Nighttime dosing of triazolam in patients with liver disease and normal subjects: kinetics and daytime effects.
This study was designed to determine whether the severity of liver dysfunction in cirrhosis affects the kinetics and next-day effects of triazolam after bedtime administration of a single oral dose. Eight patients with biopsy-proven cirrhosis and seven normal subjects matched for age, weight, and sex participated as paid volunteers. The first night was the control night, when no nighttime sedative was administered. The next day, psychomotor testing was performed at 8:30 AM, 2 PM, and 5 PM. Triazolam 0.25 mg was administered at 10:30 PM that evening. Psychomotor testing was repeated on the posttriazolam day in the same manner as on the control day. Blood samples were obtained from a venous catheter at 11 predetermined times in the 14 hours after triazolam administration. Memory testing was also performed. Apparent oral clearance of triazolam was directly related to albumin concentration and indocyanine-green elimination rate constant, and inversely related to partial thromboplastin time expressed as seconds over control. Clearance was 6.69 +/- 2.52 mL/min/kg in the normal subjects and 4.99 +/- 3.14 in the subjects with cirrhosis. There were no significant differences in Cmax between normal subjects (1.43 +/- 0.44 ng/mL) and subjects with cirrhosis (1.62 +/- 0.31 ng/mL) or in tmax (2.0 +/- 1.0 vs 2.5 +/- 1.9 hr) between normal and cirrhosis subjects, respectively. Posttriazolam, cirrhotic subjects took significantly longer to sort cards at 8:30 AM than on the control day. There was a significant correlation between extent of impairment on 8:30 AM card sorting by suit and AUC0-8 (r = 0.687; P = 0.0046).(ABSTRACT TRUNCATED AT 250 WORDS)


[The ratio of soft and hard after bimaxillary operations in patients with skeletal class III malformations].
To study the ratio between soft and hard tissue on the horizontal plane after the operations of maxillary Le Fort I advancement osteotomy and mandibular setback osteotomy in patient with skeletal class III malformations. It can help to predict precisely the post-operational profile. 20 patients with skeletal class III malformation were taken cephalometric films pre-and post-operationally. The coordinate of landmarks were given from two films by computer analysis system. Different values in X axis were analysed statistically. All mandibular soft tissue landmarks were correlated with hard tissue landmarks (r<0.5, P>0.05). The ratios were 1:1 except the Pogonion(<1:1). Point of Sn was not correlated with the maxillary hard tissue significantly(r<0.5, P>0.05). The poor correlation between maxillary Sn and hard tissue was affected by many factors. It is easy to mark the mandible landmarks clearly. The ratio should help to predict the post-operation profile in patients with skeletal class III malformations.


Unilateral pulmonary vein atresia: clinical and radiographic spectrum.
Three cases of unilateral pulmonary vein atresia are presented to illustrate part of the clinical and radiographic spectrum of this anomaly. One patient had major associated cardiovascular abnormalities and pulmonary hypertension, one had recurrent hemoptysis, and the other patient was asymptomatic with normal pulmonary artery pressure and no associated abnormalities. In one case, serial catheterizations indicated that the pulmonary vein atresia was acquired. This report stresses the radiographic, hemodynamic, and angiographic findings in patients with unilateral severe pulmonary venous obstruction. The embryology, pathology, and surgical approach are also discussed. The diagnosis should be strongly suspected before cardiac catheterization when typical features are present on the chest radiograph and isotopic ventilation perfusion scan.


Gene expression in response to acute unilateral ureteral obstruction.
Acute unilateral ureteral obstruction results in differential growth characteristics of both the ipsilateral and contralateral kidney. The obstructed kidney undergoes cellular atrophy following an initial phase of interstitial proliferation while the contralateral kidney hypertrophies. To evaluate the molecular events occurring in both kidneys after obstruction, we examined the expression of growth related (c-fos, c-myc, cH-ras, HSP 70), cell maintenance (beta-actin), and cellular damage (TRPM-2) genes at the mRNA level. In the contralateral kidney an early and transitory induction of c-fos and c-myc expression occurred while a bimodal induction was noted in the obstructed kidney. The patterns of cH-ras, HSP 70 and actin expression also differed in both kidneys. Induction of TRPM-2 was noted only in the obstructed kidney. Rapid gene activation is evident in both the contralateral and obstructed kidney following unilateral ureteral obstruction. The patterns of expression are distinct and may reflect the cellular response to stress (cell death and stromal proliferation) in the obstructed kidney versus a response to a systemic stimulus resulting in cellular hypertrophy in the contralateral kidney.


Recent advances in the production strategies of microbial pectinases-A review.
Pectinases, member of the hydrolases family of enzymes, are one of the important enzymes of the biotechnological sector with 25% share in the global food and beverage enzyme market. They hold a leading position among the commercially produced industrial enzymes. These enzymes are sustainable and environmentally-friendly tool of nature with wide application perspective in many industrial processes, such as, retting and degumming of plant fibers, fermentation of tea and coffee, oil extraction, clarification of fruit juices and wine, valorization of industrial wastes, debasement of cellulosic biomass for biofuel production, wastewater remediation, desizing, scouring and bleaching of fabric, animal feed production, and protoplast fusion technology etc. However, like many other industrial enzymes, pectinases also face the constraint of low yield and productivity in its economized production. Therefore, pectinases have been the target of studies aiming to achieve the expression levels on a commercial scale. Among the natural sources of pectinases, microbial pectinases are employed frequently owing to its ease of production and unique physicochemical properties. This review mainly focuses on the production of pectinase enzymes along with different types of recent strategies used for their production optimization to get overexpression/production. The promise of genetic engineering approaches applied so far to get the higher production of these enzymes using simpler molecular devices and simple fermentation media is also covered in this review.


Changes in plasma follicle-stimulating hormone, luteinizing hormone, estrogen and progesterone during growth of ovulatory follicles in the pig.
This experiment was conducted to determine the changes in secretion of LH, FSH, estrogen and progesterone during follicle maturation. Ovaries were recovered from 11 non-treated (control) gilts, three on day 13, four on day 16, and four on day 19 of the estrous cycle, and from four altrenogest-treated gilts on day 19. Altrenogest, a progesterone agonist, was fed at a dose of 20 mg once daily from days 13 to 18 to block spontaneous follicle maturation. Gilts were bled daily from day 12 until slaughter. For control gilts, the number of follicles/gilt 1-6 mm in diameter decreased (P less than .05) from 93.5 on day 13 to 21.5 on day 19, and the number of large (greater than 6 mm) follicles increased (P less than .05) from 5.3 to 13.2. Altrenogest treatment blocked loss of small follicles and growth of large follicles between days 13 and 19. Plasma progesterone decreased (P less than .001) between days 12 and 16 in both control and altrenogest-treated gilts. Plasma FSH decreased (P less than .05) between days 12 and 16 only in control gilts. Plasma LH was not significantly affected by day or altrenogest treatment. Plasma estrogen increased (P less than .05) between days 15 and 19 only in control gilts. These results indicate that 1) no increased LH secretion was detected in conjunction with emergence of ovulatory follicles, and 2) atresia of nonovulatory follicles was associated with decreased secretion of FSH. Both atresia and decreasing FSH secretion began before estrogen concentration increased in the systemic circulation.


Perinatal outcome and prognostic factors of fetal megacystis diagnosed at 11-14 week's gestation.
To evaluate aneuploidy rate, prognostic factors, and perinatal outcomes following a diagnosis of fetal megacystis at 11-14 week's gestation. A retrospective study of first trimester fetal megacystis from 2010 to 2020 was performed, including ultrasound finding, perinatal outcomes, pathology reports, genetic tests, and neonatal investigations. A total of 98 cases of first trimester fetal megacystis was identified with an overall aneuploidy rate of 12%. There were 54% live births and 46% fetal losses including spontaneous fetal demise and elective termination. Among the 45 fetal losses, 64% had additional structural abnormalities at index ultrasound and final diagnoses were achievable in 64% cases. Among the 53 livebirths, additional ultrasound abnormalities were detected in only 1 fetus and spontaneous resolution of megacystis was detected in 96% of cases. The two cases where fetal megacystis persisted had major postnatal diagnoses: cloacal malformation and megacystis-microcolon-intestinal hypoperistalsis syndrome, respectively. Our data showed LBD ≥ 12 mm was the best individual predictor of adverse perinatal outcome and all 11 cases of lower urinary tract obstruction (LUTO) were diagnosed in fetuses with LBD ≥ 12 mm. First trimester ultrasound provides important prognostic factors and isolated megacystis <12 mm is associated with a positive outcome.


Increased cardiovascular death rates in a COVID-19 low prevalence area.
The province of L'Aquila (Central Italy) was marginally affected by COVID-19 pandemic, but changes in health care seeking behaviors were noticed. The authors retrospectively analyzed de-identified data concerning all-cause and cardiovascular hospitalizations, cardiovascular acute phase treatments, and in-hospital cardiovascular deaths in the province of L'Aquila from January 1 to March 31, in 2020 and 2019. Incidence rate ratios (IRR) comparing 2020 and 2019 for admissions/procedures were calculated through Poisson regression. All-cause and cardiovascular mortality in the examined time windows was also assessed. Less all-cause (IRR 0.85, P < .001) and cardiovascular (IRR 0.73, P < .001) hospitalizations occurred in 2020 than in 2019. Less daily cardiovascular procedures were also performed (IRR: 0.74, P = .009). A disproportionate decrease in the number of procedures was observed in relation to cardiovascular hospitalizations in 2020 (-5.5%, P = .001). Unlike all-cause mortality, more in-hospital cardiovascular deaths occurred in March 2020 compared with March 2019 (+6.8%, P = .048).


The interwoven fibril-like structure of amyloid-beta plaques in mouse brain tissue visualized using super-resolution STED microscopy.
Standard neuropathologic analysis of Alzheimer's brain relies on traditional fluorescence microscopy, which suffers from limited spatial resolution due to light diffraction. As a result, it fails to reveal intricate details of amyloid plaques. While electron microscopy (EM) offers higher resolution, its extensive sample preparation, involving fixation, dehydration, embedding, and sectioning, can introduce artifacts and distortions in the complex brain tissue. Moreover, EM lacks molecular specificity and has limited field of view and imaging depth. In our study, we employed super-resolution Stimulated Emission Depletion (STED) microscopy in conjunction with the anti-human APP recombinant antibody 1C3 fluorescently labelled with DyLightTM633 (1C3-DyLight633). This combination allowed us to visualize amyloidogenic aggregates in vitro and in brain sections from a 17-month-old 3×Tg-AD mouse with sub-diffraction limited spatial resolution. Remarkably, we achieved a spatial resolution of 29 nm in vitro and 62 nm in brain tissue sections, surpassing the capabilities of conventional confocal microscopy by 5-10 times. Consequently, we could discern individual fibrils within plaques, an achievement previously only possible with EM. The utilization of STED microscopy represents a groundbreaking advancement in the field, enabling researchers to delve into the characterization of local mechanisms that underlie Amyloid (Aβ) deposition into plaques and their subsequent clearance. This unprecedented level of detail is especially crucial for comprehending the etiology of Alzheimer's disease and developing the next generation of anti-amyloid treatments. By facilitating the evaluation of drug candidates and non-pharmacological interventions aiming to reduce amyloid burden, STED microscopy emerges as an indispensable tool for driving scientific progress in Alzheimer's research.


Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system.
To assess 3-year data on the efficacy and safety of a new 52-mg levonorgestrel intrauterine contraceptive (LNG20) designed for up to 7 years use. Nulliparous and parous women aged 16-45 years at enrollment with regular menstrual cycles and requesting contraception were enrolled in an open-label, partially randomized trial to evaluate LNG20. The primary outcome was pregnancy rate for women aged 16-35 years calculated as the Pearl Index. Women aged 36-45 years received LNG20 for safety evaluation only. All participants had in-person or phone follow-up approximately every 3 months during the study. A total of 1600 women aged 16-35 years and 151 women aged 36-45 years agreed to LNG20 placement, including 1011 (57.7%) nulliparous and 438 (25.1%) obese women. Successful placement occurred in 1714 (97.9%) women. Six pregnancies occurred, four of which were ectopic. The Pearl Index for LNG20 was 0.15 (95% CI 0.02-0.55) through Year 1, 0.26 (95% CI 0.10-0.57) through Year 2, and 0.22 (95% CI 0.08-0.49) through Year 3. The cumulative life-table pregnancy rate was 0.55 (95% CI 0.24-1.23) through 3 years. Expulsion was reported in 62 (3.5%) participants, most (50 [80.6%]) during the first year of use. Of women who discontinued LNG20 and desired pregnancy, 86.8% conceived spontaneously within 12 months. Pelvic infection was diagnosed in 10 (0.6%) women. Only 26 (1.5%) LNG20 users discontinued due to bleeding complaints. The LNG20 intrauterine system is highly effective and safe over 3 years of use in nulliparous and parous women. A new 52-mg levonorgestrel-releasing intrauterine system is effective and safe for nulliparous and parous women for at least 3 years.


Chronic hypoxia-induced alteration of presynaptic protein profiles and neurobehavioral dysfunction are averted by supplemental oxygen in Lymnaea stagnalis.
Chronic hypoxia causes neural dysfunction. Oxygen (O(2)) supplements have been commonly used to increase the O(2) supply, yet the therapeutic benefit of this treatment remains controversial due to a lack of cellular and molecular evidence. In this study, we examined the effects of short-burst O(2) supplementation on neural behavior and presynaptic protein expression profiles in a simple chronic hypoxia model of snail Lymnaea stagnalis. We reported that hypoxia delayed the animal response to light stimuli, suppressed locomotory activity, induced expression of stress-response proteins, hypoxia inducible factor-1alpha (HIF-1alpha) and heat shock protein 70 (HSP70), repressed syntaxin-1 (a membrane-bound presynaptic protein) and elevated vesicle-associated membrane protein-1 (VAMP-1) (a vesicle-bound presynaptic protein) level. O(2) supplements relieved suppression of neural behaviors, and corrected hypoxia-induced protein alterations in a dose-dependent manner. The effectiveness of supplemental O(2) was further evaluated by determining time courses for recovery of neural behaviors and expression of stress response proteins and presynaptic proteins after relief from hypoxia conditions. Our findings suggest that O(2) supplement improves hypoxia-induced adverse alterations of presynaptic protein expression and neurobehaviors, however, the optimal level of O(2) required for improvement is protein specific and system specific.


Occurrence of hyaline droplets in renal biopsy specimens: an ultrastructural study.
Hyaline droplets are apical cytoplasmic vesicles containing an accumulation of electron-dense amorphous materials surrounded by a unit membrane. Hyaline droplets may originate from apical vesicles after conversion to osmotic vesicles and loss of internally lined glycocalyx. They are found in the proximal tubular epithelium in biopsies from patients with renal diseases; however, their biological importance is not well understood. We reviewed ultrastructural pathology records of 140 renal biopsy patients to determine the occurrence and relevance of hyaline droplets. Of the cases, 14 (10%) showed the presence of hyaline droplets in proximal tubular epithelium. The distribution of cases were 8 of the 19 (42%) with minimal change nephritic syndrome, 2 of the 37 (5%) with IgA nephropathy, 2 of the 4 (50%) with membranous glomerulonephropathy, 1 of the 4 (25%) with tubulointerstitial nephritis, and 1 of the 1 (100%) with acute renal failure. The droplets were frequently found in male patients (86%), never in children, and were mostly associated with tubular necrosis (8 of 14 cases; 56%). Many hyaline droplets were observed in the cytoplasm of necrotic proximal tubular epithelial cells, and even when tubular necrosis was not evident, the proximal tubular epithelial cells containing hyaline droplets showed degenerated microvilli and decreased basal interdigitations. These results suggest that hyaline droplets could be one marker of renal tubular necrosis and a sign of functional disorder of protein reabsorption by degenerating proximal tubular epithelium.


Impact of two-dimensional and Doppler echocardiography on care of children aged two years and younger.
To determine the impact of 2-dimensional (2-D) and Doppler echocardiography on the care of children aged 2 years and younger with suspected cardiac disease, the clinical management and outcome for the years 1975 (pre-2-D/Doppler era, 161 patients) and 1985 (2-D/Doppler era, 206 patients) were compared. Differences were: (1) decreased catheterization at our institution (48% vs 21%, p less than 0.0001); (2) trend toward decreased recatheterization of patients with referral catheterization (62% vs 38%, p = 0.08); (3) increased operation without preoperative catheterization (10% vs 37%, p less than 0.001); and (4) decreased preoperative catheterization for 7 anomalies (patent ductus arteriosus, ventricular septal defect, atrial septal defect, atrioventricular canal, aortic stenosis, tetralogy of Fallot and complete transposition of great arteries). Operative mortality rates were not statistically different in the years compared. Also, the operative mortality rates in 1985 for patients with and without preoperative catheterization were not statistically different. In 1975, cardiac catheterization changed the primary clinical diagnosis in 21%. In 1985, the primary diagnosis was not changed by catheterization; however, 2-D and Doppler echocardiography changed the diagnosis in 18%. The change in utilization of cardiac catheterization appears to be most closely related to the maximal utilization of a substitute imaging and hemodynamic modality--namely, 2-D and Doppler echocardiography.


The unhappy marriage of religion and politics: problems and pitfalls for gender equality.
This article explores how religion as a political force shapes and deflects the struggle for gender equality in contexts marked by different histories of nation building and challenges of ethnic diversity, different state-society relations (from the more authoritarian to the more democratic), and different relations between state power and religion (especially in the domain of marriage, family and personal laws). It shows how 'private' issues, related to the family, sexuality and reproduction, have become sites of intense public contestation between conservative religious actors wishing to regulate them based on some transcendent moral principle, and feminist and other human rights advocates basing their claims on pluralist and time- and context-specific solutions. Not only are claims of 'divine truth' justifying discriminatory practices against women hard to challenge, but the struggle for gender equality is further complicated by the manner in which it is closely tied up with, and inseparable from, struggles for social and economic justice, ethnic/racial recognition, and national self-determination vis--vis imperial/global domination.


Survey of pediatric urologists on the preoperative use of testosterone in the surgical correction of hypospadias.
To better characterize the current state of testosterone use in the surgical correction of hypospadias among pediatric urologists. An email was sent via the pedsurology research listserv through the American Academy of Pediatrics, inviting members to participate in an anonymous survey regarding their use of preoperative testosterone in hypospadias correction. Twenty-seven responses were obtained for a response rate of 53%. Almost all responders practiced in North America, had exclusively pediatric patients in their practice, and had been in practice for 30 years or less. 55% were classified as high-volume surgeons, completing >50 cases yearly, 87% of whom use preoperative androgen therapy currently, compared with 67% of low-volume surgeons. Testosterone was prescribed primarily for a small appearing penis, reduced glans circumference, reduced urethral plate width, and/or proximal hypospadias. The effect of testosterone was determined primarily by evaluating penile appearance (59%). However, the majority (56%) of physicians stopped giving testosterone when they completed a predetermined regimen. While many pediatric urologists use testosterone prior to hypospadias repair, the practice patterns are variable. It appears that the use of testosterone is primarily limited to patients with proximal hypospadias, small appearing penis, reduced glans circumference or reduced urethral plate.


Flow suppression in rapid FLASH NMR images.
Rapid FLASH (fast low angle shot) NMR images are very sensitive to flow phenomena. In particular, a steady reflow of unsaturated spins from outside the imaging plane results in high image intensities which depend on the flip angle, the repetition time, and the flow velocity. Here we describe a technique that suppresses these signals by saturating remote spins prior to entering the imaging plane, e.g., by intercalating the FLASH sequence with slice-selective 1-2-1 pulse packages. Experiments have been carried out on phantoms and human extremities. Flow artifacts in the phase-encoding direction of the images are strongly reduced. Vascular structures may be easily delineated using difference images obtained with and without flow suppression.


Clinical features, presentation, and tolerance of platinum-based chemotherapy in germ cell tumor patients 50 years of age and older.
Germ cell tumors (GCTs) primarily affect adolescent and young adult men. Detailed clinical and treatment characteristics in older men are lacking. Patients with GCT seen over a 20-year period at Memorial Sloan-Kettering Cancer Center were identified. Primary tumor site and histology were compared for patients aged ≥ 50 years at diagnosis versus younger men. For patients aged ≥ 50, individual chart review was performed and treatment delays, changes, and toxicities were recorded for those treated with first-line chemotherapy. Of 4235 diagnoses of GCT, 3999 (94.4%) were made at age < 50 versus 236 (5.6%) at age ≥ 50. Compared with patients diagnosed before age 50, older men more frequently had seminoma (62.7% versus 36.7%) and less frequently, nonseminoma (34.7% versus 63.2%) (P < .0001). Predominant histology switched from nonseminoma to seminoma around age 35. Distribution of primary sites also differed for older versus younger men (testis: 89.4% versus 92.9%; retroperitoneal: 3.8% versus 0.7%; CNS 0% versus 1.7%) except for mediastinal primary tumors, which remained constant across age groups. Fifty patients age ≥ 50 received first-line platinum-based chemotherapy; 30 experienced complications leading to treatment discontinuation, delay ≥ 7 days, or regimen change. Twenty-two (44%) patients experienced neutropenic fever, 6 despite prophylactic growth factor support. Estimated 5-year survival for chemotherapy-treated patients was 84.9%. Men aged ≥ 50 years comprise less than 10% of GCT diagnoses and have distinct clinical and histological characteristics as compared with younger patients. Although complications from chemotherapy occur frequently in older men, prognosis remains excellent when risk-directed treatment is administered with curative intent.


Hair-containing lesions within the anal canal.
Hair-containing lesions located in the anal canal are an exceedingly rare clinical entity of which only five cases have been reported previously. We add five more cases, including two with a bundle of hairs rooted inside the anal canal and stemming out through a mucosal opening.


The absorption of bismuth and salicylate from oral doses of Pepto-Bismol (bismuth salicylate).
Plasma bismuth and plasma salicylate concentrations were measured before and after three 30-ml oral doses of bismuth salicylate (Pepto-Bismol liquid) in 10 fasting healthy subjects. From 0 to 120 min following the first dose of bismuth salicylate, the plasma bismuth concentration was less than 1 ng/ml. The peak median plasma bismuth concentration was at +240 min (1.7 ng/ml; range 0.8-5.3 ng/ml). Salicylate appeared in the plasma of all subjects at +30 min, and it reached a peak at +120 min (median 61 mg/L; range 46-104 mg/L). The study demonstrates that, despite rapid and substantial absorption of salicylate, there is negligible absorption of bismuth into the bloodstream from standard oral doses of bismuth salicylate.


The antiatherogenic effects of components isolated from pollen typhae.
Based on the results of previous investigations that pollen Typhae, a Traditional Chinese Medicine, Had antiatherogenic effects, several components were isolated successively from the drug and their effects on porcine aortic endothelial cell (EC) and smooth muscle cell (SMC) cultures as well as on platelet aggregation were examined. 12 components isolated from Pollen Typhae have been identified on their chemical structures and biological effects. 4 of them showed different evident antiatherogenic effects. 1) Isorhamnetin-3-O-rhamnosyl-glucoside could stimulate EC to produce tPA and PGI2; 2) Quercetin-3-O-neohesperidose could protect EC from injury by fibrin, as well as raise tPA activity; 3) beta-Sitosterol palmitate could inhibit SMC proliferation and 4) beta-Sitosterol glucoside showed an inhibitory effect on platelet aggregation. These results would provide some information for the search of new drugs in the treatment and prevention of atherosclerosis.


Identification of clinical isolates of anaerobic bacteria using matrix-assisted laser desorption ionization-time of flight mass spectrometry.
We evaluated the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) for the rapid identification of anaerobic bacteria that had been isolated from clinical specimens and previously identified by 16s rRNA sequencing. The Bruker Microflex MALDI-TOF instrument with the Biotyper Software was used. We tested 152 isolates of anaerobic bacteria from 24 different genera and 75 different species. A total of 125 isolates (82%) had Biotyper software scores greater than 2.0 and the correct identification to genus and species was made by MALDI-TOF for 120 (79%) of isolates. Of the 12 isolates with a score between 1.8 and 2.0, 2 (17%) organisms were incorrectly identified by MALDI-TOF. Only 15 (10%) isolates had a score less than 1.8 and MALDI-TOF gave the wrong genus and species for four isolates, the correct genus for two isolates, and the correct genus and species for nine isolates. Therefore, we found the Bruker MALDI-TOF MicroFlex LT with an expanded database and the use of bacteria extracts rather than whole organisms correctly identified 130 of 152 (86%) isolates to genus and species when the cut-off for an acceptable identification was a spectrum score ≥1.8.


Native mutant huntingtin in human brain: evidence for prevalence of full-length monomer.
Huntington disease (HD) is caused by polyglutamine expansion in the N terminus of huntingtin (htt). Analysis of human postmortem brain lysates by SDS-PAGE and Western blot reveals htt as full-length and fragmented. Here we used Blue Native PAGE (BNP) and Western blots to study native htt in human postmortem brain. Antisera against htt detected a single band broadly migrating at 575-850 kDa in control brain and at 650-885 kDa in heterozygous and Venezuelan homozygous HD brains. Anti-polyglutamine antisera detected full-length mutant htt in HD brain. There was little htt cleavage even if lysates were pretreated with trypsin, indicating a property of native htt to resist protease cleavage. A soluble mutant htt fragment of about 180 kDa was detected with anti-htt antibody Ab1 (htt-(1-17)) and increased when lysates were treated with denaturants (SDS, 8 M urea, DTT, or trypsin) before BNP. Wild-type htt was more resistant to denaturants. Based on migration of in vitro translated htt fragments, the 180-kDa segment terminated ≈htt 670-880 amino acids. If second dimension SDS-PAGE followed BNP, the 180-kDa mutant htt was absent, and 43-50 kDa htt fragments appeared. Brain lysates from two HD mouse models expressed native full-length htt; a mutant fragment formed if lysates were pretreated with 8 M urea + DTT. Native full-length mutant htt in embryonic HD(140Q/140Q) mouse primary neurons was intact during cell death and when cell lysates were exposed to denaturants before BNP. Thus, native mutant htt occurs in brain and primary neurons as a soluble full-length monomer.


Light scattering measurements of the gels of gelatin and acto heavy meromyosin solutions by sample rotation method.
The gelation processes of gelatin and acto heavy meromyosin solutions were investigated by a new method of light scattering. The sample was given a constant slow rotation around a vertical axis in a typical dynamic light-scattering setup. The measurements were made on solutions in which polystyrene latex spheres were added as the scattering probes. When a sample reached the gel state, the intensity of the light scattered from the sample fluctuated highly. The relative standard deviation of the intensity fluctuation has been shown to be a good measure of gelation. In addition, computer simulations of this scattering system were found to simulate well the experimental results.


Anesthesia in the late 1960s at Peter Bent Brigham Hospital, Boston: A case report.
Regional and general anesthesia were widely available in the United States in the late 1960s. The risk of permanent neurological sequelae resulting from spinal anesthesia had largely been dismissed. Although many academic departments of anesthesiology had gained independent status, a significant number operated as divisions within the department of surgery. We present a case report from Peter Bent Brigham Hospital to illustrate the state of anesthetic techniques in use during the late 1960s, and the power dynamics vis-à-vis physician anesthesiologists and surgeons. Hospital records and interviews with individuals familiar with the case. An otherwise healthy patient underwent inguinal hernia repair. The resident anesthesiologist conducted a preoperative assessment the evening prior to surgery with the patient consenting to the spinal anesthesia, a plan agreeable to the faculty anesthesiologist. The attending surgeon was one of the most prominent surgeons in America and the chairman of their department. He disapproved of the planned anesthetic. Subsequent modifications to the anesthetic plans are discussed, as is the fallout from those actions. Spinal anesthesia remained a popular anesthetic option during the late 1960s. General anesthesia with ether, halothane, and other agents an alternative. This case highlights various aspects of perioperative management during a period when many American academic departments of anesthesiology existed as divisions within the department of surgery. It also touches upon the careers of two prominent American physicians.


Adenoid cystic carcinoma of the lacrimal gland: role of nuclear survivin (BIRC5) as a prognostic marker.
This study aimed to evaluate the expression of nuclear survivin in adenoid cystic carcinoma (ACC) of the lacrimal gland and to determine if this expression is associated with histopathological features, markers of apoptosis and proliferation or clinical outcomes. Immunohistochemical staining for survivin, p53, Ki-67 and Bcl-2 was analyzed in 55 cases of ACC of lacrimal gland. Thirty-one cases (56.3%) expressed nuclear survivin. All cases expressed p53, Ki-67 and Bcl-2. Eleven cases (35.5%) had a high nuclear survivin score (NS-SCORE) and 20 cases (64.5%) had a low NS-SCORE. Cases with a high NS-SCORE had a shorter progression-free survival (PFS) (P < 0.0001), higher expression of Ki-67 (P < 0.005) and a solid tumour pattern >30% (P < 0.005). Nuclear expression of survivin impacts prognosis significantly and is thus a promising prognostic marker in ACC of the lacrimal gland.


Oxidative stress affects FET proteins localization and alternative pre-mRNA processing in cellular models of ALS.
FUS/TLS, EWS and TAF15 are members of the FET family of DNA and RNA binding proteins, involved in multiple steps of DNA and RNA processing and implicated in the regulation of gene expression and cell-signaling. All members of the FET family contribute to human pathologies, as they are involved in sarcoma translocations and neurodegenerative diseases. Mutations in FUS/TLS, in EWSR1 and in TAF15 genescause Amyotrophic Lateral Sclerosis (ALS), a fatal human neurodegenerative disease that affects primarily motor neurons and is characterized by the progressive loss of motor neurons and degradation of the neuromuscular junctions.ALS-associated FET mutations cause FET protein relocalization into cytoplasmic aggregates, thus impairing their normal function. Protein aggregation has been suggested as a co-opting factor during the disease pathogenesis. Cytoplasmic mislocalization of FET proteins contributes to the formation of cytoplasmic aggregates that may alter RNA processing and initiate motor neuron degeneration. Interestingly, oxidative stress, which is implicated in the pathogenesis of ALS, triggers the accumulation of mutant FUS in cytoplasmic stress granules where it binds and sequester wild-type FUS.In order to evaluate the role of FET proteins in ALS and their involvement in the response to oxidative stress, we have developed cellular models of ALS expressing ALS-related FET mutants in neuroblastoma cell lines. Upon treatment with sodium arsenite, cells were analysed by immunofluorescence to monitor the localization of wild-type and mutated FET proteins. Furthermore, we have characterized signal transduction pathways and cell survival upon oxidative stress in our cellular models of ALS. Interestingly, we found that EWS mutant proteins display a different localization from FUS mutants and neither wild-type nor mutated EWS protein translocate into stress granules upon oxidative stress treatment. Collectively, our data provide a new link between the oxidative stress response and RNA metabolism in ALS disease.


Reduction of aflatoxin B1 levels by sheep saliva.
This study determined the decrease of aflatoxin B1 by sheep saliva at concentrations of 150 and 300 μg aflatoxin B-1/L saliva. Analyses for aflatoxins B1, M1, and aflatoxicol (R0) were performed after 2, 4, 6, 24, and 48 hours of incubation. Aflatoxin M1 and R0 were not detected and only residues of aflatoxin B1 were found. 4 to 13% of aflatoxin B1 were decomposed by sheep's saliva within 2 hrs and 33 to 43% of aflatoxin B1 after 24 hrs. Decomposition was affected by the aflatoxin concentration.Decrease of aflatoxin B1 at 2, 4, 6 hrs was nearly three times higher at the low concentration (150 ppb) compared to the high concentration (300 ppb). After 48 hrs incubation more than 80% of the initial aflatoxin B1 had been decomposed by the saliva.


The imaging revolution and radiation oncology: use of CT, ultrasound, and NMR for localization, treatment planning and treatment delivery.
The explosion of new imaging technologies such as X ray computed tomography (CT), ultrasound (US), positron emission tomography (PET), and nuclear magnetic resonance imaging (NMR) has forced a major change in radiation therapy treatment planning philosophy and procedures. Modern computer technology has been wedded to these new imaging modalities, making possible sophisticated radiation therapy treatment planning using both the detailed anatomical and density information that is made available by CT and the other imaging modalities. This has forced a revolution in the way treatments are planned, with the result that actual beam configurations are typically both more complex and more carefully tailored to the desired target volume. This increase in precision and accuracy will presumably improve the results of radiation therapy.


Correction: Monk, B.C.; Keniya, M.V. Roles for Structural Biology in the Discovery of Drugs and Agrochemicals Targeting Sterol 14α-Demethylases. J. Fungi 2021, 7, 67.
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A comprehensive review on ethnopharmacological, phytochemical, pharmacological and toxicological evaluation, and quality control of Pinellia ternata (Thunb.) Breit.
Pinellia ternata tuber (PTT), the dried tuber of Pinellia ternata (Thunb.) Breit., has a long history of use in traditional Chinese medicine for drying dampness, resolving phlegm, down-bearing counterflow to check vomiting and dissipating masses. Modern pharmacology studies have revealed that PTT has diverse pharmacological effects such as antitussive and expectorant, anti-emetic, anti-tumor, and anti-inflammatory effect, etc. AIM OF THE REVIEW: This review aims to provide a critical and comprehensive evaluation on ethnopharmacological uses, chemical constituents, pharmacological and toxicological effects, analytical methods and quality control of PTT, which would provide scientific evidence for exploring future therapeutic, and formulating quality and safety criteria of PTT. Pertinent information was systematically collected from several electronic scientific databases including Web of Science, Science Direct, PubMed, Elsevier, Wiley Online Library and China national knowledge infrastructure (CNKI), as well as the classic Chinese medical books. PTT is reported to be widely used traditionally for the treatment of cough, vomiting, infection, and inflammatory diseases in many southeast Asian countries. Phytochemical studies have revealed the presence of a total of 233 compounds belonging to alkaloids, nucleosides, organic acids, polysaccharides, volatile oils, amino acids, proteins, starches, etc. The extracts and components of PTT have possessed diverse pharmacological activities, such as antitussive, antiemetic, antitumor, antibacterial, and sedative-hypnotic activities. Raw P. ternata tuber (RPTT) with a pungent taste causes acrid irritation of the oral and laryngopharynx mucosa when taken by mistake, while its toxicity and side effects of RPTT can be dramatically reduced with proper processing. Three kinds of processed P. ternata tuber with different processing methods are available and traded in market, as well as applied in clinical treatments. Additionally, although raw or processed PTT have been recorded in several mainstream pharmacopoeias such as Chinese Pharmacopoeia, Japanese Pharmacopoeia, and Korean Pharmacopoeia, the quality items and requirements varies a lot. Therefore, a unified international standard of raw and processed PTT is urgent need to be done. The ethnopharmacological, phytochemical, pharmacological and toxicological and quality evaluation of PTT were highlighted in this review, which provides potential reference information to future investigate and commercially explore for pharmaceutical applications. Nevertheless, an efficient method for chemical profiling is still unavailable to find potent bioactive markers for quality control, and then comprehensive pharmacological effects and mechanisms and toxicological evaluation of PTT require further detailed research to ensure their quality and safety.


Heart rate variability: A biomarker of selective response to mindfulness-based treatment versus fluoxetine in generalized anxiety disorder.
Mindfulness-based interventions (MBIs) are effective for some, but not all patients with anxiety disorders, but no clinical features have been consistently able to differentiate which patients are more likely to respond. In this study, we tested heart rate variability (HRV), a proposed correlate of regulated emotional response, as a moderator of treatment response to an MBI compared with pharmacotherapy. Seventy-seven patients with GAD had HRV data collected before randomization to pharmacological treatment with fluoxetine or Body-in-Mind Training (an MBI focused on bodily movement attention). HRV was used to predict treatment response measured by the Hamilton anxiety rating scale at 0 (baseline), 5, and 8 weeks (end of the intervention). The HF (nu) index of HRV was a strong moderator of treatment response between BMT and fluoxetine (estimate = 4.27 95%CI [1.19, 8.19]). Although fluoxetine was overall slightly superior to BMT in this study, no differences were found between groups in patients with high HF (nu) scores (estimate = -1.85 CI95% [-9.21, 5.52]). In contrast, patients with low HF (nu) achieved lower anxiety rating scores with fluoxetine treatment when compared with BMT (estimate = -10.29, 95% CI [-17.59, -2.99]). A relatively small sample of patients was included. HRV was able to identify a subgroup for which MBI was less effective than pharmacotherapy and is a promising candidate as a selective biomarker for treatment response between an MBI and fluoxetine.


Triplets where monozygotic siblings are concordant for arson.
Triplets are described where the two genetically identical brothers are arsonists and both have sociopathic personality disorder rated using the Personality Assessment Schedule. The third, non-identical brother has not committed arson and does not have a personality disorder.


Review on skin and mucous-membrane irritation tests and their application.
The history and present state of routine testing for skin and eye irritation are reviewed. Various changes to the traditional Draize test have been proposed by a number of workers, and it is concluded that the adoption of the modified Draize test should be the first decisive step to be taken in the search for new methods in irritation testing. Other new methods, such as testing using organ and cell cultures, and determination of the relationship between physico-chemical properties and irritative potential, have been reported. Although at present these techniques require further validation, some of them show considerable promise of reliably predicting the irritative effects of substances on humans.


Dual Dopaminergic Regulation of Corticostriatal Plasticity by Cholinergic Interneurons and Indirect Pathway Medium Spiny Neurons.
Endocannabinoid (eCB)-mediated long-term depression (LTD) requires dopamine (DA) D2 receptors (D2Rs) for eCB mobilization. The cellular locus of the D2Rs involved in LTD induction remains highly debated. We directly examined the role in LTD induction of D2Rs expressed by striatal cholinergic interneurons (Chls) and indirect pathway medium spiny neurons (iMSNs) using neuron-specific targeted deletion of D2Rs. Deletion of Chl-D2Rs (Chl-Drd2KO) impaired LTD induction in both subtypes of MSNs. LTD induction was restored in the Chl-Drd2KO mice by an M1-selective muscarinic acetylcholine receptor antagonist. In contrast, after the deletion of iMSN-D2Rs (iMSN-Drd2KO), LTD induction was intact in MSNs. Separate interrogation of direct pathway and iMSNs revealed a deficit in LTD induction only at synapses onto iMSNs that lack D2Rs. LTD induction in iMSNs was restored by D2R agonist application. Our findings suggest that Chl D2Rs strongly modulate LTD induction in MSNs, with iMSN-D2Rs having a weaker, iMSN-specific, modulatory effect.


Health-related quality of life outcomes among breast cancer survivors.
Data from a nationwide sample of US breast cancer survivors were used to examine associations between patient characteristics (breast cancer clinical features, prognostic factors, and treatments) and health-related quality of life (HRQOL). Associations between postdiagnosis HRQOL and mortality were then evaluated. The authors identified female breast cancer survivors (n = 2453) from the Sister Study or Two Sister Study who were at least 1 year from breast cancer diagnosis and who had responded to a survivorship survey in 2012. HRQOL was assessed with the Patient-Reported Outcomes Measurement Information System (PROMIS) Global 10 measures. Multivariable linear regression was used to assess predictors associated with HRQOL. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HRQOL and all-cause mortality. HRQOL, assessed an average of 4.9 years after the cancer diagnosis (standard deviation of 1.9 years), was negatively associated with a higher cancer stage at diagnosis; a higher comorbidity score at the survey; experience of surgical complications; dissatisfaction with breast surgery; and experience of any recent recurrence, metastasis, or secondary malignancy. Since the completion of the survey, there were 85 deaths (3.5%) during a mean follow-up of 4 years (standard deviation of 0.5 years). In multivariate models, decreases in PROMIS physical T scores and mental T scores were associated with increased mortality (HR for physical T scores, 1.08; 95% CI, 1.05-1.11; HR for mental T scores, 1.03; 95% CI, 1.01-1.06). Prognostic and cancer treatment-related factors affect HRQOL in breast cancer survivors and may inform targeted survivorship care. PROMIS global health measures may offer additional insights into patients' well-being and mortality risk. Findings from a study suggest that prognostic and cancer treatment-related factors affect health-related quality of life (HRQOL) in breast cancer survivors and that poor HRQOL may increase the mortality risk. The evaluation of HRQOL is important because it may hold potential as a tool for optimizing survivorship care.


Titration of total binding sites for growth hormone in rabbit liver. Quantitative modifications of these sites during pregnancy.
The present work outlines various kinetic parameters of the interaction between bGH (bovine growth hormone) and a receptor located on the membranes of rabbit liver. A dissociation procedure, which strips the hormone off its receptor has been worked out, by varying MgCl2 concentrations and times of contact; exposure to 4 M MgCl2 for 15--30 min was found optimal for dissociation, without denaturing the receptor, as shown by the possibility of rebinding the hormone to the desaturated membranes. This method has been applied to titrate growth hormone receptors in rabbit liver, during pregnancy and lactation. The first half of pregnancy is characterized by a gradual increase of receptor levels and low saturation by endogenous hormone; conversely at parturition, there occurs a striking increase in receptors, which, however, may be demonstrated only after desaturation. During the lactational period, the receptors reamin in part saturated. The results suggest that growth hormone levels increase at parturition and during lactation in the rabbit and hence may play an important role during lactation. The factors which modulate receptor levels at the same period remain unknown.


Goldenhar syndrome complicated with subglottic airway stenosis: a case report.
Goldenhar syndrome is a congenital disease that involves an absence or underdevelopment of structures that arise from the first and second pharyngeal arches and more or less severe extracranial anomalies. A variety of supraglottic malformations may be observed, including mandibular hypoplasia, mandibular asymmetry and micrognathia. Subglottic airway stenosis (SGS), which can cause difficulties in airway management during the perioperative period, is seldom emphasized in literature descriptions of Goldenhar syndrome, but can be clinically significant. An 18-year-old female with a history of Goldenhar syndrome presented for placement of a right mandibular distractor, right retroauricular dilator, and stage I transfer of a prefabricated expanded flap under general anesthesia. During tracheal intubation, the endotracheal tube (ETT) met resistance unexpectantly when attempting to pass through the glottis. Subsequently, we attempted the procedure with a smaller size ETT but again met resistance. With fiberoptic bronchoscope, we found that the whole segment of the trachea and bilateral bronchi were obvious narrow. Given the finding of unexpected severe airway stenosis and the associated risks with proceeding with the surgery, the operation was cancelled. We removed the ETT once the patient was fully awake. Anesthesiologists should be aware of this clinical finding when evaluating the airway of a patient with Goldenhar syndrome. Coronal and sagittal measurements on computerized tomography (CT) and three-dimensional image reconstruction can be used to evaluate the degree of subglottic airway stenosis and measure the diameter of the trachea.


Diabetes case finding in the emergency department, using HbA1c: an opportunity to improve diabetes detection, prevention, and care.
We assessed the efficacy of routine glycated hemoglobin (HbA1c) testing to detect undiagnosed diabetes and prediabetes in an urban Australian public hospital emergency department (ED) located in an area of high diabetes prevalence. Over 6 weeks, all patients undergoing blood sampling in the ED had their random blood glucose measured. If ≥5.5 mmol/L (99 mg/dL), HbA1c was measured on the same sample. HbA1c levels ≥6.5% (48 mmol/mol) and 5.7-6.4% (39-46 mmol/mol) were diagnostic of diabetes and prediabetes, respectively. Hospital records were reviewed to identify patients with previously diagnosed diabetes. Among 4580 presentations, 2652 had blood sampled of which 1267 samples had HbA1c measured. Of these, 487 (38.4%) had diabetes (either HbA1c≥6.5% or a prior diagnosis), and a further 347 (27.4%) had prediabetes. Among those with diabetes, 32.2% were previously undiagnosed. Routine HbA1c testing in the ED identifies a large number of people with undiagnosed diabetes and prediabetes, and provides an opportunity to improve their care.


True Oncocytic Acinic Cell Carcinoma: A Case Image.
A 67-year-old female with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) presented with right sided otalgia and a 2-3 cm firm, tender right posterior parotid mass. Fine needle aspiration biopsy (FNAB) established a diagnosis of acinic cell carcinoma (AciCC). Further workup demonstrated lung nodules which were confirmed by FNAB to represent metastatic AciCC. A right radical parotidectomy with sacrifice of the facial nerve, segmental mandibulectomy, and selective neck dissection (levels II-IV) was performed. Microscopically, the tumor displayed an infiltrative border with a solid multinodular growth pattern and fibrosclerotic septation. The tumor was composed mainly of uniform cells with abundant eosinophilic granular cytoplasm with round nuclei with prominent nucleoli. Nuclei were fairly monomorphic, mitotic counts were 3-4 per 2mm2 and there was no necrosis despite the aggressive growth pattern. An anti-mitochondrial immunohistochemical stain showed strong reactivity in the tumor cells, with an internal positive control of adjacent striated ducts. An immunohistochemical stain for NR4A3 demonstrated strong nuclear reactivity in the tumor cells. Electron microscopy highlighted the tumor cells with numerous mitochondria and distinctive electron dense intramitochondrial inclusions. Concurrent CLL/SLL was identified on histologic examination of the lymph nodes, but they were free of AciCC. After eight weeks of follow-up, she tolerated the surgery well and is currently receiving radiation therapy to the parotid and neck. In this illustrative case, we justify the oncocytic designation of AciCC by morphology, immunohistochemistry, and electron microscopy.


The T-->C mutation at position +96 of the untranslated region 3' to the terminating codon of the beta-globin gene is a rare polymorphism that does not cause a beta-thalassemia as previously ascribed.
We have observed a T-->C mutation at position +96 of the untranslated region 3' to the terminating codon of the beta-globin gene in members of two Czech families and one black family. Data from initial studies suggested that this change was the cause of a beta-thalassemia, but continued analyses have provided convincing evidence that this mutation is a simple polymorphism.


MicroRNA-155 Suppresses Mesangial Cell Proliferation and TGF-β1 Production via Inhibiting CXCR5-ERK Signaling Pathway in Lupus Nephritis.
Increasing evidence shows miR-155 plays an important role in regulating inflammatory processes in systemic lupus erythematosus (SLE), especially in lupus nephritis (LN). Because the chemokine CXCL13 is implicated in the pathogenesis of LN, here we examined whether miR-155 can modulate the activity of CXCL13 or its receptor CXCR5. We determined the expression of CXCL13 in normal and MRL/lpr mice and found elevated levels of CXCL13 in the kidneys of MRL/lpr mice compared with normal kidneys. Besides, CXCL13 expression was mainly detected in the glomerulus, specifically to mesangial areas. We then transfected a miR-155 mimic in human renal mesangial cells (HRMCs) to overexpress miR-155 and detected decreased protein levels of CXCR5 by western blot analysis. Transfection of the miR-155 mimic into CXCL13-treated HRMCs resulted in a significantly reduced proliferation rate of HRMCs as measured by the cell-counting assay and flow cytometry. Moreover, increased intracellular miR-155 also led to decreased phosphorylation of ERK and TGF-β1 production. Together, these results revealed that miR-155 may play a role in the pathogenesis of LN.


Prevalence of myopia, hyperopia, and astigmatism in non-Hispanic white and Asian children: multi-ethnic pediatric eye disease study.
To determine the age-, gender-, and ethnicity-specific prevalence of myopia, hyperopia, and astigmatism in non-Hispanic white (NHW) and Asian preschool children. Population-based, cross-sectional study. A population-based sample of 1501 NHW children and 1507 Asian children aged 6-72 months from Los Angeles County and Riverside County, California. Eligible children underwent an in-home and in-clinic interview and a comprehensive eye examination including cycloplegic autorefraction from 100 census tracts. The proportion of children with myopia (spherical equivalent [SE] ≤-1.00 diopter [D]), hyperopia (SE ≥ +2.00 D) and cylindrical refractive error ≥1.50 D in the worse eye. The astigmatism type was defined as with-the-rule (WTR; +cylinder axis 90°±15°) and against-the-rule (ATR; + cylinder axis 180°±15°); all other orientations were considered oblique (OBL). The prevalence of myopia, hyperopia, and astigmatism in NHW children was 1.20% (95% confidence interval [CI], 0.76%-1.89%), 25.65% (95% CI, 23.5%-27.9%), and 6.33% (95% CI, 5.21%-7.68%), respectively. The prevalence of WTR, ATR, and OBL astigmatism in NHW children was 4.33%, 1.00%, and 1.00%, respectively. Prevalence was lower with older age groups for astigmatism (P = 0.0002), but not for myopia (P = 0.82) or hyperopia (P = 0.31). In Asian children, the prevalence of myopia, hyperopia, and astigmatism was 3.98% (95% CI, 3.11%-5.09%), 13.47% (95% CI, 11.8%-15.3%), and 8.29% (95% CI, 7.01%-9.80%), respectively. The prevalence of WTR, ATR, and OBL astigmatism was 6.50%, 0.80%, and 1.00% respectively. The prevalence of hyperopia was higher in girls than boys (P = 0.0002), but no differences were found for myopia and astigmatism. Hyperopia was the most common refractive error in both Asian and NHW children. However, compared with NHW children, myopia was relatively more prevalent, and hyperopia less prevalent, among Asian children. The prevalence of astigmatism was greatest in infants, and WTR astigmatism predominated at all ages. Myopia showed relatively stable prevalence across age groups, whereas hyperopia prevalence decreased after infancy and then increased again in older age groups; however, longitudinal studies are needed to evaluate refractive changes over time in individual children. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Condon's multiple-response phenomenon in severely dysfunctional children: an attempt at replication.
The present study was conducted in an attempt to replicate the findings of William Condon on multiple entrainment and dyssynchronous behavioral organization in autistic children. Three autistic and two normal children were filmed while being presented with five discrete auditory stimuli. Microkinesic analyses of the children's motor responses were performed in relation to three hypotheses designed to support the double-response and dyssynchrony effects. No firm evidence of multiple-responding to single sound was found for the autistic or normal children. There was some indication of dyssynchronous, or awkward, response organization for the autistic children, in comparison to the smooth-flowing body movements of the normal children.


Quality assessment in prospective nuchal translucency screening for Down syndrome.
To develop and apply a quality control system in a Down syndrome screening study using nuchal translucency as an interventional marker. In a prospective Down syndrome screening study fetal nuchal translucency thickness was measured in 9236 of the 10 045 examined pregnancies. For quality assessment two models were introduced: firstly, image-scoring evaluation of the nuchal translucency thickness measurements and secondly, establishment of the distributions of nuchal translucency multiples of the median over time and the influence of intervention. The observer variability in the image-scoring evaluation was high with a kappa value of 0.48 in the overall validation. A revised model showed better interobserver agreement with a kappa value of 0.58; however, comparing the individual criteria the differences were still unsatisfactory, i.e. we found highly significant differences in the criteria "position of the fetus" (P = 0.0026) and "magnification of the image" (P = 0.0001). Regarding the distributions of the nuchal translucency multiples of the median, the median stabilized after a short learning phase representing the practical part of the sonographer's certification to nuchal translucency screening. In groups of medians of 50 nuchal translucency multiples of the median the intergroup standard deviation decreased from 0.100-0.060 after the learning phase to 0.046 after intervention. When well-trained certified examiners perform nuchal translucency screening, continuous evaluation of the distribution of the nuchal translucency multiples of the median seems to be a good method to assess the quality for a center and may also be used to identify individual examiners deviating from the mean performance. The image-scoring methods we introduced cannot be recommended for quality control in a nuchal translucency screening program.


A clinicopathologic study of three carcinoid tumors metastatic to the orbit. Immunohistochemical, ultrastructural, and DNA flow cytometric studies.
Three patients with histopathologically proven orbital metastatic lesions from a carcinoid tumor are reported. Computed tomography (CT) disclosed a well-circumscribed orbital mass in two of three cases. Each tumor was studied by both light and electron microscopy as well as immunohistochemistry and DNA flow cytometry. A review of the literature discloses the relatively rare occurrence of carcinoid tumors metastasizing to the eye and orbit. With the exception of one case, the reported metastatic carcinoid tumors to the uvea all developed from primary bronchial carcinoids. In contrast, the vast majority of the reported orbital metastases arose from ileal carcinoids. Immunohistochemical markers such as chromogranin A, synaptophysin, and serotonin have proven to be useful diagnostic tools in evaluating carcinoid tumors. Furthermore, DNA flow cytometry may be of prognostic value in patients with metastatic carcinoid tumor.


Synthesis of a (N,C,C) Au(iii) pincer complex via Csp3-H bond activation: increasing catalyst robustness by rational catalyst design.
A (N,CAr,CAlk) Au(iii) pincer complex has been synthesized from Au(OAc)3 (OAc = OCOCH3) and 2-(3,5-di-tert-butylphenyl)pyridine (L1) involving a Csp3-H bond activation by electrophilic substitution. In agreement with DFT calculations, the resulting complex significantly improves the performance of Au(tpy)(OAcF)2 (tpy = 2-(p-tolyl)pyridine, OAcF = OCOCF3) in the catalytic trifluoroacetylation of acetylene.


Neurobiological similarities in antidepressant sleep deprivation and psychostimulant use: a psychostimulant theory of antidepressant sleep deprivation.
This paper attempts to summarize the evidence for the hypothesis that psychostimulant-like neurotransmitter processes within certain regions of the limbic system induce the positive effects of antidepressant sleep deprivation (SD). Preclinical and human studies indicate similar neurobiological effects of psychostimulants such as amphetamines, cocaine and SD. In clinical use, SD and psychostimulants have similar characteristics and behavioral effects. Furthermore, acute psychostimulant challenge decreases limbic metabolism in imaging studies, and SD decreases elevated limbic metabolism in SD responders, indicating that psychostimulant-like neurotransmitter release could decrease limbic metabolism in SD responders. Most antidepressant pharmacotherapies change the reactivity of the dopamine system, and a decrease of presynaptic dopamine or postsynaptic availability can induce depression. Sleep is accompanied by a reduction of catecholamine release and those processes which are increased by psychostimulants. It is concluded that a proposed regional postsynaptic deficit in catecholaminergic neurotransmission can be overcome either acutely by enhanced release during SD or psychostimulant use, or chronically by changes in receptor sensitivity or gene expression due to antidepressant therapies. A postsynaptic deficit in these areas becomes evident if presynaptic release is reduced in conditions such as sleep. Therefore, sleep is depressiogenic for predisposed individuals and the reduction of sleep avoids understimulation of subsensitive postsynaptic processes, which are enhanced by psychostimulants.


Clinical characteristics and predictors of community-acquired pseudomonas aeruginosa sepsis and nontyphoidal salmonella sepsis in infants: A matched Case-Control study.
Pseudomonas aeruginosa and nontyphoidal Salmonella (NTS) species may cause enteric illness with sepsis in infancy. The clinical predictors distinguishing the two pathogens have not been comprehensively evaluated in this population in Taiwan. A retrospective matched case-control study was conducted in a teaching hospital in southern Taiwan from January 1, 2003 to January 30, 2019. The patients with community-acquired P. aeruginosa sepsis were matched at a ratio of 1:2 by age and gender with controls (who developed NTS sepsis). A total of 21 infants with community-acquired P. aeruginosa sepsis were identified; of these, 12 (57.1%) were male, and the mean ± standard deviation of age was 6.95 ± 2.47 months. Two independent predictors indicative of P. aeruginosa sepsis, as identified by multivariate analysis using conditional logistic regression, were hemoglobin level (Hb) (matched odds ratio [mOR], 0.155; 95% confidence interval [CI], 0.027-0.900; p = 0.038) and platelet count (mOR, 0.988, 95% CI, 0.976-1.000; p = 0.049). The areas under the receiver operating characteristic (ROC) curves of Hb and platelet count for P. aeruginosa sepsis prediction were 0.855 and 0.803, respectively. With cut-off values for Hb of 10.7 g/dL and platelet count of 173,000/μL, the predictors had maximal diagnostic accuracy. Most patients with P. aeruginosa sepsis are less than one year old. A lower hemoglobin level and a lower platelet count are significant predictors of P. aeruginosa sepsis. These findings should help to reshape the policy of empirical antibiotics in infants with sepsis.


[Economic evaluation of medical devices not included in the French list of products and services qualifying for reimbursement: Example of biologic meshes].
To present a method aimed to evaluate the economic impact associated with the use of medical devices (DM) not reimbursed in addition to diagnosis related groups (DRGs) tariffs using the example of biological meshes for parietal reinforcement. In this multicenter retrospective cohort study, we included all patients who received a biological mesh between January 2010-April 2014 (University hospitals of Saint-Étienne, France) or between January 2010-March 2015 (Lyon University hospitals, France). Measured costs associated with biologic meshes were compared to those of the "Étude nationale des coûts à méthodologie commune" (2012) to weigh the economic impact of biologic meshes with the French DRGs costs. We also compared these costs to the fares perceived by the hospital from the French sickness fund (GHS). Thirty-six patients received a biological mesh and were treated by a total of 38 biological meshes. Of these, the implant was Protexa®, Permacol® and Strattice® in 66%, 29% and 5% of cases respectively. The hospitals incomes were 10,496±5562€ per stay. Meshes-related expenditures represented in average 28% of DRGs costs and 38% of GHS tariffs. The mean additional cost for biological meshes was 3793±2292 euros compared to the mean cost on implantable medical devices in the French DRGs. Given their currently restricted use, the hospital budget impact of biological meshes remains limited although the incremental cost per patient is substantial. Analytic costs data can be useful within the scope of decision-making related to DM not refunded by the French health system.


Interaction between low-density lipoprotein-cholesterolaemia, serum uric level and incident hypertension: data from the Brisighella Heart Study.
Previous evidence suggest that high low-density lipoprotein cholesterol (LDL-C) and serum uric acid (SUA) levels are risk factors for endothelial dysfunction and vascular ageing. The aim of our study was to evaluate the short-term interaction between SUA, LDL-C and incident hypertension in a sample of overall healthy individuals. In January 2018, we selected from the general database of the Brisighella Heart Study four groups of age and sex-matched nonhypertensive individuals with different levels of LDL-C and SUA level and examined during the 2008 population survey. Incident hypertension has been defined as the increase of SBP values over 140 mmHg and/or of DBP over 90 mmHg and or the beginning of an antihypertensive treatment. In a model adjusted for age, sex, baseline blood pressure, family history of hypertension, smoking status, BMI and physical activity intensity, hazard rations for hypertension development compared with individuals with baseline normal LDL-C and SUA levels are 1.14 [95% confidence interval (95% CI) 0.87-1.55] for individuals with isolated high LDL-C level, 1.55 (95% CI 0.96-2.48) for individuals with isolated high SUA level and 1.57 (95% CI 1.20-2.15) for individuals with both high SUA and LDL-C levels. In an overall healthy population sample, the contemporary presence of suboptimal LDL-C and SUA values is associated with an increased risk to develop hypertension.


Twin-to-twin transfusion syndrome: what are appropriate diagnostic criteria?
One hundred seventy-eight consecutive twin pregnancies were studied to reevaluate the standard diagnostic criteria for chronic twin-to-twin transfusion syndrome of an intertwin hemoglobin difference greater than 5 gm/dl and a birth weight difference greater than 20%. Hemoglobin differences greater than 5 gm/dl were found in six pregnancies with monochorionic placentas but also in seven with dichorionic placentas. Birth weight differences greater than 20% occurred no more commonly in monochorionic than in dichorionic pregnancies. Of the four pregnancies with a coexisting hemoglobin difference greater than 5 gm/dl and birth weight difference greater than 20%, only one had a monochorionic placenta and therefore likelihood of vascular anastomoses. Diagnosis of twin-to-twin transfusion syndrome cannot be definitively established by current standard diagnostic criteria.


Employment, social dependency and return to work after intensive care.
Quality of life is an important measure of outcome in intensive care survivors. As return to employment is a key determinant of quality of life, we performed a prospective observational, cohort study of 75 intensive care unit patients who survived to hospital discharge. Approximately 2 years after intensive care unit discharge, 64% (18/28) of those employed before intensive care unit had returned to work. Of the rest, 10 were not working, two were unemployed, one was temporarily sick and seven were permanently sick. When health utility scores were assessed in the various employment categories, quality of life was particularly poor in the unemployed and permanently sick with median (interquartile range) scores of 0.082(-0.045-0.665) and 0.053(-0.160-0.769) respectively. Of the retired population, 95% returned to their own home with 50% requiring a family member to act as their carer. This study has demonstrated that patients who returned to work after a critical illness had a better quality of life at follow up, compared to the unemployed and permanently sick. In addition, there may be a burden on family members who act as carers for their relatives on discharge from hospital after a critical illness. Further work is required in this important area.


Synthesis and structure-activity relationships of mono- and dialkyl-substituted oxaliplatin derivatives.
In order to improve the pharmacological profile of the anticancer drug oxaliplatin, (trans-R,R-cyclohexane-1,2-diamine)oxalatoplatinum(II), and to explore activity-structure relationships, new mono- and dialkyl substituted oxaliplatin analogues have been synthesized. Following a new synthetic strategy, racemates with a defined stereochemistry at carbon atoms 1, 2, 4, and 5 of the cyclohexane ring could be prepared, which are the bases for reliable structure-activity relationships and the following enantiomer resolution. The cytotoxicity was evaluated in nine tumor cell lines, indicating that bulky substituents have a negative influence on the cytotoxic potency of the oxaliplatin derivatives. With respect to the antiproliferative properties, the 4-methyl-, cis-4,5-dimethyl-, and especially the 4,4-dimethyl-trans-cyclohexane-1,2-diamine(oxalato)platinum(II) complexes are the most promising candidates to be further evaluated.


Viscoelastic characteristics of in vitro vital and devitalized rat aorta and human arterial prostheses.
The arterial wall viscoelasticity plays an essential role in the vascular responsiveness to vasoactive drugs or pathologies. The aim of this investigation was to derive and compare resonance curve (RC), natural frequency (f(0)), dynamic modulus of elasticity (E'), and coefficient of viscosity (beta) of (i) vital and devitalized preparations of rat thoracic and abdominal aorta, (ii) human arterial prostheses, and to study the histomorphology of vital and devitalized rat aorta. The method of low frequency forced oscillations was employed. RC of vital preparations showed a hardening type of elasticity whereas in devitalized preparations it was of softening type. E' increased nonlinearly, f(0) decreased and beta increased linearly with equivalent intraluminal pressure (p(eqi)). Distensibility of abdominal aorta was lower than thoracic aorta. Distensibility decreased with increasing p(eqi). E', f(0), and beta increased significantly after devitalization. It was suggested that postmortem viscoelastic characteristics should not be used directly to specify the vital arteries viscoelasticity. RC of human prostheses showed a softening type of elasticity. Arterial prostheses have low circumferential distensibility with E'-values higher than reported in the literature for human arteries. The method of forced oscillations could be employed for studying the arterial wall biomechanics and viscoelasticity of arterial prostheses.


Paradoxical punishment as it relates to the battered woman syndrome.
The main goal of this article is to suggest some processes by which the behavioral interactions of an abusive couple can be developed and maintained. A summary of these processes as they have been adapted from the animal analog and human research follows. First, the pairing of abuse (punishment) with love and affection (reinforcement) could indicate that the battered woman responds to the reinforcement that follows an abusive incident. Second, the battered woman may seek to escape the fear of the tension-building phase but during the escape behavior she is punished (physical abuse), which fortifies and strengthens her initial fear. However, after the abusive incident, there is an absence of tension and fear (negative reinforcement) compounded by the positive reinforcement of the contrition phase. Thus, a cyclical pattern of behavior evolves and sustains itself. Possibly augmenting the vicious cycle is habituation or negative adaptation to the physical abuse, as well as the lack of opportunities to learn adaptive behavioral responses that may break the cycle of violence. Finally, the need for primary reinforcement (i.e., love and affection) may be so powerful that it somewhat mitigates the abuse endured to obtain it.


Naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure.
Small-conductance (KCa2.1-2.3) and intermediate-conductance (KCa3.1) calcium-activated K(+) channels are critically involved in modulating calcium-signaling cascades and membrane potential in both excitable and nonexcitable cells. Activators of these channels constitute useful pharmacological tools and potential new drugs for the treatment of ataxia, epilepsy, and hypertension. Here, we used the neuroprotectant riluzole as a template for the design of KCa2/3 channel activators that are potent enough for in vivo studies. Of a library of 41 benzothiazoles, we identified 2 compounds, anthra[2,1-d]thiazol-2-ylamine (SKA-20) and naphtho[1,2-d]thiazol-2-ylamine (SKA-31), which are 10 to 20 times more potent than riluzole and activate KCa2.1 with EC(50) values of 430 nM and 2.9 microM, KCa2.2 with an EC(50) value of 1.9 microM, KCa2.3 with EC(50) values of 1.2 and 2.9 microM, and KCa3.1 with EC(50) values of 115 and 260 nM. Likewise, SKA-20 and SKA-31 activated native KCa2.3 and KCa3.1 channels in murine endothelial cells, and the more "drug-like" SKA-31 (half-life of 12 h) potentiated endothelium-derived hyperpolarizing factor-mediated dilations of carotid arteries from KCa3.1(+/+) mice but not from KCa3.1(-/-) mice. Administration of 10 and 30 mg/kg SKA-31 lowered mean arterial blood pressure by 4 and 6 mm Hg in normotensive mice and by 12 mm Hg in angiotensin-II-induced hypertension. These effects were absent in KCa3.1-deficient mice. In conclusion, with SKA-31, we have designed a new pharmacological tool to define the functional role of the KCa2/3 channel activation in vivo. The blood pressure-lowering effect of SKA-31 suggests KCa3.1 channel activation as a new therapeutic principle for the treatment of hypertension.


Comprehensive spectrum of the β-Thalassemia mutations in Khuzestan, southwest Iran.
β-Thalassemia (β-thal) is characterized by reduction or absence of β-globin gene expression. We describe the spectrum of mutations observed in a large cohort of β-thal carriers in Khuzestan, Southwest Iran. All together 1,241 blood samples from individuals with decreased mean corpuscular volume (MCV) and elevated Hb A(2) levels, were analyzed either by reverse dot-blot or by direct sequencing of the HBB gene. We found 42 different mutations associated with β-thal and identified eight common β-globin variants, namely, Hb S [β6(A3)Glu→Val], Hb C [β6(A3)Glu→Lys], Hb D-Punjab [β121(GH4)Glu→Gln] and Hb O-Arab [β121(GH4)Glu→Lys]. No mutations were found in two individuals. The distribution is characteristic of a heterogenous population with three preferential mutations being present [codons 36/37 (-T), IVS-II-1 (G>A) and IVS-I-110 (G>A)] at a frequency of 20.5, 20.0 and 14.2%, respectively, followed by 39 mutations in decreasing frequencies from 5.2 down to 0.1%. These data are of importance when planning prevention strategies in the country.


Fifty-six-year-old man with anaphylaxis: A novel delayed food hypersensitivity reaction.
Anaphylaxis and urticaria are commonly seen in both primary care and allergy clinics. Foods, drugs, and insects are frequent culprits for immediate reactions; however, the trigger for recurring and/or chronic episodes is often unclear. We present a 56-year-old male with recurrent symptoms of urticaria, angioedema, and anaphylaxis found to be triggered by sensitization to galactose-alpha 1, 3-galactose (alpha-gal), a novel food allergen.


The Effect of Listening to Holy Quran Recitation on Weaning Patients Receiving Mechanical Ventilation in the Intensive Care Unit: A Pilot Study.
Mechanical ventilation (MV) causes high level of stress in hospitalized patients. Weaning is the gradual process of decreasing ventilator support that in turn lead to termination of MV and increased respiratory effort, which may exacerbate symptoms and prolong MV. This study aimed to investigate the effect of listening to Holy Quran recitation (HQR) as a non-pharmacological intervention in patients during weaning from mechanical ventilation. This is a randomized controlled trial in which 55 patients admitted in the intensive care unit (ICU) and on mechanical ventilation were recruited. Patients were divided into experimental (case) and control group. In the experimental group, patients received 30 min of HQR, whereas in the control group, patients had 30 min of rest in bed before the start of the weaning. The physiological and/or clinical parameters of weaning were recorded. These parameters include rapid shallow breathing index, respiratory rate, heart rate, oxygen saturation, exhaled carbon dioxide, and blood pressure. The baseline demographic data for groups were presented in tables. The mean age was 54 ± 0.5 years for the experimental and 56.4 ± 18.5 years for the control groups. The physiological and clinical parameters were compared between case and control and found no significant difference. The preliminary findings of this pilot study suggest that there is no negative effect of HQR on weaning patients from mechanical ventilation in the ICU. The results also outline and explorthe possible utility of HQR further in ICU patients as an intervention in weaning patients off from ventilator in the ICU. Although there remains much to be done, our work generates important findings in the field of critical care management.


Ergonovine-induced coronary artery spasm and myocardial infarction after normal delivery.
Reported is the first known case of postpartum myocardial infarction probably induced by ergonovine maleate, a drug known to provoke coronary artery spasm in susceptible patients.


Modulation of melanoma-associated antigens by monoclonal antibodies as visualized by radioimmunoelectron microscopy and radioantibody binding assay.
There is a wealth of information about monoclonal antibody (MAb) specificity and function on fixed tissues, yet little is known about formation and release of antigen-antibody complexes and their functional behavior in vivo. We analyzed the pathway of radiolabeled MAbs directed against melanoma-associated antigens by radioimmunoelectron microscopy (RIEM) on metabolically active cells of the melanoma cell lines SK-MEL-28, MeWo and Colo 38 at different time intervals. In parallel, binding and release of MAbs were investigated by the radioantibody binding assay (RBA). Both procedures gave essentially concordant results. Preferentially stable binding of immune complexes (ICs) to the cell surface after 30 and 120 min was shown for the MAb L10. Internalization was demonstrated for the MAb M.2.9.4. At the ultrastructural level, direct evidence of this phenomenon was obtained by visualization of radioactivity within the cytoplasm after 120 min. In the RBA this process was indicated by resistance of bound MAbs to acid buffer desorption. RIEM pointed to different transport mechanisms: constitutive internalization by endocytotic vesicles, or receptor-mediated endocytosis by coated vesicles. Shedding was indicated for the MAb R24 by release of the ICs from the cell membrane. It was demonstrated that stable fixation of ICs on the cell surface or modulation by internalization led to high accumulation rates, while shedding of antigen-antibody complexes resulted in a low accumulation of the MAb in tumor cells. Assuming that the potential of MAbs for clinical application is determined by the biological behavior of antigen-antibody complexes, these methods are suitable for demonstration of antigenic modulation by MAbs and eventually enable us to predict the localization, penetration and distribution pattern of individual MAbs in the melanoma patient.


Relationship of thyroid status and serum N-acetyl-beta-glucosaminidase isoenzyme activities in humans.
Serum from 28 hyperthyroid, hypothyroid, and euthyroid pre- or early puberty females was examined for N-acetyl-beta-glucosaminidase (HEX) activity. Total, isoenzyme A (labile), and isoenzyme B (stable) levels were determined for this enzyme. A high degree of correlation (r = 0.76; p less than 0.001) exists between total hexosaminidase activity and thyroid hormone levels (as reflected by the Free Thyroxine Index). Examining each isoenzyme individually, A is selectively enhanced (r = 0.84; p less than 0.0005) whereas B displays no significant change regardless of thyroid activity. In hyperthyroid individuals, levels of total hexosaminidase (730 +/- 67 units) (mean +/- S.D.) and isoenzyme A (516 +/- 46) were significantly higher than levels found in either the hypothyroid (total: 547 +/- 30; isoenzyme A: 352 +/- 31) or euthyroid (total: 620 +/- 81; isoenzyme A: 423 +/- 45) groups. However, no change was observed in levels of isoenzyme B among hypothyroid (195 +/- 19), euthyroid (197 +/- 43) and hyperthyroid (215 +/- 32) groups. These data substantiate our earlier findings in the rat, wherein thyroxine administration evoked a similar response in the liver. They are of particular interest in light of the deficiency of HEX A in variants of GM2 gangliosidosis.


Retrospective review of intervention for traumatic blunt spleen injuries in adolescents by trauma center type.
Management guidelines for pediatric blunt spleen injuries (BSI) include adolescent patients but few studies have compared current management of adolescents with respect to other age groups by center type. A retrospective review of 2017-2018 National Trauma Quality Improvement (TQIP) data of children (6-12), adolescents (13-17) and young adults (18-24) with BSI presenting to an adult, pediatric only, or adult/pediatric trauma center, comparing the rate of splenic intervention for adolescents by trauma center was performed. Children had lower odds of spleen intervention than adolescents at both adult (OR 0.61 95%CI 0.39, 0.95) and adult/pediatric (OR 0.55 95%CI 0.35, 0.87) centers but did not differ at pediatric centers (OR 0.94 95%CI 0.39, 2.2) (n = 10,494). Adolescents adjusted odds of intervention was equal to adults at adult trauma centers (OR 1.2 95%CI 0.95, 1.4). Adolescents are more likely to undergo interventions for BSI as compared to children at both adult and adult/pediatric trauma centers.


High-performance liquid chromatographic method for fingerprinting and quantitative determination of E- and Z-guggulsterones in Commiphora mukul resin and its products.
A high-performance liquid chromatographic method has been developed and validated for the fingerprinting (profiling) and quantitative determination of E- and Z-guggulsterones, the hypolipidemic agents in the gum-resin exudate of Commiphora mukul, currently marketed worldwide as hypocholesterolemic. The method involves extraction of the guggul-resin from either the raw exudate or compounded tablets (or capsules) with ethyl acetate, concentration of the combined extracts and chromatography on a reversed-phase C18 column using an acetonitrile-water gradient. The method has a validated quantitation range of 15-85 microg/ml for E-guggulsterone and 25-130 microg/ml for Z-guggulsterone with a precision of +/-2% S.D. and a recovery of >99.5%. Standard curve correlation coefficients of 0.992 or greater were obtained during validation experiments. The method was applied to six commercial (OTC) products, all of which were found to contain significantly less (in most cases very little or none) of the claimed guggulsterones.


Contribution of Verbal Learning & Memory and Spectro-Temporal Discrimination to Speech Recognition in Cochlear Implant Users.
Existing cochlear implant (CI) outcomes research demonstrates a high degree of variability in device effectiveness among experienced CI users. Increasing evidence suggests that verbal learning and memory (VL&M) may have an influence on speech recognition with CIs. This study examined the relations in CI users between visual measures of VL&M and speech recognition in a series of models that also incorporated spectro-temporal discrimination. Predictions were that (1) speech recognition would be associated with VL&M abilities and (2) VL&M would contribute to speech recognition outcomes above and beyond spectro-temporal discrimination in multivariable models of speech recognition. This cross-sectional study included 30 adult postlingually deaf experienced CI users who completed a nonauditory visual version of the California Verbal Learning Test-Second Edition (v-CVLT-II) to assess VL&M, and the Spectral-Temporally Modulated Ripple Test (SMRT), an auditory measure of spectro-temporal processing. Participants also completed a battery of word and sentence recognition tasks. CI users showed significant correlations between some v-CVLT-II measures (short-delay free- and cued-recall, retroactive interference, and "subjective" organizational recall strategies) and speech recognition measures. Performance on the SMRT was correlated with all speech recognition measures. Hierarchical multivariable linear regression analyses showed that SMRT performance accounted for a significant degree of speech recognition outcome variance. Moreover, for all speech recognition measures, VL&M scores contributed independently in addition to SMRT. Measures of spectro-temporal discrimination and VL&M were associated with speech recognition in CI users. After accounting for spectro-temporal discrimination, VL&M contributed independently to performance on measures of speech recognition for words and sentences produced by single and multiple talkers. 3 Laryngoscope, 133:661-669, 2023.


Compositional data analysis of 24-hour movement behaviors and mental health in workers.
This cross-sectional study investigated the relationship between 24-hour movement behaviors and mental health among Japanese workers, accounting for the co-dependence of time spent in different behaviors during a single day. This research is part of a prospective cohort study called the Meiji Yasuda LifeStyle study. Participants were 1095 workers in Tokyo, Japan, who underwent annual health check-ups between 2017 and 2018. Time use during workdays and non-workdays was separately evaluated. Behaviors included sleep (self-reported duration), sedentary behavior (SB), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (assessed with a tri-axial accelerometer). We used the six-item Kessler Psychological Distress scale to evaluate psychological distress and the Utrecht Work Engagement Scale to assess work engagement as indicators for negative and positive mental health, respectively. We performed compositional logistic regression and compositional isotemporal substitution to examine associations between 24-hour movement behaviors and mental health. After controlling for potential confounders, time spent in workdays was significantly associated with higher psychological distress and lower work engagement (p < 0.05), respectively. Time spent sleeping was positively correlated with both mental health indicators, whereas time spent in SB or LPA was negatively correlated (p < 0.05). During workdays, higher psychological distress and lower work engagement were predicted to be 11.4-26.6% lower when 60 min/day of time spent sleeping were reallocated to SB or LPA. Reallocating time spent on SB or LPA to sleep during workdays may minimize psychological distress and optimize work engagement. Thus, proper time management focused on encouraging sleep may help improve workers' mental health.


Quantitative shotgun proteome analysis by direct infusion.
Liquid chromatography-mass spectrometry (LC-MS) delivers sensitive peptide analysis for proteomics but requires extensive analysis time, reducing throughput. Here, we demonstrate that gas-phase peptide separation instead of LC enables fast proteome analysis. Using direct infusion-shotgun proteome analysis (DI-SPA) by data-independent acquisition mass spectrometry (DIA-MS), we demonstrate the targeted quantification of over 500 proteins within minutes of MS data collection (~3.5 proteins per second). We show the utility of this technology in performing a complex multifactorial proteomic study of interactions between nutrients, genotype and mitochondrial toxins in a collection of cultured human cells. More than 45,000 quantitative protein measurements from 132 samples were achieved in only ~4.4 h of MS data collection. Enabling fast, unbiased proteome quantification without LC, DI-SPA offers an approach to boost throughput, critical to drug and biomarker discovery studies that require analysis of thousands of proteomes.


Association of Open Reduction and Internal Fixation With Volar Locking Plate for Distal Radius Fractures With Patient-Reported Outcomes in Older Adults: A Network Meta-analysis.
Randomized clinical trials (RCTs) and meta-analyses have reported inconsistent conclusions regarding optimal distal radius fracture (DRF) treatment in older adults and are limited due to the inclusion of cohort studies with small sample sizes. A network meta-analysis (NMA) addresses these limitations by only synthesizing direct and indirect evidence from RCTs and may clarify optimal DRF treatment in older adults. To examine DRF treatment results in optimal short-term and intermediate-term patient-reported outcomes. Searches of MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials were conducted for RCTs that investigated DRF treatment outcomes in older adults between January 1, 2000, and January 1, 2022. Randomized clinical trials including patients with a mean age of 50 years or older that compared the following DRF treatments were eligible for inclusion: casting, open reduction and internal fixation with volar lock plating (ORIF), external fixation, percutaneous pinning, and nail fixation. Two reviewers independently completed all data extraction. An NMA aggregated all direct and indirect evidence among DRF treatments. Treatments were ranked by surface under the cumulative ranking curve score. Data are reported as standard mean differences (SMDs) and 95% CIs. The primary outcome was short-term (≤3 months) and intermediate-term (>3 months to 1 year) Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire scores. Secondary outcomes included Patient-Rated Wrist Evaluation (PRWE) scores and 1-year complication rates. In this NMA, 23 RCTs consisting of 3054 participants (2495 women [81.7%]) with a mean (SD) age of 66 (7.8) years were included. At 3 months, DASH scores were significantly lower for nail fixation (SMD, -18.28; 95% CI, -29.93 to -6.63) and ORIF (SMD, -9.28; 95% CI, -13.90 to -4.66) compared with casting. The PRWE scores were also significantly lower for ORIF (SMD, -9.55; 95% CI, -15.31 to -3.79) at 3 months. In the intermediate term, ORIF was associated with lowered DASH (SMD, -3.35; 95% CI, -5.90 to -0.80) and PRWE (SMD, -2.90; 95% CI, -4.86 to -0.94) scores. One-year complication rates were comparable among all treatments. The findings of this NMA suggest that ORIF may be associated with clinically significant improvements in short-term recovery compared with casting for multiple patient-reported outcomes measures with no increase in 1-year complication rates. Shared decision-making with patients may be useful to identify patient preferences regarding recovery to determine optimal treatment.


Structure and methylation patterns of the gene encoding human carbonic anhydrase I.
The gene (CAI) encoding human carbonic anhydrase I (CAI) has been isolated and shown to have a total length of 50 kb. Some 36 kb of this consists of a large intron separating the erythroid-specific promoter from the coding region. A small (54 bp) noncoding exon from within this intron is occasionally found in transcripts. Two different polyadenylation sites have been found, the most distal of which is the most commonly used. Methylation levels near the promoter differ widely in cell lines. In CAI-expressing cells, a region of DNA near the promoter is demethylated in a generally highly methylated background. Surprisingly, non-CAI-expressing cell lines show much lower levels of methylation.


On measurements and their quality: Paper 2: Random measurement error and the power of statistical tests.
This is the second in a short series of papers on measurement theory and practice with particular relevance to intervention research in nursing, midwifery, and healthcare. This paper begins with an illustration of how random measurement error decreases the power of statistical tests and a review of the roles of sample size and effect size in hypothesis testing. A simple formula is presented and discussed for calculating sample size during the planning stages of intervention studies. Finally, an approach for incorporating reliability estimates into a priori power analyses is introduced and illustrated with a practical example. The approach permits researchers to compare alternative study designs, in terms of their statistical power. An SPSS program is provided to facilitate this approach and to assist researchers in making optimal decisions when choosing among alternative study designs.


Apical Relaxation during Mitotic Rounding Promotes Tension-Oriented Cell Division.
Global tissue tension anisotropy has been shown to trigger stereotypical cell division orientation by elongating mitotic cells along the main tension axis. Yet, how tissue tension elongates mitotic cells despite those cells undergoing mitotic rounding (MR) by globally upregulating cortical actomyosin tension remains unclear. We addressed this question by taking advantage of ascidian embryos, consisting of a small number of interphasic and mitotic blastomeres and displaying an invariant division pattern. We found that blastomeres undergo MR by locally relaxing cortical tension at their apex, thereby allowing extrinsic pulling forces from neighboring interphasic blastomeres to polarize their shape and thus division orientation. Consistently, interfering with extrinsic forces by reducing the contractility of interphasic blastomeres or disrupting the establishment of asynchronous mitotic domains leads to aberrant mitotic cell division orientations. Thus, apical relaxation during MR constitutes a key mechanism by which tissue tension anisotropy controls stereotypical cell division orientation.


Accurate C/D ratio estimation with elliptical fitting for OCT image based on joint segmentation and detection network.
Proper estimation of the cup-to-disc ratio (C/D ratio) plays a significant role in ophthalmic examinations, and it is urgent to improve the efficiency of C/D ratio automatic measurement. Therefore, we propose a new method for measuring the C/D ratio of OCTs in normal subjects. Firstly, the end-to-end deep convolution network is used to segment and detect the inner limiting membrane (ILM) and the two Bruch's membrane opening (BMO) terminations. Then, we introduce an ellipse fitting technique to post-process the edge of the optic disc. Finally, the proposed method is evaluated on 41 normal subjects using the optic-disc-area scanning mode of three machines: BV1000, Topcon 3D OCT-1, and Nidek ARK-1. In addition, pairwise correlation analyses are carried out to compare the C/D ratio measurement method of BV1000 to existing commercial OCT machines as well as other state-of-the-art methods. The correlation coefficient between the C/D ratio calculated by BV1000 and the C/D ratio calculated by manual annotation is 0.84, which indicates that the proposed method has a strong correlation with the results of manual annotation by ophthalmologists. Moreover, in comparison between BV1000, Topcon and Nidek in practical screening among normal subjects, the proportion of the C/D ratio less than 0.6 calculated by BV1000 accounts for 96.34%, which is the closest to the clinical statistics among the three OCT machines. The above experimental results and analysis show that the proposed method performs well in cup and disc detection and C/D ratio measurement, and compared with the existing commercial OCT equipment, the C/D ratio measurement results are relatively close to reality, which has certain clinical application value.


[Vascular emergencies in dermatology].
Life-threatening vascular complications of the skin are rare and usually reflect underlying systemic diseases. Lesions are sudden in onset, become necrotic and may be severe or life-threatening. Effective management requires an understanding of the underlying medical condition, such as arterial thrombosis, temporal arteritis, calciphylaxis and purpura fulminans. In contrast, the acute painful symptoms of erythromelalgia often lead to an urgent dermatologic consultation but pose no acute risk.