Pilonidal sinus laser-assisted closure (PiLAC) - a low-morbidity alternative to excision with excellent long-term outcomes.

INTRODUCTION: Recurrence after surgery for pilonidal sinus disease is a recognised problem and patients often re-present months after discharge. We routinely treat primary and recurrent pilonidal sinus disease with Pilonidal sinus Laser-Assisted Closure (PiLAC). Long-term outcomes following PiLAC surgery was examined following clinical and telephone review. METHODS: All patients undergoing PiLAC as a day-case between April 2016 and July 2019 were included. Patients were followed up in a nurse-led clinic until complete healing or recurrence. A prospective database and retrospective audit of notes combined with longer-term follow-up by telephone were used. RESULTS: A total of 35 patients underwent PiLAC, median age 28 (18-53 years), 28 males:7 females. A total of 28 patients had long-term (>60 days) follow-up, mean 407 days (range 67-887 days); 25/28 patients (89.3%) had healed with no recurrence on long-term follow-up. Of these 28 patients, 11 were first presentation of pilonidal disease and underwent PiLAC as their first treatment, with a 91% heal rate long term. A total of 15 patients had seton drainage prior to PiLAC, with a 93% heal rate versus no seton (83%). Fisher's exact test showed no significant difference between sex, new/recurrent pilonidal disease and seton placement (p>0.05). CONCLUSIONS: Healing after PiLAC for the treatment of primary and recurrent pilonidal sinus disease is preserved with excellent long-term outcomes. We recommend it as an alternative to surgical excision.

Identification and characterization of a Masculinizer homologue in the diamondback moth, Plutella xylostella.

Recently, a novel sex-determination system was identified in the silkworm (Bombyx mori) in which a piwi-interacting RNA (piRNA) encoded on the female-specific W chromosome silences a Z-linked gene (Masculinizer) that would otherwise initiate male sex-determination and dosage compensation. Masculinizer provides various opportunities for developing improved genetic pest management tools. A pest lepidopteran in which a genetic pest management system has been developed, but which would benefit greatly from such improved designs, is the diamondback moth, Plutella xylostella. However, Masculinizer has not yet been identified in this species. Here, focusing on the previously described 'masculinizing' domain of B. mori Masculinizer, we identify P. xylostella Masculinizer (PxyMasc). We show that PxyMasc is Z-linked, regulates sex-specific alternative splicing of doublesex and is necessary for male survival. Similar results in B. mori suggest this survival effect is possibly through failure to initiate male dosage compensation. The highly conserved function and location of this gene between these two distantly related lepidopterans suggests a deep role for Masculinizer in the sex-determination systems of the Lepidoptera.

Two-dimensional coherence for measurement of asymmetry in postural steadiness.

Two-dimensional magnitude squared coherence (2D-MSC) is developed to compare the two-valued time series which represent the center of pressure (COP) under each foot. A sinusoidal multiple taper spectral estimator is used to reduce bias and improve spectral resolution. The measure is applied to evaluate symmetry in the dual-plate postural steadiness time series obtained from healthy young and elderly volunteers, and patients with Huntington's Disease (HD), a group in which asymmetries in postural steadiness are anticipated. The results demonstrate that the 2D-MSC is a robust measure of inter-limb coordination that may be of value in studies of aging and neurologic disease.

Fullerene-based antioxidants and neurodegenerative disorders.

Water-soluble derivatives of buckminsterfullerene (C(60)) derivatives are a unique class of compounds with potent antioxidant properties. Studies on one class of these compounds, the malonic acid C(60) derivatives (carboxyfullerenes), indicated that they are capable of eliminating both superoxide anion and H(2)O(2), and were effective inhibitors of lipid peroxidation, as well. Carboxyfullerenes demonstrated robust neuroprotection against excitotoxic, apoptotic and metabolic insults in cortical cell cultures. They were also capable of rescuing mesencephalic dopaminergic neurons from both MPP(+) and 6-hydroxydopamine-induced degeneration. Although there is limited in vivo data on these compounds to date, we have previously reported that systemic administration of the C(3) carboxyfullerene isomer delayed motor deterioration and death in a mouse model of familial amyotrophic lateral sclerosis (FALS). Ongoing studies in other animal models of CNS disease states suggest that these novel antioxidants are potential neuroprotective agents for other neurodegenerative disorders, including Parkinson's disease.

Mechanisms of morbidity and mortality from exposure to ambient air particles.

The studies reported here assessed pathophysiologic mechanisms that result from exposure to concentrated ambient particles (CAPs) in animals with and without cardiopulmonary compromise. These studies were carried out to determine the biologic plausibility of epidemiologic observations of increases in particulate air pollution associated with increases in human morbidity and mortality. Dogs were exposed two at a time to CAPs or filtered air via tracheostomy for six hours per day on three consecutive days. The electrocardiogram (ECG) and breathing pattern were recorded continuously, and indicators of inflammation were also assessed. In one experimental design, normal dogs were exposed in pairs to CAPs and subsequently to filtered air or to filtered air and subsequently CAPs (the double CAPs/double sham design). Comparisons were made between the CAPs measurements and each dog's own sham responses. In another design, one dog was exposed to CAPs while the chambermate received a sham exposure; these experiments were followed by crossover of the protocol the subsequent week (the crossover design). Comparisons were made between the CAPs exposure and both the chambermate's sham and each dog's own sham responses. The crossover experiments were conducted in normal animals and in animals who had undergone balloon occlusion of the left anterior descending (LAD) coronary artery to induce myocardial compromise. The effects of CAPs in animals with induced chronic bronchitis were part of the original specific aims; because these studies were not fully pursued, the results are presented only in Appendix A. In normal dogs, analyses of all double CAPs and crossover studies revealed low frequency (LF) and high frequency (HF) powers for heart rate variability (HRV) that were significantly higher for CAPs exposure compared to sham exposure. Variation in day-to-day exposure concentrations, aerosol composition, and pathophysiologic responses were also found. The crossover design, continuous measures of aerosol mass, and biologic responses were incorporated in the development of a statistical model that allowed isolation of changes associated with CAPs from changes due to animal variations. Comparison of individual exposures with this model revealed a range from no response in any measured parameter to statistically significant changes in cardiac autonomic balance, pulmonary air flow, and breathing pattern. On days in which dogs showed statistically significant changes in responses, the findings were consistent in both cardiac and respiratory parameters. Days associated with significant increases in LF and HF HRV, LF/ HF HRV ratio, and heart rate standard deviation (HR SD) were also associated with decreases in average heart rate. These same days had decreases in respiratory frequency, tidal volume, minute volume, and peak flows with corresponding increases in respiratory cycle times and enhanced pause (Pauenh), a measure of bronchoconstriction. These cardiac and respiratory changes suggest an effect mediated via both the sympathetic nervous system and the vagus nerve. Alternatively, days associated with increased heart rate had decreases in the HR SD; decreases or no change in HF and LF HRV; increases in respiratory flows and volumes; and decreases in breathing cycle times, all suggesting only sympathetic nervous system mediation. When all data from the crossover design experiments were assessed with this model, the heart rate and respiratory rate were significantly decreased in relation to both cumulative and actual exposure and the LF HRV, LF/HF HRV ratio, HR SD, and all other respiratory parameters were significantly increased (p < 0.0001 for all). When cardiac data were grouped by days in which the air mass trajectory came from the north or northwest (versus west, south, east, or northeast), significant increases in HR SD and HF HRV and significant decreases in average heart rate were associated with the northwest trajectory. (ABSTRACT TRUNCATED)

Ambient pollution and heart rate variability.

BACKGROUND: We investigated associations between ambient pollution levels and cardiovascular function in a repeated measures study including 163 observations on twenty-one 53- to 87-year-old active Boston residents observed up to 12 times from June to September 1997. Particles with aerodynamic diameter

Patient knowledge and educational needs in irritable bowel syndrome.

OBJECTIVE: Educating patients with irritable bowel syndrome (IBS) about their disorder may promote a strong physician-patient interaction, is a recommended approach for treating mild IBS and may reduce healthcare use. Our aim was to identify the information needs, levels and associated factors in IBS, and to contrast this with patients with inflammatory bowel disease (IBD). DESIGN: Seventy adult IBS patients (Rome criteria) were prospectively recruited, together with 82 ulcerative colitis (UC) and 60 Crohn's disease (CD) patients. Demographic data, clinical data, and anxiety and depression scores (HAD scale) were recorded. Patients rated their perceived levels of disease knowledge and satisfaction with their knowledge level on visual analogue scales. Qualitative data on disease information needs were obtained by an open-ended question. SETTING: Gastroenterology out-patient clinic. RESULTS: The majority of IBS patients (77%; n = 54) and over half of IBD patients (56%; n = 79) required further information about their disease. The primary issues for IBS patients were bowel cancer risk and diet. Queries about medications ranked top for UC, while prognosis and cancer risk jointly ranked top for CD. In the IBS group, 27% rated their knowledge as < 25 out of 100 compared to 10% of IBD patients. The perceived level of knowledge in IBS was significantly negatively associated with length of hospital consulting (r(s) = -0.32; P = 0.04). CONCLUSION: Most IBS patients feel insufficiently informed, particularly in relation to risk of serious disease and role of diet. Educating IBS patients about their disorder may play a role in reducing healthcare use.

Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines.

Pulmonary inflammatory and hematologic responses of canines were studied after exposure to concentrated ambient particles (CAPs) using the Harvard ambient particle concentrator (HAPC). For pulmonary inflammatory studies, normal dogs were exposed in pairs to either CAPs or filtered air (paired studies) for 6 hr/day on 3 consecutive days. For hematologic studies, dogs were exposed for 6 hr/day for 3 consecutive days with one receiving CAPs while the other was simultaneously exposed to filtered air; crossover of exposure took place the following week (crossover studies). Physicochemical characterization of CAPs exposure samples included measurements of particle mass, size distribution, and composition. No statistical differences in biologic responses were found when all CAPs and all sham exposures were compared. However, the variability in biologic response was considerably higher with CAPs exposure. Subsequent exploratory graphical analyses and mixed linear regression analyses suggested associations between CAPs constituents and biologic responses. Factor analysis was applied to the compositional data from paired and crossover experiments to determine elements consistently associated with each other in CAPs samples. In paired experiments, four factors were identified; in crossover studies, a total of six factors were observed. Bronchoalveolar lavage (BAL) and hematologic data were regressed on the factor scores. Increased BAL neutrophil percentage, total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum/silicon factor. Increased circulating neutrophils and increased BAL macrophages were associated with the vanadium/nickel factor. Increased BAL neutrophils were associated with the bromine/lead factor when only the compositional data from the third day of CAPs exposure were used. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur factor. BAL or hematologic parameters were not associated with increases in total CAPs mass concentration. These data suggest that CAPs inhalation is associated with subtle alterations in pulmonary and systemic cell profiles, and specific components of CAPs may be responsible for these biologic responses.

Heart rate variability associated with particulate air pollution.

BACKGROUND: Epidemiologic studies have linked fine particulate air pollution with cardiopulmonary mortality, yet underlying biologic mechanisms remain unknown. Changes in heart rate variability (HRV) may reflect changes in cardiac autonomic function and risk of sudden cardiac death. This study evaluated changes in mean heart rate and HRV in human beings associated with changes in exposure to particulate air pollution. METHODS: Repeated ambulatory electrocardiographic monitoring was conducted on 7 subjects for a total of 29 person-days before, during, and after episodes of elevated pollution. Mean HR, the standard deviation of normal-to-normal (NN) intervals (SDNN), the standard deviation of the averages of NN intervals in all 5-minute segments of the recording (SDANN), and the square root of the mean of squared differences between adjacent NN intervals (r-MSSD) were calculated for 24-hour and 6-hour time segments. Associations of HRV with particulate pollution levels were evaluated with fixed-effects regression models. RESULTS: After controlling for differences across patients, elevated particulate levels were associated with (1) increased mean HR, (2) decreased SDNN, a measure of overall HRV, (3) decreased SDANN, a measure that corresponds to ultralow frequency variability, and (4) increased r-MSSD, a measure that corresponds to high-frequency variability. The associations between HRV and particulates were small but persisted even after controlling for mean HR. CONCLUSIONS: This study suggests that changes in cardiac autonomic function reflected by changes in mean HR and HRV may be part of the pathophysiologic mechanisms or pathways linking cardiovascular mortality and particulate air pollution.

Transatrial access to the normal pericardial space: a novel approach for diagnostic sampling, pericardiocentesis, and therapeutic interventions.

BACKGROUND: A nonsurgical means to access the normal pericardial space could provide opportunities for diagnostic sampling and therapeutic interventions. Because there are currently no approved nonsurgical methods to accomplish this, we tested a new approach in large animals. METHODS AND RESULTS: A catheter system was employed in a percutaneous approach from a femoral vein to pierce the right atrial appendage. Pericardial access was confirmed by placement of a radiopaque guidewire visible under fluoroscopy (6 dogs, 13 pigs). In 7 of the pigs, pericardial tamponade, produced by injection of saline or heparinized blood into the pericardial space through this route, was confirmed by fluoroscopy and hemodynamic evidence. The feasibility and safety of this access route were tested with multiple repetitions in all 19 animals. At the end of each of the 17 acute experiments, direct inspection after thoracotomy revealed no hemopericardium, laceration, or bleeding on catheter withdrawal. In 24-hour survival studies performed in 2 of the 6 dogs, the animals exhibited no behavioral signs of discomfort or untoward consequences on recovery from anesthesia. Histology revealed only a small (approximately 1-mm) fibrinous plug at the site of puncture. CONCLUSIONS: The percutaneous approach via the right atrial appendage provides a rapid, safe route to access the normal pericardial space for diagnostic sampling and to alleviate high-volume and low-volume (<200 mL) pericardial effusions. The access route is potentially useful for selective administration of therapeutic agents, growth factors, gene vectors, and cardioactive and vasoactive agents to the heart.

Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

OBJECTIVE: To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA: Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS: Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS: Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS: Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Time-frequency coherence analysis of atrial fibrillation termination during procainamide administration.

A time-frequency coherence estimator is developed and applied to study changes in signal characteristics as atrial fibrillation converts to sinus rhythm during administration of procainamide. A coherence spectrogram (CS) using multiple sinusoidal tapers is used in this study to assess phase relations between electrogram recordings at multiple atrial sites of seven patients who received procainamide to terminate atrial fibrillation. CSs are calculated (0 to 60 Hz) with 1 sec time resolution and 6.2 Hz frequency resolution. In agreement with previous studies, CSs generally exhibit low coherence during atrial fibrillation. Conversion to sinus rhythm is concomitant with an increase in coherence and emergence of structured time-frequency topography. Transition from atrial fibrillation to sinus rhythm is associated with a variety of time-frequency dynamics. Both gradual and abrupt increases in coherence coincide with conversion. Results suggest transient electrical organization in the atria during atrial fibrillation not seen in previous low-resolution coherence studies. CSs permit investigation of rhythm organization with unparalleled time and frequency resolution and thus are useful for studying transient changes in cardiac rhythms that may reflect underlying mechanisms.

Thermal unfolding in a GCN4-like leucine zipper: 13C alpha NMR chemical shifts and local unfolding curves.

13C alpha chemical shifts and site-specific unfolding curves are reported for 12 sites on a 33-residue, GCN4-like leucine zipper peptide (GCN4-lzK), ranging over most of the chain and sampling most heptad positions. Data were derived from NMR spectra of nine synthetic, isosequential peptides bearing 99% 13C alpha at sites selected to avoid spectral overlap in each peptide. At each site, separate resonances appear for unfolded and folded forms, and most sites show resonances for two folded forms near room temperature. The observed chemical shifts suggest that 1) urea-unfolded GCN4-lzK chains are randomly coiled; 2) thermally unfolded chains include significant transient structure, except at the ends; 3) the coiled-coli structure in the folded chains is atypical near the C-terminus; 4) only those interior sites surrounded by canonical interchain salt bridges fail to show two folded forms. Local unfolding curves, obtained from integrated resonance intensities, show that 1) sites differ in structure content and in melting temperature, so the equilibrium population must comprise more than two molecular conformations; 2) there is significant end-fraying, even at the lowest temperatures, but thermal unfolding is not a progressive unwinding from the ends; 3) residues 9-16 are in the lowest melting region; 4) heptad position does not dictate stability; 5) significant unfolding occurs below room temperature, so the shallow, linear decline in backbone CD seen there has conformational significance. It seems that only a relatively complex array of conformational states could underlie these findings.

Approximate minimum bias multichannel spectral estimation for heart rate variability.

Spectral decomposition of variations in heart rate permits noninvasive measurement of autonomic nervous activity in humans and animals. Autonomic metrics based on spectral analysis are useful in monitoring clinical conditions such as diabetic neuropathy and reinnervation in heart transplant patients. A persistent problem in deriving such autonomic measures is the prerequisite of an accurate and unbiased power spectrum of heart rate variability (HRV). Numerous parametric and nonparametric power spectrum estimators have been introduced, each with its own advantages and drawbacks. Estimator bias has received little attention, despite the fact that at least one common HRV spectrum estimator, the autoregressive method, is known to exhibit bias even in idealized circumstances. We introduce an approximately minimum bias, nonparametric, multichannel spectrum estimation procedure for HRV and contemporaneous signals. The procedure, which is designed specifically for irregular sampling, does not require data segmentation and provides statistically consistent, low variance multichannel spectrum estimates. Estimator performance on simulated and clinical data is presented and compared with results from autoregressive models and Welch periodograms with and without compensation for irregular sampling. Results indicate that the proposed method exhibits advantages over conventional HRV spectrum estimators. Relative computational complexity of the proposed method is also considered.

Neurophysiological changes associated with psychiatric symptoms in HIV-infected individuals without AIDS.

HIV-1 infection may be complicated by a number of psychopathological conditions. While organic mental disorders, such as HIV-related psychosis and dementia, are late manifestations, mood disorders may occur during both asymptomatic and symptomatic stages of infection. The possible impact of brain involvement due to neurotropism of HIV-1 has not been investigated systematically in these latter conditions. The psychiatric caseness of HIV-seropositive individuals without AIDS and seronegative controls was assessed using a standardized clinical interview (Present State Examination). A comparison was made between individuals with and without psychiatric caseness using clinical, neuropsychological, and neurophysiological assessments. An increased prevalence of current psychiatric illness was found in subjects with early symptomatic HIV infection compared to those with asymptomatic infection and controls. This could not be attributed to psychiatric history, as well as to clinical and immunological markers of HIV infection, however, psychiatric caseness in early symptomatic infection was associated with marked neurophysiological changes, detectable by quantitative electroencephalography. Altogether, this study provided preliminary evidence that psychiatric symptoms in symptomatic but not asymptomatic HIV infection may be associated with subtle brain involvement preceding the immunological and neurocognitive impairment characteristic for AIDS.

Measures of postural steadiness: differences between healthy young and elderly adults.

Measures of postural steadiness are used to characterize the dynamics of the postural control system associated with maintaining balance during quiet standing. The objective of this study was to evaluate the relative sensitivity of center-of-pressure (COP)-based measures to changes in postural steadiness related to age. A variety of time and frequency domain measures of postural steadiness were compared between a group of twenty healthy young adults (21-35 years) and a group of twenty healthy elderly adults (66-70 years) under both eyes-open and eyes-closed conditions. The measures that identified differences between the eyes-open and eyes-closed conditions in the young adult group were different than those that identified differences between the eye conditions in the elderly adult group. Mean velocity of the COP was the only measure that identified age-related changes in both eye conditions, and differences between eye conditions in both groups. The results of this study will be useful to researchers and clinicians using COP-based measures to evaluate postural steadiness.