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BACKGROUND: Effective seizure detection is important however, clinical signs of seizure activity may be subtle in neonates. This study aimed to systematically investigate SpO2 and respiratory pattern changes associated with EEG seizures in term-born neonates. METHOD: An observational study in term neonates at risk of seizures admitted to a single tertiary level neonatal intensive care unit. Synchronised high-resolution physiological data (ECG, pulse oximetry, respiration) and EEG/amplitude-integrated EEG (aEEG) monitoring were recorded. Sections of traces with evidence of clear EEG seizure activity were compared with physiological data recorded at the same time. RESULTS: 22/44 (50%) neonates who had aEEG monitoring were noted to have electrographic seizures. Physiologic download measurements were available for 11 of these neonates. In nine of these, an acute drop in oxygen saturation (SpO2) of at least 5% was noted in at least one seizure. Accompanying apnoeas were noted in three neonates. CONCLUSION: Acute decreases in SpO2 were seen in term neonates associated with seizures and these were not always accompanied by an apnoeic episode. Physiologic download in association with EEG monitoring may assist in improving seizure detection. Unexplained drops in SpO2 could indicate further investigation for possible seizures in at-risk neonates. IMPACT: A decrease in blood oxygen saturation (SpO2) associated with EEG seizures can occur in term infants with HIE or perinatal stroke. Drops in SpO2 associated with EEG seizures in term infants with HIE or stroke may occur in the absence of apnoeas. Unexplained acute falls in SpO2 in sick neonates may suggest possible seizures. Drops in SpO2 associated with seizures in term infants can occur over less than 3 minutes. Physiological monitoring alongside EEG monitoring could help to improve seizure detection.
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Electroencefalografía , Oximetría , Saturación de Oxígeno , Convulsiones , Humanos , Recién Nacido , Convulsiones/diagnóstico , Convulsiones/sangre , Convulsiones/fisiopatología , Femenino , Masculino , Oxígeno/sangre , Unidades de Cuidado Intensivo Neonatal , Monitoreo Fisiológico/métodosRESUMEN
INTRODUCTION: It is a shortcoming of traditional cardiotocography (CTG) classification table formats that CTG traces are frequently classified differently by different users, resulting in poor interobserver agreements. A fast-and-frugal tree (FFTree) flow chart may help provide better concordance because it is straightforward and has clearly structured binary questions with understandable "yes" or "no" responses. The initial triage to determine whether a fetus is suitable for labor when utilizing fetal ECG ST analysis (STAN) is very important, since a fetus with restricted capacity to respond to hypoxic stress may not generate STAN events and therefore may become falsely negative. This study aimed to compare physiology-focused FFTree CTG interpretation with FIGO classification for assessing the suitability for STAN monitoring. MATERIAL AND METHODS: A retrospective study of 36 CTG traces with a high proportion of adverse outcomes (17/36) selected from a European multicenter study database. Eight experienced European obstetricians evaluated the initial 40 minutes of the CTG recordings and judged whether STAN was a suitable fetal surveillance method and whether intervention was indicated. The experts rated the CTGs using the FFTree and FIGO classifications at least 6 weeks apart. Interobserver agreements were calculated using proportions of agreement and Fleiss' kappa (κ). RESULTS: The proportions of agreement for "not suitable for STAN" were for FIGO 47% (95% confidence interval [CI] 42%-52%) and for FFTree 60% (95% CI 56-64), ie a significant difference; the corresponding figures for "yes, suitable" were 74% (95% CI 71-77) and 70% (95% CI 67-74). For "intervention needed" the figures were 52% (95% CI 47-56) vs 58% (95% CI 54-62) and for "expectant management" 74% (95% CI 71-77) vs 72% (95% CI 69-75). Fleiss' κ agreement on "suitability for STAN" was 0.50 (95% CI 0.44-0.56) for the FIGO classification and 0.57 (95% CI 0.51-0.63) for the FFTree classification; the corresponding figures for "intervention or expectancy" were 0.53 (95% CI 0.47-0.59) and 0.57 (95% CI 0.51-0.63). CONCLUSIONS: The proportion of agreement among expert obstetricians using the FFTree physiological approach was significantly higher compared with the traditional FIGO classification system in rejecting cases not suitable for STAN monitoring. That might be of importance to avoid false negative STAN recordings. Other agreement figures were similar. It remains to be shown whether the FFTree simplicity will benefit less experienced users and how it will work in real-world clinical scenarios.
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Electrocardiografía , Monitoreo Fetal , Triaje , Femenino , Humanos , Embarazo , Cardiotocografía/métodos , Electrocardiografía/métodos , Monitoreo Fetal/métodos , Feto , Frecuencia Cardíaca Fetal/fisiología , Variaciones Dependientes del Observador , Estudios RetrospectivosRESUMEN
In September 2021 an eruption began of Cumbre Vieja, La Palma (Spain) that lasted 3 months. Previous studies have shown that volcanic ash particles can be associated with adverse effects on human health however, the reasons for this are unclear. Particle shape has been shown to contribute to cellular uptake in prostate cancer cells. Hence we aimed to study 3D structure, elemental composition and effects on cultured lung cells of particles collected from the La Palma volcanic eruption. 3D imaging of PM10 sized and below particles was performed using a LEXT OLS4100 confocal microscope (Olympus Corporation, Japan). A Zeiss EVO 50 (Carl Zeiss AG, Germany) Scanning Electron Microscope (SEM) was used to assess elemental composition. In addition, volcanic particle concentration dose response for pneumococcal adhesion to A549 human alveolar epithelial cells was investigated. Confocal microscopy showed that some PM10 and below sized particles had sharp or angular 3D appearance. SEM x-ray analysis indicated silicate particles with calcium, aluminium and iron. We observed increased colony forming units indicating increased Pneumococcal adhesion due to exposure of cells to volcanic particles. Thus in addition to the toxic nature of some volcanic particles, we suggest that the observed sharp surface particle features may help to explain adverse health effects associated with volcanic eruptions.
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Imagenología Tridimensional , Erupciones Volcánicas , Humanos , Erupciones Volcánicas/análisis , España , Pulmón , Microscopía ConfocalRESUMEN
Background: Unilateral posterior crossbite (UPC) with functional shift is a malocclusion that may have the potential to affect the masticatory function and the flexibility of the spine due to intrinsic occlusal, structural and functional asymmetries sustained by marked asymmetrical muscular activation. Research question: To investigate whether the presence of UPC with functional shift is associated with reverse chewing pattern and altered spine flexion. Methods: Patients with UPC and a control group of patients with normal occlusion were recorded when chewing soft and hard boluses using a Kinesiograph (Myotronics-Noromed Inc., USA) and spine alignment was assessed with an electronic inclinometer Spinal Mouse® system (Idiag AG, Switzerland). Results: There were 87 children with UPC in the patients' group among whom 38, with median (IQR) age 8.0 (7.3-9.3) years, had measurements before and after treatment. The UPC patients showed a higher percentage of anomalous/reverse chewing patterns on the crossbite side compared with a control group (p < 0.001). Moreover, a clear difference was observed between left and right flexion angles of the spine in the patients' group (p < 0.001 and p = 0.001, paired t-test) with the crossbite side being more flexible compared to the non-crossbite side. No such differences were seen in the control group, nor post-treatment for right and left crossbite (p = 0.44 and p = 0.15 respectively, paired t-test). Significance: This study suggests an association between UPC, asymmetrical chewing patterns and asymmetrical flexion of the spine. These results may help improve understanding of any association between dental malocclusions and spine posture and hence aid diagnosis and treatment strategies.
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Frecuencia Respiratoria , Infecciones del Sistema Respiratorio , Humanos , Niño , LactanteRESUMEN
BACKGROUND: Reducing the global new-born mortality is a paramount challenge for humanity. There are approximately 786,323 live births in the UK each year according to the office for National Statistics; around 10% of these newborn infants require assistance during this transition after birth. Each year around, globally around 2.5 million newborns die within their first month. The main causes are complications due to prematurity and during delivery. To act in a timely manner and prevent further damage, health professionals should rely on accurate monitoring of the main vital signs heart rate and respiratory rate. AIMS: To present a clinical perspective on innovative, non-invasive methods to monitor heart rate and respiratory rate in babies highlighting their advantages and limitations in comparison with well-established methods. METHODS: Using the data collected in our recently published systematic review we highlight the barriers and facilitators for the novel sensor devices in obtaining reliable heart rate measurements. Details about difficulties related to the application of sensors and interfaces, time to display, and user feedback are explored. We also provide a unique overview of using a non-invasive respiratory rate monitoring method by extracting RR from the pulse oximetry trace of newborn babies. RESULTS: Novel sensors to monitor heart rate offer the advantages of minimally obtrusive technologies but have limitations due to movement artefact, bad sensor coupling, intermittent measurement, and poor-quality recordings compared to gold standard well established methods. Respiratory rate can be derived accurately from pleth recordings in infants. CONCLUSION: Some limitations have been identified in current methods to monitor heart rate and respiratory rate in newborn babies. Novel minimally invasive sensors have advantages that may help clinical practice. Further research studies are needed to assess whether they are sufficiently accurate, practical, and reliable to be suitable for clinical use.
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OBJECTIVE: There is a lack of objective measures to assess children with acute wheezing episodes. Increased respiratory rate (RR) and pulsus paradoxus (PP) are recognised markers, but poorly recorded in practice. We examined whether they can be reliably assessed from a pulse oximeter plethysmogram ('pleth') trace and predict clinical outcome. PATIENTS AND METHODS: We studied 44 children aged 1-7 years attending hospital with acute wheeze, following initial 'burst' bronchodilator therapy (BT), and used custom software to measure RR and assess PP from oximeter pleth traces. Traces were examined for quality, and the accuracy of the RR measurement was validated against simultaneous respiratory inductive plethysmography (RIP). RR and PP at 1 hour after BT were compared with clinical outcomes. RESULTS: RR from pleth and RIP showed excellent agreement, with a mean difference (RIP minus pleth) of -0.5 breaths per minute (limits of agreement -3.4 to +2.3). 52% of 1 min epochs contained 10 s or more of pleth artefact. At 1 hour after BT, children who subsequently required intravenous bronchodilators had significantly higher RR (median (IQR) 63 (62-66) vs 43 (37-51) breaths per minute) than those who did not, but their heart rate and oxygen saturation were similar. Children with RR ≥55 per minute spent longer in hospital: median (IQR) 30 (22-45) vs 10 (7-21) hours. All children who subsequently required hospital admission had PP-analogous pleth waveforms 1 hour after BT. CONCLUSION: RR can be reliably measured and PP detected from the pulse oximeter pleth trace in children with acute wheeze and both markers predict clinical outcome. TRIAL REGISTRATION NUMBER: UKCRN15742.
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Frecuencia Respiratoria , Ruidos Respiratorios , Niño , Humanos , Frecuencia Respiratoria/fisiología , Oximetría , Monitoreo Fisiológico , Oxígeno , Frecuencia CardíacaRESUMEN
Echocardiography was combined with pulse oximetry plethysmography to investigate postnatal cardiovascular adaptation in late preterm and term infants. Median (IQR) pleth variability decreased over three days and similar, day2 15%(12-18%) preterm versus 16%(15-18%) term infants. Median (IQR) pulse transit time heart rate normalised was lower in term babies, day2 0.55(0.51-0.63) versus 0.64(0.62-0.68).
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Corazón , Oximetría , Ecocardiografía , Frecuencia Cardíaca/fisiología , Humanos , Lactante , Recién Nacido , Oximetría/métodos , Estudios ProspectivosRESUMEN
BACKGROUND: Commonly used methods of CTG classification do not reliably predict neonatal hypoxic-ischemic encephalopathy (HIE). OBJECTIVE: To examine whether a relationship exists between the types of hypoxia as identified on the cardiotocograph using novel physiology-based CTG classification and patterns of injury on neonatal cerebral MRI and later neurodevelopmental outcomes. STUDY DESIGN: A retrospective study of term-born infants admitted to four neonatal units with HIE as part of a brain injury biomarkers study between January 2014 and December 2015. Intrapartum CTG traces were analyzed by two obstetricians trained in physiological CTG classification, blind to neonatal outcomes. Neonatal cerebral MR images were assessed independently by a neuroradiologist and an expert neonatologist. CTG traces were classified into types of hypoxia and allocated to groups; (1) chronic hypoxia or antepartum injury; (2) gradually evolving or subacute hypoxia; and (3) acute hypoxia. RESULTS: Of 106 infants recruited to the study, records were available for 58 cases. Of these, CTGs were available for 37. All 37 had abnormal CTGs. Twenty-four infants, all of whom had received therapeutic hypothermia had cerebral MRI. Fourteen of the 24 (58%) infants had abnormal MRI. In group 1 (chronic hypoxia/antenatal injury), total brain injury was most predominant (4/6 infants). Group 2 (gradually evolving/subacute hypoxia) was associated with peripheral brain injury (5/5 infants). Group 3 (acute hypoxia) was associated with basal-ganglia thalamic injury pattern (3/3 infants). Later neurodevelopmental outcomes were available for 35 cases. Infants suspected to have a pre-labor injury on CTG (group 1) had a higher proportion of adverse neurodevelopmental outcomes (4/10, 40%) compared to groups 2 and 3 (4/25, 16%). CONCLUSION: Using this novel physiology-based CTG classification, we demonstrate an association between types of hypoxia observed on the CTG and MRI patterns of hypoxic brain injury. Infants with CTG trace suggestive of chronic hypoxia or other antenatal injuries were overrepresented in this cohort and were also more likely to have a poor neurodevelopmental outcome.
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Lesiones Encefálicas , Hipoxia-Isquemia Encefálica , Lactante , Recién Nacido , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Hipoxia-Isquemia Encefálica/terapia , Imagen por Resonancia Magnética/métodos , Hipoxia/diagnóstico por imagenRESUMEN
Monitoring patent ductus arteriosus (PDA) in premature infants is currently performed intermittently using echocardiography which requires considerable expertise. The aim of this pilot study was to investigate whether PDA status could be assessed from standard neonatal intensive care monitoring. Electrocardiography (ECG) and blood pressure (BP) waveforms were acquired from extremely preterm infants using standard neonatal monitors. We developed software using MATLAB to analyse ECG and BP waveforms and their interrelationships in terms of pulse transit time (PTT) and pulse wave velocity (PWV). The times from peak systolic BP to diastolic trough (BPFt) and from the diastolic trough to peak systolic BP (BPRt) were also calculated. PTT, BPFt and BPRt were normalised for heart rate (HR) termed NPTT, NBPFt and NBPRt, respectively. ECG, invasive aortic BP monitoring and echocardiography were performed in 14 preterm infants < 29 weeks' gestation in the first 3 days after birth. The median (range) birth weight of the infants was 0.90 (0.48-1.31) kg, gestation 26.6 (24.0-28.7) weeks, PDA diameter 1.6 (0.8-3.6) mm and mean BP 32 (16-40) mmHg. We found a significant positive correlation between PDA diameter and NPTT (r = 0.69, P = 0.007) as well as NBPFt (r = 0.65, P = 0.012) and NBPRt (r = 0.71, P = 0.005). No relationship was found between PDA diameter and pulse pressure.Conclusions: Interrelationships between ECG and BP traces as well as BP waveform time analysis are straightforward to measure and associated with PDA diameter. The results of this pilot study suggest that this approach may help provide biomarkers for continuous monitoring PDA diameter and function. What is Known: ⢠Patent ductus arteriosus (PDA) in premature infants is associated with increased risk of developing chronic lung disease, necrotising enterocolitis and cerebral injury. ⢠Currently PDA is assessed intermittently using echocardiography which requires considerable expertise and sometimes is not well tolerated by critically ill preterm infants. What is New: ⢠Blood pressure (BP) and ECG waveform interrelation and BP trace time analysis, taking account of heart rate, relate to PDA diameter. ⢠ECG and BP waveform phase difference as well as BP waveform time analysis may be useful in the continuous assessment of PDA function.
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Conducto Arterioso Permeable , Conducto Arterioso Permeable/diagnóstico por imagen , Humanos , Ibuprofeno/uso terapéutico , Lactante , Recien Nacido Extremadamente Prematuro , Recién Nacido , Cuidado Intensivo Neonatal , Proyectos Piloto , Análisis de la Onda del PulsoRESUMEN
BACKGROUND: Cycling consists of alternating periods of reduced and normal fetal heart variability, reflecting changes in fetal behavioral states. Occurrence of active and quiet sleep cycles is considered to be a hallmark of fetal autonomic nervous system integrity, demonstrating healthy interaction between the parasympathetic and sympathetic nervous systems. Cycling is an overlooked feature in most international cardiotocography (CTG) guidelines. The authors tested the hypothesis that fetuses showing no cycling in the intrapartum period have poorer outcomes. AIM: To investigate whether the absence of cycling at the commencement of intrapartum fetal monitoring is associated with poorer neonatal outcomes (umbilical arterial cord pH, Apgar scores and neonatal unit admission). METHODS: Analysis of a database of sequentially acquired intrapartum CTG traces from a single center. Only cases of singleton pregnancies over 36 weeks gestation in cephalic presentation with recorded umbilical artery cord pH were considered. Neonatal outcomes were assessed based on umbilical cord artery pH, Apgar ≤7 at 5 min and unexpected admission to the neonatal unit. Intrapartum pyrexia, presence of meconium-stained amniotic fluid and mode of delivery were also recorded. RESULTS: A total of 684 cases were analyzed. Absence of cycling from the beginning of the intrapartum CTG recording was noted in 5% of cases. Cases with no cycling were more likely to have maternal pyrexia (≥37.8 °C) (p = .006) and Apgars ≤7 at 5 min (p = .04). There was an association between increasing baseline fetal heart rate and the proportion of cases with no cycling. There was no significant difference between the two groups with regard to the mode of delivery or umbilical cord arterial pH <7.05 (p = .53). CONCLUSION: Absence of cycling is associated with intrapartum maternal pyrexia and fetuses with the absence of cycling are more likely to have poorer perinatal outcomes measured by Apgar ≤ 7 at 5 min, despite no association with fetal acidosis. Results from this research were presented at the XXVI European Congress of Perinatal Medicine in September 2018.
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Acidosis , Cardiotocografía , Recién Nacido , Femenino , Embarazo , Humanos , Cardiotocografía/métodos , Frecuencia Cardíaca Fetal/fisiología , Puntaje de Apgar , Acidosis/diagnóstico , Fiebre/diagnósticoRESUMEN
INTRODUCTION AND HYPOTHESIS: Posterior compartment prolapse is associated with severe morbidity including faecal incontinence and defaecation dysfunction. The aim of this study was to develop and validate a novel ultrasound marker (anal canal to pubis angle) for the assessment of the anal axis in the context of posterior compartment prolapse in women and in controls (healthy, nulliparous, non-pregnant volunteers). METHODS: Anal canal to pubis (AC/Pubis) angle is measured with 2D transperineal ultrasound in precisely the midsagittal plane. The image was inverted and zoomed out and the angle opened to 107° (maximum). The image includes the pubis, urethra and anal canal. The angle measurement starts from the anal canal, pivots on the anorectal junction and ends at the shadow of the pubis. Inter- and intra-observer agreement in AC/Pubis angle measurement was assessed and the angles measured in the two groups compared. RESULTS: Forty women with posterior prolapse and 17 controls were included. Close agreement was observed in inter- and intra-observer AC/Pubis angle measurements assessed with Bland-Altman analysis. AC/Pubis angle is significantly wider in prolapse patients compared to controls (t-test, p < 0.001), with mean AC/Pubis angle in prolapse patients 122.9° (SD 15.6°) and controls 98.2° (SD 15.9°). CONCLUSION: The AC/Pubis angle is a novel validated 2D ultrasound technique for the assessment of the anorectal axis that potentially can be performed using equipment that is widely available in routine clinical practice. The AC/Pubis angle is significantly wider in prolapse patients compared to controls.
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Canal Anal , Incontinencia Fecal , Canal Anal/diagnóstico por imagen , Incontinencia Fecal/diagnóstico por imagen , Femenino , Humanos , Hueso Púbico , Recto/diagnóstico por imagen , UltrasonografíaRESUMEN
The ability of mycoplasmas to persist on surfaces has been widely acknowledged, despite their fastidious nature. However, the organism's capability to form a recognisable biofilm structure has been identified more recently. In the current study Mycoplasma fermentans was found to adhere to the glass surface forming highly differentiated biofilm structures. The volumes of biofilm microcolonies were quantified and observed to be greater at late growth stage than those at early growth stage. The channel diameters within biofilms were measured with Scanning Electron Microscopy images and found to be consistent with the size observed in Confocal Laser Scanning Microscope images. The combination of imaging methods with 3D visualisation provides key findings that aid understanding of the mycoplasma biofilm formation and true biofilm architecture. The observations reported here provide better understanding of the persistence of these minimalist pathogens in nature and clinical settings.
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Biopelículas/crecimiento & desarrollo , Mycoplasma fermentans , Microscopía ConfocalRESUMEN
To date, diesel particulate matter (DPM) has been described as aggregates of spherule particles with a smooth appearing surface. We have used a new colour confocal microscope imaging method to study the 3D shape of diesel particulate matter (DPM); we observed that the particles can have sharp jagged appearing edges and consistent with these findings, 2D light microscopy demonstrated that DPM adheres to human lung epithelial cells. Importantly, the slide preparation and confocal microscopy method applied avoids possible alteration to the particles' surfaces and enables colour 3D visualisation of the particles. From twenty-one PM10 particles, the mean (standard deviation) major axis length was 5.6 (2.25) µm with corresponding values for the minor axis length of 3.8 (1.25) µm. These new findings may help explain why air pollution particulate matter (PM) has the ability to infiltrate human airway cells, potentially leading to respiratory tract, cardiovascular and neurological disease.
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Contaminantes Atmosféricos , Material Particulado , Contaminantes Atmosféricos/análisis , Humanos , Imagenología Tridimensional , Microscopía Confocal , Material Particulado/análisis , Emisiones de Vehículos/análisisRESUMEN
INTRODUCTION: The purpose of this quantitative investigation was to assess the influence of lip prominence in relation to the esthetic line (E-line) on perceived attractiveness and threshold values of desire for treatment. METHODS: The lip prominence of an idealized silhouette male white profile image was altered incrementally between -16 mm to 4 mm from the E-line. The images were rated on a Likert scale by pretreatment orthognathic patients (n = 75), laypeople (n = 75), and clinicians (n = 35). RESULTS: In terms of perceived attractiveness, lips to E-line distance within the ranges of -12 mm to -16 mm and 0-4 mm in relation to the E-line was associated with a reduction in median attractiveness scores to below 4 in the patient and clinician groups of observers; for the lay group, the corresponding ranges were -14 mm to -16 mm and 2-4 mm. Relative lip prominence appears to be viewed as more attractive than lip retrusion. Clinicians were generally least likely to suggest treatment for varying levels of bilabial position. For a number of the images, there was reasonable agreement among clinicians and laypeople regarding whether treatment is required. For the clinician group, the only categories for desire for treatment were at a lip to E-line distance within the ranges of -14 mm to -16 mm and 2-4 mm. CONCLUSIONS: It is recommended that the range of normal variability of the prominence of the lips and threshold values of the desire for treatment be considered in planning.
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Estética Dental , Labio , Humanos , MasculinoRESUMEN
BACKGROUND: The human mandible is variable in shape, size and position and any deviation from normal can affect the facial appearance and dental occlusion. OBJECTIVES: The objectives of this study were to determine whether the Sassouni cephalometric analysis could help predict two-dimensional mandibular shape in humans using cephalometric planes and landmarks. MATERIALS AND METHODS: A retrospective computerised analysis of 100 lateral cephalometric radiographs taken at Kingston Hospital Orthodontic Department was carried out. RESULTS: Results showed that the Euclidean straight-line mean difference between the estimated position of gonion and traced position of gonion was 7.89 mm and the Euclidean straight-line mean difference between the estimated position of pogonion and the traced position of pogonion was 11.15 mm. The length of the anterior cranial base as measured by sella-nasion was positively correlated with the length of the mandibular body gonion-menton, r = 0.381 and regression analysis showed the length of the anterior cranial base sella-nasion could be predictive of the length of the mandibular body gonion-menton by the equation 22.65 + 0.5426x, where x = length of the anterior cranial base (SN). There was a significant association with convex shaped palates and oblique shaped mandibles, p = 0.0004. CONCLUSIONS: The method described in this study can be used to help estimate the position of cephalometric points gonion and pogonion and thereby sagittal mandibular length. This method is more accurate in skeletal class I cases and therefore has potential applications in craniofacial anthropology and the 'missing mandible' problem in forensic and archaeological reconstruction.
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The search for an ocular drug delivery system that could provide long-acting effects without a detriment to the anatomy and physiology of the eye remains a challenge. Polyphenolic compounds (curcumin in particular) have recently gained popularity due to their powerful antioxidant properties; yet curcumin suffers poor stability and water solubility. A conventional eye drop formulation of curcumin in the form of a suspension is likely to suffer a short duration of action requiring multiple instillations. On the other hand, polymeric in-situ gelling inserts offer the prospect of overcoming these limitations. The aim of this study was to prepare, characterize and evaluate in vivo, polymeric, in-situ gelling and mucoadhesive inserts for ocular surface delivery of curcumin. Different types and ratios of biocompatible polymers (HPMC, CMC, PL 127 and PVA) and three plasticizers along with the solvent casting method were adopted to prepare curcumin inserts. The inserts were investigated for their physicochemical characteristics, applicability, and suitability of use for potential placement on the ocular surface. The prepared inserts revealed that curcumin was mainly dispersed in the molecular form. Insert surfaces remained smooth and uniform without cracks appearing during preparation and thereafter. Improved mechanical and mucoadhesive properties, enhanced in vitro release (7.5- to 9-fold increases in RRT300 min) and transcorneal permeation (5.4- to 8.86-fold increases in Papp) of curcumin was achieved by selected in-situ gelling inserts compared to a control curcumin suspension. The developed inserts demonstrated acceptable ocular tolerability, enhanced corneal permeability, and sustained release of curcumin along with retention of insert formulation F7 on the ocular surface for at least two-hours. This insert provides a viable alternative to conventional eye drop formulations of curcumin.
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OBJECTIVES: Cinch sutures attempt to counteract alar base widening but may lead to unintended increases in the nasolabial angle and nasal tip elevation. The aim of this investigation was to assess nasolabial angle changes after maxillary osteotomies with and without alar base cinch sutures in the short and long terms. STUDY DESIGN: Seventy-eight patients were assessed, with 51 in the cinch group (38 females, 13 males; age range 16-39 years) and 27 in the no-cinch group (12 females, 15 males; age range 17-27 years). The upper component (nasal tip elevation), lower component (lower lip inclination), and the overall nasolabial angle were measured on preoperative, postoperative, and long-term follow-up lateral cephalometric radiographs. RESULTS: The overall nasolabial angle (P = .006) and its upper component (P < .001) increased significantly in the cinch group immediately postoperatively but resolved by 6 to 12 months for the overall nasolabial angle and by 12+ months (up to 5.7 years) for the upper component. There were no significant changes in the no-cinch group. CONCLUSIONS: In the short term, the alar base cinch suture increases nasal tip elevation and the overall nasolabial angle. In the long term, there was no significant difference, suggesting that the initial nasal tip elevation resolves over time and that the cinch suture may have a limited effect on nasal tip elevation in the longer term.