Assessment of Preanalytical Cerebrospinal Fluid Handling and Storage Factors on Measurement of Aß1-42, Aß1-40, and pTau181 Using an Automated Chemiluminescent Platform.

BACKGROUND: Standardizing cerebrospinal fluid (CSF) laboratory protocols will improve the reliability and availability of clinical biomarker testing required for prescription of novel Alzheimer disease (AD) therapies. This study evaluated several preanalytical handling and storage factors common to ß-amyloid1-42 (Aß1-42), ß-amyloid1-40 (Aß1-40), and phosphorylated tau (pTau181) concentrations including storage at different temperatures, extended cap contact, various mixing methods, and multiple freeze-thaw cycles. METHODS: Aß1-42, Aß1-40, and pTau181 concentrations were measured using LUMIPULSE G1200 automated assays. Samples were collected in polypropylene tubes of various volumes. Sample cap-contact was evaluated by storing samples in upright and inverted positions at either 4°C for 1 week or -80°C for 1 month. To assess mixing methods, samples were freeze-thawed and mixed by inversion, vortex, horizontal roller, or unmixed prior to assay sampling. The impact of successive freeze-thaw cycles was assessed through freezing, thawing, and analyzing CSF samples. RESULTS: Short-term storage at 4°C did not affect Aß1-42, Aß1-40, or pTau181 measurements in any tube type. Tube cap contact affected Aß1-42 in 2.5 mL tubes and pTau181 levels in 10 mL tubes. No difference was observed between mixing methods. After 4 freeze-thaw cycles, Aß1-42 significantly decreased but Aß1-40 remained unchanged. Utilizing the Aß1-42/Aß1-40 ratio, Aß1-42 values normalized, maintaining ratio values within ±5% of baseline measurements. CONCLUSIONS: Storage of CSF at 4°C for 1 week or -80°C for 1 month did not significantly affect Aß1-42, Aß1-40, pTau181, or associated ratio measurements. Tube cap-contact impacted pTau181 and pTau181/Aß1-42 values in larger tubes. Mixing methods are equivalent. The Aß1-42/Aß1-40 ratio compensates for freeze-thaw variability up to 4 cycles.

CSF Biomarkers Predict Gait Outcomes in Idiopathic Normal Pressure Hydrocephalus.

Background and Objectives: The assessment of biomarkers in selecting patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery has been limited to small cohort studies and those with limited follow-up. We assessed the potential for CSF biomarkers in predicting immediate response to CSF tap test (TT) and long-term response after shunt surgery. Methods: CSF was obtained from patients with iNPH referred for CSF TT after baseline assessment of cognition and gait. CSF neurofilament light (NfL), ß-amyloid 42 (Aß1-42), ß-amyloid 40 (Aß1-40), total tau (tTau), and phosphorylated tau 181 (pTau181) and leucine-rich alpha-2-glycoprotein-1 (LRG1) were measured by ELISA. The ability of these measures to predict immediate improvement following CSF TT and long-term improvement following shunt surgery was compared by univariate and adjusted multivariate regression. Results: Lower NfL, pTau181, tTau, and Aß1-40 were individually predictive of long-term improvement in gait outcomes after shunt surgery. A multivariate model of these biomarkers and MRI Evans index, adjusted for age, improved prediction (area under the receiver operating curve 0.76, 95% confidence interval 0.66-0.86). tTau, pTau181, and Aß1-40 levels were statistically different in those whose gait improved after CSF TT compared with those who did not. Using a multivariate model, combining these markers with Evans index and transependymal flow did not significantly improve prediction of an immediate response to CSF TT. Discussion: A combination of CSF biomarkers can predict improvement following shunt surgery for iNPH. However, these measures only modestly discriminate responders from nonresponders following CSF TT. The findings further suggest that abnormal CSF biomarkers in nonresponders may represent comorbid neurodegenerative pathology or a predegenerative phase that presents with an iNPH phenotype.

The Clinical Utility of the MOCA in iNPH Assessment.

Objectives: We sought to estimate reliable change thresholds for the Montreal Cognitive Assessment (MoCA) for older adults with suspected Idiopathic Normal Pressure Hydrocephalus (iNPH). Furthermore, we aimed to determine the likelihood that shunted patients will demonstrate significant improvement on the MoCA, and to identify possible predictors of this improvement. Methods: Patients (N = 224) presenting with symptoms of iNPH were given a MoCA assessment at their first clinic visit, and also before and after tap test (TT) or extended lumbar drainage (ELD). Patients who were determined to be good candidates for shunts (N = 71, 31.7%) took another MoCA assessment following shunt insertion. Reliable change thresholds for MoCA were derived using baseline visit to pre-TT/ELD assessment using nine different methodologies. Baseline characteristics of patients whose post-shunt MoCA did and did not exceed the reliable change threshold were compared. Results: All nine of reliable change methods indicated that a 5-point increase in MoCA would be reliable for patients with a baseline MoCA from 16 to 22 (38.4% of patients). Furthermore, a majority of reliable change methods indicated that a 5-point increase in MoCA would be reliable for patients with a baseline MoCA from 14 to 25. Reliable change thresholds varied across methods from 4 to 7 points for patients outside of this range. 10.1% had at least a 5-point increase from baseline to post-TT/ELD. Compared to patients who did not receive a shunt, patients who received a shunt did not have lower average MoCA at baseline (p = 0.88) or have better improvement in MoCA scores after the tap test (p = 0.17). Among shunted patients, 23.4% improved by at least 5 points on the MoCA from baseline to post-shunt. Time since onset of memory problems and post-TT/ELD gait function were the only clinical factors significantly associated with having a reliable change in MoCA after shunt insertion (p = 0.019; p = 0.03, respectively). Conclusions: In patients with iNPH, clinicians could consider using a threshold of 5 points for determining whether iNPH-symptomatic patients have experienced cognitive benefits from cerebrospinal fluid drainage at an individual level. However, a reliable change cannot be detected for patients with a baseline MoCA of 26 or greater, necessitating a different cognitive assessment tool for these patients.

Predictors of cognitive impairment in pseudotumor cerebri.

AIMS OF THE STUDY: We aimed to define the cognitive burden of the largest pseudotumor cerebri syndrome (PTCS) population to date, compare objective to subjective cognitive dysfunction, and determine clinical predictors of cognitive dysfunction amongst an array of previously unstudied factors. CLINICAL RATIONALE: Patients with PTCS commonly report cognitive dysfunction, a factor associated with poor quality of life. It is not definitively known whether cognitive impairment is present in these patients, and what features of the syndrome predict impairment. MATERIALS AND METHODS: We administered a cognitive battery consisting of the National Adult Reading Test, Mini-Mental Status Exam, Digit Span, Boston Naming Test, Rey Auditory Verbal Learning Test, Clock Drawing, Trail Making Test, Controlled Oral Word Association, and Category Fluency. Cognitive impairment was defined as mild-single domain with one test score, and mild-multiple domain with two scores, more than two standard deviations below the mean for age-, gender-, and education-adjusted norms. RESULTS: One-hundred and one prospectively recruited PTCS patients were enrolled. The objective testing showed 30 patients had mild-single domain impairment, and 25 had mild-multi domain impairment. More patients without objective cognitive impairment had transverse venous sinus stenosis, but otherwise the groups did not differ. Two measures of headache severity, the Headache Impact Test and pain on the Numeric Rating Scale, were negatively associated with the composite cognitive score, as was ocular pain, vision-related disability, and mental health. Opening pressure and visual function were not associated with objective cognitive impairment. We found no association between subjective and objective cognitive impairment. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients with PTCS may be cognitively impaired, and this correlates with measures of headache burden. Studies evaluating cognitive impairment before and after remission of the headache disorder would have to be performed to investigate this relationship further. Patients with self-perception of cognitive burden are no more likely to be cognitively impaired.

Ocular surface temperature measurement in diabetic retinopathy.

Infrared thermography provides functional imaging by picturing the temperature pattern of the region imaged. The temperature correlates to the blood flow pattern and is used in the diagnosis of diseases like breast cancer, peripheral vascular disorders, diabetic neuropathy and fever screening. In the present study, the usage of ocular thermography for diagnosis of diabetic retinopathy is explored. Ocular thermograms using infrared imaging camera were obtained for normal subjects (80 volunteers - 40 males and 40 females) age groups 21-30, 31-40, 41-50 and 51-60 years, non-proliferative diabetic retinopathy (NPDR) patients (50 volunteers -25 males and 25 females) and proliferative diabetic retinopathy (PDR) patients (20 volunteers -10 males and 10 females) belonging to age group of 51-60 years. The temperature at various points of interest (POIs) and horizontal temperature profiles were studied. Ocular surface temperature (OST) and effect of eye dilation on OST was studied for control, age matched NPDR and PDR. Statistical analyses were carried out to find the significance of correlation between OST of controls and NPDR and PDR. The global minimum temperature on the ocular surface for controls (21-60 years) was found to be at cornea which is about 34.79 ± 0.68 °C, and maximum at the inner canthus viz. 36.08 ± 0.62 °C. Dilation studies showed an average increase of 0.82 ± 0.13 °C in cornea and 0.75 ± 0.14 °C in conjunctiva and limbus (p < 0.001). The temperature of cornea is around 33.22 ± 0.12 °C and 32.64 ± 0.12 °C for NPDR and PDR patients respectively, in the age group of 51-60 years. OST of NPDR patients was 0.60 ± 0.15 °C lesser than that of age matched normal eyes (p < 0.001) at cornea and limbus regions and 0.71 ± 0.20 °C at inner canthus. The OST of PDR patients was lesser than age matched controls by 1.18 ± 0.12 °C at cornea, 0.9 ± 0.13 °C at inner canthus and 1.0 ± 0.14 °C at other POIs. During dilation studies a positive variation of 0.61 ± 0.12 °C in cornea and 0.48 ± 0.13 °C in conjunctiva and limbus was observed (p < 0.001) in NPDR eyes. Similarly an average increase of 0.62 ± 0.11 °C in cornea and an average increase of 0.47 ± 0.15 °C in conjunctiva and limbus were observed (p < 0.001) in PDR eyes. The OST of NPDR and PDR patients was less compared with age matched counterparts in both pre and post dilation studies. Dilation of eye showed increase in OST for both controls and diabetic retinopathy patients. The degree of increase is less compared with controls. The variation in OST observed during pre and post dilatation studies of diabetic retinopathy patients is a functional marker of pathology, and can be used as a parameter for diagnosis.

Effect of Patient-Specific Preanalytic Variables on CSF Aß1-42 Concentrations Measured on an Automated Chemiluminescent Platform.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly used to confirm the accuracy of a clinical diagnosis of mild cognitive impairment or dementia due to Alzheimer disease (AD). Recent evidence suggests that fully automated assays reduce the impact of some preanalytical factors on the variability of these measures. This study evaluated the effect of several preanalytical variables common in clinical settings on the variability of CSF ß-amyloid 1-42 (Aß1-42) concentrations. METHODS: Aß1-42 concentrations were measured using the LUMIPULSE G1200 from both freshly collected and frozen CSF samples. Preanalytic variables examined were: (1) patient fasting prior to CSF collection, (2) blood contamination of specimens, and (3) aliquoting specimens sequentially over the course of collection (i.e., CSF gradients). RESULTS: Patient fasting did not significantly affect CSF Aß1-42 levels. While assessing gradient effects, Aß1-42 concentrations remained stable within the first 5 1-mL aliquots. However, there is evidence of a gradient effect toward higher concentrations over successive aliquots. Aß1-42 levels were stable when fresh CSF samples were spiked with up to 2.5% of blood. However, in frozen CSF samples, even 0.25% blood contamination significantly decreased Aß1-42 concentrations. CONCLUSIONS: The preanalytical variables examined here do not have significant effects on Aß1-42 concentrations if fresh samples are processed within 2 h. However, a gradient effect can be observed on Aß1-42 concentrations after the first 5 mL of collection and blood contamination has a significant impact on Aß1-42 concentrations once specimens have been frozen.

Hybrid Ni-Boron Nitride Nanotube Magnetic Semiconductor-A New Material for Spintronics.

Here, we report the presence of ferromagnetism in hybrid nickel-boron nitride nanotubes (BNNTs) with an ordered structure, synthesized by chemical vapor deposition using elemental boron, nickel oxide as the catalyst, and ammonia gas as the source for nitrogen. In previous studies, the nanotubes were synthesized with two metal oxide catalysts, whereas here, only a single catalyst was used. The nanotube's structure was determined by X-ray diffraction, scanning electron microscopy, and high-resolution transmission electron microscopy. Purity of the nanotubes synthesized at 1150 °C was exceptional and this was determined by Raman spectroscopy. The average diameter of the nanotubes was 63 nm. Based on the magnetic studies carried out, it can be confirmed that the synthesized hybrid material is ferromagnetic at room temperature. Cyclic voltammetry was carried out to confirm the dielectric nature of the nanotubes. These materials could pave ways to nanoscale devices. The well-known thermal stability of BNNTs would play a vital role in preventing thermal failures in such small-scale devices where overheating is a major concern. The presence of semiconducting and magnetic properties in a single material could be confirmed, which might be highly significant in the field of spintronics.

Standardized regression-based clinical change score cutoffs for normal pressure hydrocephalus.

BACKGROUND: Presently, for patients presenting with suspected Normal Pressure Hydrocephalus (NPH) who undergo temporary drainage of cerebrospinal fluid (CSF) there is no defined model to differentiate chance improvement form clinical significance change at the individual patient level. To address this lack of information we computed standard regression based clinical change models for the 10 Meter Walk Test, Timed Up & Go, Dual Timed Up & Go, 6-Minute Walk Test, Mini-Balance Evaluation Systems Test, Montreal Cognitive Assessment, and Symbol Digit Modalities using data from patients with suspected NPH that underwent temporary drainage of CSF. These clinically significant change modes can classify clinically significant improvement following temporary drainage of CSF at the individual patient level. This allows for physicians to differentiate a clinically significant improvement in symptoms from chance improvement. METHODS: Data was collected from 323 patients, over the age of 60, with suspected NPH that underwent temporary drainage of CSF with corresponding gait and cognitive testing. McSweeney Standardized Regression Based Clinical Change Models were computed for standard gait and cognitive measures: Timed Up & Go, Dual Timed Up & Go, 10 Meter Walk Test, MiniBESTest, 6-Minute Walk Test, Montreal Cognitive Assessment, and Symbol Digit Modalities Test. To assess the discriminate validity of the measures we used correlations, Chi2, and regression analyses. RESULTS: The clinical change models explained 69-91.8% of the variability in post-drain performance (p <  0.001). As patient scores became more impaired, the percent change required for improvement to be clinically significant increased for all measures. We found that the measures were not discriminate, the Timed Up & Go was highly related to the 10 Meter Walk Test (r = 0.85, R2 = 0.769-0.738, p <  0.001), MiniBESTest (r = - 0.67, R2 = 0.589-0.734, p <  0.001), and 6 Minute Walk Test (r = - 0.77, R2 = 0.71-0.734, p <  0.001). CONCLUSION: Standardized Regression Based Clinically Significant Change Models allow for physicians to use an evidence-based approach to differentiate clinically significant change from chance improvement at the individual patient level. The Timed Up & Go was shown to be predictive of detailed measures of gait velocity, balance, and endurance.

The Efficacy of Botulinum Toxin in Cluster Headache: A Systematic Review.

AIMS: To conduct a systematic review of the literature on the use of botulinum toxin for the treatment of cluster headache. METHODS: A systematic review and data quality analysis were performed using PRISMA and GRADE guidelines, respectively. Inclusion and exclusion criteria were outlined prior to the search and aimed to select prospective studies that examined the use of botulinum toxin for the treatment of cluster headache. RESULTS: Three studies resulted from the search that each included 10 to 17 subjects. All three demonstrated significant improvement in the frequency of headaches that occurred as quickly as 1 week following treatment. There was low-quality evidence that botulinum toxin was effective in reducing headache frequency and severity by at least 50%. Injections into the sphenopalatine ganglion may have a higher incidence of adverse events. CONCLUSION: This review summarizes the only prospectively collected efficacy and safety data regarding the use of botulinum toxin in cluster headache. Off-label use should be considered in certain cases. Further study is warranted to better characterize injection paradigms and patient selection, given the encouraging but limited data available.

Efficacy of Botulinum Toxin in Tension-Type Headaches: A Systematic Review of the Literature.

BACKGROUND: Botulinum toxin is approved to treat chronic migraine and has been shown to confer significant benefit in refractory cases. Due to its effect on pain by sensory modulation, there may also be efficacy in its use in chronic tension-type headache (CTTH). METHODS: A systematic review of the literature was performed using our predefined inclusion and exclusion criteria. We targeted prospective trials, randomized or nonrandomized, studying botulinum toxin in tension-type headaches (TTHs) in adults. RESULTS: Twenty-two studies were included, including 9 nonrandomized, uncontrolled studies, 8 randomized, placebo-controlled and double-blinded trials (RCTs), 3 RCTs with a crossover, open-label period, 1 comparative, randomized, single-blinded evaluation, and 1 retrospective study with prospective evaluation of headache response to cosmetic botulinum toxin. Studies included 11 to 300 subjects, with duration typically less than 6 months and with only 1 treatment period. Results were mixed, likely due to variable study design, including toxin dosing, injection paradigms, duration/frequency of treatment, and outcome measures. There was moderate-quality evidence that botulinum toxin improved VAS scoring, and some studies demonstrated efficacy based on improved frequency/severity. CONCLUSION: This systematic review demonstrates variable study designs contributing to the low quality of evidence available regarding botulinum toxin in TTH, but some data suggest efficacy. There does not appear to be irrefutable evidence of a lack of efficacy of botulinum toxin in TTH. Using the paradigm for botulinum toxin in chronic migraine may prove fruitful in treating CTTH. Further studies are warranted to evaluate the utility of botulinum toxin in this common debilitating condition.

Spontaneous Intracranial Hypotension after Vestibular Schwannoma Resection Due to an Unexpected Pathology: Tarlov Cysts.

While infrequent, cerebrospinal fluid (CSF) leaks are known to occur after surgical resection of vestibular schwannomas. Early signs of CSF leak often include headache and altered mental status. If untreated, life-threatening complications can occur, including brainstem herniation and meningitis. The appropriate surgical treatment for a CSF leak requires accurate localization of the source. While the most likely location of a CSF leak after lateral skull base surgery is through the aerated portions of the temporal bone, we present a unique case of a man with a prolonged CSF leak after an acoustic tumor removal who was ultimately found to have an occult spinal perineural (Tarlov) cyst as the source. Accurate localization was ultimately achieved with CT myelogram after empirically obliterating his mastoid failed to restore intracranial CSF volume. Tarlov cysts are the most common cause of idiopathic intracranial hypotension, and this case highlights the importance of considering this entity in the differential diagnosis of postoperative CSF leaks.

A Randomized Trial of Ketorolac vs. Sumatripan vs. Placebo Nasal Spray (KSPN) for Acute Migraine.

OBJECTIVE: To compare the efficacy of ketorolac nasal spray (NS) vs. placebo and sumatriptan NS for the acute treatment of migraine. METHODS: This was a randomized, double-blind, placebo and active-comparator, crossover study. Adult migraineurs were randomized to ketorolac NS 31.5 mg, sumatriptan NS 20 mg, or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack. Patients seeking headache care at a headache center or in response to community advertisement were recruited. Adult participants with episodic migraine who experienced ≥2 migraine attacks per month were eligible for the Ketorolac vs. Sumatriptan vs. Placebo Nasal Spray migraine study. Participants were randomized to treatment arms by a research pharmacist, in a 1:1:1 ratio using computer-generated lists. The primary outcome was 2-hour pain relief. Secondary outcomes included 2-hour pain freedom and absence of migraine associated symptoms, and 24-hour sustained pain relief and pain freedom. RESULTS: Of the 72 randomized participants, 54 (75%) treated at least one attack and 49 (68%) completed all three treatments, for a total of 152 treated migraine attacks. Both ketorolac NS (72.5%, P < .001) and sumatriptan NS (69.4%, P = .001) were more effective than placebo (38.3%) for 2-hour pain relief and 2-hour pain freedom (ketorolac: 43.1%, P = .004; sumatriptan: 36.7%, P = .046; placebo: 18.4%). Ketorolac NS, but not sumatriptan NS, was more effective than placebo in 2-hour absence of nausea. Both ketorolac NS and sumatriptan NS were more effective than placebo for 24-hour sustained pain relief (ketorolac: 49%, P < .001; sumatriptan: 31%, P = .01, placebo: 20%). Only ketorolac NS was superior to placebo for 24-hour (ketorolac: 35.3%, P = .003; sumatriptan: 22.4%, P = .18, placebo: 12.2%) sustained pain freedom. Nasal burning and dysgeusia were the most common adverse effects for active treatments. CONCLUSIONS: This study supports that ketorolac NS is superior to placebo and that it is non-inferior to sumatriptan NS for the acute abortive treatment of migraine.

The Impact of Post-Traumatic Stress Disorder on the Burden of Migraine: Results From the National Comorbidity Survey-Replication.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been linked with migraine in prior studies. OBJECTIVE: To evaluate the individual and joint burdens of migraine and PTSD in a population-based cohort. METHODS: The National Comorbidity Survey-Replication (NCS-R) is a general population study conducted in the United States from February 2001-April 2003. PTSD and migraine were assessed, and four groups defined based on their migraine and PTSD status. The four groups included those with no migraine and no PTSD (controls, n=4535), those with migraine and without PTSD (migraine alone, n=236), those with PTSD and without migraine (PTSD alone, n=244), and those with both migraine and PTSD (mig+PTSD, n=68). Logistic and Poisson regression models were used to assess the association between dichotomous/multilevel outcome variables indicating financial, health, and interpersonal burdens and each migraine/PTSD group. RESULTS: Compared to controls, those with Mig+PTSD were more likely to be in the low poverty index (48% vs 41%, AOR 2.16; CI: 1.10, 4.24) and were less likely to be working for pay or profit in the past week (50% vs 68%, AOR 0.42; CI: 0.24, 0.74) but not those with migraine or PTSD alone. Additionally, the number of days where work quality was cut due to physical or mental health or substance abuse in the past month was greater in all groups compared to controls: (1) migraine alone: mean 2.57 (SEM 0.32) vs mean 1.09 (SEM 0.08) days, ARR=2.39; CI: 2.19, 2.62; (2) PTSD alone: mean 2.43 (SEM 0.33) vs mean 1.09 (SEM 0.08) days, ARR=2.09; CI: 1.91, 2.29; (3) mig+PTSD: mean 8.2 (SEM 0.79) vs 1.09 (SEM 0.08) days, ARR 6.79; CI 6.16, 7.49; and was over 2.5-fold greater in those mig+PTSD than migraine alone (mean 8.0 [SEM 0.79] vs 2.6 days [SEM 0.72], ARR 2.77; CI: 2.45, 3.14). The likelihood of having difficulty getting along or maintaining a social life was also increased in all groups relative to controls: (1) migraine alone: 21% vs 5.4%, AOR 4.20; CI: 2.62, 6.74; (2) PTSD alone: 18% vs 5.4%, AOR 3.40; CI: 2.40, 4.82; (3) Mig+PTSD: 39% vs 5.4%, AOR 9.95; CI: 5.72, 17.32, and was 2-fold greater in those with Mig+PTSD as compared to those with migraine alone (AOR 2.32; CI: 1.15, 4.69). CONCLUSIONS: These findings support the need for those who treat migraine patients to be aware of the comorbidity with PTSD, as these patients may be particularly prone to adverse financial, health, and interpersonal disease burdens.

Protoporphyrin IX-Gold Nanoparticle Conjugates for Targeted Photodynamic Therapy--An In-Vitro Study.

Targeted drug delivery system using nanoparticles is a promising strategy for efficient Photodynamic therapy (PDT) as they have the potential to overcome the problems of photosensitizer and enhance the effectiveness and specificity of PDT. In this study, Protoporphyrin IX (PpIX) conjugated gold nanoparticles were synthesized using electrostatic and covalent conjugation scheme. Folic acid (FA) was also conjugated suitably to the covalent complex to vectorize the complex. Optical characterizations of the complex prove the formation of the complex. The size of the synthesized nanocomplexes was studied using light scattering measurements. The photo-toxicity of the free PpIX and PpIX-nanoparticle complexes were studied using MTT assay technique against Vero and HeLa cell lines. These In-vitro results of this study indicates that, the nanoparticle complexes are more phototoxic compared to free PpIX, with the covalent complex being the better of the two complexes and the folate-mediated nanocomplex is the superior of the studied complexes. These results ensures that nanoparticle conjugated photosensitizers equipped with FA may be an effective drug delivery mechanism for PDT.

Fluorescence spectroscopic characterization of salivary metabolites of oral cancer patients.

A pilot study has been carried out using human saliva in differentiating the normal subjects from that of oral squamous cell carcinoma (OSCC) patients, using the autofluorescence spectroscopy at 405nm excitation. A markable difference in the spectral signatures between the saliva of normal subjects and that of oral cancer patients has been noticed. The possible reasons for the altered spectral signature may be due to the presence of endogenous porphyrin, NAD(P)H and FAD in the exfoliated cells from saliva. The elevated level of porphyrin in saliva of OSCC patients may be attributed to the disturbances in the amino acid degradation pathway and heme biosynthetic pathway, during the transformation of normal into malignant cells. The integrated area under the curve of fluorescence emission spectrum at 405nm excitation and also fluorescence excitation spectrum for 625nm emission were compared for the saliva of normal and oral cancer patients. The area under the curve for the emission spectrum provides 85.7% sensitivity and 93.3% specificity, where as the fluorescence excitation spectrum discriminates the same with 84.1% sensitivity and 93.2% specificity.

A step out of the dark: improving the sleep medicine knowledge of trainees.

OBJECTIVE: Over 40-million Americans are undiagnosed, misdiagnosed, or untreated for sleep disorders. Despite the growing need to integrate sleep medicine knowledge into the medical education curriculum, educational leaders have struggled to incorporate contemporary medical topics such as sleep medicine into the already packed curricula. We set out to examine the efficacy of an online, self-paced, sleep medicine learning module as an educational tool for medical students. METHODS: We studied 87 Johns Hopkins medical students. Participants were randomly assigned to the sham module (SM, n=40) or learning module (LM, n=47). The efficacy of the tool was assessed based on changes in performance (pre- and post-module completion) on a validated sleep knowledge questionnaire (the Dartmouth Sleep Knowledge and Attitude Survey). RESULTS: Improvement in overall sleep knowledge, as measured by the Dartmouth Sleep Knowledge and Attitude Survey, was significantly higher in the LM group compared to the SM group (F(1,84)=9.71, p<.01, η(2)=0.10). Although the SM group's improvement was significantly lower than the LM group, within-subject comparisons did show improvement from their pre- to post-assessment scores as well. CONCLUSION: A self-paced learning module is an effective educational tool for delivering sleep medicine knowledge to medical students.

Periodontal disease in pregnancy is a risk factor for preeclampsia.

Many recent studies have evaluated the relation between periodontitis and pregnancy complications. This study aimed to examine the association between preeclampsia and periodontitis in Indian women. A total of 130 pregnant women were enrolled between 26-32 weeks of gestation. Oral health examinations were performed at recruitment and again within 48 hours of delivery to determine the presence and/or progression of periodontitis in all subjects. Pocket depth, clinical attachment loss (CAL), and gingival index were measured in all subjects. There was significant (p < 0.05) difference between the preeclampsia and normotensive groups in the distribution of periodontitis both at recruitment and after delivery. Multiple logistic regression demonstrated that periodontitis both at enrolment (OR = 5.78, 95% CI 2.41-13.89) as well as within 48 hours of delivery (OR = 20.15, 95% CI 4.55-89.29), may be associated with an increased risk of preeclampsia.

Concentration dependent aggregation properties of chlorhexidine salts.

PURPOSE: Chlorhexidine (CHX), a chemical antiseptic, is known to bind to dentin and has been shown to be effective in treating bacterial infections caused by microbes. The solubility and aggregation properties of CHX salts were determined to guide the development of a sustained release formulation for long-term disinfection. METHODS: The amount of CHX in solution was determined as a function of counterion concentration (chloride, acetate (Ac) or gluconate (G)) by UV spectrophotometry at 255nm. The weight average molecular weight was determined from the angular dependence of the scattered light. Proton NMR spectroscopy was used to investigate the dependence of the peak intensity and chemical shift on solution concentration and diffusion measurements were performed by Fourier-transform pulsed-field gradient spin-echo (PFG-SE) (1)H NMR. RESULTS: The observed CHX concentration was highly dependent on the type and concentration of salt present in solution with the greatest CHX concentration achieved with gluconate, moderate to low with diacetate, and very low with dichloride solutions. Addition of sodium gluconate enhanced the amount of CHX-Ac(2) in solution; however, only low concentrations of chlorhexidine can be achieved in the presence of chloride ions. For solutions of CHX-G(2), the aggregate number appeared to range from a dimer at 40mM to perhaps a pentamer at 150mM. In contrast, no aggregation of CHX-Cl(2) or CHX-Ac(2) was detected, which was corroborated by diffusion NMR results. The change in chemical shift of protons is consistent with association of the phenyl group of one CHX with the hexamethylene chain of a second CHX. Based on the analysis of NMR peak intensities of CHX, gluconate, and acetate in saturated solutions, it appears that solubilization of the diacetate species occurs within digluconate aggregates, since the solubility product of chlorhexidine diacetate is such that the concentration of CHX will exceed the critical micelle concentration (CMC). However, no solubilization of CHX-Cl(2) occurs because the solubility product falls below the CMC. CONCLUSIONS: The low concentration of CHX that can be achieved in physiological concentrations of chloride in the oral cavity may be problematic for dental and slow release formulations. Achieving a high concentration of CHX appears to require that the monomer be present at a concentration greater than that required to produce self-association.