[Reconstructive surgery in patients with a ventricular assist device (VAD)--an interdisciplinary challenge].
Ventricular assist devices (VAD) are implanted with a growing frequency in patients with end-stage heart failure. In spite of technical and therapeutic advances, there is still a high incidence of device infections and healing disturbances with a considerable mortality. Reconstructive plastic surgery is able to provide help in erradicating infections and covering defects. 11 patients with device infections and soft tissue defects were treated in our institution. All cases were treated with local myocutaneous or muscle flaps. Three patients had postoperative haematomas which had to be revised surgically. One patient had a persistent fistula of mediastinal origin but without clinical symptoms of infection. One patient exhibited an enterocutaneous fistula after defect coverage. Patients with VADs have a high possibility of perioperative complications. Therefore a close interdisciplinary approach with plastic and cardiovascular surgeons is absolutely essential.


Phosphorylation of gastrin-related peptides: physiological casein kinase like enzyme in Golgi membranes from bovine adrenal chromaffin cells and GH3 cells.
Prohormones such as the gastrin precursor can be phosphorylated at Ser residues, on passage along the secretory pathway. The phosphorylation site occurs in a sequence (-Ser-Ala-Glu-) that suggests these peptides are substrates for physiological casein kinase, but the presence of this enzyme in endocrine cells is unknown. We have examined the specificity of Golgi membrane kinases from lactating rat mammary gland, bovine adrenal medulla and the GH3 cell line, for phosphorylation of progastrin fragments and analogues. The kinetics of phosphorylation of peptides with the native sequence, -Arg-Arg-Ser-Ala-Glu- were similar to those of tryptic cleavage fragments (Ser-Ala-Glu-) in both mammary and endocrine cell preparations. The product of in vitro phosphorylation was chromatographically indistinguishable from native peptide. Peptides with the sequence Ser-Ala-Ala (i.e., substitution of Glu to Ala) were not phosphorylated. We conclude that a physiological casein kinase like enzyme can act on both the gastrin precursor and its COOH-terminal cleavage product, and occurs in the Golgi complex of both mammary gland and peptide-producing endocrine cells.


Preliminary results of ozone therapy as a possible treatment for patients with chronic hepatitis C.
Medical ozone is more bactericidal, fungicidal, and virucidal than any other natural substance. Some studies proved that ozone infused into donated blood samples can kill viruses 100% of the time. Ozone, because of its special biologic properties, has theoretical and practical attributes to make it a potent hepatitis C virus (HCV) inactivator, which suggests an important role in the therapy for hepatitis C. The study aim is to evaluate the role of ozone therapy in decreasing HCV ribonucleic acid (HCV RNA) load and its effect on the liver enzymes among patients with chronic hepatitis C. This study included 52 patients with chronic hepatitis C (positive polymerase chain reaction [PCR] for HCV RNA and raised serum alanine transaminase [ALT] for more than 6 months). All patients were subjected to meticulous history taking and clinical examination. Complete blood count, liver function tests, and abdominal ultrasonography were requested for all patients. The ozone group included 40 patients who received major autohemotherapy, minor autohemotherapy, and rectal ozone insufflation. The other 12 patients (conventional group) received silymarin and/or multivitamins. There were significant improvements of most of the presenting symptoms of the patients in the ozone group in comparison to the conventional group. ALT and aspartate transaminase (AST) levels normalized in 57.5% and 60% in the ozone group, respectively, in comparison to 16.7% and 8% in the conventional group, respectively. Polymerase chain reaction (PCR) for HCV RNA was negative among 25% and 44.4% after 30 and 60 sessions of ozone therapy, respectively, in comparison to 8% among the conventional group. Ozone therapy significantly improves the clinical symptoms associated with chronic hepatitis C and is associated with normalized ALT and AST levels among a significant number of patients. Ozone therapy is associated with disappearance of HCV RNA from the serum (-ve PCR for HCV RNA) in 25%-45% of patients with chronic hepatitis C.


Spontaneous Resolution of Bilateral Bullous Serous Retinal Detachment in Preeclampsia: A Case Report from Somalia.
A 29-year-old preeclamptic postpartum patient with no symptoms of hypertension in her medical history before pregnancy was referred to the ophthalmology outpatient clinic with the complaint of sudden bilateral vision loss. Slit-lamp fundus examination and B-scan ultrasonography showed serous retinal detachment (SRD) in both eyes. She was diagnosed with bullous SRD due to preeclampsia (PE). The patient's fundoscopy findings regressed spontaneously, and visual acuities improved within one month. SRD should be considered in case of vision loss before or after birth in patients with PE, and such patients should undergo retinal examination.


O-GlcNAc modification of MYPT1 modulates lysophosphatidic acid-induced cell contraction in fibroblasts.
Thousands of proteins have been found to be modified by O-GlcNAc, a common glycosylation modification of serine and threonine residues throughout the cytosol and nucleus. O-GlcNAc is enzymatically added and removed from proteins, making it a potential dynamic regulator of cell signaling. However, compared with other posttranslational modifications like phosphorylation, relatively few O-GlcNAc-regulated pathways have been discovered and biochemically characterized. We previously discovered one such pathway, where O-GlcNAc controls the contraction of fibroblasts initiated by the signaling lipid sphingosine-1-phosphate. Specifically, we found that O-GlcNAc modification of the phosphatase MYPT1 maintains its activity, resulting in dephosphorylation and deactivation of the myosin light chain of the actinomyosin complex. Another signaling lipid that leads to contraction of fibroblasts is lysophosphatidic acid, and this signaling pathway also converges on MYPT1 and actinomyosin. We therefore rationalized that O-GlcNAc would also control this pathway. Here, we used a combination of small molecule inhibitors, 2D and 3D cell cultures, and biochemistry to confirm our hypothesis. Specifically, we found that O-GlcNAc levels control the sensitivity of mouse and primary human dermal fibroblasts to lysophosphatidic acid-induced contraction in culture and the phosphorylation of MLC and that MYPT1 O-GlcNAc modification is responsible. These findings further solidify the importance of O-GlcNAc in regulating the biology of fibroblasts in response to procontractile stimuli.


Otoacoustic emissions in neonates exposed to smoke during pregnancy.
The toxic substances present in cigarette smoke can damage cochlea hair cells. This effect has been investigated by measuring otoacoustic emissions. To investigate the impact of stimuli on otoacoustic emissions, comparing neonates with and without exposure to cigarette smoke during pregnancy. Transient-evoked otoacoustic emissions, evoked by a click stimulus, and distortion product otoacoustic emissions, evoked by two tones tests were conducted in both ears, using an Interacoustic TITAN device. The study included 105 neonates divided into two groups: a study group, comprising 47 neonates exposed to smoke during pregnancy; and a control group comprized of 58 neonates who were not exposed. All participants had normal neonatal hearing screening. No statistical differences in distortion product otoacoustic emissions response levels were found between the groups. In the transient-evoked otoacoustic emissions tests lower response levels were observed in the study group than the control group in frequency band analysis of the right ear, with statistically significant differences in signals and signal-noise ratio (except at 1kHz). The impact of smoking exposure could be analyzed through transient-evoked otoacoustic emissions in neonates. The group effect of smoke exposure during pregnancy was evidenced by a reduction in transient-evoked otoacoustic emissions levels. This same effect was not observed for the analyses performed on distortion product otoacoustic emissions levels.


Neuronal Polarity: MAP2 Shifts Secretory Vesicles into High Gear for Long-Haul Transport down the Axon.
Accurate control of polarized cargo trafficking is essential for neuronal function. In this issue of Neuron, Gumy et al. (2017) show that MAP2 defines a pre-axonal filtering zone and controls axonal cargo transport by influencing the activities of distinct kinesin motors.


Targeting alarmin release reverses Sjogren's syndrome phenotype by revitalizing Ca2+ signalling.
Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that is embodied by the loss of salivary gland function and immune cell infiltration, but the mechanism(s) are still unknown. The aim of this study was to understand the mechanisms and identify key factors that leads to the development and progression of pSS. Immunohistochemistry staining, FACS analysis and cytokine levels were used to detect immune cells infiltration and activation in salivary glands. RNA sequencing was performed to identify the molecular mechanisms involved in the development of pSS. The function assays include in vivo saliva collection along with calcium imaging and electrophysiology on isolated salivary gland cells in mice models of pSS. Western blotting, real-time PCR, alarmin release, and immunohistochemistry was performed to identify the channels involved in salivary function in pSS. We provide evidence that loss of Ca2+ signaling precedes a decrease in saliva secretion and/or immune cell infiltration in IL14α, a mouse model for pSS. We also showed that Ca2+ homeostasis was mediated by transient receptor potential canonical-1 (TRPC1) channels and inhibition of TRPC1, resulting in the loss of salivary acinar cells, which promoted alarmin release essential for immune cell infiltration/release of pro-inflammatory cytokines. In addition, both IL14α and samples from human pSS patients showed a decrease in TRPC1 expression and increased acinar cell death. Finally, paquinimod treatment in IL14α restored Ca2+ homeostasis that inhibited alarmin release thereby reverting the pSS phenotype. These results indicate that loss of Ca2+ signaling is one of the initial factors, which induces loss of salivary gland function along with immune infiltration that exaggerates pSS. Importantly, restoration of Ca2+ signaling upon paquinimod treatment reversed the pSS phenotype thereby inhibiting the progressive development of pSS.


Initial two-year results of the Oregon Liver Transplantation Program.
During the first 24 months of the Oregon Liver Transplantation Program, which began in October 1988, 94 patients were formally evaluated and 47 adults underwent 54 liver transplantations. Thirty-four percent of patients were veterans. The recipient operation lasted a mean of 7.4 hours (range: 4 to 16 hours). Veno-venous bypass was used routinely at first but selectively later (7 of the last 26 cases), resulting in reduced operating time. Hepatic artery reconstruction was end-to-end anastomosis in 52 cases and iliac conduit in 2. No arterial thrombosis occurred. Biliary reconstruction was choledochocholedochostomy in 83% and choledochojejunostomy in 17%. Biliary complications occurred in 28%. Operative mortality was 2%, and 1-year actual survival was 80%. Patients with hepatitis B fared worse, with four of six dying at a mean of 7.6 months. Overall, the median hospital stay was 30 days. Patients surviving more than 3 months had a mean Karnofsky score of 82%. No significant difference in outcome was noted in patients receiving prophylactic OKT3 monoclonal antibody (used in 45%) versus conventional immunosuppressive therapy. Overall, allograft rejection occurred in 55% of patients. Retransplantation was required in seven patients, three for primary graft nonfunction, two for uncontrolled rejection during induction therapy with OKT3, and two for graft failure secondary to recurrent hepatitis B.


Oxidative Coupling of Benzylamines with Indoles in Aqueous Medium to Realize Bis-(Indolyl)Methanes Using a Water-Soluble Cobalt Catalyst and Air as the Oxidant.
Oxidative coupling of benzylamines with indoles to bis-(indolyl)methanes (BIMs) was achieved using an inexpensive water-soluble cobalt complex, Co(bpb). The catalyst was found to be quite effective when air was used as the oxidant and water as solvent under mild reaction conditions. Aromatic amines were successfully converted to the corresponding BIMs with yields up to 85 %. We have successfully carried out a 1 gram scale reaction, and few pharmaceutically relevant compounds were also synthesised by this method in good yields. Control experiments have also been carried out to understand the possible reaction mechanism.


Recent advances in the development of β-lactamase inhibitors.
β-Lactam antibiotics are the most commonly prescribed antibiotics worldwide; however, antimicrobial resistance (AMR) is a global challenge. The β-lactam resistance in Gram-negative bacteria is due to the production of β-lactamases, including extended-spectrum β-lactamases, metallo-β-lactamases, and carbapenem-hydrolyzing class D β-lactamases. To restore the efficacy of BLAs, the most successful strategy is to use them in combination with β-lactamase inhibitors (BLI). Here we review the medically relevant β-lactamase families and penicillins, diazabicyclooctanes, boronic acids, and novel chemical scaffold-based BLIs, in particular approved and under clinical development.


Interdisciplinary approaches are fundamental to decode the biology of adversity.
The COVID-19 pandemic has highlighted structural inequalities and racism promoting health disparities among communities of color. Taking cardiovascular disease as an example, we provide a framework for multidisciplinary efforts leveraging translational and epidemiologic approaches to decode the biological impacts of inequalities and racism and develop targeted interventions that promote health equity.


Cardiovascular dysfunction risk in young adults with congenital adrenal hyperplasia caused by 21-hydroxylase enzyme deficiency.
The association of congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase enzyme (21OHase) deficiency, duration of treatment and dosage with cardiovascular dysfunction in young adults remains unclear. We aimed to evaluate myocardial function, vascular structures and epicardial fat thickness in young adults with CAH as a result of 21OHase deficiency. Correlations between the duration and dose of glucocorticoid therapy and cardiovascular parameters were analysed. This case-control study of young adults (18-31 years old) included 20 patients (5 men and 15 women) and 16 control subjects (8 men and 8 women). Echocardiographic analysis was performed using high-resolution ultrasound. No ultrasonographic changes in any indices of myocardial function, vascular structures and epicardial fat thickness were found in patients, except for an impaired left ventricular end-diastolic diameter in female patients (28.1 ± 1.6 vs 26.0 ± 2.4 mm/m2 , P = .021), compared with those in individuals in the control group. Nevertheless, the individual patient values were within the normal range. Multiple linear regression analysis in female patients demonstrated that an elevated daily dose of glucocorticoids correlated with increased indices of left ventricular posterior wall thickness (Partial r = 0.68, P = .007), left ventricular end-diastolic diameter (Partial r = 0.62, P = .017), aortic diameter (Partial r = 0.60, P = .022) and left carotid artery intima-media thickness (Partial r = 0.61, P = .021), independently of treatment duration. No signs of cardiovascular dysfunction were observed in any patient. The daily dose of glucocorticoids may play a role in the mechanisms of some markers of cardiac hypertrophy, left ventricular and aortic dilation and subclinical atherosclerosis.


Workforce turnover at local health departments: nature, characteristics, and implications.
Employee turnover, defined as total separations from employment, is expensive, can result in lost capacity, and can limit local health departments' (LHDs') ability to respond to public health needs. Despite the importance of workforce capacity in public health, little is known about workforce turnover in LHDs. To examine the extent to which LHDs experience turnover and identify LHD characteristics that are associated with turnover. A cross-sectional data set of employee turnover and LHD characteristics from the 2013 National Profile of LHDs was analyzed. Descriptive statistics and bivariate analyses were conducted in 2014 on turnover rates. The effect of the following LHD characteristics on turnover rates were examined: population size, governance type, degree of urbanization, top executive experience level, expenditures per capita, and LHD budget cuts. In 2013, LHDs experienced a mean turnover rate of 9.88%; approximately one third of turnover was due to retirements. LHDs with shared state and local governance experienced a higher turnover rate than LHDs with exclusive state or local governance. LHDs that are units of state agencies had a significantly higher retirement rate than those governed by local authorities. Top executive experience level, per capita expenditures, and LHD budget cuts were also related to turnover rates. LHDs experienced a lower overall turnover rate than state health departments in 2011 and lower than all local and state government agencies in 2012. Strengthening leadership skills of new top executives and ensuring adequate funding may reduce turnover in LHDs.


Rodenticide Poisoning: Critical Appraisal of Patients at a Tertiary Care Center.
Rodenticide poisoning is a common occurrence in India. Of the different classes of rodenticides available, yellow phosphorus is considered highly toxic. There are scarce epidemiological data regarding the ingestion of yellow phosphorus in the subcontinent. This study aimed to identify the clinical profile of rodenticide-poisoned patients and delineate mortality predictors. Prospective observational study. Study was conducted at the Department of Internal Medicine, Government Villupuram Medical College and Hospital. All adult inpatients with a history of rodenticide poison exposure were eligible participants. A total of 99 patients completed the study protocol. Survival with or without morbidity and death. In all, 90.91% of patients consumed the paste formulation of rodenticide [yellow phosphorus (67.2%) and yellow phosphorus + zinc phosphide (24%)].The time to resuscitation showed significance to mortality. Survival rate among patients instituted gastric decontamination within 2 hours of exposure (97.87%) was significantly higher than those who were not (84.62%) (p = 0.033). The clinical picture revealed conspicuous absence of signs and symptoms during the first 24 hours. In all, 72.73% (n = 72) manifested with toxidrome after a lag period of 24-36 hours (range 18-72 hours). The dominant clinical manifestations included abdominal pain (52.53%), jaundice (22.21%), coagulopathy (15.15%), encephalopathy (10.10%), shock (10.10%), acute kidney injury (AKI; 7.08%), and multi-organ failure (17.17%). Laboratory data showed elevated aspartate transaminase (AST; 48.47%), alanine aminotransferase (ALT; 49.50%), bilirubin levels (22.21%), metabolic acidosis (10.12%), serum creatinine (7.08%), prothrombin time prolongation (PT/INR; 15.15%), and activated partial thromboplastin time (aPTT) (3.30%). The mortality was 9.1% (n = 9) of which 77.78% (n = 7) died of fulminant hepatic failure. The mean time for death was 4.22 days since exposure (range 2-8 days). Rodenticide poisoning in Southern India is dominated by yellow phosphorus. In this study, we identified delayed resuscitation, jaundice, hepatic encephalopathy, elevation of AST and ALT to >1000 IU/L, metabolic acidosis, and refractory shock as reliable predictors of bad outcome in this patient population. The common mode of death was fulminant hepatic failure. Rodenticide poisoning ranks second in mortality hierarchy at our institute, and systematic analysis of this patient population is an urgent need. Gopalakrishnan S, Kandasamy S, Iyyadurai R. Rodenticide Poisoning: Critical Appraisal of Patients at a Tertiary Care Center. Indian J Crit Care Med 2020;24(5):295-298.


Good clinical outcomes can be expected after meniscal allograft transplantation at 15 years of follow-up.
The aim of this study was to evaluate graft survivorship and report the functional and radiographic results of Meniscal allograft transplantation (MAT) throughout a minimum 15-year follow-up period. Fifty-one patients that had undergone an isolated MAT procedure during the period studied were included. The results were assessed with the Lysholm and Tegner scores as well as the Visual Analog Scale. Magnetic resonance imaging and a complete radiographic series were carried out to determine the degree of meniscal extrusion and joint space narrowing. A comparison was made between the radiological findings of the last follow-up, the 5-year mid-term follow-up and those from the preoperative period. Thirty-eight patients were available for the final follow-up. The mean follow-up was 17.4 years. There were 23 (60.5%) medial menisci and 15 lateral menisci (39.4%). Meniscal extrusion increased from the 29.7% ± 14.9 obtained at the 5-year follow-up to the 72.5% ± 22.5 seen at the end of the follow-up (p = 0.0001). The joint space distance was almost unchanged from the initial evaluation (3.3 ± 1.5 mm) to the 5-year follow-up measurement (3.1 ± 1.7 mm, n.s.). However, it did decrease at the last follow-up (1.9 ± 1.5 mm, p < 0.05). The functional outcomes improved from the preoperative period to the mid-term follow-up and later worsened at the final follow-up. The mean preoperative Lysholm score at the initial follow-up was 61.5 ± 9.6, 86.9 ± 10.9 for the 5-year evaluation and stood at 77.4 ± 11.5 (p = 0.0001) at the final follow-up. Regarding the Tegner score, those pre-operative scores were compared to the ones at the last follow-up (median: 3; range 0-6 vs. 5.5; 3-6, respectively; p = 0.0001). The VAS went down from 6.6 ± 1.7 at the initial evaluation to 2.5 ± 1.9 at the final follow-up (p = 0.0001). The joint-space width remained unchanged from the initial evaluation (3.35 ± 1.5 mm) up to the 5-year follow-up measurement (3.1 ± 1.7 mm, n.s.). However, this joint-space distance had decreased by the last evaluation in the long-term follow-up (1.9 ± 1.4 mm, p < 0.05). Five patients (13.1%) presented with a MAT failure at 5 years, which was followed by extirpation of the meniscal graft. At the final follow-up, a total of 16 patients (42.1%) presented with a failure. At that time, there were 4 more MAT removals and seven patients that required a total knee replacement. The mean time to failure of the meniscal graft was 206.2 months ± 13.4 (18.0 years). Meniscal allograft transplantation produces good functional results at a minimum 15-year follow-up. However, degenerative arthritis in the affected compartment progressed during that period. III.


Long term results of radial tunnel release--the effect of co-existing tennis elbow, multiple compression syndromes and workers' compensation.
Surgical decompression of radial tunnel syndrome (RTS) remains controversial because the results are unpredictable. This study is a retrospective analysis of the long term outcomes of RTS release and a comparison of our findings with previous studies. Thirty-three extremities in 31 patients underwent decompression for radial tunnel syndrome between 1994 and 2003, of which 27 extremities in 25 patients were available for long term follow up after an average of 57 months (range 16 to 106 months). Outcomes were evaluated using the criteria of Ritts et al. (1987). For 16 patients (18 of 27 extremities), the outcome was rated as good (67%), for four patients (four extremities) as fair (15%), and for five patients (five extremities) as poor (18%). The outcome was better in patients with simple RTS (86% good results) compared with patients with additional nerve compression syndromes (57% good results), or patients with coexisting lateral epicondylitis (70% vs 43% good results), or patients who were receiving workers' compensation (73% vs 58% good results). One-third of patients still had moderate or severe disability which affected their ability to work, but 82% had relief of their pain. Surgical decompression is therefore beneficial for simple RTS, but may be less successful if there are co-existing additional nerve compression syndromes or lateral epicondylitis or if the patient is receiving workers'compensation.


Criminal responsibility evaluations: Benchmarking in different countries.
Forensic mental health experts play a crucial role in criminal responsibility evaluations. However, the quality of these assessments has at time come under scrutiny and has been heavily criticized. A literature review revealed significant differences between countries concerning legal frameworks and procedures for conducting these assessments. The findings suggest that although some countries can be seen as a "role model", there still is room for improvement.


Cognitive impairment in spontaneously hypertensive rats: role of central nicotinic receptors. I.
Both human essential hypertension and genetically induced hypertension in rats have been associated with a range of impairments of cognitive ability. The spontaneous hypertensive rat (SHR) previously has been shown to exhibit a decrease in the expression of brain nicotinic acetylcholine receptors, a factor that could play a role in the impaired ability of this strain in the performance of learning and memory-related tasks. The purpose of this study was to help determine whether task impairment by SHR was related to the reduced expression of central nicotinic acetylcholine receptors. Twelve-week-old SHR were tested in two phases of a water maze (spatial memory) task, and their performance was compared with that of two age-matched normotensive strains, Wistar Kyoto (WKY) and Wistar rats. During Phase 1, SHR exhibited significantly increased latencies to locate a hidden platform as compared with either WKY or Wistar rats. During Phase 2 (subsequent series of trials after a 4-day inter-phase period), where rats were required to find a new platform location, SHR again exhibited significantly impaired performance compared to the normotensive strains. In a single trial passive avoidance paradigm, SHR again displayed significantly reduced avoidance behavior as compared with both WKY and Wistar rats. In consecutive coronal sections, the density of [3H]cytisine binding sites was decreased in SHR by up to 25% in about half of the brain regions examined, with the deficits particularly apparent in cephalic regions. The binding of [125I]alpha-bungarotoxin to brain sections also was decreased in SHR; however, only certain brain areas exhibited significant interstrain differences. These alterations in the expression of putative nicotinic receptor subtypes in SHR were not due to changes in the density of cholinergic neurons since there were no interstrain differences in the binding densities for [3H]vesamicol, which labels the vesicular acetylcholine transporter. Moreover, the magnitude of nicotine-stimulated rubidium efflux from cortical and striatal synaptosomes in vitro was significantly reduced in samples derived from SHR as compared with those from normotensive rats. These results are consistent with the possibility that a reduction in the expression of cortical nicotinic receptors in SHR plays a role in this strain's impaired performance of both spatial and non-spatial learning and memory-related tasks.


The effect of maternal treatment with diclofenac sodium and thymoquinone on testicular parameters in rat offspring.
Diclofenac sodium (DS) can have toxic effects on various tissues and organs, as well as causing foetal and new-born malformations. Thymoquinone (TQ), the basic bioactive compound of black seed oil, is an antioxidant and antineoplastic substance. The aim of our study was to explore the effects of DS and TQ exposure during gestation on offspring rat testicular histology. Mother pregnant rats were divided into five groups: control, saline, DS, TQ and DS plus TQ (DS+TQ) four animals for each group. They were then treated as follows between day of 5 and 15 of gestation: the control group received no treatment. The saline group received physiological saline (1mg/kg/d) via the intraperitoneal (IP) route; the DS group received an intramuscular (IM) injection of DS (6.1mg/kg/d); the TQ group received TQ (5mg/kg/d) dissolved in drinking water; and the DS+TQ group received DS (6.1mg/kg/d) and TQ (5mg/kg/d) dissolved in water. After birth, the male rats were fed for four weeks, and at the end of this period offspring were sacrificed. Stereological methods, physical disector and Cavalieri principle were used for particle counting and volume estimation respectively. The results revealed a significant decrease in the total number of Sertoli and Leydig cells in 4-week-old rats in the DS group (p<0.05), and TQ not have provide protection against this adverse effect of DS. In this study, DS at a dose of 6.1mg/kg, equivalent to a dose of 1mg/kg in humans, decreased the number of Sertoli and Leydig cells, and TQ did not have a protective effect against the adverse effect of DS during the gestation period. These results show that new dose depend studies on TQ and DS interaction are requested to see protective effect of TQ.


Therapeutic potential of potassium channel openers in peripheral vascular disease and asthma.
Potassium channel opener's (KCOs) were originally thought of as nonselective smooth muscle relaxants. However, recent investigations in animal models of both peripheral vascular disease (PVD) and asthma have revealed interesting effects of these drugs as unexpectedly low doses. Hemodynamically, KCOs are interesting in PVD since they have little effect on blood supply to normally perfused skeletal muscle, but enhance perfusion to chronically ligated ischemic tissue. In animal PVD models, SDZ PCO-400 and cromakalim have been shown to improve recovery of muscle energy stores from ischemia or to preserve performance under conditions of ischemic contracture. Beneficial effects in rat PVD models were manifest at doses below those affecting systemic blood pressure and may be attributable to a selective dilatation of collateral vessels. With regard to the airways, the apparent efficacy of KCOs as antiasthmatic drugs seems not to be attributable solely to their bronchodilator activity. Although KCOs elicit no antiinflammatory effect in animal models, studies with SDZ PCO-400 in guinea pigs sensitized to antigen or treated with immune complexes have revealed that expression of airway hyperreactivity is significantly inhibited at drug doses exhibiting only modest bronchodilator activity. At least part of this action can be attributed to inhibition at the level of neural innervation of the airways, possibly through attenuation of nonadrenergic noncholinergic (NANC) transmission.(ABSTRACT TRUNCATED AT 250 WORDS)


Total colonoscopy: is it always possible?
One-thousand three hundred fifty-one consecutive colonoscopies were performed in an office setting without fluoroscopy. Three different models of colonoscopies were utilized; all were manufactured by the Olympus Corporation of America, and included a videoendoscope, a CF-20L immersible OES-type instrument, and an older fiberoptic colonoscope, CFLB-3W. In all colonoscopies, the cecum was reached in 95.9%, even when an obstructing lesion or stenosis was present. Total intubation was performed in 97% of cases with the videoendoscope, 95.5% with the CF-20L, and 95.7% with the CFLB-3W. In a subgroup of 865 colonoscopies, total colonoscopy was performed in 98% of cases when obstructing lesions (carcinoma or stricture) were excluded from analysis. In this subgroup, total colonoscopy could not be performed in 16 patients because of colonic fixation, tortuosity, or for unknown anatomical reasons. Forty-five percent of this subgroup was female, but of the 16 patients in whom total colonoscopy was not possible, 15 were women, 5 of whom had a previous hysterectomy. We conclude that in the absence of any obstructing lesion, an expert can perform complete colonoscopy in 98% of examinations, and in 95% of all patients presenting for colonoscopy. Total colonoscopy may be more difficult in women than men, but a previous hysterectomy does not seem to adversely affect the ability to perform colonoscopy. The type of instrument used for colonoscopy does not impact on the ability to visualize the entire colon.


Secretion of 6beta-hydroxycortisol by normal human adrenals and adrenocortical adenomas.
Although 6beta-hydroxycortisol (6betaOHF) is usually considered a cortisol metabolite produced by the liver, a few reports suggest that it may also originate from extrahepatic sources. To examine whether human adrenal cells are capable of 6beta-hydroxylating cortisol, we measured 6betaOHF secretion with a radioimmunoassay method in isolated human adrenal cell systems obtained from three normal adrenals, four nonhyperfunctioning adrenocortical adenomas, two adrenal adenomas causing Cushing's syndrome, and five aldosterone (Aldo)-producing adenomas. Cells were examined both under basal conditions and after stimulation with adrenocorticotrophic hormone (ACTH). In addition, 6betaOHF concentrations were determined in inferior vena cava and suprarenal vein plasma samples obtained from the side of nonhyperfunctioning adrenal adenomas (five patients) and aldosterone-producing adenomas (five patients). Under basal incubation conditions, 6betaOHF secretion, expressed as a percent of cortisol secretion, was between 0.5 and 2.0% in normal adrenal cells, between 1.0 and 7% in cells from nonhyperfunctioning adenomas, 12 and 15% in cells from Cushing's syndrome patients, and between 2.6 and 3.9% in cells from aldosterone-producing adenomas. In these cells, increasing doses of ACTH produced a dose-dependent stimulation of both 6betaOHF and cortisol secretion. The 6betaOHF concentration in suprarenal vein samples obtained from the side of adenomas was markedly increased; the suprarenal vein/inferior vena cava 6betaOHF ratios were 13.1+/-2.1 (mean+/-S.E.) in the case of nonhyperfunctioning adenomas and 17.8+/-4.5 in the case of aldosterone-producing adenomas. These results firmly suggest that 6betaOHF is not only a hepatic metabolite, but also a secretory product of human adrenals and that similarly to cortisol, its secretion may be controlled by ACTH.


Double-Positive Anti-Glomerular Basement Membrane Antibody and Myeloperoxidase Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis Post COVID-19 mRNA vaccine: A Case Series of 4 Patients.
Vaccines remain central to the management of COVID-19 pandemic, including the need for repeat doses of vaccines to boost immunity. There has been an accumulating case count of glomerulopathies temporally associated with COVID-19 vaccination. This case series presents 4 patients who developed double-positive anti-glomerular basement membrane antibody (anti-GBM) and myeloperoxidase (MPO) antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis after COVID-19 mRNA vaccination. This report contributes to our collective knowledge about the pathophysiology and clinical outcomes associated with this rare complication. Four patients developed nephritic syndrome within 1 to 6 weeks after receiving a COVID-19 mRNA vaccine (3 post Pfizer-BioNTech and 1 post Moderna vaccination). Three of the 4 patients also had hemoptysis. Three of the 4 patients had double-positive serology, whereas the fourth patient had renal biopsy findings consistent with double-positive disease, although anti-GBM serology was negative. All patients had renal biopsy findings consistent with double-positive anti-GBM and ANCA-associated glomerulonephritis. All 4 patients were treated with pulse steroids, cyclophosphamide, and plasmapheresis. Of the 4 patients, 1 demonstrated complete remission, 2 remained dialysis-dependent, and the fourth is deceased. Of the 2 patients who received repeat vaccination with COVID-19 mRNA vaccine, 1 patient had second serologic flare of anti-GBM in response to the vaccine. This case series reinforces growing evidence that COVID-19 mRNA vaccine-induced glomerulonephritis is a rare but real phenomenon. Dual ANCA and anti-GBM nephritis can present after the first dose of COVID-19 mRNA vaccine or after several administrations of the vaccine. We are the first to report cases of double-positive MPO ANCA and anti-GBM nephritis after Pfizer-BioNTech vaccination. To our knowledge, we are also the first to report outcomes of repeat COVID-19 vaccination in patients with de novo flare of ANCA and anti-GBM nephritis temporally associated with COVID-19 vaccination.


One 3-oxoacyl-(acyl-Carrier-protein) reductase functions as 17β-hydroxysteroid dehydrogenase in the estrogen-degrading Pseudomonas putida SJTE-1.
Pseudomonas putida SJTE-1 can utilize 17β-estradiol (E2) as its carbon source, while the enzymes for E2 transformation in this strain is still unclear. 17β-hydroxysteroid dehydrogenases (17β-HSD) can catalyze the reduction/oxidation at C17 site of steroid hormone specifically, critical for steroid transformation. Here a novel 3-oxoacyl-(acyl-carrier protein) (ACP) reductase (ANI02794.1) was identified as it could bβ-estradiol, and was proved to be capable of functioning as 17β-HSD. Sequences alignment showed it contained the two consensus regions and the conserved residues of short-chain dehydrogenase/reductase (SDR). Its encoding gene was cloned and over-expressed in Escherichia coli BL21(DE3) strain, and the recombinant protein was purified by the metal-ion affinity chromatography with the yield of 18 mg/L culture. HPLC (High Performance Liquid Chromatography) detection showed this enzyme could convert 17β-estradiol into estrone using NAD+ as cofactor. Its Km value was 0.082 mM and its Vmax value was 0.81 mM/s; its transformation efficiency of 17β-estradiol into estrone was over 96.6% in five minutes. Its optimal temperature was 37 °C and optimal was pH 9.0; the divalent ions had different effects on the enzymatic activity. In conclusion, this 3-oxoacyl-ACP reductase functioned as 17β-HSD in P. putida SJTE-1 and played important role in its estrogen metabolism.


Why aren't all deep superior colliculus neurons multisensory? A Bayes' ratio analysis.
Multisensory neurons in the deep superior colliculus (SC) show response enhancement to cross-modal stimuli that coincide in time and space. However, multisensory SC neurons respond to unimodal input as well. It is thus legitimate to ask why not all deep SC neurons are multisensory or, at least, develop multisensory behavior during an organism's maturation. The novel answer given here derives from a signal detection theory perspective. A Bayes' ratio model of multisensory enhancement is suggested. It holds that deep SC neurons operate under the Bayes' ratio rule, which guarantees optimal performance-that is, it maximizes the probability of target detection while minimizing the false alarm rate. It is shown that optimal performance of multisensory neurons vis-à-vis cross-modal stimuli implies, at the same time, that modality-specific neurons will outperform multisensory neurons in processing unimodal targets. Thus, only the existence of both multisensory and modality-specific neurons allows optimal performance when targets of one or several modalities may occur.


Community-acquired Acinetobacter calcoaceticus pneumonia in a patient with agammaglobulinaemia.
We herein describe the case of a 38-year-old patient with congenital agammaglobulinemia who presented with community-acquired pneumonia; acute respiratory failure with sepsis ensued requiring ICU admission, mechanical ventilation and vasopressors administration. The causative organism was identified as Acinetobacter calcoaceticus, sensitive to multiple agents. Stewardship was effectively applied; clinical, biologic and radiologic improvement resulted, and the patient was later discharged on ciprofloxacin therapy; improvement being maintained thereafter. This is the first reported case of community-acquired Acinetobacter pneumonia in our region.


Synthesis of fused tricyclic amines from enolizable acyclic aldehydes by cyclization then dipolar cycloaddition cascade: synthesis of myrioxazine A.
A tandem one-pot reaction involving a condensation, then cyclization (N-alkylation), followed by an azomethine ylide or nitrone dipolar cycloaddition allows a synthesis of tricyclic amines from acyclic enolizable aldehydes. The reaction was unsuccessful using amino acids or esters but was successful with (tributylstannyl)methylamine or hydroxylamine. One of the products was converted in two steps to the alkaloid (+/-)-myrioxazine A. The chemistry also provides a formal synthesis of the antimalarial alkaloids myrionidine and schoberine.


Reversible surface oxidation and efficient luminescence quenching in semiconductor single-wall carbon nanotubes.
We have investigated reversible single-wall carbon nanotube (SWNT) oxidation by quantitative analysis of the oxide-induced absorption bleaching and luminescence quenching at low pH. These data, in combination with DFT structure calculations, suggest that the nanotube oxide is a 1,4-endoperoxide. At low pH, the endoperoxide protonates to create a hydroperoxide carbocation, introducing a hole in the SWNT valence band. Nanotube luminescence is extremely sensitive to quenching by hole-doping, while the absorption is relatively robust.


Q fever endocarditis: diagnostic approaches and monitoring of therapeutic effects.
The scope of current diagnostic methods for Q fever endocarditis includes serology, direct demonstration of Coxiella burnetii in the resected heart valve tissue, and animal inoculation studies. Illustrated by a clinical case report, the different methods are presented and discussed. Serology represents the primary method, using the techniques of complement fixation, indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). The latter two techniques allow the detection of immunoglobulins G, M, and A to the phase I and II antigens of C. burnetii. After cardiac surgery, we visualized C. burnetii on smears and specifically stained it on histologic sections of the resected heart valve by light and electron microscopic immunohistochemistry. In addition, seroconversion in animals after inoculation with valve specimens confirmed the presence of C. burnetii in the heart valve. The antibody titers determined by ELISA correlated well with the patient's clinical course during the treatment period. Therefore it is suggested that its usefulness for monitoring the efficacy of antimicrobial agents in patients with Q fever endocarditis should be further evaluated.


Pentacam vs SP3000P specular microscopy in measuring corneal thickness.
To compare corneal thickness (CT) measurements obtained with SP3000P specular microscope and Pentacam in eyes screened to undergo refractive surgery (RS). In this prospective study, a non-randomized consecutive series of 73 healthy eyes (age range: 14-78 years; mean=38.4±14.9) underwent CT measurement with both Oculus Pentacam and Topcon SP3000P specular microscope to assess their suitability to undergo corneal RS. CT measurements with SP3000P ranged from 451 to 609 μs (mean 523.1±34.4 μs). The measurements obtained with Pentacam ranged at the corneal apex from 477 to 672 μs (mean 558.9±38.9 μs), at the pupil center from 477 to 672 μs (mean 557.9±38.9 μs) and at the thinnest point from 474 to 669 μs (mean 551.1±39.4 μs). CT measurements showed a good correlation but a statistically significant difference at the pupil center (mean -34.9±14.6 μs, R(2)=0.860, p<0.001), at the apex (mean -35.9±14.9 μs, R(2)=0.856, p<0.001) and at the thinnest point (mean -32±14.8 μs, R(2)=0.862, p<0.001). The calculated regression formulas were: y=0.816x+66.94 for the apex, y=0.819x+66.07 for the pupil center and y=0.810x+73.13 for the thinnest point; where y is the CT measured with the SP3000P and x is the measurement obtained with the Oculus Pentacam. Our results suggest that SP3000P measures thinner corneas compared to the Pentacam and that the correcting factor we identified should be applied to make comparisons between these two devices.


Coagulation, Vascular Morphology, and Vasculogenesis in Spinal Ligament Ossification Model Mice.
In vivo studies of the vascular system in ossification of the posterior longitudinal ligament (OPLL) model mice. The aim of this study was to investigate blood coagulability, vascular morphology, and vasculogenesis capability, known as venous thromboembolism (VTE) risk factors in the ossification model, tiptoe walking (ttw) mice. Patients with OPLL are more likely to develop VTE after spinal cord injury. Capillary mesh invasion of spinal ligaments precedes spinal ligament ossification in ttw mice. Investigation on vascular systems of ttw mice may contribute to clarifying its pathology. Coagulability of blood samples from ttw and C57BL/6 (WT) mice were evaluated at 8, 16, and 24 weeks of age. Vascular morphology was assessed from a Hematoxylin-Eosin stained section by measuring vessel area. A tube formation assay was performed with endothelial cells isolated from the aorta to assess vasculogenesis. Prothrombin time was significantly shorter in ttw mice than in WT at 8 and 16 weeks. Fibrinogen had a greater increase in ttw mice than in WT at 16 weeks. The vascular area and vascular wall area were significantly smaller in ttw mice than in WT at all timepoints. The ratio of vascular wall area to vascular area was significantly smaller in ttw mice than in WT at 24 weeks. The endothelial cells from ttw mice formed significantly higher numbers of total branching points than WT cells. Ossification model mice had impaired blood coagulation and vascular morphology and high capacity for vasculogenesis. With regard to the pathogenesis of VTE, ttw mice harbor an environment that promotes the development of VTE.Level of Evidence: N/A.


Australian public hospital inpatient satisfaction related to early patient involvement and shared decision-making in discharge planning.
Surveys of hospital inpatient satisfaction may help develop actionable plans for quality improvement, and patients have preferred to give feedback during admission at the point of service compared to after discharge. However, patient satisfaction measurement has often been done by questionnaires post-discharge, and without focussing on an Australian general internal medicine setting. To understand patients' perceptions of their admission experiences in an Australian public teaching hospital's general internal medicine unit, and to understand the opportunities for quality improvement. A prospective study of 50 inpatients of a general internal medicine unit at an Australian public teaching hospital was carried out using a patient satisfaction questionnaire given to patients on the day of discharge. Patients perceived deficits in early communication about discharge destination planning, and provision of written discharge instructions. Responses highlighted the importance of checking with patients to elicit further information that was not previously captured during initial history-taking, patient-centred communication to enable informed consent and decision making, use of language readily understandable to laypersons, and checking for patients' understanding of messages as communicated by the treating clinician. In an Australian general internal medicine service, early involvement and shared decision-making in discharge planning are valued by patients. Incorporating checking of patients' understanding of diagnoses, management, discharge instructions, and follow-up plans into ward round routines may benefit patient satisfaction. This study stimulates further research into the use of a proforma to capture and check patients' understanding of discharge diagnoses and plans.


Equating accelerometer estimates of moderate-to-vigorous physical activity: in search of the Rosetta Stone.
No universally accepted ActiGraph accelerometer cutpoints for quantifying moderate-to-vigorous physical activity (MVPA) exist. Estimates of MVPA from one set of cutpoints cannot be directly compared to MVPA estimates using different cutpoints, even when the same outcome units are reported (MVPA mind(-1)). The purpose of this study was to illustrate the utility of an equating system that translates reported MVPA estimates from one set of cutpoints into another, to better inform public health policy. Secondary data analysis. ActiGraph data from a large preschool project (N=419, 3-6-yr-olds, CHAMPS) was used to conduct the analyses. Conversions were made among five different published MVPA cutpoints for children: Pate (PT), Sirard (SR), Puyau (PY), Van Cauwengerghe (VC), and Freedson Equation (FR). A 10-fold cross-validation procedure was used to develop prediction equations using MVPA estimated from each of the five sets of cutpoints as the dependent variable, with estimated MVPA from one of the other four sets of cutpoints (e.g., PT MVPA predicted from FR MVPA). The mean levels of MVPA for the total sample ranged from 22.5 (PY) to 269.0 (FR) mind(-1). Across the prediction models (5 total), the median proportion of variance explained (R(2)) was 0.76 (range 0.48-0.97). The median absolute percent error was 17.2% (range 6.3-38.4%). The prediction equations developed here allow for direct comparisons between studies employing different ActiGraph cutpoints in preschool-age children. These prediction equations give public health researchers and policy makers a more concise picture of physical activity levels of preschool-aged children.


FTO regulates the DNA damage response via effects on cell-cycle progression.
The fat mass and obesity-associated protein FTO is an "eraser" of N6-methyladenosine, the most abundant mRNA modification. FTO plays important roles in tumorigenesis. However, its activities have not been fully elucidated and its possible involvement in DNA damage - the early driving event in tumorigenesis - remains poorly characterized. Here, we have investigated the role of FTO in the DNA damage response (DDR) and its underlying mechanisms. We demonstrate that FTO responds to various DNA damage stimuli. FTO is overexpressed in mice following exposure to the promutagens aristolochic acid I and benzo[a]pyrene. Knockout of the FTO gene in TK6 cells, via CRISPR/Cas9, increased genotoxicity induced by DNA damage stimuli (micronucleus and TK mutation assays). Cisplatin- and diepoxybutane-induced micronucleus frequencies and methyl methanesulfonate- and azathioprine-induced TK mutant frequencies were also higher in FTO KO cells. We investigated the potential roles of FTO in DDR. RNA sequencing and enrichment analysis revealed that FTO deletion disrupted the p38 MAPK pathway and inhibited the activation of nucleotide excision repair and cell-cycle-related pathways following cisplatin (DNA intrastrand cross-links) treatment. These effects were confirmed by western blotting and qRT-PCR. FTO deletion impaired cell-cycle arrest at the G2/M phase following cisplatin and diepoxybutane treatment (flow cytometry analysis). Our findings demonstrated that FTO is involved in several aspects of DDR, acting, at least in part, by impairing cell cycle progression.


A corneal-PAMPA-based in silico model for predicting corneal permeability.
The capability to predict corneal permeability based on physicochemical parameters has always been a desirable objective of ophthalmic drug development. However, previous work has been limited to cases where either the diversity of compounds used was lacking or the performance of the models was poor. Our study provides extensive quantitative structure-property relationship (QSPR) models for corneal permeability predictions. The models involved in vitro corneal permeability measurements of 189 diverse compounds. Preliminary analysis of data showed that there is no significant correlation between corneal-PAMPA (Parallel Artificial Membrane Permeability Assay) permeability values and other pharmacokinetically relevant in silico drug transport parameters like Caco-2, jejunal permeability and blood-brain partition coefficient (logBB). Two different QSPR models were developed: one for corneal permeability and one for corneal membrane retention, based on experimental corneal-PAMPA permeability data. Partial least squares regression was applied for producing the models, which contained classical molecular descriptors and ECFP fingerprints in combination. A complex validation protocol (including internal and external validation) was carried out to provide robust and appropriate predictions for the permeability and membrane retention values. Both models had an overall fit of R2 > 0.90, including R2-values not lower than 0.85 for validation runs, and provide quick and accurate predictions of corneal permeability values for a diverse set of compounds.


Surveillance of premalignant gastric cardia lesions: A population-based prospective cohort study in China.
In our study, we aimed to assess the long-term risk of gastric cardia adenocarcinoma (GCA) for patients with different histological cardia lesions to inform future guidelines for GCA screening in China. We conducted a population-based prospective study among 9740 subjects who underwent upper endoscopy screening during 2005 to 2009 and followed until December 2017. Cumulative incidence and mortality rates of GCA were calculated by the baseline histological diagnoses, and the hazard ratios (HRs), overall and by age and sex, were analyzed by Cox proportional hazards models. During a median follow-up of 10 years, we identified 123 new GCA cases (1.26%) and 31 GCA deaths (0.32%). The age-standardized incidence and mortality rates of GCA were 128.71/100 000 and 35.69/100 000 person-years, and cumulative incidence rate in patients with cardia high-grade dysplasia (CHGD), cardia low-grade dysplasia (CLGD) and atrophic carditis (AC)/cardia intestinal metaplasia (CIM) was 25%, 3.05% and 1.58%, respectively. The progression rate and cancer risk of GCA increased monotonically with each step in Correa's cascade. Individuals aged 50 to 69 years had 4.4 times higher GCA incidence than those aged 40 to 49 years. Patients with CLGD had a significantly higher 3-year GCA incidence than the normal group, while patients with AC/CIM had a comparable GCA risk during 3-year follow-up but a higher risk at 5-year intervals. Our results suggested a postponed starting age of 50 years for GCA screening, immediate treatment for patients with CHGD, a 3-year surveillance interval for patients with CLGD, and a lengthened surveillance interval of 5 years for patients with AC/CIM.


Two wild female bonobos adopted infants from a different social group at Wamba.
Adoption, the act of taking another individual's offspring and treating it as one's own, is rare but widely observed in various mammal species and may increase the survival of adoptees. Adoption may also benefit adoptive mothers, for example they might care for close kin to gain indirect fitness or to learn caregiving behaviours. Here, we report two cases of a wild bonobo adopting an infant from a different social group, the first report of cross-group adoption in great apes. In one case, the adoptive mother was already a mother of two dependent offspring. In the other case, the adoptive mother was an old parous female whose own offspring had already emigrated into a different social group. The adoptive mothers provided various maternal care to the adoptees, such as carrying, grooming, nursing, and sharing food. No aggression was observed by group members towards the out-group adoptees. In both cases, adoptees had no maternal kin-relationship with their adoptive mothers. Both adoptive mothers already had experience of rearing their own offspring. Instead, these cases of adoption may have been driven by other evolutionary adaptive traits of bonobos, such as their strong attraction to infants and high tolerance towards immatures and out-group individuals.


A De Novo case of autosomal dominant mitochondrial membrane protein-associated neurodegeneration.
Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a genetic neurodegenerative condition previously thought to be inherited only in an autosomal recessive pattern through biallelic pathogenic variants in C19orf12. Recent evidence has proposed that MPAN can also follow autosomal dominant forms of inheritance. We present a case of a de novo pathogenic variant in C19orf12 identified in a female with clinical features consistent with a diagnosis of MPAN, adding further evidence that the disease can be inherited in an autosomal dominant fashion. A 17-year-old Hispanic female was born to non-consanguineous healthy parents. She developed progressive muscle weakness and dystonia beginning when she was 12 years old. Trio, whole-exome sequencing with mitochondrial genome sequencing, and deletion/duplication analysis of both nuclear and mitochondrial genomes was performed in December 2019. Whole-exome sequencing analysis revealed a single de novo variant in C19orf12. The specific variant is c.256C>T (p.Q86X) located in exon 3. Our clinical report provides further clinical evidence that MPAN can be inherited in an autosomal dominant or recessive fashion. The patient's age of onset and clinical symptoms are very similar to the previous patient published with this specific variant as well as others with heterozygous pathogenic variants in C19orf12 in Gregory et al. 2019. Our case report highlights the importance of considering both autosomal dominant and autosomal recessive version of MPAN with all patients demonstrating clinical features suggestive of MPAN.


Socio-demographic and clinical characteristics of individuals with diagnoses of eating disorder in a university hospital in Istanbul.
This paper reports the first-ever description of a clinical eating disorder population from Turkey. The aim of this study was to examine the socio-demographic and clinical characteristics of individuals with diagnosis of eating disorders (IDED) referred to a university psychiatry clinic in Istanbul between 2003 and 2009. The diagnoses and subtype of 111 IDEDs, the referral type to the hospital, setting of treatment, and state of involuntary hospitalization were evaluated by interview and semi-structured questionnaire. The clinical sample included 64 individuals with anorexia nervosa (AN), 38 with bulimia nervosa (BN), and 9 with eating disorder not otherwise specified (EDNOS), including only one male. Younger individuals and those with a lower BMI were significantly more likely to be family referred and hospitalized involuntarily. The overall socio-demographic features of the sample are generally consistent with data collected in other communities. However, aspects of the clinical features, referral types of eating disorders and subtypes exhibit some characteristics peculiar to our sample.


The Views of Patients and Partners Toward Patient-Delivered Partner Therapy for Chlamydia: A Systematic Review.
The majority of research on patient-delivered partner therapy (PDPT) has focused on its impact on reinfections. This study aimed to systematically review the evidence regarding the acceptability of PDPT by patients and partners for chlamydia infection. Three electronic databases were searched in March 2019 using terms related to PDPT. Studies were included if they reported on patient or partner acceptance of PDPT for chlamydia and were conducted in high-income countries. Actual and perceived acceptabilities of PDPT were assessed. Thirty-three studies were included: 24 quantitative, 3 qualitative, and 6 mixed methods. Most were clinic based. Quantitative data showed that participants' perceived willingness to give PDPT to their partner(s) ranged from 44.7% to 96.3% (median, 84%), and 24% to 71% (median, 65%) of people who offered PDPT for their partner(s) accepted it. Partners' perceived willingness to accept ranged from 42.7% to 67% (median, 62%), and actual acceptance ranged from 44.7% to 80% (median, 77%). Those in longer-term relationships were generally more likely to accept PDPT; however, beyond this, we identified few clear trends. Qualitative studies found that convenience of PDPT and assurance of partner treatment were benefits, whereas partners not seeing a health care professional was viewed as a downside. Packaging that appeared legitimate and coaching on delivering PDPT were facilitators. Because patients bear responsibility for the success of PDPT, this information is crucial in clinical settings. Acceptance, perceived and real, of PDPT was generally high. Patients are best placed to determine whether PDPT is appropriate for them, and it should be offered as an option.


Radiographic Analysis of Pedicle Screw Retractor-Assisted Transforaminal Lumbar Interbody Fusion for Single-Segment Spondylolisthesis in Adults: A Retrospective Study and Technical Note.
The objective of this study was to introduce a retractor that can be temporarily installed on unilateral pedicle screws to achieve distraction-reduction and nerve root protection, and to analyze the efficacy and safety of retractor-assisted transforaminal lumbar interbody fusion (TLIF) in the treatment of lumbar spondylolisthesis. This was a retrospective study of 125 patients who underwent retractor-assisted TLIF for single-segment spondylolisthesis from November 2017 to February 2021. Based on morphology, patients were divided into degenerative (N = 66) and isthmic groups (N = 59). Differences in demographics and preoperative characteristics between the groups were analyzed using the independent samples t-test and χ2 test. Changes in radiographic parameters (disc height, foramen height, spondylolisthesis degree, slippage length, and segmental lordosis) before and after surgery were compared using the paired samples t-test. Logistic regression analysis was performed to analyze the relationship between facet joint angle (FJA) and degenerative lumbar spondylolisthesis (DLS). Unilateral screw retractor-assisted TLIF significantly corrected spondylolisthesis and improved disc height and segmental lordosis (p < 0.05). There was no significant difference in foramen height between the two sides before and after operation (pre: 15.81 ± 3.58 mm vs 15.69 ± 3.68 mm, p = 0.599; post: 18.65 ± 2.31 mm vs 18.74 ± 2.26 mm, p = 0.516). The degree of spondylolisthesis in the DLS group before surgery was significantly lower than that in the isthmic spondylolisthesis group (17.70 ± 5.62% vs 25.18 ± 9.73%, p < 0.001), whereas a similar degree of correction could be achieved after surgery (5.91 ± 3.12% vs 7.16 ± 5.69%, p = 0.135). FJAs from L3/4 to L5/S1 were significantly smaller in patients with DLS than those in with isthmic spondylolisthesis (p < 0.05). Patients with facet sagittalization were more likely to have DLS (β: -0.101, odds ratio [OR]:0.904, 95% confidence interval [CI]: 0.874-0.934, p < 0.001), while the cut-off FJA of L4/5 for predicting L4 spondylolisthesis was 53.19. Pedicle screw retractor-assisted TLIF is effective and safe in treating both degenerative and isthmic lumbar spondylolisthesis. The unilateral retractor has the capacity to maintain the disc height achieved by paddle distractors, which optimizes the nerve protection and distractor placement. Patients with an FJA on L4/5 <53.19 were more likely to have DLS.


Production of proteases type plasminogen activator and their inhibitor in cornea.
Corneal epithelial cells secrete tissue plasminogen activator (t-PA), urokinase type plasminogen activator (u-PA) and their inhibitor (PAI), whereas these cell types in other tissues are known to secrete only u-PA hitherto. Endothelial cells in the cornea produce mostly u-PA and only small amounts of t-PA and PAI which remain confined in the cellular compartment contrary to the situation in the vascular endothelial cells where they are liberated into the circulation in the order PAI greater than t-PA greater than U-PA. These unique features of activator/inhibitor secretion and production may play an important role in the remodeling of the corneal matrix.


Pre-clinical activity of the oral DNA-PK inhibitor, peposertib (M3814), combined with radiation in xenograft models of cervical cancer.
DNA-dependent protein kinase (DNA-PK) plays a crucial role in repair of DNA double-strand breaks by facilitating non-homologous end-joining. Inhibitors of DNA-PK have the potential to block DNA repair and enhance DNA-damaging agents. Peposertib (M3814) is a DNA-PK inhibitor that has shown preclinical activity in combination with DNA-damaging agents, including ionizing radiation (IR) and topoisomerase II inhibitors. Here we evaluated the activity of peposertib (M3814) in combination with radiation in a mouse xenograft model of HPV-associated cervical cancer. Athymic nude female mice with established tumors derived from HeLa cells injected into the flank were treated with vehicle alone (n = 3), IR alone (n = 4), and peposertib (M38814) in combination with IR (M3814 + IR; n = 4). While IR alone was associated with a trend towards decreased tumor volume compared with untreated, only the M3814 + IR treatment arm was associated with consistent and significant reduction in tumor burden, which correlated with higher levels of γ-H2AX in tumor cells, a marker of double-strand DNA breaks. Our data support further clinical evaluation of the combination of peposertib (M38814) and IR in cervical cancer.


Decreased recurrence of symptoms in oral lichen planus with intralesional injection of hyaluronic acid and triamcinolone.
Oral lichen planus (OLP) is a chronic non-infectious, inflammatory, immunological disease. In contrast to skin lesions, which are often self-limiting, oral lesions rarely heal on their own and can be resistant to local and systemic treatments. In this clinical trial, hyaluronic acid (HA) was mixed with triamcinolone for intralesional injection to reduce side effects in the treatment of OLP. This randomized clinical trial with a split-mouth design was performed on 28 patients with OLP. The mouth was divided randomly into two sides: a test side, which received HA combined with triamcinolone, and a control side, which received triamcinolone alone. The rate of symptom recurrence was 74.1% on the control side and 11.1% on the test side (significant difference, P<0.01). Pain scores did not differ between the two groups when assessed after 2 weeks. The group treated with a combination of HA and triamcinolone experienced a significantly better resolution of lesions and symptoms. Considering the role of HA in tissue healing and in regulating inflammatory responses, as well as its antioxidant and hydration properties, it appears that HA could be effective in improving of OLP and decreasing the rate of symptom recurrence.


The level of FC receptor leukocytes in primary and secondary skin allograft recipients.
DA (Ag-B4) rats were grafted with allogeneic Lewis (Ag-B1) skin on the region of the thorax drained by the left brachial and axillary lymph nodes. A DA isograft was placed on the right side of the thorax. From 1 to 14 days after grafting the rats were either given injections of colloidal carbon, killed, and spleen and lymph nodes were assayed for noncarbon-containing Fc rosette-forming leukocytes (RFL), or allowed to complete rejection of the graft. In order to assess secondary allograft rejection within the latter animals after the grafted areas was healed, a second Lewis allograft was placed in the same region as the first and another DA isograft on the right side. Compartmental Fc RFL were enumerated 2 to 16 days thereafter by rosette formation with erythrocyte-antibody. The regional lymph nodes of animals rejecting a primary allograft exhibited a significantly (P less than 0.05) higher level of Fc RFL compared with their contralateral controls. These higher levels were evident on days 6 to 8 and disappear by day 10. However, animals undergoing a secondary allograft response exhibited significant differences by day 4. A greater density of Fc RFL were also evident in cryostat sections of the graft bed of allografts as opposed to isografts.


The relation between sexuality and obesity: the role of psychological factors in a sample of obese men undergoing bariatric surgery.
Obesity produces a significant deterioration in general and sexual health. The aim of this cross-sectional study was to investigate the impact of obesity on sexuality, illustrating the psychological constructs that may play a significant role in determining sexual functioning and satisfaction. During the psychological assessment for bariatric surgery eligibility, 171 obese men filled out a socio-demographic questionnaire, the International Index of Erectile Function (IIEF), the 20 Item-Toronto Alexithymia Scale, the Symptom Checklist-90-Revised, the Body Uneasiness Test, and the Obesity-related Disability test. A series of hierarchical multiple regression analyses highlighted how obese men sexual desire (F(11,159) = 10.128, p < 0.001), erectile function (F(10,160) = 63.578, p < 0.001), orgasmic function (F(10,160) = 33.967, p < 0.001), intercourse satisfaction (F(7,163) = 159.752, p < 0.001), and general satisfaction (F(10,160) = 18.707, p < 0.001) were significantly associated with other IIEF sexual domains, difficulties in identifying feelings, psychopathological symptoms (such as depression and paranoid ideation), body image, and quality of life. Findings are useful for deepening understanding of obese male sexual response, and more generally, for analyzing the complex and multivariate relation between obesity and sexuality, supporting the need of a multidisciplinary approach to obesity care that includes professionals with specific training in sexology.


Binding of human fibrinogen and its polypeptide chains to group B streptococci.
Of 51 group-B streptococcal cultures, 20 bound 125I-labelled human fibrinogen. In contrast to the streptococci of groups A, C and G, the group-B streptococci interacted more with the alpha, beta-chain of fibrinogen than with whole fibrinogen. None of the streptococcal cultures reacted with gamma-chain. The fibrinogen-negative group-B streptococci still bound the alpha, beta-chain. The binding of 125I-labelled, alpha, beta-chain could be inhibited by unlabelled fibrinogen with fibrinogen-positive, but not with fibrinogen-negative streptococci of group B.


3'-Deamino-3'-(2-methoxy-4-morpholinyl)-doxorubicin (FCE 23762): a new anthracycline derivative with enhanced cytotoxicity and reduced cardiotoxicity.
The purpose of this study was to examine the cytotoxicity and cardiotoxicity of the new doxorubicin derivative, 3'-deamino-3'-(2-methoxy-4-morpholinyl)-doxorubicin (FEC 23762). The concentration of FCE 23762 that resulted in a 50% reduction in colony formation of DU 145, COLO 320DM, A549 and A2780 human cancer cell lines ranged from 1.1 and 3.2 nmol/l and was 3-9 times as low as doxorubicin. In the isolated perfused rat hearts, doxorubicin 10(-5) mol/l induced a significant prolongation of S alpha T segment and Q-Fmax interval, and reduction in dF/dtmax and coronary flow while only FCE 23762 10(-5) mol/l induced a widening of QRS complex. Anaesthetised rats given a single intravenous (i.v.) dose of doxorubicin 10 mg/kg showed significant changes in both ECG (S alpha T segment and QRS complex enlargement) and haemodynamic parameters (increase in mean arterial blood pressure and reduction in systemic arterial dP/dtmax), while animals given FCE 23762 (0.1 and 0.3 mg/kg) had a significant increase in QRS complex duration after the highest dose. In the chronic cardiotoxicity study animals receiving FCE 23762 (0.03 mg/kg i.v. once a week for 3 weeks) did not show any significant alteration of ECG and minor changes of cardiac histological picture; by contrast doxorubicin (3 mg/kg i.v. once a week for 3 weeks) induced a severe cardiomyopathy, characterised by progressive widening of S alpha T segment, increase in T wave and histological damage consisting of vacuolations and loss of myofibrils. These results indicate that FCE 23762 is more active in vitro than doxorubicin and markedly less cardiotoxic in vivo at the doses used in the present study.


Use of Job Classifications, Career Ladders, and the Applied Epidemiology Competencies to Support Recruitment, Retention, and Practice of State Health Department Epidemiologists.
State health departments report that recruitment and retention of qualified epidemiologists is a significant challenge to ensuring epidemiology capacity to support essential public health services. To collect information on the use of epidemiology job classifications, career ladders, and professional competencies in state health departments to inform workforce development activities that improve epidemiology capacity. Electronic survey of the designated state epidemiologist. Fifty state health departments and the District of Columbia. State epidemiologists working in state health departments. Use and perceived benefit of epidemiology job classifications, career ladders, and professional competencies. All 50 states and the District of Columbia responded to the survey. Most state health departments reported having epidemiology-specific job classifications (n = 44, 90%) and career ladders (n = 36, 71%) in place. State epidemiologists strongly agreed or agreed that having an epidemiology-specific classification positively contributed to recruitment (n = 37, 84%) and retention (n = 29, 66%) of epidemiologists in their agency. State epidemiologists strongly agreed or agreed that having an epidemiology-specific career ladder positively contributed to recruitment (n = 24, 69%) and retention (n = 23, 66%) of epidemiologists in their agency. Only 10 (29%) state epidemiologists reported using the applied epidemiology competencies to develop or revise their jurisdiction's epidemiology career ladder. State health departments should implement well-maintained epidemiology-specific job classifications and career ladders that are based on current epidemiology competencies. Career ladders should be supported with opportunities for competency-based training to support career progression.


Biochemical screening for Down syndrome in pregnancies following renal transplantation.
To assess the performance of the double marker test [free beta-human chorionic gonadotrophin (beta-hCG) and alpha-fetoprotein (AFP)] as a screening test for Down syndrome in pregnant patients who had a prior renal transplant. A retrospective study. The Fetal Medicine Unit, Royal Free Hospital, London, UK. Detailed records of 14 post-renal transplant pregnancies were obtained from the Renal Unit of our hospital where the patients were followed up. The serum concentrations of urea, creatinine, free beta-hCG and AFP at the time of the double marker test were recorded, with a cut-off point of 1:250 for the double marker test. A control group of 14 normal pregnancies matched for age, parity and gestational age was used. The Mann-Whitney U-test and t-tests of unequal variance were applied to compare parameters of the study and the control groups. Two patients in each group were high risk for Down syndrome and amniocentesis revealed normal karyotype. No babies with Down syndrome were delivered in either group. Regression analysis showed significant correlation between free beta-hCG and urea concentrations (p<0.001) and free beta-hCG and creatinine concentrations (p<0.001), but not for AFP. The present study demonstrates that residual renal function alterations persisting after renal transplantation can affect the levels of free beta-hCG and AFP, thus resulting in false-positive screening for Down syndrome. First trimester nuchal translucency (NT) measurement in combination with second trimester ultrasonographic markers can be used in these patients, or alternatively the free beta-hCG levels should be corrected according to the serum creatinine levels.


Kidney metastasis in a case of Merkel cell carcinoma.
Merkel cell carcinoma is a rare neuroendocrine skin tumor with a poor prognosis. Metastasis is frequent and is seen in the first few years after diagnosis. This report describes a case of renal metastasis from Merkel cell carcinoma which is an unusual clinical presentation.


Editorial Commentary: Arthroscopic Treatment for Diminutive Hip Labral Size: Go Big or Go Home?
The diminutive (or hypoplastic or hypotrophic) hip labrum presents a unique surgical challenge in the setting of femoroacetabular impingement syndrome for many hip arthroscopists. Insufficient labral tissue leads to increased risk for suture cutout or overeversion, with resulting loss of suction seal when attempting arthroscopic repair. Although some surgeons have demonstrated clinical improvement after performing primary refixation of the diminutive labrum, others have reported inferior outcomes for patients with labral width <4 mm compared with patients having normal or larger labral width. Alternative treatment methods, including labral reconstruction or labral augmentation with autograft or allograft, may be effective, based on select single-surgeon studies. As further research is needed to fully evaluate outcomes of these techniques, hip arthroscopists should recognize the difficult task at hand and be prepared to use assorted treatment options to augment a diminutive labrum. Larger labra can maintain contact with the femoral head after repair, and techniques such as labral base fixation can help to preserve this interaction and recreate the suction seal.


Duloxetine for management of stress urinary incontinence.
The aim of this article was to review data regarding the efficacy and tolerability of duloxetine, a selective serotonin (5-HT)-norepinephrine (NE) reuptake inhibitor that has received US Food and Drug Administration marketing approval for the treatment of major depressive disorder and painful diabetic neuropathy, and that has been investigated as a treatment for stress urinary incontinence. A MEDLINE/PubMed search was conducted to identify English-language study reports. In addition, proceedings of meetings of the International Continence Society, European Association of Urology, American Urological Association, and American College of Obstetrics and Gynecology were reviewed for relevant abstracts (search terms included duloxetine, thiophenes, serotonin uptake inhibitors, adrenergic uptake inhibitors, and stress urinary incontinence). Additional references were obtained from the bibliographies of these sources. Data for the period from 1986 through January 2005 were reviewed. All in vitro and in vivo studies of duloxetine were included. Because both 5-HT and NE are involved in the maintenance of urinary continence, duloxetine may have a role in the treatment of urinary incontinence. Duloxetine is primarily eliminated via metabolism, with < 1% of the parent compound excreted via urine. Duloxetine QD or BID has been found to be significantly superior to placebo in reducing incontinence episode frequency (P < 0.001 to P < 0.05), increasing the interval between micturitions (P < 0.001 to P = 0.004), and improving the condition as measured by patient self-report (P < 0.001 to P = 0.028) and incontinence quality-of-life scores (P = 0.002 to P = 0.03). The most problematic adverse events are nausea, dry mouth, constipation, dizziness, and insomnia. Although statistically superior to placebo in efficacy trials, the clinical effects of duloxetine therapy on incontinence are small, suggesting that any benefits to the patient would be modest and must be weighed against the drug's adverse event profile. No comparative efficacy/tolerability data with alpha-receptor agonists (eg, pseudoephedrine) are available. On the basis of available data, duloxetine is a modest, but welcome, advance in the pharmacotherapeutic management of stress urinary incontinence.


Phorbol ester induces the transcriptional stimulatory activity of the SV40 enhancer.
Phorbol ester tumour promoters can induce the transcription of a number of genes, including c-myc and c-fos. These genes are part of a group referred to as 'competence' genes because they are expressed very early after quiescent cells are stimulated to enter the cell cycle. The 'competence' genes are coordinately induced by serum and by factors such as platelet-derived growth factor and fibroblast growth factor. These factors, as well as the tumour promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), are thought to exert their action by a mechanism involving the activation of protein kinase C. It is likely that these factors induce the transcription of the 'competence' genes either by activating specific transcription factors or by increasing their intracellular concentration; either mechanism may be mediated by protein kinase C. One approach to identifying such a putative transcription factor is to characterize the cis-acting transcriptional control elements that serve as a target site for the factor. Here we report that, in a human hepatoma cell line, TPA can specifically induce the activity of the simian virus 40 (SV40) transcriptional enhancer element. Since the SV40 enhancer is a thoroughly characterized cis-acting element, this system may facilitate the eventual identification of the trans-acting factor(s) whose activity is modified by TPA treatment.


Fingolimod ameliorates imiquimod-induced psoriasiform dermatitis by sequestrating interleukin-17-producing ?d T cells in secondary lymph nodes.
Psoriasis is a chronic inflammatory skin disease. Interleukin (IL)-17A plays a key role in the pathogenesis of psoriasis. Fingolimod, which is available for the treatment of multiple sclerosis, exerts anti-inflammatory effects by sequestrating inflammatory lymphocytes in secondary lymphoid tissues and the thymus. The effect of fingolimod on psoriasis has not been reported yet. Our objectives were to investigate the effect of fingolimod on psoriasis utilizing mice with imiquimod (IMQ)-induced psoriasiform dermatitis, and explore the possibility of fingolimod as a therapeutic agent for psoriasis. Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Fingolimod prepared in phosphate-buffered saline (PBS), or PBS alone as a control, was administered intraperitoneally daily from days 0 to 5. Fingolimod ameliorated IMQ-induced psoriasis dermatitis clinically and histologically. On day 6, the mRNA expression level of IL-17A was lower in the skin of fingolimod-treated mice than in that of PBS-treated mice, whereas it was higher in the inguinal lymph nodes of fingolimod-treated mice than in those of PBS-treated mice. Flow cytometric analyses revealed that fingolimod reduced IL-17A-producing ?d T cells infiltrating into the skin, whereas it increased these cells in the inguinal lymph nodes. Fingolimod inhibited egress of Langerhans cells from the skin to lymph nodes. Our results demonstrated that fingolimod showed effectiveness for IMQ-induced psoriasiform dermatitis by hindering the emigration of IL-17A-producing ?d T cells from the lymph nodes to the skin, and suggest that fingolimod is a promising candidate for the treatment of psoriasis.


Low serum 25-hydroxyvitamin D levels are associated with depression in an adult Norwegian population.
Observational and intervention studies have suggested an association between low levels of 25-hydroxyvitamin D (25(OH)D) and depressive symptoms in several subgroups of disease and age. This study tests the hypothesis in a general population. Our data are based on 10,086 persons who participated in the sixth Tromsø study carried out in 2007-2008. Depressive symptoms were evaluated using the Hopkins Symptoms Check List 10 (SCL-10) based on answers from a questionnaire. Results were adjusted for known confounders such as age, gender, body-mass index, physical exercise, alcohol, education, marital status, kidney function and chronic disease. Results are presented for smokers (N=1966) and non-smokers (N=8120) separately as our immunoassay seems to overestimate 25(OH)D levels for smokers. Low serum 25(OH)D levels were found to be a significant predictor of depressive symptoms in both smokers and non-smokers. The association seemed to be stronger in women. The odds ratios for depression in the highest 25(OH)D quartile were 0.59 (0.39-0.89) in smokers and 0.74 (0.58-0.95) in non-smokers compared with the lowest quartile. However, no conclusions with regard to causality can be drawn due to the cross-sectional design of the study.


Inhibitory effect of acteoside isolated from Cistanche tubulosa on chemical mediator release and inflammatory cytokine production by RBL-2H3 and KU812 cells.
The immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis, and sinusitis. In this study, we investigated the effect of acteoside extracted from CISTANCHE TUBULOSA (Schrenk) R. Wight on the basophilic cell-mediated allergic reaction. The effect of acteoside on β-hexosaminidase release and intracellular [Ca (2+)] I level from rat basophilic leukemia (RBL-2H3) cells was determined. Also, ELISA was used to determine the level of histamine, tumor necrosis factor (TNF)- α, and interleukin (IL)-4 on human basophilic (KU812) cells. The effect of acteoside on basophilic cell viability was determined using the 3-[4,5-dimethylthiazolyl]-2,5-diphenyltetrazolium bromide (MTT) assay. These results indicated that 0.1-10.0 µg/mL acteoside inhibits the release of β-hexosaminidase and [Ca (2+)] I influx from IgE-mediated RBL-2H3 cells. Moreover, acteoside inhibited histamine release, TNF- α, and IL-4 production in a dose-dependent manner from calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA) or compound 48/80-stimulated KU812 cells. Our findings provide evidence that acteoside inhibits basophilic cell-derived immediate-type and delayed-type allergic reactions. This is the first report describing antiallergic activity of acteoside extracted from CISTANCHE TUBULOSA on basophilic cells.


Circular RNAs: Promising biomarkers for cancer diagnosis and prognosis.
Circular RNAs (circRNAs), a group of non-coding RNA characterized by the presence of covalent bonds linking 3' and 5' ends, act as miRNA sponges to participate in the tumorigenesis. Being stable, conserved and cell- or tissue-specific, circRNAs have shown their potentials as molecular markers for cancer. Convenient and noninvasive approaches may be developed based on the roles of circRNAs to diagnose or predict the prognosis of tumors. Although most of the potential mechanisms are not entirely clear, circRNAs have shown a universal and critical role in regulating cellular processes of cancers. This review summarized the classification, formation, characteristics, detection, and biological functions of circRNAs. We proposed the possibility of using circRNAs as biomarkers for cancer diagnosis, treatment and prognosis.


A gas mixer for computer calibration of an anesthetic mass spectrometer.
To calibrate an anesthetic mass spectrometer without the use of premixed gases and vapors in cylinders, we devised a gas mixer using fixed resistances of capillary needle tubings and adjustable needle valves to dilute test gases and vapors with oxygen. The dilution ratio was determined during each calibration by diluting air with oxygen and noting the reduction in the ratio of nitrogen to oxygen. Empiric correction was made by the computer for the effects of density and viscosity, relative to air, on the flow of nitrous oxide, carbon dioxide, and the saturated vapors of the three anesthetics through the capillary resistor. The computer was programmed to control solenoid valves both for calibration and for the multiplexed sampling of operating rooms. Oxygen, nitrous oxide, and carbon dioxide were used as pure gases, and halothane, enflurane, and isoflurane were vaporized at room temperature in 50-ml vaporizers. The resulting calibrations were found to be accurate to within +/- 2%.


(2E)-2-(2-Phenyl-hydrazin-1-yl-idene)propanoic acid.
The 13 non-H atoms comprising the title compound, C(9)H(10)N(2)O(2), are close to planar (r.m.s. deviation = 0.140 Å), with maximum deviations of 0.292 (1) and 0.210 (1) Å to either side of the least-squares plane exhibited by the hy-droxy and carbonyl O atoms, respectively. The observed conformation is stabilized by an intra-molecular O-H⋯N hydrogen bond. The conformation about the N=C double bond [1.2909 (16) Å] is E. The hy-droxy OH group also forms an inter-molecular hydrogen bond to a carbonyl O atom, and the amine H atom similarly forms an N-H⋯O hydrogen bond to a second carbonyl O atom. The result is the formation of a double layer with a flat topology. Layers stack along the a-axis direction connected by C-H⋯π inter-actions.


Single-cell mapping of combinatorial target antigens for CAR switches using logic gates.
Identification of optimal target antigens that distinguish cancer cells from normal surrounding tissue cells remains a key challenge in chimeric antigen receptor (CAR) cell therapy for tumors with intratumoral heterogeneity. In this study, we dissected tissue complexity to the level of individual cells through the construction of a single-cell expression atlas that integrates ~1.4 million tumor, tumor-infiltrating normal and reference normal cells from 412 tumors and 12 normal organs. We used a two-step screening method using random forest and convolutional neural networks to select gene pairs that contribute most to discrimination between individual malignant and normal cells. Tumor coverage and specificity are evaluated for the AND, OR and NOT logic gates based on the combinatorial expression pattern of the pairing genes across individual single cells. Single-cell transcriptome-coupled epitope profiling validates the AND, OR and NOT switch targets identified in ovarian cancer and colorectal cancer.


Cytotoxicity to cultured human keratinocytes of topical antimicrobial agents.
Cultured skin grafts administered clinically for closure of burn wounds may be contacted by topically applied antimicrobial agents. A study was performed to assess whether commonly used topical antimicrobial agents are toxic to cultured human keratinocytes (HK) in vitro. Serum-free MCDB 153 culture medium containing Neosporin G.U. irrigant (Neomycin, 40 micrograms/ml-polymyxin B sulfate, 200 units/ml) and a standard tissue culture antimicrobial agent of penicillin (10,000 units/ml)-streptomycin (10,000 micrograms/ml)-amphotericin B (25 micrograms/ml) had no effect on the keratinocyte growth rates when compared to standard MCDB 153 medium without antibiotics. Medium containing Sulfamylon (mafenide acetate, 0.85%), Polysporin (polymyxin B sulfate, 1 x 10(4) units/ml-bacitracin, 500 units/ml), gentamicin sulfate (0.1%), modified Dakins solution (25%), and acetic acid (0.25%) all showed statistically significant (P less than 0.01) decreases in keratinocyte growth rates. This data suggests that commonly applied antimicrobials may not be appropriate for cultured grafts in the concentrations that are used clinically.


Prognostic value of suction drain tip culture in determining joint infection in primary and non-infected revision total hip arthroplasty: a prospective comparative study and review of the literature.
Closed suction drainage in joint replacement surgery has been considered to carry an obvious risk of bacteria invasion. Previous studies have shown controversial results regarding the role of suction drain culture in predicting artificial joint infection. Furthermore, the efficacy of the method has not been established in revision total hip or knee arthroplasty. Suction drain tips from 110 patients who underwent 73 primary and 37 revision non-infected total hip arthroplasties were prospectively cultured. The drains removed at 48 h postoperatively. The patients had an average age of 64.3 years (range 25-81 years) and followed up for 2-4 years (average 2.8 years). Positive cultures were identified in two primary (2.74%) and six revision (16.22%) total hip replacements (p = 0.017). The most frequently isolated microorganisms were Staphylococcus aureus (3 cases) and S. epidermidis (2 cases). Resistance to perioperative antibiotics was found in three out of eight isolated pathogens. However, no infection was recorded in any of the eight patients whose cultures found positive. Although suction drains are more often contaminated in revision total hip arthroplasty, the prognostic value of the method in determining joint infection is very limited and its routine use is not supported from the clinical data.


Regional lymph node staging in prostate cancer: prognostic and therapeutic implications.
The role of pelvic lymph node dissection (PLND) in prostate cancer, in which patients and to what extent it should be performed, remains a controversial topic. Preoperative diagnostic methods are more or less unreliable for lymph node staging and PLND remains the most reliable and accurate method. PLND is indicated in all patients with a PSA value >10 ng/ml and in those with a PSA <10 ng/ml if the Gleason score is > or = 7. If PLND is performed then it should always include the tissue along the external iliac vein, in the obturator fossa and on either side of the internal iliac vessels, up to where the ureter crosses the common iliac vessels. In conjunction with RRP extended PLND may increase staging accuracy, influence decision making with respect to adjuvant therapy and possibly impact outcome.


Composition and Antioxidant Activity of Anthocyanins and Non-Anthocyanin Flavonoids in Blackberry from Different Growth Stages.
The high nutritional value and unique flavor of blackberries make them a popular food choice among consumers. Anthocyanin content (AC) and non-anthocyanin flavonoid content (NAFC) are important functional components in blackberry. We tested the AC, NAFC, and antioxidant activities of two blackberry-Ningzhi 1 and Hull-during the following ripening stages: green-fruit stage (GFS), color-turning stage (CTS), reddening stage (RDS), and ripening stage (RPS). The results showed that NAFC decreased and AC increased gradually during the ripening stages. The NAFC of Hull blackberry was the highest during GFS (889.74 μg/g), while the AC of Ningzhi 1 blackberry was the highest during RPS (1027.08 μg/g). NAFC was the highest at the initial stage and gradually decreased with ripening. Anthocyanin accumulation mainly occurred during the later ripening stages. These results provide a reference for comparing the NAFC, AC, and antioxidant activity of Ningzhi 1 and Hull and their changes during different ripening stages.


A single amino acid substitution confers progesterone 6 beta-hydroxylase activity to rabbit cytochrome P450 2C3.
A cDNA encoding a naturally occurring variant of cytochrome P450 (P450) 2C3 that catalyzes the 6 beta- and 16 alpha-hydroxylation of progesterone exhibits six differences of nucleotide sequence leading to five amino acid substitutions from that encoding 2C3, a progesterone 16 alpha-hydroxylase that does not catalyze 6 beta-hydroxylation. Analysis of chimeric and mutant enzymes indicates that a Ser/Thr difference at position 364 underlies the difference between the two enzymes in 6 beta-hydroxylase activity as well as sensitivity to the inhibitor, 16 alpha-methylprogesterone. In addition, an Ile/Met difference at position 178 influences the apparent Km for progesterone. The two mutations, S364T and 1178M, together convert 2C3 to a form that exhibits kinetic properties which are similar to the 2C3v enzyme, and the reciprocal mutations in 2C3v convert it to an enzyme that resembles 2C3. Interestingly, position 364 of 2C3 maps to a substrate-contacting domain suggested by models for mammalian P450 enzymes based on the structure of P450cam. Ile178 is highly conserved among mammalian microsomal P450s with the exception of CYP4A and CYP19 enzymes which exhibit a Met at this alignment position.


Pharmacokinetics of bupropion and its metabolites in cigarette smokers versus nonsmokers.
Bupropion is an antidepressant agent that is also effective as an aid to quit cigarette smoking. A single 150-mg tablet of sustained-release bupropion hydrochloride was administered to two groups of volunteers, cigarette smokers and nonsmokers, who were matched for race, gender, body frame, age, and weight. Pharmacokinetic parameters were calculated for bupropion, and three major metabolites (hydroxybupropion and the aminoalcohol isomers, threohydrobupropion and erythrohydrobupropion, expressed as a composite total). Mean (+/-SD) values of area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-infinity), maximum concentration (Cmax), time to reach Cmax (tmax), and half-life (t1/2) of bupropion in smokers and nonsmokers, respectively, were 1,164 +/- 220 ng.hr/mL and 1,161 +/- 292 ng.hr/mL; 144 +/- 28 ng/mL and 143 +/- 39 ng/mL; 3.00 +/- 0.50 hours and 2.88 +/- 0.49 hours; and 19 +/- 5 hours and 18 +/- 3 hours. No clinically significant differences between smokers and nonsmokers or between male and female volunteers were observed for the pharmacokinetics of bupropion or its metabolites. The absence of pharmacokinetic differences indicates that dosage adjustments are not necessary when bupropion is prescribed to male and female cigarette smokers.


Evaluation of a deaf child.
One should be aware that the measurement of hearing is really an evaluation of a child's behavioural responses in a controlled setting to the presentation of various acoustic stimuli. The determination of hearing loss in some children is an ongoing process and may require more than one test session. Difficult to test children should be evaluated with as many techniques as possible for accurate cross checking of test results. Flexibility, patience and understanding and persistence are the watch words of successful hearing testing with children. For the bulk of patients who require audiological assessment however, the test battery (BOA, IMPEDANCE & BSER) approach seems to be the best available present day approach coupled with long term follow ups and careful management.