The effect of aging on the density and distribution of oral mucosal Langerhans cells.
Previous studies localizing the Langerhans cells in the hamster cheek pouch by ATPase staining have shown these cells to be distributed in a nonrandom pattern. The Langerhans cells have been found in both focal and interfocal arrangements. In this study we utilized two groups, Group 1 (six animals), was 5-6 weeks old, and Group 2 (six animals), was 78-80 weeks old. The Langerhans cells were stained for ATPase, following the epidermal stripping of the cheek pouch with 1% glacial acetic acid. The number of Langerhans was statistically decreased interfocally and there was a decrease in the number of focal aggregations, while there was a concomitant increase in the number of Langerhans cells in each unit. These alterations in the density and distribution of the Langerhans cells may suggest a lowering of the immune response, and increase susceptibility to irritants and carcinogenic agents in the oral cavity.


Chronoamperometric determination of lead ions using PEDOT:PSS modified carbon electrodes.
A new simple chronoamperometry methodology was developed for the ultrasensitive determination of lead ions using a PEDOT:PSS coated graphite carbon electrode. The polymer was directly coated on a graphite carbon electrode and characterized using simple cycle voltammetric measurements. The presence of lead ions induced a cathodic peak starting at -550 ± 10 mV vs. Ag/AgCl, and an anodic peak starting at -360 ± 10 mV vs. Ag/AgCl. Electroaccumulation of lead ions onto the PEDOT:PSS modified electrode was performed at -650 mV vs. Ag/AgCl for 30s in a pH 2.2 hydrochloric acid solution. Chronoamperometry measurements were carried out at -350 mV vs. Ag/AgCl allowing the oxidation of accumulated lead. Using this method, lead ions were detected for concentrations ranging between 2.0 nmol L(-1) and 0.1 μmol L(-1) (R(2)=0.999). The detection limit was calculated to be 0.19 nmol L(-1) and the quantification limit of 0.63 nmol L(-1). The method was shown to be highly precise and sensitive, negligible interference was detected from other metal ions. The proposed method was successfully applied for the detection of lead ions in vegetables.


Bladder involvement with lymphoma.
Two case reports of different ways lymphoma involves the bladder are presented, with a brief updating of diagnosis and management. Symptoms and cystoscopic and roentgenographic findings are discussed. While primary lymphoma of the bladder has been reported in a few instances, the disorder is generally considered a widespread lymphatic disease.


Prevalence of and factors associated with dental service utilization among early elderly in Lithuania.
There is no recent information about dental service utilization (DSU) among elderly in Lithuania. We examined DSU and its associated factors in Lithuanian early elderly based on the Andersen's behavioural model. The cross-sectional study conducted in 2017-2019 included a nationally representative stratified sample of 370 Lithuanian early elderly aged 65-74 years (response rate of 54.5%). Information on predisposing factors (age, sex, nationality and education), enabling factor (residence), need-based factors (status of teeth, oral pain or discomfort, and dry mouth), general health, personal health practices and perceived stress was obtained from a structured, self-administered questionnaire. Clinically-assessed need-based factors included number of missing teeth and dental treatment need. Multivariable Poisson regression with robust variance estimates was used. A total of 239 study participants (64.6%) reported a dental visit during the last year and 338 (91.4%) needed dental treatments. A higher level of education (adjusted prevalence ratio [aPR] = 1.21, 95% confidence interval [CI]:1.04-1.40), pain or discomfort in teeth/mouth (aPR = 1.35, 95%CI: 1.13-1.62) and lower number of missing teeth (aPR = 0.99, 95%CI: 0.98-1.00) were associated with DSU. Even though majority of early elderly needed dental treatments, only two-thirds visited a dentist during the last year. Predisposing and need-based factors were significant predictors of having a dental visit in the last year. A national oral health program for Lithuanian elderly with the focus on regular preventive dental check-ups is needed. More studies, both quantitative and qualitative, are warranted to investigate in depth the barriers for DSU among elderly in Lithuania.


Hepatocellular adenomas in men: MRI findings in four patients.
To demonstrate both MRI and histopathological findings of hepatocellular adenomas (HCAs) in men. HCAs in four men are reported. All patients underwent MR studies at 1.5T including serial gadolinium-enhanced gradient echo imaging. Three men had solitary non-hemorrhagic adenomas that exhibited a uniform capillary blush with no central scar, and uniform fading of the tumor to near isointensity with the liver parenchyma by one minute. One of the subjects had uniform fat content as shown by uniform low signal on out-of-phase images. One patient had a solitary hemorrhagic adenoma that measured 17 cm in diameter and was heterogeneous on all sequences. Two of the four patients had a history of anabolic steroid use, and in the other two patients no underlying explanation for the tumor was found. Although three of the four patients had tumors that exhibited uniform homogeneous tumor blush and rapid fading of enhancement, because HCAs are rare in men and resemble hepatocellular carcinoma (HCC) in appearance, our findings suggest that histological confirmation of HCAs may not be avoidable in men.


Cryptococcal meningitis with atypical paradoxical inflammatory reactions after antifungal treatment in acquired immune deficiency syndrome: A case report.
Cryptococcal meningitis (CM) is a life-threatening disease that primarily affects patients with human immunodeficiency virus (HIV). Antifungal therapy with antiretroviral treatment (ART) usually leads to the clinical remission of CM; however, in some cases, these treatments exacerbate intracranial inflammation because of paradoxical inflammatory reaction or immune reconstitution inflammatory syndrome (IRIS). Here we report two CM cases that presented atypical clinical courses attributed to paradoxical inflammatory reactions. The first case was a 43-year-old man with headache and vertigo diagnosed with CM and HIV. The patient's CM not only was refractory to the antifungal combination therapy of liposomal amphotericin B (L-AMB) and fluconazole (FLCZ) but suddenly worsened because of a paradoxical inflammatory reaction after 18 days of treatment. He passed away from brain herniation on day 23. The second case was a 43-year-old man diagnosed with CM and HIV. After receiving antifungal therapy and ART, the patient's status was stable for more than 3 years with undetectable HIV-RNA. He suddenly presented with brain inflammation and was diagnosed with IRIS due to CM (CM-IRIS). His brain lesions were migratory and refractory to various antifungal therapies such as L-AMB, FLCZ, flucytosine, and intrathecal amphotericin B. Although the cryptococcal antigen in the patient's cerebrospinal fluid gradually diminished after continuous antifungal therapies, his cognitive function declined, and right hemiparesis persisted. These two cases of CM presented atypical clinical courses, presumably because of paradoxical inflammatory reactions. It should be noted that the onset of CM-IRIS may not necessarily depend on the timing of ART initiation.


Trace metals in tissues of gray whale (Eschrichtius robustus) carcasses from the Northern Pacific Mexican Coast.
Samples of liver, lung, heart, muscle, and blubber tissue from the carcasses of juvenile gray whales (Eschrichtius robustus) found stranded on the coast off the Sea of Cortez, México were analyzed for a range of trace metals (Cu, Fe, Zn, Mn, Ni, Pb, and Cd). The highest concentrations of copper, iron, zinc, and manganese were found in liver; nickel and lead in heart, and cadmium in kidney. In all tissues analyzed, iron, zinc and copper were present in the highest concentrations; however, some whales also showed high levels of cadmium in the kidney which could be related to their diet. Elevated concentrations of copper were found only in the liver of one whale. In general, where low levels of iron were found in the liver, they were associated with poor nutrition. Lead, nickel, manganese and zinc levels in liver were within the normal range, indicating that these whales had not been exposed to high levels of these metals.


The Impact of Immunosuppression and Autoimmune Disease on Severe Outcomes in Patients Hospitalized with COVID-19.
Immunosuppression (IS) and autoimmune disease (AD) are prevalent in patients with severe coronavirus disease 2019 (COVID-19), but their impact on its clinical course is unknown. We investigated relationships between IS, AD, and outcomes in patients hospitalized with COVID-19. Data on consecutive admissions for COVID-19 were extracted retrospectively from medical records. Patients were assigned to one of four cohorts, according to whether or not they had an AD (AD and NAD) or were immunosuppressed (IS and NIS). The primary endpoint was development of severe acute respiratory distress syndrome (ARDS); secondary endpoints included death, and a composite of mechanical ventilation (MV) or death. A total of 789 patients were included: 569 (72.1%) male, 76 (9.6%) with an AD, and 63 (8.0%) with IS. Relative to the NIS-NAD cohort, patients in the IS-AD cohort had a significantly reduced risk of severe ARDS (adjusted hazard ratio [aHR] 0.42; 95% confidence interval [CI] 0.23-0.80; p = 0.008). No significant relationships between IS or AD status and either death or the composite of MV and death were identified, although a trend towards higher mortality was identified in the IS-NAD cohort (aHR vs NIS-NAD 1.71; 95% CI 0.94-3.12; p = 0.081). Patients in this cohort also had higher median serum levels of interleukin-6 compared with IS-AD patients (98.2 vs 21.6 pg/mL; p = 0.0328) and NIS-NAD patients (29.1 pg/mL; p = 0.0057). In conclusion, among patients hospitalized with COVID-19, those receiving immunosuppressive treatment for an AD may have a reduced risk of developing severe ARDS.


Natural history of propionic acidemia in the Amish population.
Propionic acidemia (PA) in the Amish is caused by a homozygous pathogenic variant (c.1606A>G; p.Asn536Asp) in the PCCB gene. Amish patients can have borderline or normal newborn screening (NBS) results and symptoms can present at any time from early childhood to mid-adulthood. Early diagnosis and initiation of treatment for PA in the non-Amish population improves patient outcomes. Here, we present data from a retrospective chart review of Amish patients diagnosed with PA from three different medical centers in order to document its natural history in the Amish and determine the influence of treatment on outcomes in this population. A total of 38 patients with average current age 19.9 years (range 4y-45y), 57.9% males, were enrolled in the study. Fourteen patients (36.8%) were diagnosed with a positive newborn screening (NBS) while 24 patients (63.2%) had negative or inconclusive NBS or had no record of NBS in their charts. These 24 patients were diagnosed by screening after a family member was diagnosed with PA (14; 58.3%), following a hospitalization for metabolic acidosis (5; 20.8%), hospitalization for seizures (3; 12.5%) or via cord blood (2; 8.3%). The majority of patients were prescribed a protein restricted diet (32; 84.2%), including metabolic formula (29; 76.3%). Most were treated with carnitine (35; 92.1%), biotin (2; 76.3%) and/or Coenzyme Q10 (16; 42.1%). However, treatment adherence varied widely among patients, with 7 (24.1%) of the patients prescribed metabolic formula reportedly nonadherent. Cardiomyopathy was the most prevalent finding (22; 63.2%), followed by developmental delay/intellectual disability (15; 39.5%), long QT (14; 36.8%), seizures (12; 31.6%), failure to thrive (4; 10.5%), and basal ganglia strokes (3; 7.9%). No difference in outcome was obvious for those diagnosed by NBS and treated early with dietary and supplement management, especially for cardiomyopathy. However, this is a limited retrospective observational study. A prospective study with strict documentation of treatment adherence and universal screening for cardiomyopathy and long QT should be conducted to better study the impact of early detection and treatment. Additional treatment options such as liver transplantation and future therapies such as mRNA or gene therapy should be explored in this population.


[Secondary hypertension in women].
The two main non-iatrogenic causes of secondary hypertension in women of childbearing age are primary aldosteronism and renal fibromuscular dysplasia. It is recommended to look for a secondary hypertension in women who remain hypertensive three months after pregnancy, in patients under 40 years of age or in patients with a grade 3 HTN (BP≥180/110mm Hg) (Professional agreement). It is suggested that the initial assessment of a secondary HTN in women is performed by a HTN specialist; it will include an assessment of renin and aldosterone concentrations and an angio-CT of the renal arteries (or angio-MRI if contraindicated) (Grade C - Class 2).


Fetal aortic valvuloplasty: first report of two cases from Saudi Arabia.
Fetal aortic stenosis may progress to hypoplastic left heart syndrome (HLHS), which carries a poor prognosis. We report two infants with fetal aortic stenosis successfully treated with fetal aortic valvuloplasty (FAV) using balloon dilatation. Of five fetuses with aortic stenosis fulfilling the FAV criteria of severe aortic stenosis with a left ventricular length Z-score of ≥ - 2, retrograde flow in the transverse aortic arch, left-to-right flow across the foramen ovale, monophasic mitral inflow, and significant left ventricular dysfunction, we obtained permission for FAV in two fetuses. FAV was performed successfully under echocardiographic guidance using balloon dilatation. Both fetuses survived to birth. During FAV, mild pericardial effusion developed when introducing the stylet needle in the second fetus, and this resolved within 48 h. No intraprocedural complications occurred in the first patient, and no maternal complications occurred. The first infant underwent the Ross procedure after birth and is currently 7 years old and doing well. The second patient underwent aortic and mitral valve repair with endocardial fibroelastosis resection approximately 2 weeks after birth, which temporarily addressed the mitral valve stenosis; high doses of inotropes were subsequently required. The infant died of sepsis at 2 months of age. FAV using balloon dilatation to treat fetal aortic stenosis was successful in our two patients, with subsequent neonatal biventricular repair resulting in long-term survival in one patient and death secondary to sepsis in the second patient.


Sarcomeric visco-elasticity of chemically skinned skeletal muscle fibres of the rabbit at rest.
The giant muscle protein titin (connectin), contained in the gap filament that connect a thick filament to the Z-line in a sarcomere, is generally considered to be responsible for the passive force (tension) and visco-elasticity in resting striated muscle. However, whether it can account for all the features of the resting tension response remains unclear. In this paper, we examine the basic features of the 'sarcomeric visco-elasticity' in a single resting mammalian muscle fibre and attempt to account for various tension components on the basis of known structural features of a sarcomere. At sarcomere length of approximately 2.6 microm, the force response to a ramp stretch of 2-5% is complex but can be resolved into four functionally different components. The behaviour displayed by the components ranges from pure viscous type (directly proportional to stretch velocity, ranging from 0.1 to 30 lengths s(-1)) to predominantly elastic type (insensitive to stretch velocity at 1-2 s time scale); simulations show two components of visco-elasticity with characteristically different relaxation times. The velocity-sensitive components (only) are enhanced by filament lattice compression (dextran - 500 kD) and by increased medium viscosity (dextran - 12 kD); also, the relaxation time of visco-elasticity is longer with increased medium viscosity. Amplitude of all the components and the relaxation time of visco-elasticity are increased at longer sarcomere length (range approximately 2.5 - 3.0 microm). The study, and quantitative analyses, extend our previous work on intact muscle fibres and suggest that the velocity-sensitive tension components in intact sarcomere arise from interactions between sarcomeric filaments, filament segments and inter-filamentary medium; the two components of visco-elasticity arise from distinct regions of titin (connectin) molecules.


Comparative reproducibility of the noninvasive ultrasound methods for the assessment of vascular function.
The aim of this work was to assess the reproducibility of ultrasound parameters of vascular function, since these measurements are currently recommended by the guidelines for the evaluation of the cardiovascular risk. Twenty subjects (51 ± 17 years, 11 men) had vascular ultrasound (Aloka Prosound α10) performed by two observers, at the level of the right common carotid artery for assessment of intima-media thickness (IMT), "wall tracking", and "wave-intensity analysis", and at the level of the right brachial artery for the assessment of flow-mediated dilation (FMD). Wave intensity is a hemodynamic index, evaluating ventriculo-arterial interaction and can be measured in real time by a double-beam ultrasound technique through simultaneous recording of carotid arterial blood flow velocity and diameter. Carotido-femoral pulse wave velocity (PWV) was determined using the Complior method. Intra- and inter-observer reproducibility was assessed during a first session, when three consecutive acquisitions were made (first observer → second observer → first observer); repeatability was evaluated 1 week later (second observer). The most reproducible and repeatable parameters were PWV (intraobserver ±3.3%, interobserver ±2.6%, repeatability ±5.6%) and IMT (±3.7, ±4.3, ±4.9%, respectively). Intraobserver reproducibility for arterial stiffness and ventriculo-arterial coupling parameters was the highest for the beta index (±3.8%), and the lowest for the second systolic peak (±22.4%). Interobserver reproducibility and repeatability varied between very good for the wave speed (±5.5 and ±4.3%), and unsatisfactory for the negative area (±31.8 and ±38.6%). FMD had good reproducibility (intraobserver ±11.6%, interobserver ±8%, repeatability ±7%), whereas augmentation index had only satisfactory results (±17.8, ±8.4, ±23.8%, respectively). Only some parameters of vascular function have good reproducibility and repeatability, better or similar to other ultrasound methods and, therefore, these are ready to be used in routine clinical practice.


The ventral spino-olivocerebellar system in the cat. III. Functional characteristics of the five paths.
1. Five spino-olivocerebellar paths ascending through the ventral funiculus (VF-SOCPs) with different projection zones in the cerebellar cortex have been distinguished (Oscarsson and Sjöuld, 1977). The paths are denoted the a-, b1-, b2-, c1- and c3-VF-SOCPs according to the labelling of the projection zones. The functional organization of these paths has now been investigated. 2. All five paths are activated by the flexor reflex afferents from wide receptive fields (one or more limbs). Distal nerves are more effective in evoking responses than proximal nerves. 3. The a-, c1- and c3-paths are activated from the ipsilateral hindlimb only. The b1- and b2-paths are activated bilaterally from the forelimbs and hindlimbs, respectively. 4. The a-, b1- and b2-paths have long segmental delays indicating a polysynaptic linkage between the primary afferents and the tract neurones, whereas the c1- and c3-paths have short delays demonstrating a monosynaptic linkage. 5. The neurones giving origin to the paths are situated within a few segments of the dorsal root entrance. The axons cross the midline, ascend through the contralateral ventral funiculus, and activate the olivary neurones monosynaptically. 6. The spino-olivary tract of the c3-path has an upper conduction velocity of 30 m/s, whereas the other paths have upper conduction velocities of 40--45 m/s. 7. The segmental delay of the b1-VF-SOCP is much longer (mean 8.7 ms) than that of the b2-VF-SOCP (mean 3.9 ms). As a result simultaneous stimuli to the hindlimbs and forelimbs are signalled to reach the cerebellar cortex at the same time. 8. It is suggested that the information carried by the different paths is concerned with the segmental motor control.


Selective effects of tocainide in canine acute myocardial infarction.
We examined the in vivo electrophysiologic effects of tocainide in canine acute myocardial infarction. We compared the effects of tocainide in infarcted and non-infarcted zones. The left anterior descending coronary artery of 8 dogs was ligated and bipolar ventricular electrograms were recorded from a needle electrode placed transmurally in the infarcted zone and from electrodes in the non-infarcted zone. Conduction intervals were measured from the onset of the limb lead QRS to the major deflection of the recorded electrograms in the infarcted and non-infarcted zones. Effective refractory periods were also determined. Measurements were made before, during and after intravenous infusion of tocainide in therapeutic doses 2 hours after infarct. Tocainide prolonged conduction intervals by 26-31% in the infarcted zone at peak (P less than 0.001), but by only 6% in the non-infarcted zone. Similarly, tocainide prolonged the effective refractory period by 27% (P less than 0.001) on the infarcted, but by 8% the non-infarcted zone. Tocainide had very slight effects on QRS duration. The present study shows that tocainide had selective effects in the infarcted zone on both conduction and effective refractory period. These selective effects may explain its antiarrhythmic effects in acute myocardial infarction.


Prospective, comparative study of cemented, smooth-surfaced titanium stems and polish-surfaced, stainless steel stems at a minimum follow-up of 10 years.
Excellent results have been reported with cemented total hip arthroplasty (THA) using both smooth-surfaced and polished-surfaced stems. However, the superiority of polished-surfaced over smooth-surfaced in cemented THA, or vice versa, is still debated. Forty-six smooth-surfaced, triple-tapered, titanium-alloy stem (Group C) and 46 Exeter stems (Group T) have been fixed consecutively at different periods at our institute and prospectively evaluated clinically and radiologically. The area and location demonstrating cortical hypertrophy (CH) was measured in the serial radiograph and compared. The mean postoperative follow-up period was 12.4 years for group C and 10.8 years for group T. No significant difference of clinical results was found between both groups. CH was observed in 8 hips (18.6%) of group C and in 7 hips (17.1%) of group T (NS). Among the hips in which distribution of CH was observed at the medial side, a significantly low proportion belonged to group C (adjusted standardized residual = - 2.3) and a significantly high proportion belonged to group T (adjusted standardized residual = 2.3). The largest area of CH found in each group was 166.1 mm2 in group C and 227.6 mm2 in group T (NS). The peak location of CH was 100.4% in group C and 84.3% in group T (p = 0.02). Medium-term results of both stems were excellent. CH was observed medially and proximally in group T and laterally and distally in group C.


Functional domains of the rDNA promoter display a differential recognition in Leishmania.
A construct containing the RNA polymerase I promoter of Leishmania (L.) amazonensis, driving the expression of cloramphenicol acetyl transferase reporter gene, was better recognised by heterologous hosts species Leishmania (L.) major and Leishmania (L.) mexicana than by the homologous host L. (L.) amazonensis. The rDNA promoter domains responsible for recognition were functionally mapped. The core domain (-74 to +170) conferred a barely equal recognition on homologous or heterologous cells, slightly favouring to the later. Addition of the upstream domain (-196 to -74) repressed the expression in all cells tested. The third domain, consisting of repeated elements (upstream to -196 in L. (L.) amazonensis), enhanced by about 20 times the core activity of homologous species and by about 40 times the heterologous ones. Gel mobility shift patterns generated by the binding of core sequence of L. (L.) amazonensis to nuclear extracts of the Leishmania species suggested that the rDNA transcriptional machinery is a complex DNA-protein association particular for each species. A model is proposed to explain the mechanism and possible interactions of transcription machinery in the regulation of rDNA expression in phylogenically related organisms.


Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus.
Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesized to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluA2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluA2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluA2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation.


Chemical composition and deterioration mechanism of Pleurotus tuoliensis during postharvest storage.
Pleurotus tuoliensis is a popular edible and medical mushroom, but it is highly perishable during postharvest storage. The quality parameters, chemical composition, malondialdehyde (MDA) concentration, and activity of metabolic enzymes were studied during 12 days of storage at 4 °C and 6 days of storage at 25 °C. Degradation was well described by changes in quality parameters, losses in nutritional value, increased metabolic enzyme activity, the accumulation of MDA concentrations, and the increase of total phenolic (TP) content. The phenylalanine ammonia lyase (PAL) significantly positively correlated with TP, which suggested an underlying mechanism of browning that the increased PAL activity stimulates the biosynthesis of phenols through the phenylalanine pathway. These results suggest that increased activity of laccase, lipoxygenase, PAL, TP and MDA accumulation, together with polysaccharide degradation, are the main factors involved in the deterioration of P. tuoliensis during storage.


Effects of treadmill inclination on the gait of individuals with chronic hemiparesis.
To analyze the effects of electric treadmill inclination on the gait of individuals with chronic hemiparesis. Descriptive, observational study. Laboratory for human movement analyses of UFRN. Individuals (N=18) with a mean age of 55.3 ± 9.3 years and a lesion time of 36 ± 22.8 months. Not applicable. Subjects were assessed for functional independence (FIM) and balance (Berg Balance Scale). Spatial-temporal variables were observed as well as the angular variation of the hip, knee, and ankle in the sagittal plane, while the individuals walked on the treadmill at 3 different inclinations (0%, 5%, and 10%). There was an increase in stance time between 0% and 5% (0.83 ± 0.21 vs 0.87 ± 0.20; P=.011) and 0% and 10% (0.83 ± 0.21 vs 0.88 ± 0.23; P=.021). The other spatial-temporal variables did not change. During initial contact there was an increase in the hip, knee, and ankle flexion angle. An increase in hip amplitude was also observed between 0% and 10% (37.83 ± 5.23 vs 41.12 ± 5.63; P<.001) and 5% and 10% (38.80 ± 5.96 vs 41.12 ± 5.63; P=.002) and in knee amplitude between 0% and 10% (47.51 ± 15.07 vs 50.30 ± 12.82; P=.040), as well as decreased hip extension and increased dorsiflexion. Treadmill inclination promoted angular alterations such as an increase in hip, knee, and ankle angle during initial contact and the swing phase and an increase in the amplitude of movement of the hip and knee, as well as an increase in stance time of the paretic lower limb.


Minimally invasive treatment of mid-low rectovaginal fistula: a transanal endoscopic surgery study.
Treatment of rectovaginal fistulas (RVFs) is extremely difficult. No standard surgical procedure is accepted worldwide. The aim of this article was to evaluate a minimally invasive procedure for the repair of mid-low rectovaginal fistula. This is a retrospective review of 17 patients who underwent minimally invasive surgery for the repair of mid-low rectovaginal fistulas (located in the lower or middle one-third of the vaginal wall) at our center between August 2016 and October 2018. The anal approach was adopted for 12 patients: 6 patients were treated directly by rectal mucosal advancement flap (RMAF) with transanal endoscopic surgery (TES), while the other 6 patients underwent initial TES exploration followed by RMAF procedure under direct vision. The vaginal approach was adopted for 5 patients: 3 patients were treated under TES directly and the other 2 were treated under direct vision after initial TES exploration. A total of 9 (52.94%) patients received diverting ileostomy-5 anal approach patients and 4 vaginal approach patients. Median age of the patients was 46 years (range 10-76 years), and median BMI was 21.9 (range 17.9-28.1). Median operative time was 75 min (range 60-120 min), and median duration of postoperative hospital stay was 8 days (range 6-15 days). Recurrence was seen in 3/12 anal approach patients vs. 0/5 vaginal approach patients. Both the median preoperative and the median postoperative Wexner score were 0 (range 0-2). The median follow-up time was 8 months (range 2-24). No severe complications occurred in any patient. The TES procedure for the treatment of mid-low rectovaginal fistulas avoids any incision of the abdomen and perineal area and appears to be a safe and feasible procedure. This minimally invasive technique is still evolving and is likely to gain wide acceptance in the near future.


(Pro)renin Receptor Blockade Ameliorates Cardiac Injury and Remodeling and Improves Function After Myocardial Infarction.
The (pro)renin receptor [(P)RR] is implicated in the pathogenesis of cardiovascular disease. We investigated the effects of (P)RR blockade after myocardial infarction (MI) in a mouse coronary-ligation model. Mice underwent sham control surgeries (n = 8) or induction of MI followed by 28 days' treatment with a vehicle control (n = 8) or (P)RR antagonist (n = 8). Compared with sham control subjects, MI + vehicle mice demonstrated reduced left ventricular (LV) ejection fraction (LVEF: P < .001) and fractional shortening (P < .001), and increased LV end-systolic and -diastolic volumes (LVESV: P < .001; LVEDV: P < .001) 28 days after MI. In addition, MI decreased LV posterior wall and septal diameters (both P < .001), increased heart weight-body weight ratios (P < .05), LV collagen deposition, and cardiomyocyte diameter (both P < .001), and up-regulated collagen 1 (P < .01) and β-myosin heavy chain (β-MHC: P < .05) mRNA. Compared with MI + vehicle mice, (P)RR antagonism after MI reduced infarct size (P < .01), improved LVEF (P < .001), fractional shortening (P < .001), and stroke volume (P < .05), and decreased LVESV (P < .001) and LVEDV (P < .001). (P)RR antagonism also reversed MI-induced transmural thinning (P < .001) and reduced LV fibrosis (P < .01), cardiomyocyte size (P < .001), and ventricular collagen 1 (P < .01), β-MHC (P = .06), transforming growth factor β1 (P < .01), and angiotensin-converting enzyme (P < .05) expression. The present study found that (P)RR blockade after MI in mice ameliorates infarct size, cardiac fibrosis/hypertrophy, and cardiac dysfunction and identifies the receptor as a potential therapeutic target in this setting.


[Talcosis as an occupational disease. Case histories].
The case are examined of 49 people (45 males, 4 females), mean age 60 exposed to the risk of talc inhalation in a talc processing and packing factory who were granted disability pensions by the Turin I.N.A.I.L. on the grounds of silicosis in 1975-86. Radiologically the cases presented small round patches in 28 subjects small irregular ones in 15 and large patches in 6. In functional terms, examination revealed ventilatory insufficiency that was primarily restrictive in 17 cases, obstructive in 11 and mixed in 21.


Trends in searching for new cognition enhancing drugs.
1. The great interest for new drugs having cognition enhancing properties is highlighted, particularly for the treatment of dementia of Alzheimer type. 2. A short survey is given of the pharmacological models currently used to mimic cognitive impairment. 3. A systematic survey is given of the major cognition enhancing drugs and of the new compounds showing activity.


Liver X receptors and fat cell metabolism.
Liver X receptors (LXRs) are members of the nuclear receptor family and are present in two isoforms, α and β, encoded by two separate genes. Originally described in the liver, LXRs have in the last 15 years been implicated in central metabolic pathways, including bile acid synthesis, lipid and glucose homeostasis. Although the vast majority of studies have been performed in non-adipose cells/tissues, results in recent years suggest that LXRs may have important modulatory roles in adipose tissue and adipocytes. Although several authors have published reviews on LXR, there have been no attempts to summarize the effects reported specifically in adipose systems. This overview gives a brief introduction to LXR and describes the sometimes-contradictory results obtained in murine cell systems and in rodent adipose tissue. The so far very limited number of studies performed in human adipocytes and adipose tissue are also presented. It should be apparent that although LXR may impact on several different pathways in metabolism, the clinical role of LXR modulation in adipose tissue is still not clear.


Analysis of penetration depth and healing process of a needleless laser lancet using swept-source optical coherence tomography.
Needleless laser lancets have been used to reduce needle pain in people who undertake self-monitoring of blood glucose (SMBG). Although clinical trials have been conducted to understand the degree of pain associated with the developed laser blood sampling device, it is only judged by the patients' subjective judgment. This study aimed to analyze the performance and healing process of a needleless laser lancet. In particular, the penetration depth and healing process of a conventional lancet and a needleless laser lancet were quantitatively analyzed using a swept-source optical coherence tomography (SS-OCT) system. To reduce unnecessary animal sacrifice, pig skin was used to establish and set the conditions for needleless laser lancets (wavelength of 2.94 μm; LMT-5000; Lameditech), and the penetration depth and healing process were quantitatively assessed at 0, 6, 9, and 16 h after laser (energy, 150-270 mJ in stages; voltage, 7.4 Vdc ; pulse width, approximately 200 microsecond) irradiation using 7-week-old male BALB/c nude mice. The penetration depth and healing process were measured using homemade SS-OCT, and histopathological examination was performed to observe the healing process. Four 7-week-old male BALB/c nude mice were tested at intensity levels of 1-3 using a needleless laser lancet and compared with the experimental values using a conventional lancet. After the lancet test, the diameter and depth of the puncture were measured using SS-OCT and the healing process was confirmed using SS-OCT and pathological slides. The puncture diameter of the needleless laser lancet was about 0.5 mm regardless of the level. In addition, the average depths at Levels 1, 2, and 3 of the measured needleless laser lancet were approximately 1.05, 1.18, and 1.52 mm, respectively, and the last common lancet was approximately 0.9 mm. In addition, the healing process of the needleless laser lancet and conventional lancet was confirmed through the SS-OCT system. After using the needleless laser lancet, quantitative indicators such as the diameter of puncture, penetration depth, and healing process were confirmed through two-dimensional and three-dimensional images of the homemade SS-OCT system and microscopic imaging of pathological slides.


Tissue Heavy Metals in Liver Diseases.
Our objective was to determine the levels of heavy metals, oxidants, and antioxidants in liver tissue of patients with chronic liver disease (CLD) compared with healthy living liver donors (LLDs). We obtained liver specimens from patients undergoing liver transplant for CLD. Samples were also obtained from LLDs. Biochemical analyses were performed on all samples, and the levels of liver tissue, heavy metal, and oxidant-antioxidants biomarker levels in patients with CLD were compared with those measured in LLDs. One hundred and eighteen individuals were included for analyses. Fifty-nine were patients with CLD, and 59 were LLDs. The median levels of liver tissue of superoxide dismutase (P = .009), glutathione peroxidase (P = .042), total oxidant status (P = .006), oxidative stress index (P < .001), and copper (P = .035) were prominently more elevated in CLD than LLDs. On the other hand, the median levels of liver tissue of cadmium (P < .001), selenium (P = .042), and zinc (P < .001) levels were more elevated in the LLDs than patients with CLD. The 2 groups were similar in terms of total antioxidant status, manganese, arsenic, and lead levels. Superoxide accumulation in the liver was higher in patients with CLD. Concerning heavy metals, only the median tissue copper was elevated in patients with CLD with higher Cu/Zn ratio. Cadmium, selenium, and zinc were significantly higher in the healthy LLDs.


A bionic solar-driven interfacial evaporation system with a photothermal-photocatalytic hydrogel for VOC removal during solar distillation.
Solar-driven interfacial evaporation is a breakthrough water treatment method because it harvests solar energy for producing clean water. However, evaporated volatile organic compounds (VOCs) in distilled water are the greatest barrier to this technology. Herein, a bionic solar-driven interfacial evaporation system integrating photothermal and photocatalysis technology was developed based on a new combined material TiO2/Ti3C2/C3N4/PVA (TTCP) hydrogel as an evaporator. Phenol-contaminated water, especially actual water (seawater, lake water and reclaimed water), is used to evaluate the water evaporation and VOC photocatalytic degradation performance. The results show that the evaporation rate of TTCP hydrogel was 1.54 kg m - 2h - 1 under 1 kW m - 2, and the removal efficiency of phenol ranged from 69.4% to 100% at different concentrations (1-50 mg/L) in source water. Particularly, the capacity of the bionic evaporator was first evaluated for different types of actual water. Despite the initial TOC (38.12-57.93 mg/L) and total dissolved solids (TDS, 1.35×103-8.78×104 mg/L) for seawater, lake water and reclaimed water being very different, the TDS was decreased by more than two orders of magnitude, below the US EPA drinking water standard (500 mg/L). The maximum TOC removal efficiency reached 80% under simulated sunlight (1 kW m - 2), which is comparable to the efficiency of the ultrafiltration technique previously reported except for seawater. Furthermore, real sunlight (average solar irradiation ∼0.82 kW m- 2) was used to assess the practicability. The bionic evaporator can produce 0.72 kg m - 2h - 1 of vapor from reclaimed water and run with steadily efficient TDS and TOC removals, reaching 99% and 74%, respectively. This technology, as a small, decentralized water treatment method, is a good choice for remote and off-grid areas.


ABCB1 polymorphisms correlate with susceptibility to adult acute leukemia and response to high-dose methotrexate.
The aim of this study is to investigate the association of ABCB1 polymorphisms with susceptibility to adult acute leukemia, and the influence of ABCB1 polymorphisms on the efficacy of high-dose methotrexate (HDMTX). ABCB1 polymorphisms in 178 acute leukemia patients (case group) and 150 healthy subjects (control group) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. All patients received HDMTX therapy. Correlation analysis was performed to explore the associations of ABCB1 polymorphisms with MTX concentration and efficacy of MTX therapy. All statistical analyses were conducted with SPSS 19.0 software. The frequency of TT genotype and T allele on ABCB1 3435C > T in case group were significantly higher than the control group (P < 0.05), while no statistical difference between the two groups was observed in genotypic distribution and allele frequencies of ABCB1 2677G > T/A (P > 0.05). Furthermore, 24-h MTX concentration of patients carrying TT and TA genotypes on 2677G > T/A was higher than carriers with other genotypes (P < 0.05), and 24-h MTX concentration of patients with TT and CT genotypes on 3435C > T was also apparently higher than carriers with CC genotype (P < 0.05). In addition, ABCB1 polymorphisms were connected with increased risk of liver dysfunction and infection (P < 0.05). Complete remission (CR) rate in patients carrying GG on 2677G > T/A was markedly lower than carriers with non-GG genotype (P < 0.05). ABCB1 3435C > T polymorphisms may be associated with susceptibility to acute leukemia, and ABCB1 polymorphisms might be a sensitive indicator for predicting efficacy of MTX therapy in the treatment of acute leukemia.


Enzyme trafficking and coclustering precede and accurately predict human breast cancer recurrences: an interdisciplinary review.
Although great effort has been expended to understand cancer's origins, less attention has been given to the primary cause of cancer deaths-cancer recurrences and their sequelae. This interdisciplinary review addresses mechanistic features of aggressive cancer by studying metabolic enzyme patterns within ductal carcinoma in situ (DCIS) of the breast lesions. DCIS lesions from patients who did or did not experience a breast cancer recurrence were compared. Several proteins, including phospho-Ser226-glucose transporter type 1, phosphofructokinase type L and phosphofructokinase/fructose 2,6-bisphosphatase type 4 are found in nucleoli of ductal epithelial cells in samples from patients who will not subsequently recur, but traffic to the cell periphery in samples from patients who will experience a cancer recurrence. Large coclusters of enzymes near plasmalemmata will enhance product formation because enzyme concentrations in clusters are very high while solvent molecules and solutes diffuse through small channels. These structural changes will accelerate aerobic glycolysis. Agglomerations of pentose phosphate pathway and glutathione synthesis enzymes enhance GSH formation. As aggressive cancer lesions are incomplete at early stages, they may be unrecognizable. We have found that machine learning provides superior analyses of tissue images and may be used to identify biomarker patterns associated with recurrent and nonrecurrent patients with high accuracy. This suggests a new prognostic test to predict patients with DCIS who are likely to recur and those who are at low risk for recurrence. Mechanistic interpretations provide a deeper understanding of anticancer drug action and suggest that aggressive metastatic cancer cells are sensitive to reductive chemotherapy.


Cognitive deficits in marijuana users: Effects on motivational enhancement therapy plus cognitive behavioral therapy treatment outcome.
Clinical variables that affect treatment outcome for marijuana-dependent individuals are not yet well understood, including the effects of cognitive functioning. To address this, level of cognitive functioning and treatment outcome were investigated. Twenty marijuana-dependent outpatients were administered a neuropsychological battery at treatment entry. All patients received 12 weekly individual sessions of combined motivational enhancement therapy and cognitive behavioral therapy. The Wilcoxon Exact Test was used to compare cognitive functioning test scores between completers and dropouts, and the Fisher Exact Test was used to compare proportion of negative urines between those with higher and lower scores on the cognitive tests. Marijuana abstinence was unrelated to cognitive functioning. However, dropouts scored significantly lower than completers on measures of abstract reasoning and processing accuracy, providing initial evidence that cognitive functioning plays a role in treatment retention of adult marijuana-dependent patients. If supported by further studies, the findings may help inform the development of interventions tailored for cognitively impaired marijuana-dependent patients.


Overexpression of the ZIP1 zinc transporter induces an osteogenic phenotype in mesenchymal stem cells.
Zinc is an essential trace element that is involved in diverse metabolic and signaling pathways. Zinc deficiency is associated with retardation of bone growth. Previous in vitro studies have suggested a direct effect of zinc on both the proliferation and differentiation of osteoblast-like cells. However, the mechanisms for uptake of zinc into osteoblasts have not been examined in detail. Several families of zinc transporters have previously been characterized in mammalian cells; such transporters function in the uptake, intracellular sequestration or efflux of zinc. In the current study, we examined zinc transport in osteoprogenitor cells and have attempted to define a functional role for a zinc transport mechanism in osteogenic differentiation. We identified at least two zinc transporters in both human mesenchymal stem cells (MSCs) and in osteoblastic cells--the ubiquitous zinc transporter, ZIP1, and LIV-1, which was previously characterized as a protein that is expressed in breast cancer cells. The subcellular localization of both these zinc transporters suggested distribution in both the plasma membrane and also diffusely in the cytoplasm. During the differentiation process of pluripotent MSCs into osteoblast-like cells, both zinc uptake and expression of the ZIP1 protein were increased. An adenoviral-mediated overexpression of ZIP1 in MSCs resulted in Alizarin-red-positive mineralization and also increased expression of specific osteoblast-associated markers, such as alkaline phosphatase, and of several osteoblast differentiation genes, including osteopontin, Cbfa1/Runx2, promyelocytic leukemia zinc finger and bone sialoprotein. An siRNA-mediated reduction of ZIP1 protein expression in MSCs caused decreased zinc uptake and inhibition of osteoblastic differentiation under osteogenic culture conditions. Finally, following overexpression of ZIP1 in MSCs, cDNA microarray analysis revealed differential regulation of several genes associated with the proliferation of osteoprogenitor cells and osteoblast differentiation. In conclusion, these studies provide important insights into the role of a plasma membrane zinc transporter in the initiation of an osteogenic lineage from MSCs.


Chlorhexidine-induced anaphylaxis in surgical patients: a review of the literature.
Chlorhexidine (CHL) has antiseptic and disinfectant properties used to prevent hospital-acquired infections. CHL-induced anaphylaxis is poorly reported in surgical literature despite government warnings and growing recognition. The aim of this review is to increase awareness of CHL-induced anaphylaxis in the surgical population. Literature review of Embase, Medline, PubMed and the Cochrane library using 'anaphylaxis (and) chlorhexidine' search terms. Thirty-six articles were published on surgical patients suffering anaphylaxis to CHL. Within these, seven patients had two proven separate anaphylactic reactions and one had three separate proven anaphylactic reactions. The most commonly affected speciality was urology. The majority occurred during elective procedures. A history of atopy was surprisingly uncommon as was bronchospasm. Six patients required active chest compressions and 39.71% of patients had their surgical procedure abandoned. Unplanned intensive care admissions occurred in 27.94%. In order to reduce abandoned procedures, unplanned intensive care unit admissions, morbidity and mortality associated with CHL-induced anaphylaxis we recommend the following: rationalization of CHL-containing products, greater vigilance regarding subtle symptoms of CHL allergy, appropriate investigation of these symptoms and a greater awareness of CHL-containing products. Lastly, we outline the appropriate investigations and highlight the need for meticulous documentation in those who are CHL allergic.


Antimalarial activity and inhibition of monoamine oxidases A and B by exo-erythrocytic antimalarials. Optical isomers of primaquine, N-acylated congeners, primaquine metabolites and 5-phenoxy-substituted analogues.
When the terminal amino group in the side chain of primaquine was blocked with an ethoxyacetyl group shown in 2, or eliminated by oxidative deamination to carboxylic acid 3, the antimalarial effect was markedly reduced in a screening assay which measures tissue schizonticidal activity. The optical isomers 1A and 1B of primaquine had similar antimalarial potency to the racemic mixture but 1B appeared less toxic. The 5-phenoxy-substituted analogue 4, belonging to a new class of antimalarials, showed similar potency in the assays to either 1A or 1B but seemed less cytotoxic than (+/-)-primaquine. Compounds 1A and 1B were found to be competitive inhibitors of human monoamine oxidase (MAO) A and B (Ki range 103-225 microM), but 4 showed 10-30-fold greater competitive inhibition of MAO A (Ki = 6.8 microM) and 40-90-fold greater non-competitive inhibition of MAO B (Ki = 2.3 microM).


Corrigendum to 'An Overview of Coronaviruses including the SARS-2 Coronavirus - Molecular Biology, Epidemiology and Clinical Implications' [Cur Med Res Pract. (2019) Vol. 10, pages 54-64].
[This corrects the article DOI: 10.1016/j.cmrp.2020.04.001.].


Combined effects of metal contamination and temperature on the potworm Enchytraeus doerjesi (Oligochaeta).
Cadmium (Cd) and zinc (Zn) toxicity in Enchytraeus doerjesi after 28-day exposure experiments was studied at 15, 20, and 25 °C. Cd lethal concentration (LC)(50) decreased with increasing temperature (293.01 mg kg(-1) at 15 °C, 261.62 mg kg(-1) at 20 °C, 231.79 mg kg(-1) at 25 °C). In contrast, Zn LC(50) increased with increasing temperature (420.21 mg kg(-1) at 15 °C and 518.42 mg kg(-1) at 20 °C). At 25 °C, a Zn LC50 could not be computed owing to the lack of sufficient adult mortality (LC(50) > 640 mg kg(-1)). The reproductive output at 20 and 25 °C was similar for each metal. Cd EC(50) for reproduction increased between 15 and 20 °C (from 23.93 to 35.11 mg kg(-1)) and decreased between 20 °C and 25 °C (to 16.84 mg/kg). Zn EC(50) increased dramatically from 15 °C (41.47 mg kg(-1)) to 20 °C (111.75 mg kg(-1)), and then slightly from 20 °C to 25 °C (112.17 mg kg(-1)). This indicated that metal-temperature effects on E. doerjesi may vary depending on the endpoint. The deleterious effects of Cd on the survival of E. doerjesi increased steadily with increasing temperature. With regard to reproduction, Cd toxicity could be exacerbated by extreme temperatures (15 and 25 °C) although conflicting pressures between high temperature and Cd toxicity may have prevented higher reproduction beyond 20 °C. The effects of Zn toxicity on survival decreased consistently with increasing temperature. The marginal increase in Zn EC(50) between 20 and 25 °C may explain the lack of a significant change in reproduction between the two temperatures. Energy redistribution between the below organism and higher organization endpoints in response to metal contamination may further explain these results.


A new approach to stability of neural networks with time-varying delays.
The stability of neural networks is a prerequisite for successful applications of the networks as either associative memories or optimization solvers. Because the integration and communication delays are ubiquitous, the stability of neural networks with delays has received extensive attention. However, the approach used in the previous investigation is mainly based on Liapunov's direct method. Since the construction of Liapunov function is very skilful, there is little compatibility among the existing results. In this paper, we develop a new approach to stability analysis of Hopfield-type neural networks with time-varying delays by defining two novel quantities of nonlinear function similar to the matrix norm and the matrix measure, respectively. With the new approach, we present sufficient conditions of the stability, which are either the generalization of those existing or new. The developed approach may be also applied for any general system with time delays rather than Hopfield-type neural networks.


Correlation between the visual prostate symptom score and international prostate symptom score in patients with lower urinary tract symptoms.
To evaluate the correlation between the Visual Prostate Symptom Score (VPSS) and International Prostate Symptom Score (IPSS). We enrolled 240 new male patients who had visited National Police Hospital more than twice during a 6-month period starting from July 2013. At initial visit, the Korean version of the IPSS and VPSS, uroflowmetry, and transrectal ultrasonography were used to evaluate urinary symptoms. After medication, IPSS and VPSS questionnaires were issued again. The Spearman correlation test and the Mantel-Haenszel test were used to evaluate the relationship between the IPSS and VPSS. The median age, total prostate volume, total IPSS, and total VPSS were 59.0 years, 28.0 mL, 12, and 9, respectively. Total VPSS, VPSS obstructive symptoms, VPSS irritative symptoms, and VPSS quality of life (QoL) significantly correlated with the total IPSS, IPSS obstructive symptoms, IPSS irritative symptoms, and IPSS QoL, respectively (correlation coefficient, P-value: 0.632, <0.001; 0.431, <0.001; 0.696, <0.001; and 0.799, <0.001; respectively). The change in the total IPSS after treatment also significantly correlated with the change in total VPSS after treatment (correlation coefficient, P-value: 0.364, <0.001). There were significant correlations between maximal flow rate and IPSS/VPSS obstructive symptoms (correlation coefficient, P-value: -0.190, 0.004; -0.269, <0.001, respectively). Additionally, there was a significant increase in the ratio of the maximal flow rate <15 mL/sec to VPSS obstructive symptoms as the severity of the VPSS obstructive symptoms increased (P trend <0.001). VPSS might be useful in evaluating lower urinary tract symptoms at the initial visit and assessing these symptoms at longitudinal follow-up examinations.


A case of bilateral iris mammillations with unusual pupillary appearance and pseudo-hypertension.
Iris mammillations are congenital abnormalities characterised by villiform elevations regularly spaced on the surface of the iris. The aetiology of iris mammillations is unknown. They can be either isolated or associated with melanocytosis involving the uveal tract and the periocular tissue, resulting in a risk for uveal melanoma. These lesions can be complicated by high intraocular pressure and, in the case of associated melanocytosis of the iris, sclera or periocular tissues, by uveal melanoma. Patients with iris mammillations should be followed regularly due to these potential complications. We report a case of bilateral iris mammillations with unusual pupillary appearance and pseudo-hypertension and emphasise the importance of iris mammillations and that central corneal thickness should be considered when intraocular pressure is measured.


Aerated Static Pile Composting for Industrial Biowastes: From Engineering to Microbiology.
This work demonstrated the feasibility of an industrial-scale aerated static pile composting system for treating one of the common biowastes-soybean curd residue. The mixing ratios of the feedstock were optimized to achieve a carbon-nitrogen ratio and a moisture level in the ranges of 25-35 and 60-70%, respectively. This open-air composting system required 6-7 months to obtain a mature compost. Solvita and seed germination tests further confirmed the maturity of the compost, with 25% compost extract concentration yielding the best germination index in the absence of phytotoxicity. The bacterial and fungal compositions of the compost piles were further examined with metagenomic analysis. Thermoactinomyces spp., Oceanobacillus spp., and Kroppenstedtia spp. were among the unique bacteria found, and Diutina rugosa, Thermomyces dupontii, and Candida taylorii were among the unique fungi found in the compost piles, suggesting the presence of good microorganisms for degrading the organic biowastes.


DNA sequence, structure, and phylogenetic relationship of the mitochondrial small-subunit rRNA from the red alga Chondrus crispus (Gigartinales rhodophytes).
The entire nucleotide sequence containing the small-subunit ribosomal RNA gene (SSU rRNA) from the mitochondrial genome of Chondrus crispus was determined. To our knowledge, this is the first sequence of a mitochondrial 16S-like rRNA from a red alga. The length of this gene is 1,376 nucleotides. Its secondary structure was constructed and compared with other known secondary structures from eubacteria and from mitochondria of land plants, green and brown algae, and fungi. Phylogenetic trees were built upon SSU rRNA sequence alignment from mitochondria and eubacteria. The results show that rhodophytes and chromophytes provide additional links in the evolution of mitochondria between the green plant lineage and the "nonplant" lineages.


Generation of multinucleated giant cells in vitro by culture of human monocytes with Mycobacterium bovis BCG in combination with cytokine-containing supernatants.
Multinucleated giant cells (MGC), a characteristic feature of tuberculous granulomas, form by fusion of monocytes or macrophages, but little is known about the mechanism of the fusion process itself. Several studies report an indirect effect of mycobacteria, i.e., induction of a soluble lymphocyte-derived fusion factor following stimulation by mycobacteria or mycobacterial products. The aim of our study was to determine whether contact with mycobacteria can induce MGC formation from human monocytes in vitro. Stimulation of monocytes with Mycobacterium bovis bacillus Calmette-Guérin (BCG) in combination with cytokine-containing supernatants of herpesvirus saimiri-transformed human T-cell clones (T-SN) led to MGC formation with fusion rates of about 27%. In contrast, stimulation with one component alone induced only low fusion rates of up to 10%. Heat-killed BCG in combination with T-SN induced monocyte fusion to the same extent as live mycobacteria. BCG culture supernatant, BCG lysate, or inert particles in combination with T-SN did not induce MGC formation. Experiments using transwell plates containing a semipermeable membrane revealed that induction of the fusion process is dependent on direct contact of monocytes and mycobacteria. MGC formation induced by BCG plus T-SN could be inhibited by addition of monoclonal antibodies to gamma interferon (but not tumor necrosis factor alpha) as well as to the beta chain (CD18) of beta2-integrins. These results demonstrate that contact with mycobacteria in combination with cytokine-containing supernatants is able to induce human monocytes to form MGC and that membrane-bound molecules of mycobacteria and monocytes are involved in the fusion process.


Current approaches to the management of early active diffuse scleroderma skin disease.
Skin sclerosis is a clinical hallmark of systemic sclerosis (SSc) and provides a means to classify and evaluate patients. In the diffuse cutaneous subset, skin involvement is often extensive and warrants direct therapy. Currently, broad spectrum immunosuppressive strategies are used, but more targeted specific approaches are now emerging. This article reviews the evidence for efficacy of current treatment approaches and future developments for managing skin disease in early diffuse cutaneous SSc.


Regional localization and molecular characterization of a DNA sequence on the long arm of chromosome 22.
A human genomic DNA fragment, p22hom13 (D22S16), was isolated from a chromosome 22-specific library. After elimination of repetitive sequences, a single copy BamHI-EcoRI fragment was subcloned into pTZ18. By using mouse/human somatic cell hybrids and in situ hybridization, the new DNA probe was mapped to chromosome 22q13-qter. Its application in the analysis of the distal part of chromosome 22 and its diagnostic use in translocations are discussed.


The histology of seeded PTFE grafts in humans.
To define the histology of PTFE femoral-popliteal grafts seeded with enzymatically-derived endothelium, we examined light level and selected scanning electron micrographs of 20 graft biopsies. Thirteen grafts were chronically occluded and the midgraft samples had a thin lining of fibrin with scattered erythrocytes and leukocytes. One anastomotic sample showed a similar pattern, while three others had neointimal fibrous hyperplasia. Six of the seven remaining midgraft samples demonstrated confluent endothelial healing over parts of the flow surface. The cells were commonly distributed along one side of the graft as viewed in cross-section. Distribution patterns were not improved by changing from a single inoculum with two graft rotation-incubation periods to a sequential inoculation separated by a graft rotation. Circumferential distribution was achieved in one instance in which inoculation was characterized by a relatively high cell density. No luminal endothelium was seen when inoculation cell densities were very low. Smooth muscle cells and fibroblasts were not seen in the subendothelial "inner capsules" of the midgrafts. We conclude that endothelialization occurs in a high proportion of seeded PTFE grafts in humans, that the donor vein surface area should measure at least 5.25% of the inoculated graft surface, that further modifications in the seeding technique will be required to achieve consistent circumferential endothelial distribution, that subendothelial smooth muscle cell invasion is uncommon in the midgraft, but that anastomotic neointimal fibrous hyperplasia probably contributed to some graft failures.


Characteristics of infant mortality in the RSA 1929-1983. Part II. Causes of death among white and coloured infants.
The relative contribution of different causes of death in the first year of life is presented for the period 1929-1983. Infections and perinatal and respiratory causes most commonly result in infant death among coloureds, while perinatal and congenital causes are commonest among whites. Over the 54-year period studied the mortality rate due to infections has fallen dramatically among whites but much less so among coloureds. The two causes of death for which the ratios of coloured to white mortality are highest, viz. infections (28 times) and respiratory causes (9 times), are those which have the greatest post-neonatal mortality component.


Risk Factors for the Drift Phenomenon in O-arm Navigation-Assisted Pedicle Screw Placement during Spinal Deformity Surgery.
Intraoperative O-arm navigation systems improve the accuracy of spinal instrumentation placement. However, deviation of the pedicle screw from the guide line might occur. The aim of the present study was to explore the causes of and countermeasures for the drift phenomenon during pedicle screw implantation with the aid of an O-arm three-dimensional navigation system in spinal deformity surgery. This was a retrospective analysis of 341 patients with spinal deformity who underwent O-arm navigation system-assisted pedicle screw placement from July 2015 to June 2019. The patient's general condition, Cobb angle, apical vertebra position, softness index, spinal release status, fixed reference frame position, and distance between the navigation vertebral body and the reference frame were collected and compared by independent-samples t test or Pearson's chi-square analysis. The potential risk factors for the drift phenomenon were identified using binary logistic regression analysis. The drift phenomenon occurred in 57 patients during the first navigation-assisted pedicle screw placement, for an incidence of 16.7% (57/341). There were significant differences in factors such as the apical vertebra position, softness index, spinal release status, and distance between the vertebral body and the reference frame when the drift phenomenon occurred (P < 0.05). Binary logistic regression analysis showed that the softness index, spinal release status, and distance between the vertebral body and the reference frame when drifting occurred were independent risk factors for the drift phenomenon during O-arm navigation-assisted pedicle screw placement. During the use of an O-arm navigation system to assist with pedicle screw placement, pedicle screws should not be placed away from the reference frame, and spinal osteotomy and release should be performed after pedicle screw placement. In addition, the accuracy of O-arm navigation-assisted pedicle screw placement will be affected more in those with larger softness indices.


Central projections of primary vestibular fibers in the bullfrog: I. The vestibular nuclei.
The central projections of the vestibular end organs in the bullfrog Rana calesbeiana were analyzed by using horseradish peroxidase labeling of the primary vestibular afferents. Separate extracellular injections were made of the anterior branch, the posterior branch, the ampullary nerve of each of the three semicircular canals, and the branch to the saccule. The anterior and posterior branches of the bullfrog eighth nerve, each containing both vestibular and auditory fibers, merge and enter the brain stem as a single nerve root. The thin caliber fibers of the anterior branch enter the brain stem on the ventral-posterior aspect of the nerve and immediately divide dichotomously into ascending (rostral) and descending (caudal) branches. The thick caliber fibers of the anterior branch enter the brain stem on the ventral-anterior aspect of the eighth nerve and traverse medially into the alar plate before dividing into ascending and descending branches. The primary afferent fibers of the vestibular nerve innervate an ipsilateral area of the brain stem which extends caudally from the rhombencephalon at the level of the twelfth nerve nucleus and rostrally up to and including the cerebellar nucleus and the cerebellum. The following vestibular nuclei can be identified by the fact that they receive primary vestibular afferents: the ventral vestibular nucleus, medial vestibular nucleus, descending vestibular nucleus, superior vestibular nucleus, and cerebellar nucleus. The dorsal (acoustic) nucleus, which receives primary auditory input, also receives afferents from the saccule. In addition to these nuclei, the cerebellum and the reticular formation receive significant primary input from the various vestibular receptors. The primary vestibulo-cerebellar fibers terminate mainly among the granular cells of the lobus auricularis and of the corpus cerebelli on the ipsilateral side. Each of the three semicircular canals projects into the cerebellum, while no such projection was observed in the saccular nerve preparations. Fibers from each of the three semicircular canals project to all of the vestibular nuclei. Heavily labeled large neurons, presumably vestibular efferents, are seen in the ipsilateral reticular formation, adjacent to the seventh motor nucleus.


The effect of Qigong on menopausal symptoms and quality of sleep for perimenopausal women: a preliminary observational study.
The study objectives were to examine the effect of a 12-week 30-minute-a-day Ping Shuai Qigong exercise program on climacteric symptoms and sleep quality in perimenopausal women. This was a prospective observational study. The subjects (N=70) from two communities were women aged 45 years and above who were experiencing menopausal symptoms. Thirty-five (35) women from one community were assigned to a Ping Shuai Qigong intervention group, while 35 women from the other community were assigned to the control group. This was a 12-week, 30-minute-a-day Ping Shuai Qigong program. The Greene Climacteric Symptom scale and the Pittsburgh Sleep Quality Index were the outcome measures. Descriptive analysis and repeated-measures analysis of variance were used. Pretest scores at baseline found no significant group differences in climacteric symptoms or sleep quality. Significant improvements in climacteric symptoms were found at 6 weeks and 12 weeks (t=4.07, p<0.001 and t=11.83, p<0.001) in the intervention group. They were also found to have significant improvements in sleep quality in those times (t=5.93, p<0.001 and t=10.58, p<0.001, respectively). Ping Shuai Qigong improved climacteric symptoms and sleep quality in perimenopausal women at 6 weeks and 12 weeks. The longer a person practiced this form of meditative exercise, the greater the improvement in sleeping quality and climacteric symptoms.


[A new phoretic species, simulium melanocephalum sp. n. (simuliidae: Diptera) from kivu, zaire, with taxonomic notes on the S. diceros-group (author's transl)].
A new species of the Simulium diceros-group (subgenus Phoretomyia) is described, the larvae and pupae of which are living in phoretic association with mayfly nymphs. The systematic position of the group, and the taxonomy of its species are discussed.


Endovascular repair of a traumatic inferior vena cava injury after exploratory laparotomy.
The incidence of traumatic inferior vena cava (IVC) injury is infrequent but is associated with high mortality. No clear and current society-based guidelines are available to dictate the role of endovascular therapy. In the present case report, we have described a unique clinical presentation of a patient in extremis after emergent exploratory laparotomy who had experienced an IVC injury that could not be controlled with open surgery. The IVC injury was treated with an endovascular approach with a Gore TAG endograft (W.L. Gore & Associates, Flagstaff, AZ). We have reported a technique for successful treatment of a complex IVC injury, with the aim of adding to the current body of literature supporting the use of endovascular approaches.


Use of hand-held ultrasonography to confirm the correct placement of a central venous catheter tip.
To avoid severe complications resulting from malpositioning of a central venous catheter, removal and recannulation of the catheter may be necessary, thus wasting medical equipment and increasing stress on the patient. Therefore, central venous catheters should be inserted correctly the first time. We tested whether real-time hand-held ultrasound-guided confirmation of the location of the tip of a central venous catheter inserted from the femoral vein could reduce the rate of malpositioning. Catheters were inserted using conventional methods for 65 patients, and using ultrasound guidance for 29 patients. For the latter group, when a central venous catheter was inserted, the ultrasound examiner first identified its tip located dorsal to the liver in the inferior vena cava and then fixed the catheter in position. We considered a central venous catheter to be malpositioned when its tip appeared in neither the inferior vena cava nor the right atrium-inferior vena cava junction in X-rays. Flexed or inverted catheters were also considered to be malpositioned. We compared the malpositioning rates for the ultrasound and conventional groups. Malpositioning was identified for two (6.9%) patients in the ultrasound group and 19 (29.2%) patients in the conventional group. The relative risk of ultrasound-guided versus conventional catheter insertion was 0.23 (95% confidence interval, 0.09-0.62). Our data suggest that real-time ultrasound monitoring is useful for avoiding malpositioning of central venous catheters inserted from the femoral vein.


New insights into the musculotendinous and ligamentous attachments at the pubic symphysis: A systematic review.
Collection and meta-analysis of all relevant anatomical studies related to the pubic symphysis to provide a state of the art review of its musculotendinous and ligamentous attachments from 2010 to date. A systematic search of published literature databases (PubMed, Web of Science and Embase) was conducted according to the PRISMA guidelines from January 2010 up until now. All papers investigating the anatomy of the musculotendinous attachments of the pubis and the pubic ligaments were eligible. Methodological quality was assessed using the Quality Appraisal for Cadaveric Studies (QUACS scale). A narrative analysis approach was adopted to synthesize the findings. After screening and review of 1313 papers, a total of six studies investigating the anatomy of the pubic ligaments and tendons were included. Of the six articles included in this systematic review, five articles performed a macroscopic anatomical dissection, three articles performed a microscopic (histological) study, and one article combined microscopic examination with an MRI imaging examination. The anatomy of the pubic symphysis was examined in 76 anatomical cadavers (60 embalmed, 16 fresh frozen). In total 44 male cadavers (58%), 28 female cadavers (37%) and four cadavers whose gender was not stated were dissected. The age-old accepted concept of the fusion of the rectus abdominis with the adductor longus via the aponeurotic plate is outdated. New anatomical concepts like the pyramidalis-anterior pubic ligament-adductor longus complex (PLAC), recto-gracilis tendon, fusion of adductor brevis with gracilis, etc. are recently introduced. The awareness of anatomy and morphology of the pubic ligaments plays a significant role in understanding the diagnosis and treatment of groin pain.


Arteriovenous malformations and headache.
Brain arteriovenous malformations (AVM) are complex vascular lesions commonly associated with chronic headache. An occipital location appears to increase the risk of concurrent migraine-like headaches in AVM patients. We have experienced great success in treating these headaches through a multidisciplinary approach to eradicate cerebral AVM. However, the specific clinical characteristics of AVM-associated headaches and the most effective treatment strategies for these patients remain unclear. Here, we provide a comprehensive review of the literature on AVM-associated headaches. We detail the history, classification, epidemiology, presentation, pathophysiology, treatment options, and outcomes for this poorly described condition. Additionally, we illustrate our approach to the management of patients with occipital AVM and associated intractable headaches.


Mitigating effects of hUCB-MSCs on the hematopoietic syndrome resulting from total body irradiation.
This study evaluated the clinical and pathologic effects of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the recovery from total body irradiation by comparing it with the effects of granulocyte-colony stimulating factor (G-CSF), an efficacious drug in the treatment of acute bone marrow radiation syndrome. BALB/c mice were treated with G-CSF or hUCB-MSCs after they were irradiated with 7 Gy cobalt-60 γ-rays. Circulating blood counts, histopathologic changes in the bone marrow, and plasma level of Flt-3L and transforming growth factor (TGF-β1) were monitored in the postirradiation period. Hematologic analysis revealed that the peripheral leukocyte counts were markedly increased in the hUCB-MSCs-treated group, whereas G-CSF-treated mice did not recover significantly. Moreover, differential counts showed that hUCB-MSC treatment has regenerative effects on white blood cells, lymphocytes, and monocytes compared with the irradiated group. Treatment with hUCB-MSCs or G-CSF significantly increased immunoreactivity of Ki-67 until 3 weeks after total body irradiation. However, at 3 weeks, the number of Ki-67 immunoreactive cells significantly increased in the hUCB-MSCs-treated group compared with the G-CSF-treated group. Furthermore, hUCB-MSC treatment significantly modulated plasma levels of the hematopoietic cytokines Flt-3L and TGF-β1, whereas G-CSF treatment failed to decrease the plasma Flt-3L levels at 2 weeks after irradiation. Based on the differences in circulating blood cell reconstitution and cell density of bone marrow, the authors suggest that MSC treatment is superior to G-CSF treatment for hematopoietic reconstitution following sublethal dose radiation exposure.


DNA-protein and membrane-lipid: competing paradigms in biomedical research.
Most current biomedical science research is based on the idea that DNA and the RNA and proteins whose structures are specified by DNA are of overwhelming importance in human disease. While they are undoubtedly of major significance, their practical importance may have been exaggerated. Lipids which make up the bulk of cell and other membranes, and which modulate the behaviour of most proteins may be of at least equal importance. Moreover, lipids offer more opportunities for practical therapeutic intervention.


Effects of Polydextrose Supplementation on Intestinal Function in Hemodialysis Patients: A Double-Blind, Randomized, Placebo-Controlled Trial.
Intestinal constipation is a frequent complication in hemodialysis (HD) patients. Polydextrose (PDX), a nondigestible oligosaccharide, has been reported as a fermentable fiber with potential benefits. This study aimed to investigate the possible influence of PDX supplementation on intestinal function in HD patients. This randomized, double-blind, placebo-controlled trial included 28 patients who received daily oral supplementation with 12 g of PDX or placebo (corn starch) for 2 months. ROME IV criteria were used to define constipation and questionnaires were applied to patient assessment of constipation symptoms (PAC-SYM) and their impact on the patient assessment of constipation quality of life. The Bristol scale was used to assess stool consistency. Commercial Enzyme-Linked Immuno Sorbent Assay kits were used to evaluate the interleukin-6 and tumor necrosis factor-α plasma levels. 25 patients completed the study; 16 in the PDX group [7 females, 48.5 years (IQR = 15.5)] and 9 in the control group [3 females, 44.0 years (IQR = 6.0)]. According to ROME IV criteria, 55% of patients were diagnosed with constipation. PAC-SYM faecal symptoms domain was reduced after 2 months of PDX supplementation (P = .004). We also observed a significant reduction in the PAC-QoL-concerns domain (P = .02). The average values for PAC-SYM and patient assessment of constipation quality of lifewere reduced significantly after intervention with PDX. There were no significant changes after the intervention period concerning biochemical variables, food intake, and inflammation markers. No adverse effects were observed during the supplementation period. The results of the present study suggest that short-term PDX supplementation may have favourable results on intestinal function and the quality of life of chronic kidney disease patients in HD.


Application of immunohistochemistry to cytology.
The uses of monoclonal antibodies via immunochemistry have been reported frequently within the literature using various methodologies with applications to cytology specimens. The direct application of immunochemistry to cytology may have a variety of pitfalls that the general pathologist familiar with its application to histology may be unaware of when applying it prospectively to patient specimens. To review common pitfalls when applying immunochemistry to cytology specimens and to suggest approaches to the more common differential dilemmas that apply to a variety of cytology specimens that could be seen in a general pathology practice. The authors' own experiences of applying immunochemistry to cytopathology specimens within an academic setting along with supportive data from the literature. Immunochemistry can be used to increase the predictability of a cytology diagnosis if care is taken with the cytology sample preparation methodology and there is judicious use of select monoclonal antibody panels to support a specific cytology diagnosis. Up-to-date evidence-based antibody databases should be used when selecting antibody panels.


Failure of a single day metronidazole desensitization protocol, and success of a modified two-day protocol in an outpatient setting.
True allergy to metronidazole, a common anti-infective in clinical practice, is rarely reported in the literature. In the case of Trichomonas, there are few alternatives to the nitrimidazole class of drugs, and the alternatives that do exist are associated with worse clinical outcomes. Accordingly, for the rare patients with Type 1 hypersensitivity reactions to metronidazole but compelling need, desensitization protocols have been adapted previously. Reactions during these protocols appear common. Patients in previous regimens have required higher level care for observation, which is costly and resource-intensive. We report here on a successful outpatient two-day regimen for metronidazole desensitization. Our patient had compelling indication for metronidazole, but reacted after receiving the very first dose of a previously described desensitization protocol. Accordingly, the protocol was adapted further. Despite this, she went on to develop objective hives prior to reaching the full intended dose. With appropriate symptom management and pre-medication on the second day in clinic, she was successfully desensitized and able to complete a week of full-dose metronidazole. No acute care resources were needed. We propose this two-day desensitization regimen for patients who react during the previously described desensitization protocols. This regimen was effective and safe, and did not necessitate the use of acute-care resources. Two-day desensitization protocols while relatively uncommon, can be successful.


Medical Use and Misuse of Prescription Opioids in US 12th-Grade Youth: School-Level Correlates.
Opioid misuse and overdose remains a leading US public health concern, and many youth are first exposed to opioids via medical use. In this study, we examine school-level prevalence and correlates of medical use and misuse of prescription opioids among US 12th-grade students. A sample of 228 507 US 12th-graders in 1079 public and private schools from 2002 to 2017 from the Monitoring the Future study was used to identify school-level prevalence and correlates associated with medical use and misuse of prescription opioids. The past-year prevalence of prescription opioid misuse was 7.6% and ranged from 0% to 73% across US high schools. Lifetime medical use of prescription opioids was 16.9% and ranged from 0% to 85% across US high schools. The odds of prescription opioid misuse were higher at schools with higher proportions of male students, more white students, higher rates of marijuana use, and more medical use of prescription opioids. Students attending schools with the highest rates of medical use of prescription opioids had 57% increased odds of past-year prescription opioid misuse compared with schools with no medical use (adjusted odds ratio = 1.57, 95% confidence interval = 1.35-1.83); this association was found to weaken in recent years. Differences exist in the prevalence of prescription opioid misuse among US high schools. The association between greater school-level medical use of prescription opioids and higher prevalence of prescription opioid misuse, although declining, indicates a key risk factor to target for prevention efforts.


Magnesium (mg) retention and mood effects after intravenous mg infusion in premenstrual dysphoric disorder.
Conflicting data exist regarding the presence of magnesium (Mg) deficiency and the therapeutic efficacy of Mg in premenstrual syndrome or premenstrual dysphoric disorder (PMDD). The % Mg retention was determined using 24-hour urinary Mg excretion and the total dose of Mg given intravenously. In women with (n = 17) and without (n = 14) prospectively diagnosed PMDD, several blood measures of Mg and mood were obtained before, immediately after, and the day following an intravenous Mg (.1 mmol/kg) loading dose. A positive mood response was seen under open conditions; as open Mg infusion improved mood, subsequent PMDD patients (n = 10) were randomized in a double-blind, placebo-controlled, crossover fashion. Patients (31.5%) and control subjects (27.5%) retained comparable mean percentages of Mg. Neither group differed in measures of mean Mg before, immediately after, or the day following Mg infusion. Although there was a time effect for all mood measures in the patient group (p < .01 for all), there was neither a treatment nor time-by-treatment effect. Contrary to prior reports, we found no evidence of Mg deficiency in women with PMDD compared with control subjects. Furthermore, Mg was not superior to placebo in the mitigation of mood symptoms in women with PMDD.


Upregulated long noncoding RNA LINC01296 indicates a dismal prognosis for pancreatic ductal adenocarcinoma and promotes cell metastatic properties by affecting EMT.
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to chemotherapy and radiotherapy and whose incidence has increased worldwide. Long noncoding RNAs have been demonstrated to play important roles in cancer initiation and progression. Long intergenic non-coding RNA 01296 (LINC01296) has been reported to be upregulated in several malignancies, but the clinical relevance and biological role of LINC01296 in PDAC are still unclear. RT-qPCR was performed to evaluate the expression of LINC01296 in 85 pared PDAC tissue samples and a panel of PDAC cell lines. The clinical value and prognostic role of LINC01296 in patients with PDAC were further explored. Furthermore, we explored the functional roles of LINC01296 depletion in PANC-1 and SW1990 cells, including cell proliferation, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT). LINC01296 was enhanced in PDAC tissues and cell lines, and this overexpression was correlated with advanced tumor stages and positive lymph node metastasis in patients with PDAC. In addition, upregulation of LINC01296 was an independent prognostic predictor for patients with PDAC after surgery. Moreover, silencing of LINC01296 followed by treatment with small interfering RNAs suppressed cell proliferation and promoted cell apoptosis by affecting the Bcl-2/caspase-3 pathway. Importantly, LINC01296 attenuation impaired the migratory and invasive potential partly by reversing EMT. Overall, our work may help to develop a novel prognostic biomarker and therapeutic target for PDAC.


Effect of opioids on mechanoreflexive respiration control.
The effects of opioids (morphine and fentanyl) on the function of mechanoreceptive respiration regulatory loop were demonstrated. In most opioid-treated rats (74% cases) vagotomy was followed by apneustic respiration with inspiration pause. Excess of opioids in rat CNS produced minor disturbances in the respiration rhythm, but in the absence afferent input from the mechanoreceptors of respiratory pathways and lungs, pronounced periodic apneustic respiration with inspiration pauses developed. The opioidergic system is involved in the formation of respiratory rhythm, but had no appreciable effect on transmission of mechanoreceptive nerve pulses from respiratory pathways and the lungs to the respiratory center.


Knee scooter related injuries and satisfaction in patients following foot and ankle surgery.
Knee scooters have become popular amongst foot and ankle surgeons for patients who are required to be non-weight bearing. Information is limited regarding falls and injuries sustained while using a knee scooter and potential contraindications to their use are ill-defined. No study has assessed patient reported injuries and satisfaction. This study aims to evaluates the patient's perspective with regards to the use of a knee scooter. As a secondary aim we assessed for risk factors associated with knee scooter related injuries to try make recommendations for the safe use of a knee scooter. Patients who used a knee scooter during 2018-2020 were emailed a questionnaire assessing (1) demographic data, (2) medical history, (3) falls and injuries sustained, including the management of these injuries, and (4) patient satisfaction. This study is a descriptive, cross-sectional survey analysis. 101/196 (51,5%) responses were received, which included 32 males and 69 females. The cohort had a mean age of 56.4 years, and BMI of 28.5. Mean time spent using the scooter was 6.7 weeks. Twenty-five respondents had fallen off the scooter, with 5 reporting injuries. One patient required medical attention for a shoulder injury. Cause of falls included hitting an obstacle, making a sharp turn, moving too fast, and moving downhill. There was no correlation between falls and patient comorbidities. Ninety-six percent of respondents reported a high satisfaction and preferred the scooter to crutches. The knee scooter is a safe, and well-tolerated, mobility aid for patients requiring non-weight bearing during their recovery, with a high satisfaction rate. Educating patients on correct use and common causes for falling is important as a preventative measure. IV, retrospective case series.


DNA fragmentation in focal cortical freeze injury of rats.
This study examined the appearance of double-strand DNA breaks in rat brain after a focal cortical freeze injury in vivo. DNA fragments of oligonucleosome size appeared 3 h after the injury, and increased in a time-dependent manner. At 24 h, the amount of DNA fragmentation reached a maximum and then declined. When nuclei from freeze-injured brain tissue were incubated with Ca2+ in vitro, increased endonuclease activity, which can cause DNA fragmentation, was found. These findings indicate that the activation of a Ca(2+)-dependent endonuclease may be involved in the evolution of freeze-traumatized brain tissue.


Interconversion of the molecular forms of biliverdin reductase from rat liver.
Rat liver biliverdin reductase exists in two molecular forms. The major molecular form 1 has a high reduction rate for biliverdin IX alpha, while the minor molecular from 2 has high reduction rates for both biliverdins IX alpha and IX beta. The major molecular form 1 was gradually transformed into a second major form (form 3) by treatment of the rats with CoCl2. Form 1 reduces biliverdin IX alpha at two and a half times the rate of biliverdin IX beta while form 3 reduces both isomers at about the same rate. This transformation involves a de novo mRNA and protein synthesis since it could be prevented by cycloheximide and actinomycin D. Molecular form 3 can be transformed back into molecular form 1 by an in vitro treatment with reduced thioredoxin. Phenylhydrazine treatment also induced the transformation of molecular form 1 into molecular form 3 in rat liver. Biliverdin reductase from rat spleen and kidney exists only in molecular form 1 and is not transformed into molecular form 3 by either CoCl2 or phenylhydrazine treatments.


DNA extraction method affects microbial community profiles from soils and sediment.
To evaluate whether different deoxyribonucleic acid (DNA) extraction procedures can affect estimates of bacterial community composition, based on the 16S ribosomal ribonucleic acid gene denaturing gradient gel electrophoresis (DGGE) profiles, we compared four in situ lysis procedures using three soils and one marine sediment. Analysis of DGGE profiles, generated by polymerase chain reaction of purified DNA extracts, demonstrated that the choice of DNA extraction method significantly influenced the bacterial community profiles generated. This was reflected both in the number of bands or ribotypes detected from each sample and in subsequent principle coordinate analysis and unweighted-pair group method using arithmetic average analyses. The methods also differed significantly in their robustness, i.e. reproducibility across multiple analyses. Two methods, both based on bead beating, were demonstrated to be suitable for comparative studies of a range of soil and sediment types.


Barrier contraceptive practice and male infertility as related factors to breast cancer in married women.
A case-control study was conducted in order to test the hypothesis that a reduced exposure to human seminal factors in the early reproductive life of women is a risk factor in breast cancer. The relative risk of exposure to the hypothetical semen-factor deficiency is 4.7 times greater for breast-cancer patients than for the controls. When the contraceptive methods alone are taken into account, the relative risk increases up to 5.3. About 16 percent of the women using barrier methods (condom, and other) and 3.4 percent of women using non-barrier contraceptive methods (diaphragm, pill, IUDs, rhythm, tubal ligation, and other) would develop breast cancer. The risk of developing breast cancer within the same population in the U.S. is 5 times greater in women who use barrier methods than in women who use non-barrier contraceptive methods. The reduction in the incidence of breast cancer by eliminating the barrier contraceptive techniques would be not less than 50 percent in married women in the entire population. The possibility of preventive measures within an adequate family planning program is emphasized.


Treatment of small (< 2 cm) umbilical hernias: guidelines and current trends from the Herniamed Registry.
Based on meta-analyses and registry data, the European Hernia Society and the Americas Hernia Society have published guidelines for the treatment of umbilical hernias. These recommend that umbilical hernia should generally be treated by placing a non-absorbable (permanent) flat mesh into the preperitoneal space with an overlap of the hernia defect of 3 cm. Suture repair should only be considered for small hernia defects of less than 1 cm. Hence, the use of a mesh in general is subject to controversial debate particularly for small (< 2 cm) umbilical hernias. This analysis of data from the Herniamed Registry now presents data on the treatment of small (< 2 cm) umbilical hernias over the past 10 years. Herniamed is an Internet-based hernia registry in which hospitals and surgical centers in Germany, Austria and Switzerland can voluntarily enter data on their routine hernia operations. Between 2010 and 2019, data were entered into the Herniamed Registry by 737 hospitals/surgery centers on a total of 111,765 patients with primary elective umbilical hernia repair. The prospective data were analyzed retrospectively for each year and statistically compared. Due to a higher number of cases, the years 2013 and 2019 were compared for the perioperative outcome and the years 2013 and 2018 for 1-year follow-up. Fisher's exact test was applied for unadjusted analyses between the years, using a significance level of alpha = 5%. For post hoc tests of single categories, a Bonferroni adjustment for multiple testing was implemented. A mesh technique was used to treat 45.4% of all umbilical hernias. The proportion of small (< 2 cm) umbilical hernias in the total collective of umbilical hernias was 55.6%. Suture repair was used consistently over the 10-year period to treat around 75% of all small (< 2 cm) umbilical hernias. Preperitoneal mesh placement as recommended in the guidelines was used only in 1.8% of cases. Between 2013 and 2019, stable values of 2 and 0.7% were observed for the postoperative complications and complication-related reoperations, respectively, with no relevant effect identified for the surgical technique. At 1-year follow-up, significantly higher rates of pain at rest (2.6 vs. 3.3), pain on exertion (5.7 vs. 6.6), and recurrences (1.3 vs. 1.8) (all p < 0.05) were identified for 2018 compared with 2013. A suture technique is still used to treat 75% of patients with small (< 2 cm) umbilical hernias. The pain and recurrence rates are significantly less favorable for 2018 compared with 2013.


Genitourinary fistulae. Vaginal approach for repair of vesicovaginal fistulae.
Controversy still remains concerning the timing of repair, the type of approach, and the technical guidelines most likely to prevent recurrence of both radiated and nonradiated vesicovaginal fistulae. The authors advocate the transvaginal approach because it avoids a cystotomy and involves minimal blood loss and consequently is followed by less postoperative discomfort and a shorter hospital stay. Included in this discussion are the techniques and results of the transvaginal approach for simple vesicovaginal fistulae as well as for complex cases and radiation fistulae.


Comparative efficacy of nucleoside/nucleotide reverse transcriptase inhibitors in combination with efavirenz: results of a systematic overview.
Many trials of antiretroviral therapy in treatment-naïve subjects have investigated the relative efficacy of the third drug in a treatment regimen. However, the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) components may also affect efficacy. A systematic overview of clinical trials studying initial treatment in naïve subjects receiving efavirenz-containing regimens and providing week 48 time to loss of virologic response (TLOVR) results was undertaken to compare results with different NRTI combinations. Seven trials studying 3,807 subjects were identified that met the inclusion criteria. Baseline characteristics were similar across studies. Using the week 48 TLOVR results as the primary method of comparison, combinations of tenofovir and lamivudine or emtricitabine appeared to provide improved virologic responses. Similar results were obtained when the proportions of subjects with plasma HIV RNA levels <50 copies/mL were examined.