPO inhibition is dependent on glutamatergic inputs to DMH and rRPa, but these excitatory inputs do not arise from MnPO neurons. The activation of neurons in the vLPO also inhibits cold- and prostaglandin-evoked muscle shivering, and vLPO inhibition is sufficient to evoke shivering. The vLPO contains neurons that are required for the warm ambient-evoked inhibition of muscle shivering and of BAT thermogenesis, mediated through a direct or indirect GABAergic input to rRPa from vLPO.