Portable Pocket colposcopy performs comparably to standard-of-care clinical colposcopy using acetic acid and Lugol's iodine as contrast mediators: an investigational study in Peru.

OBJECTIVE: Our goal was to develop a tele-colposcopy platform for primary-care clinics to improve screening sensitivity and access. Specifically, we developed a low-cost, portable Pocket colposcope and evaluated its performance in a tertiary healthcare centre in Peru. DESIGN AND SETTING: Images of the cervix were captured with a standard-of-care and Pocket colposcope at la Liga Contra el Cáncer in Lima, Peru. POPULATION: Two hundred Peruvian women with abnormal cytology and/or human papillomavirus positivity were enrolled. METHODS: Images were collected using acetic acid and Lugol's iodine as contrast agents. Biopsies were taken as per standard-of-care procedures. MAIN OUTCOME MEASURES: After passing quality review, images from 129 women were sent to four physicians who provided a diagnosis for each image. RESULTS: Physician interpretation of images from the two colposcopes agreed 83.1% of the time. The average sensitivity and specificity of physician interpretation compared with pathology was similar for the Pocket (sensitivity = 71.2%, specificity = 57.5%) and standard-of-care (sensitivity = 79.8%, specificity = 56.6%) colposcopes. When compared with a previous study where only acetic acid was applied to the cervix, results indicated that adding Lugol's iodine as a secondary contrast agent improved the percent agreement between colposcopes for all pathological categories by up to 8.9% and the sensitivity and specificity of physician interpretation compared with pathology by over 6.0 and 9.0%, respectively. CONCLUSIONS: The Pocket colposcope performance was similar to that of a standard-of-care colposcope when used to identify precancerous and cancerous lesions using acetic acid and Lugol's iodine during colposcopy examinations in Peru. TWEETABLE ABSTRACT: The Pocket colposcope performance was similar to that of a standard-of-care colposcope when identifying cervical lesions.

Resveratrol, a natural polyphenol, prevents chemotherapy-induced cognitive impairment: Involvement of cytokine modulation and neuroprotection.

Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment. Water maze test and manganese-enhanced magnetic resonance imaging were used to evaluate animals' cognitive performance and brain neuronal activity, respectively. Blood and brain tissues were collected for measurement of cytokines, cytokine regulators, and biomarkers for neuroplasticity. DAC treatment produced a striking cognitive impairment. Cotreatment with 100 mg/kg resveratrol ameliorated DAC-induced cognitive impairment and decreases in prefrontal and hippocampal neuronal activity. Mice co-treated with both doses of resveratrol displayed significantly lower levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but markedly higher levels of the anti-inflammatory cytokines IL-4 and IL-10 in several sera and brain tissues than those co-treated with vehicle. Resveratrol modulated the cytokine-regulating pathway peroxisome proliferator activated receptor (PPAR)-γ/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protected against DAC-induced decreases in the expression of the neuroplasticity biomarkers, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), amino acid neurotransmitter receptors, and calmodulin-dependent protein kinase II (CaMKII). These results demonstrate the efficacy of resveratrol in preventing chemobrain and its association with cytokine modulation and neuroprotection.

A survey on the prevalence and utilization characteristics of gua sha in the Hong Kong community.

OBJECTIVE: To conduct a community-based survey to describe the demographics, experience, and utilization variables among the users of gua sha living in Hong Kong. METHOD: A total of 3209 adult respondents were surveyed by using a short Chinese questionnaire. RESULTS: Gua sha was found to have a one-year prevalence of 22.7% and four-week prevalence of 6.6%. The users were seen to be old of age and less educated. The majority believed that gua sha is beneficial to health, practiced in non-regular basis, and mainly employed for treating illnesses. For both male and female, the top two common illnesses to be treated were the respiratory and pain problems, which accounting for 74% of all users. Other illnesses included nervousness, heat stroke, fever, infection, dizziness, diarrhoea and vomiting, oedema, and constipation. As practiced by most respondents, unidirectional pressured stroking was applied repeatedly on the lubricated skin surface at the back region using various smooth-edged tools typically spoons. Almost all users reported the occurrence of skin blemishing and subsequently faded within 7 days after the gua sha treatment. CONCLUSION: The general population of Hong Kong was found to have high prevalence of gua sha usage. The utilization characteristics as reported by the users were generally aligned with the current scientific knowledge, in particular the treatment procedures and response.

Is automatic mode switching effective for atrial arrhythmias occurring at different rates? A study of the efficacy of automatic mode and rate switching to simulated atrial arrhythmias by chest wall stimulation.

Automatic mode switching (AMS) is a useful means to avoid rapid ventricular response during atrial fibrillation (AF), but AMS cannot occur if the detected atrial rate during AF is below the mode switching criteria. This may be the result of antiarrhythmic medications, or when the atrial events fall within the atrial blanking period, or if the atrial amplitudes during AF are too small to be sensed. We hypothesize that the addition of an automatic rate switching (ARS) algorithm may complement AMS response during AF with different detected atrial rates. We studied the Marathon DDDR pacemaker (Model 294-09, Intermedics Inc.) with the AMS and ARS algorithms that are independently programmable but can also operate in combination. AF sensed above the AMS rate (160 beats/min) will lead to VDIR pacing, whereas AF below AMS rate will be tracked at an interim rate as dictate by the ARS, at a ventricular response that is 20 beats/min above the sensor indicated rate. Atrial tachyarrhythmias were simulated by chest wall stimulation (CWS). CWS was applied to 33 patients (16 men, 17 women, mean age 69 +/- 11 years) with a Marathon DDDR pacemaker using an external pacer to simulate AF occurring at two rate levels: above the AMS rate (programmed at 160 beats/min) at 180 beats/min and below the AMS rate at 120 beats/min. The maximum, minimum, and mean ventricular rates during CWS in DDDR mode with AMS alone, ARS alone, and their combination were compared. During CWS at 120 beats/min, the AMS plus ARS setting showed a mean ventricular rate of 79 +/- 3 beats/min and 124 +/- 14 beats/min in the AMS setting alone (P < 0.01). With CWS at 180 beats/min, the mean ventricular rate in the AMS plus ARS setting compared to the AMS setting alone was not significantly different. However, the variation in ventricular pacing rate was 7 +/- 14 beats/min in the AMS plus ARS setting and 40 +/- 42 beats/min in the AMS setting (P < 0.05). In conclusion, AMS is effective for simulated atrial tachyarrhythmias sensed above the AMS rate. Combined AMS with ARS is useful to handle simulated atrial tachyarrhythmia at a slower rate and to avoid rate fluctuation during AMS. There is also a possibility that this can be applied to the naturally occurring atrial tachyarrhythmias.

A comparative study on the behavior of three different automatic mode switching dual chamber pacemakers to intracardiac recordings of clinical atrial fibrillation.

Automatic mode switching (AMS) allows patients with dual chamber pacemakers who develop paroxysmal AF to have a controlled ventricular rate. The aim of this study was to (1) compare the rate-controlled behavior of three AMS algorithms in response to AF, in terms of speed and stability of response and resynchronization to sinus rhythm, and (2) compare the influence of pacemaker programming on optimal mode switching. We studied 17 patients (12 men, 5 women; mean age 59 +/- 15 years) who developed AF during electrophysiological study. Unfiltered bipolar atrial electrograms during sinus rhythm and AF were recorded onto high fidelity tapes and replayed into the atrial port of three dual chamber pacemakers with different mode switching algorithms (Thera, Marathon, Meta). The Thera pacemaker uses rate smoothing, and mode switches occur when mean sensed atrial rate exceeds the predefined AMS rate (MR). Marathon mode switches after a programmable number of consecutive rapid atrial events (NR). Meta DDDR monitors the atrial rate by a counter for atrial cycles faster than the programmed AMS rate. It increases or decreases the counter if the atrial cycle length is shorter or longer than the programmed AMS interval, respectively. Mode switch occurs when the AF detection criteria are met (CR). A total of 260 rhythms were studied. NR was significantly faster than MR and CR (latency 2.5 +/- 3 s vs 26 +/- 7 s vs 15 +/- 22 s, respectively, P < 0.0001). During sustained AF, MR resulted in the most stable and regular ventricular rhythm compared to NR or CR. In CR, ventricular rate oscillated between AMS and atrial tracking (cycle length variations: 44 +/- 2 s vs 346 +/- 109 s vs 672 +/- 84 s, P < 0.05). At resumption of sinus rhythm, MR resynchronized after 143 +/- 22 s versus 3.4 +/- 0.7 s for NR and 5.9 +/- 1.1 s for CR, resulting in long periods of AV dissociation when a VVI/VVIR mode is used after AMS. Programming of atrial refractory periods did not affect AMS response, although the speed of AMS onset can be adjusted by programming of onset criteria in the Meta DDDR. AMS algorithms differ in their ability to handle recorded clinical atrial arrhythmias. The rapid-responding algorithm exhibits rate instability, whereas slow responding algorithm shows a long delay in response and risk of AV dissociation. Thus different instrumentation of AMS may have clinical implications in patients with dual chamber pacemakers who develop AF.

Efficacy and tolerability of continuous overdrive atrial pacing in atrial fibrillation.

Overdrive right atrial pacing has been used to prevent atrial fibrillation, but its efficacy in atrial fibrillation prevention and the patient tolerability and quality of life during high rate pacing remain uncertain. The objective of this study was to test the effects of a consistent atrial pacing algorithm that automatically paced the atrium at 30 ms shorter than the sinus P-P interval for atrial fibrillation prevention. Fifteen patients with sick sinus syndrome implanted with a Thera DR (model 7940 or 7960, Medtronic Inc.) were randomly programmed to rate adaptive dual chamber pacing (DDDR) or DDDR + consistent atrial pacing mode, each for an 8-week study period. The efficacy of consistent atrial pacing was assessed by the number of automatic mode switching and the number of premature atrial complexes. Symptoms and quality of life were assessed by the SF-36 quality of life questionnaire and an atrial fibrillation symptom checklist. The percentage of atrial pacing increased from 57 +/- 32% to 86 +/- 28%. Overall, there was no significant difference in the number of automatic mode switching episodes between DDDR and DDDR + consistent atrial pacing (47 +/- 90 vs 42 +/- 87, P > 0.05), but a significant reduction in premature atrial complexes by 74.7% (P < 0.001). There was no undue increase in atrial rate by the DDDR + consistent atrial pacing mode versus DDDR (63 +/- 13 vs 70 +/- 7 bpm). There was no significant difference in quality of life scores and symptom severity on frequency between the two modes of pacing, but a trend towards a lower frequency of symptoms in the DDDR + consistent atrial pacing mode compared with baseline (29.5 +/- 10.2 vs 25.1 +/- 9.7, P = 0.07). An algorithm that provides consistent atrial overdrive pacing can suppress atrial fibrillation triggering premature atrial complexes without the need to increase the overall atrial rate compared with conventional pacing. The algorithm appears to be well-tolerated, but further studies are needed to address the clinical impact of this atrial fibrillation prevention algorithm.

Automatic optimization of resting and exercise atrioventricular interval using a peak endocardial acceleration sensor: validation with Doppler echocardiography and direct cardiac output measurements.

Peak endocardial acceleration (PEA) measured by an implantable acceleration sensor inside the tip of a pacing lead reflects ventricular filling and myocardial contractility. The contribution of the plateau phase of PEA as an indicator of optimal ventricular filling, hence of the appropriate atrioventricular interval (AVI) at rest and during exercise, was studied in 12 patients (age 69 +/- 6 years) with complete AV block and a PEA sensing DDDR pacemakers (Living 1 Plus, Sorin Biomedica). At a mean resting heart rate of 79 +/- 15 beats/min, the mean AVI optimized by PEA versus Doppler echocardiography (echo) were identical (142 +/- 37 vs 146 +/- 26 ms, P = 0.59). During submaximal exercise at a mean heart rate of 134 +/- 6 beats/min, AVI optimized by PEA was 135 +/- 37 ms. Cardiac output at rest, measured by the CO2 rebreathing method, was comparable with AVI determined by echo versus PEA (4.3 +/- 2.9 and 3.7 +/- 2.4 L/min, respectively), and increased to the same extent (8.0 +/- 3.9 vs 8.3 +/- 5.2 L/min) during submaximal exercise. In patients with AV block, AVI automatically set by PEA was comparable with AVI manually optimized by Doppler echocardiography and was associated with comparable exercise induced hemodynamic changes.

Improved efficacy of mode switching during atrial fibrillation using automatic atrial sensitivity adjustment.

Automatic mode switching (AMS) during atrial fibrillation (AF) in a dual chamber pacemaker is dependent on the accurate detection of an atrial electrogram. As atrial amplitude is often reduced during AF compared with sinus rhythm, this may result in failure of the AMS and a rapid ventricular response. In addition, undersensing of AF may result in competitive atrial pacing that sustains AF. We hypothesize that the use of automatic atrial sensitivity adjustment (ASA) may enhance AF sensing in a dual chamber pacemaker. We studied the AMS response with and without ASA of the Marathon DDDR (model 294-09, Intermedics, Inc.) pacemaker in 10 patients with paroxysmal AF. Intracardiac atrial electrograms during sinus rhythm and induced AF were recorded onto an analog tape recorder. They were replayed into the pacemaker to assess the AMS response at various starting atrial sensitivities from 3.5 to 0.8 mV with ASA activated and without. Atrial amplitude was reduced during AF. The higher the initial atrial sensitivity, the better is the AMS response and the lower the incidence of AF undersensing. The percentage of AMS before ASA ranged from 2.1% at an atrial sensitivity 3.5 mV to 95.6% at highest sensitivity of 0.5 mV (P < 0.05). After 10 minutes of ASA, the AMS response was improved from 1.7% to 50.6% and from 9.5% to 50.9% at starting atrial sensitivities of 3.5 mV and 2.5 mV, respectively (P < 0.05 in both instances). Undersensing during AF was also significantly reduced after ASA from 70% to 10% at a sensitivity of 3.5 mV and from 33.8% to 10.8% at 2.5 mV. There was no increase in oversensing. In four patients with paroxysmal AF with an implanted pacemaker, ASA improved AMS response in patients with a low implant atrial amplitude. In conclusion, efficacy of mode switching and AF sensing are dependent on the programmed atrial sensitivity, which can be enhanced with the use of ASA, particularly when P wave sensing during AF is borderline.

Programmed atrial sensitivity: a critical determinant in atrial fibrillation detection and optimal automatic mode switching.

Automatic mode switching (AMS) prevents tracking of paroxysmal atrial fibrillation (AF) in dual chamber pacing. The correct detection of AF can be affected by the programmed atrial sensitivity (AS). We prospectively studied the relationship between AS, AF undersensing, and AMS, using unfiltered bipolar intracardiac atrial electrograms recorded from 17 patients during sinus rhythm (SR) and in AF. Overall, 780 rhythms were recorded and replayed onto three dual chamber pacemaker models using different AMS algorithms (Thera DR 7940, Marathon DDDR 294-09, and Meta DDDR 1254), and the ventricular responses were measured. AS was randomly programmed in steps from the highest available AS to half of the mean atrial P wave amplitude (PWA), and the percentage of appropriate AMS responses (defined as a ventricular pacing rate at the expected AMS mode) were recorded. AMS efficacy was related to the programmed AS settings in an exponential manner. At low AS settings, a higher percentage of tests were associated with absence of, or with intermittent AMS and tracking of AF, whereas at higher AS, oversensing of noise during SR occurred. An optimal AS measured approximately 1.3 mV, representing about one-third of the PWA measured during SR, although oversensing of SR and undersensing of AF continued to occur in 14% of tests and time, respectively, due to the high variation in PWA during AF. Thus, a fixed AS cannot eliminate AF undersensing without inviting noise oversensing, suggesting the need for automatic adjustments of AS, or the use of a rate-limiting algorithm to prevent rate oscillation during intermittent AF sensing. In conclusion, AMS functions of existing pacemakers were significantly limited by the undersensing of AF and oversensing of noise. Proper adjustment of the AS is important to enable effective AMS during AF.

Determination of kanamycin concentration in serum by substrate-labeled fluorescent immunoassay.

A homogeneous substrate-labeled fluorescent immunoassay was developed for the measurement of kanamycin concentrations in serum. A fluorogenic drug reagent (FDR) (beta-galactosyl-umbelliferone-tobramycin) was prepared that is nonfluorescent under the conditions of the assay but is hydrolyzed upon catalysis by beta-galactosidase to yield a fluorescent product. Binding of the FDR to the antiserum to kanamycin prevented enzyme hydrolysis. The fixed level of FDR in the assay competed with kanamycin in the sample for a limited number of antibody-binding sites. Unbound FDR was hydrolyzed by beta-galactosidase to release a fluorescent product that is proportional to the kanamycin concentration in the sample. The assay exhibited good sensitivity, precision, and accuracy and correlated well with other methods.

The contingent negative variation in antisocial behaviour: a pilot study of Broadmoor patients.

Using a classical click/flash paradigm, the CNV was recorded from the following three groups of subjects at Broadmoor Hospital: (1) 14 'psychopathic' patients selected by use of the 4/9 MMPI profile and confirmed by independent clinical diagnosis; (2) 15 'non psychopathic' patients, all psychotic and mainly schizophrenic; (3) 14 healthy staff control subjects. All three groups were matched for age and sex; the two patients groups were also matched for length of stay. Two series of 32 paired stimuli were used, separated by an interval of 30 minutes. The mean CNV voltage was significantly lower in the 'non-psychopathic' patients. The amplitude of the 'psychopath's' CNV response did not differ significantly from that of the staff controls, but the response variability between the first and second series of trials was much greater in the 'psychopathic' patients than in the other two subject groups. The 'psychopathic' subjects tended to show more rapid initial development of the CNV.