Distribution and factors associated with salivary secretory leukocyte protease inhibitor concentrations.

OBJECTIVES: This cross-sectional study examined the distribution and correlates of salivary secretory leukocyte protease inhibitor (SLPI) concentrations within a multinational cohort of men. METHODS: Extracellular SLPI was measured in oral gargle cell supernatants of 378 men from three countries using an ELISA-based assay. Risk factor data were collected by a questionnaire. Factors associated with SLPI were assessed using linear and logistic regression for continuous and categorical SLPI, respectively. RESULTS: Among men aged 18-73 years, the median SLPI concentration was 492.0 ng ml-1 (range: 2.3-1919.9). In multivariable modeling, men in Brazil and younger men (18-30 years) were more likely to have higher levels of SLPI [adjusted odds ratio (aOR) 3.84; 95% confidence interval (CI): 1.94-7.59, and aOR 3.84; 95% CI: 1.98-7.43, respectively]. Men with a self-reported sexually transmitted diseases diagnosis in the past 6 months were more likely to have higher SLPI levels (aOR 2.98; 95% CI: 1.1-7.83) and men reporting bleeding/swollen gums were less likely to have higher SLPI (aOR 0.34; 95% CI: 0.15-0.79). Similar results were observed for linear regression models. CONCLUSIONS: Secretory leukocyte protease inhibitor concentrations varied significantly by country and decreased with increasing age. The interaction between SLPI, modifiable factors, and oral infections that influence cancer risk warrants further investigation.

Bevacizumab compared with diode laser in stage 3 posterior retinopathy of prematurity: A 5 year follow up.

We conducted a prospective randomized study to compare outcomes of intravitreal Bevacizumab versus diode laser in thirty eyes of fifteen premature babies with zone 1 or posterior zone 2 retinopathy of prematurity (ROP). We recorded complications, regression/reactivation of ROP, visual outcome, refractive error and systemic complications. The Bevacizumab treated eyes showed rapid regression of the ROP with resolution of plus disease and flattening of the ridge at 48 hours post injection. In 3 Bevacizumab treated eyes, reactivation occurred and were treated with laser (3 eyes) or a further Bevacizumab injection (1 eye). Of the diode laser treated eyes, one showed progression and was treated with Bevacizumab. At 5 year follow up, good outcomes were observed in both treatment groups. Hoever, less myopia was found in the Bevacizumab compared with the diode laser treated eyes.

MouseMine: a new data warehouse for MGI.

MouseMine (www.mousemine.org) is a new data warehouse for accessing mouse data from Mouse Genome Informatics (MGI). Based on the InterMine software framework, MouseMine supports powerful query, reporting, and analysis capabilities, the ability to save and combine results from different queries, easy integration into larger workflows, and a comprehensive Web Services layer. Through MouseMine, users can access a significant portion of MGI data in new and useful ways. Importantly, MouseMine is also a member of a growing community of online data resources based on InterMine, including those established by other model organism databases. Adopting common interfaces and collaborating on data representation standards are critical to fostering cross-species data analysis. This paper presents a general introduction to MouseMine, presents examples of its use, and discusses the potential for further integration into the MGI interface.

Evidence of soft dipole resonance in

The first conclusive evidence of a dipole resonance in ^{11}Li having isoscalar character observed from inelastic scattering with a novel solid deuteron target is reported. The experiment was performed at the newly commissioned IRIS facility at TRIUMF. The results show a resonance peak at an excitation energy of 1.03±0.03 MeV with a width of 0.51±0.11 MeV (FWHM). The angular distribution is consistent with a dipole excitation in the distorted-wave Born approximation framework. The observed resonance energy together with shell model calculations show the first signature that the monopole tensor interaction is important in ^{11}Li. The first ab initio calculations in the coupled cluster framework are also presented.

Patient motivation and satisfaction from orthognathic surgery-a case series.

OBJECTIVE: This study attempted to understand the specific motivations of patients who undergo orthognathic surgery and determine their satisfaction with the surgery. The study also assessed the prevalence of complications and how they may impact patient satisfaction. STUDY DESIGN: Patients who underwent orthognathic surgery at the University of California between 2016 and 2019 and had completed postoperative orthodontic treatment for ≥9 months were interviewed. They responded to an open-ended telephone interview regarding their motivations, satisfaction, and complications. RESULTS: The patients showed a high level of satisfaction with the surgery, but there were persistent complications that affected satisfaction. The predominant complication was paresthesia over the distribution of the inferior alveolar nerve. The majority of patients who reported prior headaches and temporomandibular joint problems described improvement in those areas. Comparing the patients' motivations before and after surgery showed that before surgery, patients reported functional concerns, whereas postoperatively they were much more likely to recall aesthetic reasons for the surgery. CONCLUSION: This study showed that although patients are generally satisfied after orthognathic surgery, patients need to be realistically informed of their expectations and adequately informed of possible complications.

Mesna-induced photodistributed dermatosis.

We present the case of a 41-year-old man who developed a photodistributed eruption 1 month after being started on 2-mercaptoethane sulfonate sodium (mesna) for treatment of cyclophosphamide-induced haemorrhagic cystitis. The patient had a background history of Wegener granulomatosis, and had been taking cyclophosphamide at a stable dose of 150 mg daily for the previous 3 years. Complete resolution of the rash occurred within 8 weeks of cessation of mesna. This is the first reported case, to our knowledge, of mesna-induced photodistributed dermatosis. Early recognition of this condition will ensure prompt cessation of the culprit medication, and consideration of alternative management of haemorrhagic cystitis.

Impulsivity and self-control in elementary school children and adult females: Using identical task and procedural parameters.

Results of studies examining the relationship between impulsivity and age are limited because different tasks, procedural parameters, and different reinforcers have been used with different aged participants. Thus, the current study sought to rectify these differences in two experiments with children (42, ages 5-12) and adults (69 college-aged females) using the same task with identical procedural parameters. In the Self-Control Video Software Task (SCVST; Forzano and Schunk, 2008; Forzano et al., 2014) participants repeatedly choose between larger, more delayed and smaller, less delayed access to viewing video cartoons. No differences in impulsivity were found between adults and children. No age or gender differences were found among children. Differences in task and procedural parameters are identified as important in their implications for research on impulsivity.

Merkel cell carcinoma metastasis to the iris in a 23 year old female.

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine malignancy which predominantly affects elderly caucasians. The pathogenesis is poorly understood but ultraviolet light and immunosuppression have both been implicated. MCC most commonly arises on sun exposed areas of the head and neck or extremities and has a propensity for local recurrence and regional lymph node metastasis. It may present as a violaceous or non specific firm nodule or as a small plaque. Histological diagnosis can be difficult and electron microscopy or immunohistochemistry are frequently required in addition to light microscopy. Management is stage dependant and frequently involves wide surgical excision with or without chemotherapy or radiation therapy. Early diagnosis and complete surgical excision is associated with a favourable prognosis. However, aggressive tumours with regional recurrence or distant metastases result in a median survival of 9 months. Reports of primary MCC of the eyelids have been reported in the literature. Intra-ocular metastases to the choroid and ciliary body have also been reported.

Machine Learning Algorithm Helps Identify Non-Diagnosed Prodromal Alzheimer's Disease Patients in the General Population.

BACKGROUND: Recruiting patients for clinical trials of potential therapies for Alzheimer's disease (AD) remains a major challenge, with demand for trial participants at an all-time high. The AD treatment R and D pipeline includes around 112 agents. In the United States alone, 150 clinical trials are seeking 70,000 participants. Most people with early cognitive impairment consult primary care providers, who may lack time, diagnostic skills and awareness of local clinical trials. Machine learning and predictive analytics offer promise to boost enrollment by predicting which patients have prodromal AD, and which will go on to develop AD. OBJECTIVES: The authors set out to develop a machine learning predictive model that identifies prodromal AD patients in the general population, to aid early AD detection by primary care physicians and timely referral to expert sites for biomarker confirmation of diagnosis and clinical trial enrollment. DESIGN: The authors use a classification machine learning algorithm to extract patterns within healthcare claims and prescription data three years prior to AD diagnosis/AD drug initiation. SETTING: The study focused on subjects included within proprietary IQVIA US data assets (claims and prescription databases). Patient information was extracted from January 2010 to July 2018, for cohorts aged between 50 and 85 years. PARTICIPANTS: A total of 88,298,289 subjects aged between 50 and 85 years were identified. For the positive cohort, 667,288 subjects were identified who had 24 months of medical history and at least one record with AD or AD treatment. For the negative cohort, 3,670,254 patients were selected who had a similar length of medical history and who were matched to positive cohort subjects based on the prevalence rate. The scoring cohort was selected based on availability of recent medical data of 2-5 years and included 72,670,283 subjects between the ages of 50 and 85 years. Intervention (if any): None. MEASUREMENTS: A list of clinically-relevant and interpretable predictors was generated and extracted from the data sets for each subject, including pharmacological treatments (NDC/product), office/specialist visits (specialty), tests and procedures (HCPCS and CPT), and diagnosis (ICD). The positive cohort was defined as patients who have AD diagnosis/AD treatment with a 3 years offset as an estimate for prodromal AD diagnosis. Supervised ML techniques were used to develop algorithms to predict the occurrence of prodromal AD cases. The sample dataset was divided randomly into a training dataset and a test dataset. The classification models were trained and executed in the PySpark framework. Training and evaluation of LogisticRegression, DecisionTreeClassifier, RandomForestClassifier, and GBTClassifier were executed using PySpark's mllib module. The area under the precision-recall curve (AUCPR) was used to compare the results of the various models. RESULTS: The AUCPRs are 0.426, 0.157, 0.436, and 0.440 for LogisticRegression, DecisionTreeClassifier, RandomForestClassifier, and GBTClassifier, respectively, meaning that GBTClassifier (Gradient Boosted Tree) outperforms the other three classifiers. The GBT model identified 222,721 subjects in the prodromal AD stage with 80% precision. Some 76% of identified prodromal AD patients were in the primary care setting. CONCLUSIONS: Applying the developed predictive model to 72,670,283 U.S. residents, 222,721 prodromal AD patients were identified, the majority of whom were in the primary care setting. This could drive major advances in AD research by enabling more accurate and earlier prodromal AD diagnosis at the primary care physician level , which would facilitate timely referral to expert sites for in-depth assessment and potential enrolment in clinical trials.

Necrobiotic xanthogranuloma occurring in an eyelid scar.

We present a case report of necrobiotic xanthogranuloma (NXG) in a 76-year-old Caucasian lady occurring as a nodule in a blepharoplasty scar. NXG is a rare histiocytic disease with progressive orbital and systemic features. Management options of excision biopsy or chemotherapy are discussed.

Golf--recognising the risk of severe eye injury.

Golf related ocular injuries are uncommon but frequently result in severe injury necessitating removal of the eye. As golf increases in popularity, it is vital that awareness is raised among both players and spectators regarding the potential hazards. We determined the nature and frequency of golf related eye injury at our unit from 1990 to 2007. Patient age, nature of injury, management and visual outcome were documented. 10 patients (7 adults, 3 children) sustained golf related eye trauma over this time. 7 cases involved injury inflicted by a golf ball and 3 by a golf club. 7 eyes required enucleation or evisceration. Visual acuity in the remaining 3 eyes ranged from 6/6 to less than 6/60. Golf related ocular injuries while uncommon, frequently have devastating consequences. Public awareness must be raised in order to promote greater safety on the golf course.

A comparison of the pharmacological properties of guinea-pig and human recombinant 5-HT4 receptors.

BACKGROUND AND PURPOSE: 5-HT(4) receptor agonists are used therapeutically to treat disorders of reduced gastrointestinal motility. Since such compounds are evaluated in guinea-pigs, we cloned, expressed and pharmacologically characterized the guinea-pig 5-HT(4) and human 5-HT(4(b)) splice variant, which share 95% homology. The functional properties of guinea-pig 5-HT(4(b)) receptors were compared with native receptors in guinea-pig colon. EXPERIMENTAL APPROACH: Membrane radioligand binding and whole cell cAMP accumulation assays were used to determine the affinities, potencies and intrinsic activities (IA). Contraction of the guinea-pig distal colon longitudinal muscle myenteric plexus preparation (LMMP) was monitored to evaluate functional activity. KEY RESULTS: pK(i) values for guinea-pig and human recombinant receptors, and guinea-pig striatum 5-HT(4) receptors, were in agreement, as were the potency and IA values for guinea-pig and human 5-HT(4) receptors expressed at a similar density ( approximately 0.2 pmol mg(-1) protein). Tegaserod was a potent (pEC(50)=8.4 and 8.7, respectively), full agonist at both guinea-pig and human 5-HT(4) receptors. In contrast, in the LMMP preparation, tegaserod was a potent, partial agonist (pEC(50)=8.2; IA=66%). CONCLUSIONS AND IMPLICATIONS: Close agreement between the pharmacological properties of guinea-pig and human 5-HT(4) receptors support the use of guinea-pig model systems for the identification of 5-HT(4) receptor therapeutics. However, the mechanisms underlying the different agonist properties of tegaserod in recombinant and isolated tissue preparations, and the extent to which these impact the clinical efficacy of tegaserod as a prokinetic agent, remain to be determined.

The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone.

This study characterized the pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, its metabolite, ADL 08-0011, and methylnaltrexone. The activities of the compounds were investigated with respect to human or guinea pig opioid receptor binding and function in recombinant cell lines and mechanical responsiveness of the guinea pig ileum. Alvimopan and ADL 08-0011 had higher binding affinity than methylnaltrexone at human mu opioid receptors (pK (i) values of 9.6, 9.6, and 8.0, respectively). The compounds had different selectivities for the mu receptor over human delta and guinea pig kappa opioid receptors. ADL 08-0011 had the highest mu receptor selectivity. With respect to their mu opioid receptor functional activity ([(35)S]GTPgammaS incorporation), methylnaltrexone had a positive intrinsic activity, consistent with partial agonism, unlike alvimopan and ADL 08-0011, which had negative intrinsic activities. Alvimopan, ADL 08-0011, and methylnaltrexone antagonized inhibitory responses mediated by the mu opioid agonist, endomorphin-1 (pA (2) values of 9.6, 9.4, and 7.6, respectively) and by U69593, a kappa opioid agonist (pA (2) values of 8.4, 7.2, and 6.7, respectively). In morphine-naive guinea pig ileum, methylnaltrexone reduced, while alvimopan and ADL 08-0011 increased, the amplitude of electrically evoked contractions and spontaneous mechanical activity. In tissue from morphine-dependent animals, alvimopan and ADL 08-0011 increased spontaneous activity to a greater degree than methylnaltrexone. The data suggested that alvimopan-induced contractions resulted predominantly from an interaction with kappa opioid receptors. It is concluded that alvimopan, ADL 08-0011, and methylnaltrexone differ in their in vitro pharmacological properties, particularly with respect to opioid receptor subtype selectivity and intrinsic activity. The clinical significance of the data from this study remains to be determined.

Changing pattern of childhood blindness.

All children under the age of 16 who fulfilled the criteria of blindness and low vision as defined by WHO were included in the study. These children were recruited from 1990 to 2004 from all the Ophthalmology Departments of Ireland, National Council of Blind and Visually impaired. Data was collected from history, detailed ocular examination and investigations including CT, MRI, ultrasound and chromosomal analysis. The prevalence of blindness in 2004 was 0.05% compared to 0.02% in 1989. The aetiologies were divided in (1) genetic, (2) prenatal, (3) perinatal, (4) childhood categories. The genetic group was 33% of the total, (15.63%) had albinism (11%) had retinal dystrophies. The perinatal group of 27% optic nerve hypoplasia, structural anomalies like microphthalmos, anophthalmos comprised of 15.85% and cataract (5.47%). The perinatal group was 26%, cortical blindness (17.45%), ROP (5.5%) and the childhood group comprised of 12.4% of the total. The overall prevalence of childhood blindness and low vision was shown to have increased compared to 1989. The most significant observation was the decrease in childhood blindness due to ROP, owing to the early diagnosis and treatment and an increase in brain blindness due to cortical disease and disability. This has been shown in other studies and is due to increased survival of preterm neonate.

Long term functional and structural outcomes of laser therapy for retinopathy of prematurity.

AIMS: To assess the long term functional and structural outcomes of premature babies who received diode laser photocoagulation for threshold retinopathy of prematurity (ROP). METHODS: 25 patients (43 eyes) treated with laser were recalled for assessment at a mean follow up of 11 years. A further seven patients (14 eyes) with subthreshold ROP, which had regressed spontaneously without laser treatment, were also examined. All children underwent distance acuity, near acuity, contrast sensitivity (CS), and colour vision assessments followed by a dilated fundal examination and cycloplegic autorefraction. RESULTS: The laser treated eyes had a mean distance visual acuity of 0.37 logMAR, a mean near visual acuity of 0.39 logMAR, a mean contrast sensitivity of 1.49 log CS units, and a mean spherical equivalent of -2.10D. An unfavourable distance visual acuity outcome occurred in five eyes (13.5%). An unfavourable near visual acuity outcome was also noted in the five eyes (13.5%) with poor distance visual outcome. 7% had an unfavourable structural outcome. On comparison with the control group, there was no significant difference in near acuity, CS, refraction, or colour vision between the two groups. However, there was a statistically significant difference in terms of distance visual acuity (p = 0.03). CONCLUSIONS: Laser treated eyes with favourable structural outcome have a good visual outcome. The results show a long term benefit from diode laser photocoagulation in preserving distance and near vision in eyes with threshold ROP.

RetCam image analysis of optic disc morphology in premature infants and its relation to ischaemic brain injury.

AIMS: To assess optic disc characteristics in premature infants with and without ischaemic brain injury and to evaluate the role of optic disc morphology in dating the injury. METHODS: RetCam fundal images, cranial ultrasounds and magnetic resonance imaging (MRI) of 109 premature infants were analysed. The study cohort was divided into subgroups depending on the presence or absence of periventricular leucomalacia (PVL) and intraventricular haemorrhage (IVH). The control group consisted of infants with normal neuroimaging at term and 2 years of age. Using the image analysis software of the RetCam, optic disc diameter (ODD), optic disc area (ODA), and optic cup area (OCA) were measured at 33-34 weeks gestational age. As serial cranial ultrasonography had been performed, it was possible to date the brain injury in those infants with periventricular white matter (PVWM) damage. RESULTS: Although there was a trend towards reducing ODD, ODA, and OCA with increasing severity of IVH, only the IVH 4 group differed significantly from the controls for these parameters (p = 0.002, p = 0.02, and p = 0.04, respectively). 44.4% of infants with grade 4 IVH had small discs. Only one patient had a large cup in a normal sized disc; this patient had IVH 4. In patients with PVWM damage, the median time of insult was 27 weeks in those with small discs and 28 weeks in those with normal discs. This difference was not significant (p = 0.23). CONCLUSIONS: Premature infants with IVH 4 have an increased incidence of optic nerve hypoplasia. We found no association between disc morphology and timing of brain injury.

Taxane-resistant lymphoepithelial-like carcinoma: excellent response to VIP chemotherapy.

BACKGROUND: Lymphoepithelial-like carcinoma is a rare tumour type. The optimal treatment for this disease is not known. No effective therapies are described in the literature. AIMS: This report describes a case of lymphoepithelial-like carcinoma and documents a therapeutic strategy which has proved effective. RESULTS: The patient was initially treated with a common platinum-based chemotherapy regimen incorporating a taxane (Carbplatin and Docetaxel). Disease stabilization initially occurred but the patient soon progressed. The patient was then treated with VIP chemotherapy and had a complete response. CONCLUSION: VIP chemotherapy appears to be an effective therapeutic strategy in lymphoepithelial-like carcinoma.