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Objective: To evaluate the effects of intradialytic exercise (IDE) (exercise performed during dialysis) on sarcopenia and quality of life (QoL) in patients with end-stage renal disease (ESRD)., Data Sources: A comprehensive search of 7 electronic databases was performed to identify randomized controlled trials measuring the effects of IDE in adults with ESRD. Searches were limited to the English language., Study Selection: Included studies were randomized controlled trials that measured the effects of IDE in adults with ESRD. Comparator groups received usual care or low-intensity sham interventions. Outcomes of interest were muscle mass, strength, physical function, and QoL. Papers were independently screened for eligibility by 2 authors, and any discrepancies resolved by a third author., Data Extraction: One author extracted the data from the included studies. Data were compared and discussed across the team members. Two authors independently assessed risk of bias using the Cochrane Risk of Bias 2 tool. Quality was assessed using the van Tulder scale and a narrative synthesis was conducted. Best evidence synthesis was used to structure the reviews findings., Data Synthesis: Fourteen studies were included in this review (n=837). While risk of bias was found high in 11 studies, demonstrating mainly selection, performance, and detection bias, the best evidence synthesis indicated strong evidence of resistance training improving muscle mass (16%-4.2%) and strength (45%-18%), and moderate evidence of combined exercise improving strength (37%), and various physical function scores., Conclusions: Overall, there is strong evidence of resistance exercise, with moderate evidence of combined exercise, improving sarcopenia-related muscle and strength loss, and QoL in end-stage kidney disease. Adequately powered, good quality studies are required to determine the optimal exercise prescription to maximize outcomes., (© 2023 Published by Elsevier Inc. on behalf of American Congress of Rehabilitation Medicine.)

Sleep apnea is characterized by bouts of chronic intermittent hypoxia (CIH) that elicit sympathetic hyperactivity resulting in residual hypertension. We previously demonstrated that exposure to CIH increases cardiac output and sought to determine if enhanced cardiac contractility manifests prior to hypertension.Male Wistar rats were exposed to cyclical bouts of hypoxia (FiO 2  = 0.05 nadir; 90 s) and normoxia (FiO 2  = 0.21; 210 s) 8 h/day for 3 days (CIH; n = 6). Control animals (n = 7) were exposed to room air. Data are presented as mean ± SD and were analyzed using unpaired Student t-tests.Three-day exposure to CIH did not elicit changes in heart rate and blood pressure (p > 0.05). However, baseline left ventricular contractility (dP/dt MAX ) was significantly increased in CIH-exposed animals compared with control (15300 ± 2002 vs. 12320 ± 2725 mmHg/s; p = 0.025), despite no difference in catecholamine concentrations. Acute β 1 -adrenoceptor inhibition reduced contractility in CIH-exposed animals (-7604 ± 1298 vs. -4747 ± 2080 mmHg/s; p = 0.014), to levels equivalent to control, while preserving cardiovascular parameters. Sympathetic ganglion blockade (hexamethonium 25 mg/kg; i.v.) produced equivalent cardiovascular responses suggesting similar global sympathetic activity between groups. Interestingly, gene expression of the β 1 -adrenoceptor pathway in cardiac tissue was unchanged.Our results suggest that CIH increases cardiac contractility via β 1 -adrenoceptor dependent mechanisms prior to development of global sympathetic hyperactivity suggesting that positive cardiac inotropy contributes to the development of hypertension in CIH-exposed rats., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Despite significant efforts to translate nanotechnology for cancer application, lack of identification of biodistribution/accumulation of these nanovehicles in vivo remains a substantial barrier for successful implementation of theranostic nanoparticles in the clinic. The purpose of the study was to develop a tumor-targeted theranostic nanovehicle for pancreatic cancer detectable by multispectral optoacoustic tomography (MSOT). To improve the tumor specificity of our mesoporous silica nanoparticle (MSN), we utilized a dual targeting strategy: 1) an elevated tumor receptor, urokinase plasminogen activator receptor (UPAR), and 2) the acidic tumor microenvironment. The tumor specificity of the MSN particle was improved with the addition of both chitosan, targeting acidic pH, and urokinase plasminogen activator (UPA), targeting UPAR. Drug release assays confirmed pH responsive release of gemcitabine in vitro. The UPAR specific binding of MSN-UPA nanoparticles was confirmed by reduction in fluorescence signal following MSN-UPA nanoparticle treatment in UPAR positive cells blocked with a UPAR-blocking antibody. Based upon Indocyanine Green encapsulation within the nanoparticles, UPA ligand targeted MSNs demonstrated increased intensity compared to untargeted MSNs at both pH7.4 (7×) and 6.5 (20×); however the signal was much more pronounced at a pH of 6.5 using tissue phantoms (p<0.05). In vivo, MSN-UPA particles demonstrated orthotopic pancreatic tumor specific accumulation compared to liver or kidney as identified using multispectral optoacoustic tomography (p<0.05) and confirmed by ex vivo analysis. By tracking in vivo nanoparticle biodistribution with MSOT, it was shown that pH responsive, ligand targeted MSNs preferentially bind to pancreatic tumors for payload delivery., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To determine whether the distribution of membrane lesions associated with Ménière's disease is random, as might be expected from a pervasive process such as hydrops, or orderly, as might be expected if membrane resistance is graded., Method: A meta-analysis of temporal bone reports on 184 specimens demonstrating endolymphatic hydrops was undertaken to determine membrane lesion evolution and distribution., Results: Lesion distribution was found to be orderly and cochleocentric. No random scattershot lesions were reported in any study. Disease always started in the cochlear apex, even in non-symptomatic cases, and then involved the saccule, utricle, ampullae and canal system in that precise sequence as the disease progressed., Conclusion: The orderly lesion progression in the otopathology associated with Ménière's disease suggests that the hydropic process has a graded non-random effect on the labyrinth. These findings suggest a pathological staging system that may be useful in temporal bone evaluation.

Crisis intervention work is a distinct specialty within the broader field of professional helping. This article presents two themes in recognizing the essential characteristics of successful crisis interventionists. We discuss the Aristotelian types of knowledge, techne, episteme, and phronesis as they apply to crisis work; identify core characteristics of therapeutic wisdom; and review the empirical findings on the characteristics of effective crisis counselors.

A clinico-pathological study was carried out in two series of patients in order to determine: the prevalence of adenocarcinoma in Barrett's oesophagus in patients undergoing surgical resection for columnar cancer of the oesophagus, the incidence of Barrett's oesophagus in patients with complications of gastro-oesophageal reflux, and the subsequent cancer development in 3-20 years follow-up of such patients, compared with others who had no Barrett's oesophagus. Group 1 consisted of 264 patients with adenocarcinoma of the oesophagus undergoing resection and reconstruction; 18 (6.8%) had concomitant carcinoma and Barrett's oesophagus. These were predominantly male (male/female ratio 8/1) and had worse long-term survival than the other adenocarcinomas. Group 2 consisted of 782 patients with complications of gastro-oesophageal reflux, 26 (3.3%) of whom were found to have Barrett's oesophagus. When followed up for a period of up to 20 years, 4 (15.4%) of these developed cancer in the mean period of 11.5 years (1 case per 74 person-years). This is highly significant compared with 4 others (0.5%) who developed cancer amongst the 756 remaining patients in group 2 with no Barrett's oesophagus, in the mean interval of 8 years 2 months (1 case per over 1500 person-years). Of the 18 patients with Barrett's stricture, 4 (22%) developed cancer at a mean interval of 11.5 years representing one case per 51.7 person-years indicating a higher risk of cancer development in patients with Barrett's stricture compared with other patients with complications of gastro-oesophageal reflux with/without columnar epithelial-lined oesophagus and no stricture. Anti-reflux operation has not protected our patients with Barrett's oesophagus against cancer development.

Handwritten-signature verification is treated as a two-class synthetic discriminant function (SDF) problem. Images of valid and casually forged signatures are collected and binarized, using an electronic digitizing camera. Performance of this approach with a small number of valid signatures in the training set is examined, and substantial improvement is demonstrated when forgeries are included in the set. In particular, the equal-error rate for the SDF classifier with forgeries included is shown to average approximately 4% across nine different subjects. The effects of image preprocessing on false acceptance and true rejection rates are examined. The use of alternatives to forged signatures in the training matrix is explored. Finally, SDF performance is shown to deteriorate when the tested forgeries are produced with some a priori knowledge of the target signature.

Colorful lying is a central feature of Munchausen's, a syndrome well characterized despite an imperfect understanding of its psychiatric aspects. Reported otolaryngologic presentations are infrequent. A classic case is described in detail. A new name, "Otolaryngologica Prevarica," is proposed to maintain awareness of the entity in the specialty. The psychodynamics and the relation to sadomasochism, hysteria and malingering are discussed.

Bilateral vocal cord immobility in adduction is an uncommon, yet potentially life threatening, disorder. Endolaryngeal and neuromuscular causes are well known and for the most part readily diagnosed by the otolaryngologist. Central neurologic etiologies are more unusual. A case of transient spastic laryngeal paralysis secondary to cardiac emboli and brain stem ischemia is presented. A mechanistic analysis suggests that this entity occurs in the setting of pseudobulbar paralysis, and that the ultimate ischemic event may be loss of glycine mediated inhibition of laryngeal motoneurons.

The records of 39 patients who had developed a perforation of the oesophagus after instrumentation were reviewed. Ten (group A) had cervical and 29 (group B) thoracic oesophageal perforation. Twenty three perforations occurred during dilatation of an oesophageal stricture, 10 during oesophagoscopic removal of a foreign body, and six during diagnostic oesophagoscopy. Of the 21 patients treated within 36 hours (early treatment group), four (19%) died; of the 18 treated more than 36 hours after the perforation (late treatment group), nine (50%) died. None of the 10 patients in group A had strictures and only two presented late. After drainage of the neck and mediastinum the outcome was successful in all patients. Thirteen of the 29 in group B were treated early and four of these died; nine of the 16 treated late died, the total mortality for thoracic perforation being 48%. An oesophageal stricture was present in 23 patients. Twelve of these underwent various forms of conservative surgery and there were 10 deaths. This contrasts with the 11 who received radical treatment with resection and reconstruction, only two of whom died. The six patients with no pre-existing stricture were treated with conservative forms of surgery, with one death.

The oronasal speculum is a standard nasal speculum with a metal tongue depressor incorporated into one of the handles. It permits the physician to examine the oral cavity and pharynx immediately after examination of the nose without changing instruments.

Gentamicin application to the middle ear may relieve Meniere's disease, presumably by reducing endolymph secretion by the dark cells. To explore this possibility, the ears of adult cats were treated with daily intratympanic infusions of gentamicin until ataxia occurred. The temporal bones of these cats were then examined using electron microscopy. A 3 per cent solution of gentamicin resulted in ataxia after four treatments. Acute dark cell damage to basal infoldings seen after one month persisted at six months. Treatment with a 0.3 per cent solution required 15 and 21 days to effect ataxia and resulted in a similar damage pattern. Treatment with the 0.3 per cent solution for 13 days (i.e., before ataxia developed) resulted in subtle early lesions in the basal infoldings. Such lesions might affect the rate of endolymph secretion.

Thirty-two patients with proximal oesophageal stricture who were treated under one surgeon (K.M.) during a 17-year period are reviewed. The cause of the stricture in these cases was widely varied and included: gastro-oesophageal reflux (Barrett-type oesophagus), radiotherapy and post-surgical anastomosis following oesophageal reconstruction. Seventeen patients were treated by repeated endoscopic dilatation. Of the remaining 15, 3 patients only (1 with suspected malignancy and 2 with occult cancer) needed resection and reconstruction of the oesophagus. Twelve patients underwent simple conservative operations. There was no hospital or treatment related mortality in this series. We concluded that the majority of such strictures respond to repeated endoscopic dilatation or conservative surgical operation. It is mandatory to exclude malignancy in obstructive lesions of the proximal oesophagus and it is important to establish the aetiology of the lesion in order to undertake the most appropriate treatment.

In a 12-month prospective study incorporating four neighbouring district general hospitals, 228 patients required a total of 236 admissions with intestinal obstruction. The aetiological factors included adhesions 75 (32 per cent), malignant disease 61 (26 per cent), strangulated hernias 59 (25 per cent), volvulus 10 (4 per cent), acquired megacolon 6 (3 per cent), pseudo-obstruction 4 (2 per cent), faecal impaction 6 (3 per cent) and miscellaneous 15 (6 per cent). The peak incidence for obstruction due to adhesions, malignant disease and strangulated hernias each occurred in the eighth decade. Surgery was performed within 48 h of admission in 29 per cent adhesive obstructions (22), 30 per cent obstructions due to malignant disease (18) and 68 per cent strangulated hernias (40)--bowel resection rates in these three groups were 13.5, 50 and 29 per cent, respectively. The overall mortality was 11.4 per cent (26 deaths) and postoperative mortality was 12.3 per cent (19 deaths). During the 12-month study period, 228 patients required a total of 2993 inpatient hospital days as a result of intestinal obstruction. Postoperative adhesions have become the commonest cause of intestinal obstruction but strangulated hernias and intra-abdominal malignant disease still account for 50 per cent of all cases and mortalities. Obstruction due to strangulated hernias and intra-abdominal malignant disease typically occurs in the elderly age group where a more aggressive policy of elective surgical intervention is likely to be associated with increased postoperative morbidity and mortality.