The effects of angiotensin II blockade and nephrectomy on the renin-angiotensin-aldosterone system in the newborn lamb.
Six newborn lambs were studied during continuous infusion of saralasin acetate, 5 micrograms/kg/min for 135 min; 40 min after beginning saralasin, furosemide (2 mg/kg) was injected over 1--2 min. In addition, six anephric lambs were studied after injection of furosemide. Plasma renin activity (PRA) increases from 23 +/- 2.7 ng/ml/hr (M and SE) to 85.8 +/- 16.5 (P less than 0.05) during infusion of saralasin alone and remained at this level after injection of furosemide. PRA did not increase above base line after injection of furosemide in the anephric lambs. Blood pressure dropped after saralasin infusion in the normal lambs (P less than 0.05), and after furosemide injection (P less than 0.05) in both groups. Plasma aldosterone concentrations did not increase in response to furosemide in either group. The results suggest that angiotensin II is important in maintaining blood pressure in the newborn and exerts antagonistic effects on the renal renin secretion mechanism. The renin-angiotensin-aldosterone system is activated in the normal newborn. Possible reasons for the activation include decreased circumferential tension of small arteries and salt wasting.


Mentoring. Perceptions of the process and its significance.
My recommendations are to learn about the mentoring process, prepare for the role, and take advantage of the opportunity to mentor someone, or many people, throughout your professional lifetime. In the process, you will learn about your cognitive, affective, and behavioral competencies and gifts. Share them. Join me and other mentors in knowing that you have opened doors and contributed in more than the usual ways to both well and ill people, to both present and future leaders in nursing or other disciplines, in whatever role, and to society in general. Deepen your generativity.


Computed tomography in intracranial, supratentorial metastases in children.
This study compares the CT characteristics in a consecutive sample of supratentorial metastases (n = 31) with primary tumors of the same location (n = 49) in childhood. Postcontrast CT was performed in all but one of the metastases cases. In all but one of these children the location and type of primary tumor was known at time of occurrence of cerebral metastasis. Primary CNS tumors (n = 12) had a higher incidense of supratentorial metastatic spread than tumor originating elsewhere. Three children had diffuse subarachnoid seeding, while 28 had solid tumors (21 solitary, 7 multiple). The predilection location for the solid metastases was the gray-white matter junction (n = 12). The following CT findings were significantly less frequent in metastases than in primary tumors (P less than 0.05): Midline location, calcification and cyst formation. On the other hand bleeding, pronounced contrast enhancement and location in the gray-white matter junction were more frequent in the metastatic group (P less than 0.05).


A prospective test of cognitive vulnerability models of depression with adolescent girls.
This study sought to provide a more rigorous prospective test of two cognitive vulnerability models of depression with longitudinal data from 496 adolescent girls. Results supported the cognitive vulnerability model in that stressors predicted future increases in depressive symptoms and onset of clinically significant major depression for individuals with a negative attributional style, but not for those with a positive attributional style, although these effects were small. This model appeared to be specific to depression, in that it did not predict future increases in bulimia nervosa or substance abuse symptoms. In contrast, results did not support the integrated cognitive vulnerability self-esteem model that asserts stressors should only predict increased depression for individuals with a confluence of negative attributional style and low self-esteem, and this model did not appear to be specific to depression.


A novel semi-solidifying liquid formula via the nasogastric route to maintain enteral nutrition in the event of recurrent aspiration pneumonia: A case report.
Recurrent aspiration pneumonia can impede the continuation of enteral nutrition. Semi-solid feeds have been demonstrated to reduce the incidence of aspiration pneumonia but are difficult to administer via the nasogastric tube. A novel semi-solidifying enteral formula may be used instead to avoid the occurrence of severe gastroesophageal reflux.


Exercise training to improve health related quality of life in long term survivors of major burn injury: a matched controlled study.
Patients often experience reduced health-related quality of life (HRQOL) following burn injury. Exercise training has been demonstrated to improve HRQOL in a number of clinical populations, yet it is unknown whether exercise can improve HRQOL in burns patients. Nine burn-injured participants (42±18.38%TBSA: 6.56±3.68 years after injury) and 9 matched controls participated in a 12-week exercise programme. HRQOL was assessed via the Burn Specific Health Scale-Brief (BSHS-B) and the Medical Outcomes Study 36-Item Short Form (SF-36). Activity limitation was measured using the quick Disabilities of the Arm, Shoulder and Hand (QuickDASH). The burns group had decreased HRQOL compared to the controls at baseline, as reported by the BSHS-B (t (16)=3.51, p=0.003) and some domains of the SF-36 including role physical (t (16)=3.79, p=0.002). Burned participants reported decreased activity levels compared to the controls as measured by the QuickDASH (t (16)=2.19, p=0.044). Exercise training improved SF-36 scores in both burn (t (8)=3.77, p=0.005) and control groups (t (8)=2.71, p=0.027). Following training there was no difference between the groups on the SF-36 or QuickDASH. Exercise training improves HRQOL and activity limitations in burn-injured patients to a level that is equivalent to that of their uninjured counterparts.


Oral and vocal fold diadochokinesis in dysphonic women.
The evaluation of oral and vocal fold diadochokinesis (DDK) in individuals with voice disorders may contribute to the understanding of factors that affect the balanced vocal production. Scientific studies that make use of this assessment tool support the knowledge advance of this area, reflecting the development of more appropriate therapeutic planning. To compare the results of oral and vocal fold DDK in dysphonic women and in women without vocal disorders. For this study, 28 voice recordings of women from 19 to 54 years old, diagnosed with dysphonia and submitted to a voice assessment from speech pathologist and otorhinolaryngologist, were used. The control group included 30 nondysphonic women evaluated in prior research from normal adults. The analysis parameters like number and duration of emissions, as well as the regularity of the repetition of syllables "pa", "ta", "ka" and the vowels "a" and "i," were provided by the Advanced Motor Speech Profile program (MSP) Model-5141, version-2.5.2 (KayPentax). The DDK sequence "pataka" was analyzed quantitatively through the Sound Forge 7.0 program, as well as manually with the audio-visual help of sound waves. Average values of oral and vocal fold DDK dysphonic and nondysphonic women were compared using the "t Student" test and were considered significant when p<0.05. The findings showed no significant differences between populations; however, the coefficient of variation of period (CvP) and jitter of period (JittP) average of the "ka," "a" and "i" emissions, respectively, were higher in dysphonic women (CvP=10.42%, 12.79%, 12.05%; JittP=2.05%, 6.05%, 3.63%) compared to the control group (CvP=8.86%; 10.95%, 11.20%; JittP=1.82%, 2.98%, 3.15%). Although the results do not indicate any difficulties in oral and laryngeal motor control in the dysphonic group, the largest instability in vocal fold DDK in the experimental group should be considered, and studies of this ability in individuals with communication disorders must be intensified.


Erratum to the effects of a biodegradable Mg-based alloy on the function of VSMCs via immunoregulation of macrophages through Mg-induced responses.
[This corrects the article DOI: 10.21037/atm-21-1375.].


The sacroiliac joint. Nothing is sacred.
One hundred years ago, the sacroiliac joint was considered to be the most common cause of sciatica; over time, however, it became increasingly apparent that the major back enterprise lay in disc extractions. Still, despite the lack of specific clinical tests, the same clinical symptoms suggesting lumbar disc and lumbar facet joint pathology may also justify consideration of the sacroiliac joint as the pain generator. Treatment approaches, including manual therapies, bracing, and exercises, may benefit both the facet and sacroiliac joints as well as intradiscal pathologies. The possibility of utilizing specific local intra-articular steroid injections into the sacroiliac joint may add another useful tool to the armamentarium of back pain relief strategies.


Axial rotation component of thoracic scoliosis.
The axial rotation (rotation about a vertical axis) of the vertebrae, of the ribs, and of the back surface are components of the deformity recognized clinically as the "rib hump" in thoracic scoliosis. Relationships of these rotations to the lateral deviation and lateral curvature of the spine were studied in 40 patients with idiopathic scoliosis. Stereoradiographs of the spine and rib cage were used to measure three components of axial rotation: rotation of the vertebrae, of the rib cage, and of the plane of maximum curvature of the spine. Stereotopographs of the back surface were digitized to measure the axial rotation of the back surface. In individual patients, there were high correlations of all components of axial rotation at each spinal level with the corresponding vertebral lateral deviation from the spinal axis. By regression analyses of the maximum values of each rotation in each curve, the rotation of the apex vertebra was found to be generally of lesser magnitude than the rotation of the plane of maximum curvature of the spine and in an opposite sense in kyphotic curves. The rib cage rotation was generally of lesser magnitude than the vertebra rotation, and the back surface rotation was less than both of these skeletal rotations. Vertebra rotation correlated most closely with lateral deviation of the spine. Simple segmental coupling of axial rotation and lateral bending could not be responsible for this axial rotation.


Effects of arsenic disulfide on apoptosis, histone acetylation, toll like receptor 2 activation, and erythropoiesis in bone marrow mononuclear cells of myelodysplastic syndromes patients in vitro.
As the main component of traditional Chinese medicine realgar, arsenic disulfide (As2S2) is widely used in treating myelodysplastic syndromes (MDS). The goal of the current study is to assess the effects of As2S2 on bone marrow mononuclear cells (BMMNC) of MDS. BMMNCs were obtained from 10 lower risk MDS patients, 5 higher risk MDS patients, and 3 healthy controls. Then, the cells were treated with As2S2 for 48h, using vorinostat (also known as SAHA) as control. Cell proliferation and apoptosis were detected. mRNA and protein levels of histone deacetylase-1 (HDAC1), Toll-like receptor 2 (TLR2), and erythroid transcription factor (GATA-1) were detected by quantitative real-time PCR and western blot analysis. After As2S2 treatment in concentrations ranging from 3.125 to 100μmol/L, cell proliferation was inhibited in both lower risk and higher risk MDS. Fifty percent inhibitory concentrations were 24.4μmol/L and 23.6μmol/L, respectively, for lower and higher risk MDS. Apoptotic cells significantly increased in both types of MDS. mRNA and protein levels of HDAC1 and TLR2 were reduced, whereas GATA-1 was increased in both types of MDS. As2S2 could inhibit cell proliferation and induce apoptosis through histone acetylation modulation in MDS. Similar to SAHA, As2S2 could reduce TLR2 activation and increase GATA-1 expression. Current data suggest epigenetic and immunological alternations are involved in therapeutic mechanisms of realgar in the treatment of MDS.


Long-term effect of Helicobacter pylori eradication on colorectal cancer incidences.
There is evidence supporting the association between Helicobacter pylori infection and colorectal cancer (CRC), but whether H. pylori eradication reduces the risk of CRC is still unknown. To compare the incidence of CRC in subjects who had received H. pylori eradication therapy with general population. A population-based retrospective cohort study. This study included all H. pylori-infected subjects who had received their first course of clarithromycin-containing triple therapy in 2003-2015 in Hong Kong. We compared the observed incidences of CRC in this H. pylori eradicated cohort with the expected incidences in the age- and sex-matched general population. The standardized incidence ratio (SIR) with 95% confidence interval (CI) was computed. Among 96,572 H. pylori-eradicated subjects with a median follow-up of 9.7 years, 1417 (1.5%) developed CRC. Primary analysis showed no significant difference in the observed and expected incidences of CRC (SIR: 1.03, 95% CI: 0.97-1.09). However, when stratified according to the follow-up period, higher incidence of CRC was only observed in the first 5 years after eradication (SIR: 1.47, 95% CI: 1.39-1.55), but it was lower (SIR: 0.85, 95% CI: 0.74-0.99) than general population after 11 years. When stratified by tumor location, the observed incidence was higher for colon (SIR: 1.20, 95% CI: 1.12-1.29) but lower for rectal cancer (SIR: 0.90, 95% CI: 0.81-0.999) among H. pylori-eradicated subjects. H. pylori-infected subjects appeared to have a higher incidence of CRC initially, which declined progressively to a level lower than general population 10 years after H. pylori eradication, particularly for rectal cancer.


Evidence Supporting Predation of 4-m Marine Reptile by Triassic Megapredator.
Air-breathing marine predators have been essential components of the marine ecosystem since the Triassic. Many of them are considered the apex predators but without direct evidence-dietary inferences are usually based on circumstantial evidence, such as tooth shape. Here we report a fossil that likely represents the oldest evidence for predation on megafauna, i.e., animals equal to or larger than humans, by marine tetrapods-a thalattosaur (∼4 m in total length) in the stomach of a Middle Triassic ichthyosaur (∼5 m). The predator has grasping teeth yet swallowed the body trunk of the prey in one to several pieces. There were many more Mesozoic marine reptiles with similar grasping teeth, so megafaunal predation was likely more widespread than presently conceived. Megafaunal predation probably started nearly simultaneously in multiple lineages of marine reptiles in the Illyrian (about 242-243 million years ago).


Anatomical variations in the posterior part of the circle of willis and vascular pathology in bilateral thalamic infarction.
Bilateral paramedian thalamic infarction is a rare subtype of stroke the etiology of which still remains undetermined in many patients. From a computed tomography (CT)/magnetic resonance imaging report database, we identified and analyzed 48 patients with bilateral paramedian thalamic infarction on diffusion-weighted imaging. Vascular pathologies were noted on CT angiography (CTA)/magnetic resonance angiography (MRA) and the P1 segments of the posterior cerebral artery (PCA) described as normal, hypoplastic, or absent. Vascular imaging revealed top of the basilar artery (BA) occlusion in 6 (12.5%), BA occlusion in 4 (8.3%), BA stenosis in 1 (2.1%), and BA hypoplasia in 3 (6.3%), PCA occlusion in 4 (8.3%), and PCA stenosis in 4 (8.3%) patients. In 18 (37.5%) patients, one or both P1 segments of the PCA were hypoplastic or absent. Patients with hypoplastic/absent P1 segments were more likely to have exclusively bilateral paramedian thalamic lesions (P < .001). An embolic source could be identified in 25 (55.6%) patients; there were no significant differences between both groups. Vascular imaging is useful to determine underlying vascular pathologies and may support the diagnosis of small vessel disease in those patients with isolated bilateral paramedian thalamic infarction, hypoplastic/absent P1 segment of the PCA, and lack of vascular pathology.


Solid state NMR: new tools for insight into enzyme function.
NMR has had considerable impact in enzymology, probing evidence for ionization states, conformational 'strain', compressed interactions, electronically unusual species, and conformational dynamics of enzymes. Solid-state NMR is becoming increasingly important in studying enzymes because of a number of recent tools for analysis of proteins by SSNMR, and because of the growing ability to isolate the species of interest for analysis. Here, we review recent studies of a Michaelis complex, of the dynamic functioning of membrane-associated enzymes, and initial studies of several enzymes with redox-active and paramagnetic centers.


Structural basis of α1A-adrenergic receptor activation and recognition by an extracellular nanobody.
The α1A-adrenergic receptor (α1AAR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. α1AAR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human α1AAR bound to the endogenous agonist noradrenaline, its selective agonist oxymetazoline, and the antagonist tamsulosin, with resolutions range from 2.9 Å to 3.5 Å. Our active and inactive α1AAR structures reveal the activation mechanism and distinct ligand binding modes for noradrenaline compared with other adrenergic receptor subtypes. In addition, we identified a nanobody that preferentially binds to the extracellular vestibule of α1AAR when bound to the selective agonist oxymetazoline. These results should facilitate the design of more selective therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family.


Photocatalytic degradation of bisphenol a from aqueous solution using bismuth ferric magnetic nanoparticle: synthesis, characterization and response surface methodology-central composite design modeling.
Bisphenol A (BPA), as endocrine-disrupting compound (EDC), is extensively used as an important chemical in the synthesis of polycarbonate polymers and epoxy resins. BPA absorption into the body can result in the development of metabolic disorders such as low sex-specific neurodevelopment, immune toxicity, neurotoxicity and interference of cellular pathway. Therefore, the presence of BPA in the body and the environment can create hazards that must reach standards before being discharged into the environment. In this study, bismuth ferric nanomagnetic (BFO NMPs) were successfully synthesized via sol-gel method and developed as photocatalysts for BPA removal under visible light irradiation. FE-SEM, TEM, PL, XRD, UV-Vis DRS, VSM, EDX, and FTIR were used to characterize the BFO NMPs. RSM model (R2 = 0.9745) showed a good correlation between experimental and predicted removal efficiency of BPA. The investigation of four independent variables indicated that pH had the most significant positive effect on the degradation of BPA. Under optimal conditions (pH = 4.042, catalyst dose = 7.617 mg, contact time = 122.742 min and BPA concentration = 15.065 mg/L), maximum degradation was calculated to be 98.7%. After five recycles, the removal of BPA remained >82%, which indicated the proper ability to reuse the catalyst. In conclusion, it can be stated like BPA, the prepared BFO NMPs is a promising photocatalyst for practical application in organic pollutant decomposition.


Coexpression of VGLUT1 and VGLUT2 in precerebellar neurons in the lateral reticular nucleus of the rat.
Vesicular glutamate transporter (VGLUT) 1 and VGLUT2 have been reported to distribute complementally in most brain regions and have been assumed to define distinct functional elements. Previous studies have shown the expression of VGLUT1 mRNA and VGLUT2 mRNA in the lateral reticular nucleus (LRN), a key precerebellar nucleus sending mossy fibers to the cerebellum. In the present study, we firstly examined the coexpression of VGLUT1 and VGLUT2 mRNA in the LRN of the rat by dual-fluorescence in situ hybridization. About 81.89 % of glutamatergic LRN neurons coexpressed VGLUT1 and VGLUT2 mRNA, and the others expressed either VGLUT1 or VGLUT2 mRNA. We then injected the retrograde tracer Fluogold (FG) into the vermal cortex of cerebellum, and observed that 95.01 % and 86.80 % of FG-labeled LRN neurons expressed VGLUT1 or VGLUT2 mRNA respectively. We further injected the anterograde tracer biotinylated dextran amine (BDA) into the LRN, and found about 82.6 % of BDA labeled axon terminals in the granular layer of cerebellar cortex showed both VGLUT1- and VGLUT2-immunoreactivities. Afterwards, we observed under electron microscopy that anterogradely labeled axon terminals showing immunoreactivity for VGLUT1 or VGLUT2 made asymmetric synapses with dendritic profiles of cerebellar neurons. Finally, we selectively down-regulated the expression of VGLUT1 mRNA or VGLUT2 mRNA by using viral vector mediated siRNA transfection and detected that the fine movements of the forelimb of rats were disturbed. These results indicated that LRN neurons coexpressing VGLUT1 and VGLUT2 project to the cerebellar cortex and these neurons might be critical in mediating the forelimb movements.


Thoracoscopic lobectomy and segmentectomy for infectious lung disease.
The potential benefits of thoracoscopic lobectomy and segmentectomy for early stage non-small cell lung cancer have been well documented in the literature. However, little is known about the use of these techniques in patients requiring resection for infectious or inflammatory lung disease. Using a prospectively collected database, we performed a retrospective review of consecutive operations from July 2004 to June 2010. All patients who underwent elective thoracoscopic lobectomy or segmentectomy for focal bronchiectasis or cavitary lung disease associated with active pulmonary infection were included. In all, 212 resections were performed in 171 patients. The average age was 59 years (range, 26 to 82 years). Patients were predominately white (93%) and female (93%). Indications for surgery included recurrent active infection, hemoptysis, or antibiotic intolerance associated with focal bronchiectasis (86%), cavitary disease (7%), or both (7%). Operations included 126 lobectomies, 73 segmentectomies, 10 lobe plus segmental resections, and 3 bilobectomies. Conversion to thoracotomy occurred in 10 patients. The operative mortality rate was zero. Complications occurred in 9%, consisting largely of prolonged air leak and atrial fibrillation. The mean hospital length of stay was 3.7 days. Thoracoscopic lobectomy and segmentectomy for individuals with infectious lung disease can be accomplished safely with minimal morbidity and mortality. These techniques may provide the optimal surgical approach for patients with focal bronchiectasis or cavitary lung disease requiring resection.


Dynamic Anterior Stabilization of the Shoulder: Onlay Biceps Transfer to the Anterior Glenoid Using the Double Double-Pulley Technique.
The treatment of anterior glenohumeral instability includes several surgical options, ranging from soft tissue to bony procedures-open or arthroscopic. In arthroscopic dynamic anterior stabilization (DAS) of the shoulder, the long head of the biceps is transferred to the anterior glenoid through a subscapularis tendon split. The biceps may be fixed either in an inlay or in an onlay position. Inlay DAS theoretically increases anterior glenohumeral stability through 3 different effects: the hammock effect, sling effect, and the tensioning effect. Onlay DAS may additionally increase stability through a labroplasty effect, produced by the onlay positioning of the biceps on the anterior glenoid rim. The current technical note presents tips and tricks, and pearls and pitfalls, to reproducibly perform onlay DAS using all-suture anchors and the double double-pulley technique.


Mortality among hospitalized COVID-19 patients during surges of SARS-CoV-2 alpha (B.1.1.7) and delta (B.1.617.2) variants.
The aim of this study was to evaluate the death proportion and death risk of COVID-19 hospitalized patients over time and in different surges of COVID-19. This multi-center observational study was conducted from March 21, 2021 to October 3, 2021 which included the alpha and delta SARS-CoV-2 surges occurred in April and August in Tehran, respectively. The risk of COVID-19 death was compared in different months of admission. A total of 270,624 patients with COVID-19, of whom 6.9% died, were admitted to hospitals in Tehran province. Compared to patients admitted in March, a higher risk of COVID-19 death was observed among patients admitted to the hospital in July (HR 1.28; 95% CI 1.17, 1.40), August (HR 1.40; 95% CI 1.28, 1.52), September (HR 1.37; 95% CI 1.25, 1.50) and October (HR 4.63; 95% CI 2.77, 7.74). The ICU death proportion was 36.8% (95% CI: 35.5, 38.1) in alpha surge and increased significantly to 39.8 (95% CI 38.6, 41.1) in delta surge. The risk of COVID-19 death was significantly higher in delta surge compared to alpha surge (HR 1.22; 95% CI 1.17, 1.27). Delta surge was associated with a higher risk of death compared to alpha surge. High number of hospitalizations, a shortage of hospital beds, ICU spaces and medical supplies, poor nutritional status of hospitalized patients, and lack of the intensivist physicians or specialized nurses in the ICU were factors that contributed to the high mortality rate in the delta surge in Iran.


Data-driven comparison of multiple high-dimensional single-cell expression profiles.
Comparing multiple single-cell expression datasets such as cytometry and scRNA-seq data between case and control donors provides information to elucidate the mechanisms of disease. We propose a completely data-driven computational biological method for this task. This overcomes the challenges of conventional cellular subset-based comparisons and facilitates further analyses such as machine learning and gene set analysis of single-cell expression datasets.


Lateralized auditory brain function in children with normal reading ability and in children with dyslexia.
We examined central auditory processing in typically- and atypically-developing readers. Concurrent EEG and MEG brain measurements were obtained from a group of 16 children with dyslexia aged 8-12 years, and a group of 16 age-matched children with normal reading ability. Auditory responses were elicited using 500ms duration broadband noise. These responses were strongly lateralized in control children. Children with dyslexia showed significantly less lateralisation of auditory cortical functioning, and a different pattern of development of auditory lateralization with age. These results provide further evidence that the core neurophysiological deficit of dyslexia is a problem in the balance of auditory function between the two hemispheres.


TRPC6 and kidney disease: sclerosing more than just glomeruli?
Fibrosis is a common response to injury but can also perpetuate tissue dysfunction. Transient receptor potential C6 (TRPC6) is implicated in cardiac and skin healing via regulation of myofibroblast differentiation. Wu et al. now demonstrate a role for TRPC6 in renal fibrosis, via a mechanism that also relies on TRPC3 and is antagonized by soluble klotho. Modulation of TRPC3/6 activity may provide a means of dampening the fibrotic response involved in chronic kidney disease progression.


Defining causal mediation with a longitudinal mediator and a survival outcome.
In the context of causal mediation analysis, prevailing notions of direct and indirect effects are based on nested counterfactuals. These can be problematic regarding interpretation and identifiability especially when the mediator is a time-dependent process and the outcome is survival or, more generally, a time-to-event outcome. We propose and discuss an alternative definition of mediated effects that does not suffer from these problems, and is more transparent than the current alternatives. Our proposal is based on the extended graphical approach of Robins and Richardson (in: Shrout (ed) Causality and psychopathology: finding the determinants of disorders and their cures, Oxford University Press, Oxford, 2011), where treatment is decomposed into different components, or aspects, along different causal paths corresponding to real world mechanisms. This is an interesting alternative motivation for any causal mediation setting, but especially for survival outcomes. We give assumptions allowing identifiability of such alternative mediated effects leading to the familiar mediation g-formula (Robins in Math Model 7:1393, 1986); this implies that a number of available methods of estimation can be applied.


The effects of mirex on the neonatal rat lens in vitro, with a comparison to kepone.
Lenses were removed from 12-day-old rats and incubated in medium containing 20 microM mirex. Lenses were removed from the medium at 2, 4, 6, and 8 h and assayed for K+ and Na+ concentrations and hydration. Mirex had no in vitro effect on these lens parameters compared to controls, and produced no changes in lens clarity. In contrast, incubation for 8 h in medium containing 20 microM kepone resulted in elevated lens Na+ and lower lens K+. Thus, cataracts induced by mirex in vivo are probably not due to a direct toxic effect on the lens.


[Acute phase of stroke: every minute counts].
Cerebral infarction (CI) is caused by intracranial artery occlusion. The main treatment approach is recanalisation, which is performed either medically, by intravenous thrombolysis within 4 hours and a half of the event, or by mechanical thrombectomy, which is possible up to 24 hours after CI.


Protein kinase C inhibitors enhance concanavalin A cap formation in polymorphonuclear leukocytes.
The potent protein kinase C (PKC) inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine, significantly enhanced concanavalin A (Con A)-induced cap formation in polymorphonuclear leukocytes (PMNs) from C57BL/6 mice after pretreatment for 30 min at concentrations of 10 microM and 1 nM, respectively. However, neither 10 microM of N-(2-aminoethyl)-5-isoquinolinesulfonamide dihydrochloride (H-9) nor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004), which inhibit cyclic nucleotide-dependent protein kinases more effectively than other kinases, affected the capping. Meanwhile, treatment of PMNs with Con A induced the translocation of PKC from the cytosol to the membrane fraction within 5 min, which is considered to be important for the activation of this enzyme. When cells were pretreated with H-7 or staurosporine for 30 min at the concentrations that enhanced the capping, both the cytosolic and the membrane-bound PKC activity was inhibited during the further incubation with Con A. These results suggest that PKC may play an important role in the regulation of Con A-induced cap formation in PMNs.


Insertion of amphiphilic molecules into membranes is catalyzed by a high molecular weight non-ionic surfactant.
We have employed an amphiphilic fluorescent probe to elucidate the mechanism by which a class of oxyethylene-oxypropylene copolymers catalyzes the insertion of hydrophobic or amphiphilic molecules into membranes. The rate of binding can be accelerated by over two orders of magnitude in the presence of the catalyst which does not itself disrupt the lipid bilayer. The rate of probe binding to lipid vesicles does not depend on the lipid concentration in the presence or absence of catalyst but is linearly related to the concentration of the catalyst. Probe binding to the polyol surfactant appears to be a component of the catalytic mechanism and equilibrium binding parameters can be determined; these are used to indirectly establish quantitative binding parameters for the probe to the vesicle membrane. The polyol surfactant is also shown to catalyze insertion of the probe into the outer leaflet of a hemispherical lipid bilayer and the plasma membrane of HeLa cells. The latter were also stained by catalyzed transfer of a fluorescent lipid from lipid vesicles. The permeability of the cell membrane is not significantly altered under any of the catalytic conditions. These data, taken together, suggest that the polyol surfactant extracts a monomeric substrate molecule from its aggregate or microcrystal and passes it to the membrane via a loose and transient contact.


The factors associated with mortality and progressive disease of nontuberculous mycobacterial lung disease: a systematic review and meta-analysis.
This systematic review and meta-analysis aimed to comprehensively evaluate the factors associated with mortality and progressive disease in NTM-LD patients. We conducted a literature search to identify the eligible studies, dated between January 1, 2007, and April 12, 2021. Forty-one studies with total 10,452 patients were included. The overall all-cause mortality rate was 20% (95% CI 17-24%). The overall rates of clinical and radiographic progressive disease were 46% (95% CI 39-53%) and 43% (95% CI 31-55%), respectively. Older age, male sex, history of TB, diabetes, chronic heart disease, malignancy, systemic immunosuppression, chronic liver disease, presence of cavity, consolidative radiologic features, acid-fast bacillus (AFB) smear positivity, hypoalbuminemia, anemia, increasing platelet count, high CRP, and high ESR were significantly associated with increased all-cause mortality, whereas increasing body mass index (BMI), hemoptysis, and treatment with rifamycin regimen (in M. xenopi) were significantly associated with decreased all-cause mortality in multivariable analysis. History of TB, Aspergillus co-infection, cough, increased sputum, weight loss, presence of cavity, and AFB smear positivity were significantly associated with increased clinical progression with treatment, while older age and low BMI were significantly associated with decreased clinical progression in multivariable analysis. Older age, interstitial lung disease, presence of cavity, consolidative radiologic feature, anemia, high CRP, and leukocytosis were significantly associated with increased radiographic progression after adjusting for covariates. Older age, history of tuberculosis, presence of cavity, consolidative radiologic features, AFB smear positivity, anemia, and high C-reactive protein were common significant factors associated with the all-cause mortality and clinical or radiographic progressive disease of NTM-LD. These factors are thought to directly affect NTM-LD related mortality. The future prediction models for the prognosis of NTM-LD should be established considering these factors.


Alpha/beta intraepithelial lymphocytes, serum gliadin antibodies and allergy test positivity in children.
To determine whether the amount of alphabeta-positive intraepithelial lymphocytes (IELs) is connected to allergy test positivity in children with gastrointestinal symptoms and whether elevated serum gliadin antibodies have any role in the diagnosis. Twenty-seven children suffering from gastrointestinal-symptoms in whom intestinal biopsies had previously been obtained via endoscopy or with capsule biopsy to exclude coeliac disease were included into the study. The other inclusion criteria were increased amounts of CD3 and alphabeta-positive IELs with normal amounts of gammadelta-positive IELs in duodenal or jejunal biopsy specimens. At the control visit, the children underwent a physical examination and parents filled in a questionnaire concerning gastrointestinal- and atopic symptoms. Skin prick- and patch tests were done and serum gliadin, endomysium, transglutaminase antibodies and specific IgEs were measured. Only nine children (33%) had at least one positive result in the allergy tests, the rest remaining test negative. In children with digestive symptoms, IgG-class gliadin antibody titres were higher than those of the non-symptomatic children. A significant correlation was found between IgG-class gliadin antibodies and total amount of alphabeta-positive IELs (p = 0.017). No positive skin test or specific IgE positivity for cereals in children with high intestinal T-cell densities was observed. The correlation between IgG-class gliadin antibodies and the total amount of alphabeta-TCR positive-cells is likely to be a reflection of local immune response of the gut.


The effect of estrogens and antiestrogens in a rat model for hot flush.
The present studies evaluated the effect of estrogens and the selective estrogen receptor modulator (SERM) tamoxifen and raloxifene in a rat model for hot flush. In this model, ovariectomized rats were treated for 8 or 9 days either sc or po. Rats were dependent to morphine by implanting a morphine pellet (75 mg each) sc on days 3 and 5 of treatment. On the last day of treatment, a thermistor, connected to a data acquisition system, was placed on the tail of each animal and morphine addiction was withdrawn by naloxone injection (1.0 mg/kg, sc). Temperature measurements were taken for 1 h under ketamine (80 mg/kg, im) anesthesia. In general, vehicle treated rats showed a 5-6 degrees C elevation of their tail skin temperature with the peak occurring about 15 min after naloxone injection. 17 alpha-Ethinyl estradiol (EE) was evaluated both sc and po using a broad range of doses. The IC50 for inhibition of tail skin temperature rise was approximately 0.1 mg/kg, sc and 0.2 mg/kg, po. 17 beta-Estradiol and 17 alpha-estradiol were also active in this model whereas non-estrogenic steroids were inactive. Raloxifene and tamoxifen were tested for estrogen agonist and antagonist activity administered sc and po. Raloxifene did not demonstrate reproducible estrogen agonist activity at doses up to 10 mg/kg, whereas it demonstrated significant antagonistic activity at the 10 mg/kg dose regardless of the route of administration. Tamoxifen exhibited significant estrogen agonist activity at all doses tested (0.1-10.0 mg/kg) and was a significant antagonist of EE at the 1.0 mg/kg dose. Our results demonstrate the potential utility of this model to evaluate and discriminate among classes of compounds with varying degrees of estrogen agonist and antagonist activity.


Effect of a low-dose endotoxin pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine in rats.
The effect of endotoxin pretreatment (1 mg/kg body weight, i.p., once daily for 2 days) on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine has been studied in albino rats. When given alone, endotoxin did not produce any visibly discernible gastric lesions. It produced a significant augmentation of the gastric lesions produced by phenylbutazone and reserpine but did not significantly alter the ulcerogenicity of aspirin. The involvement of endogenous histamine formation and its release following phenylbutazone and reserpine administration and also in response to endotoxin pretreatment may be responsible for the exacerbation of gastric lesions induced by these drugs. Recent reports indicate the involvement of endorphins and platelet activating factor (PAF) in the ulcerogenic activity of endotoxin when used in high doses and their role in the potentiation of phenylbutazone- and reserpine-induced gastric lesions has to be worked out.


[Potentials of and approaches to prevention. Current developments in Germany].
Prevention and health promotion are rewarding investments to stabilize our health security systems. They yield sustainable social and individual profit. This is precisely one of the explicitly declared aims of the government's coalition agreement of October 2002 - to upgrade and extend prevention and health promotion in Germany. The Federal Ministry of Health and Social Security is initiating measures and strategies to improve the framework for effective prevention and health promotion, for instance by initiating measures in the field of legislation and by establishing the German Platform for Prevention und Health Promotion.


The impact of paternal mental illness on child development: an umbrella review of systematic reviews and meta-analyses.
Whilst there is growing evidence highlighting the importance of paternal mental illness (PMI) on child development, this relationship still remains under-studied and often over-looked. Considering the increasingly active role of fathers in their children's upbringing, a comprehensive overview of the impact of PMI on child development is overdue. This study aimed to combine and synthesise currently available evidence on the relationship between PMI and multiple domains of child development. Narrative synthesis of systematic reviews and meta-analyses on the relationship between PMI and child development (mental health and social, emotional, language, cognitive or adaptive behaviour), published between 1980 to December 2021, was conducted in line with PRISMA 2020 guidelines. Review quality was assessed based on AMSTAR-2 criteria and respective study confidence was interpreted in line with GRADE scoring. All relevant meta-analytic effect sizes were converted to odds ratios (OR) and grouped using a random effects model. Grouped meta-analyses saw PMI to have a significant, detrimental effect on all studied domains of child development [OR: 1.54; 95% CI (1.36-1.74)]. Subgroup analyses saw PMI affecting both internalising [OR: 1.62; 95% CI (1.27-2.08)] and externalising [OR: 1.63; 95% CI (1.28-2.08)] child behaviours to a similar extent. However, included reviews were of poor methodological quality, demonstrating either low or critically low confidence. These results show a consistent and influential effect of PMI on child development. The relationship between fathers' mental illness and child development warrants further investigation, as current research is limited in scope, particularly regarding cognitive domains of child development and non-affective PMI diagnoses.


Trainee Distress When Faced with End-of-Life Care in Neurology: A Qualitative Analysis.
To identify sources of distress experienced by trainees when providing neuropalliative care and to explore the perceived and unperceived educational needs of trainees learning to deliver neuropalliative care. This study is a post hoc analysis of a qualitative investigation performed at a single Canadian academic center with active clinical services in palliative medicine, neurology, and neurosurgery. Grounded theory methodology was used to explore trainees' perspectives when learning neuropalliative care. This study used focus groups, using open-ended questions, to elicit participants' experiences providing neuropalliative care as well as to explore the challenges in neuropalliative care. Qualitative analysis identified multiple sources of distress for trainees in neuropalliative care and broad themes emerged: 1) a lack of experience and knowledge, 2) the emotional toll of learning neuropalliative care, and 3) prognostic uncertainty in neuropalliative care. Our results suggest that palliative neurology curricula should focus not only on symptom management but also on strategies for improving communication about prognosis and managing clinical uncertainty. Improving trainee comfort and confidence in neuropalliative care throughout the illness trajectory may alleviate sources of distress during training and increase quality of care.


Risk comparison of osteonecrosis of the jaw in osteoporotic patients treated with bisphosphonates vs. denosumab: a multi-institutional retrospective cohort study in Taiwan.
In this multi-institutional retrospective cohort study, we compared the long-term risk of osteonecrosis of the jaw following the use of denosumab vs. bisphosphonates in osteoporotic patients. After 2-year use, the likelihood of osteonecrosis of the jaw is lower with denosumab compared to bisphosphonates, and the difference increases with time. To compare the long-term risk of osteonecrosis of the jaw (ONJ) between osteoporotic patients treated with bisphosphonates (BPs) and denosumab. This multi-institutional retrospective cohort study included patients aged > 40 years with osteoporosis between January 2010 and December 2018. Patients who met the eligibility criteria were divided into BPs and denosumab groups by propensity score matching (PSM). The risk of ONJ of denosumab vs. BPs was estimated using a Cox proportional hazards model and was described by the cumulative incidence rate using the Kaplan-Meier method. A total of 84,102 patients with osteoporosis were enrolled, among whom, 8962 were eligible for inclusion based on their first-line drug use (denosumab, n = 3,823; BPs, n = 5,139). Following PCM matching (1:1), the BPs and denosumab groups included 3665 patients each. The incidence density of ONJ in the denosumab and BPs matching groups was 1.47 vs. 2.49 events (per 1000 person-years), respectively. The hazard ratio of ONJ in the denosumab vs. BPs group was estimated as 0.581 (95% confidence interval: 0.33-1.04, p = 0.07). The cumulative incidence rates of ONJ in both groups were similar for the first and second years of drug use (p = 0.062), but significantly different from the third year onwards (p = 0.022). The severity of ONJ was not significantly different between the two groups. In osteoporotic patients, after 2 years of use, the likelihood of ONJ being induced by denosumab is lower than that of BPs, and the difference increases with time.


Role of minimally invasive surgery in the treatment of diverticular disease: an evidence-based analysis.
The clinical spectrum of diverticular disease varies from asymptomatic diverticulosis to symptomatic disease with potentially fatal complications, such as perforation or bleeding. While the presence of diverticula is common, symptomatic diverticulitis is relatively uncommon, occurring in an estimated 10-30 % of patients. There is continued debate as to whether patients should undergo elective resection for diverticular disease and regarding the role of minimally invasive surgery. Since the first publication on laparoscopic colorectal procedures, the interest in minimally invasive surgery has kept growing. Laparoscopic sigmoid resection with restoration of continuity is currently the prevailing modality for treating acute and recurrent sigmoid diverticulitis. However, it still remains unclear whether laparoscopy should be recommended also for complicated sigmoid diverticulitis. The potential benefits of reduced pain and analgesic requirements, smaller scars, and shorter hospital stay but longer operative times are appealing to both patients and surgeons. Nevertheless, there many concerns regarding the time and the type of surgery. Although the role of minimally invasive surgery in the treatment of colonic diseases is progressively increased, current randomized controlled trials should demonstrate whether laparoscopic lavage, Hartmann's procedure or resection and anastomosis achieve the best results for patients. This review aimed to analyze the results of laparoscopic colonic resection for patients with uncomplicated and complicated forms of sigmoid diverticular disease and to determine what stages profit from a laparoscopic procedure and whether the approach can be performed with a low complication rate even for patients with complicated forms of the disease.


Osteonecrosis of the jaw: who gets it, and why?
Osteonecrosis of the jaw (ONJ) is now defined by the presence of exposed bone in the mouth, which fails to heal after appropriate intervention over a period of six or eight weeks. It is commonly precipitated by a tooth extraction in patients treated with zoledronate, pamidronate or a combination of these agents, for the management of myeloma, breast cancer or prostate cancer. In patients with these malignancies who are treated with bisphosphonates, the overall prevalence is about 5%. There is a need to clearly delineate the incidence of ONJ in osteoporosis patients treated with bisphosphonates, and in appropriate control populations. Based on current evidence, the risk of ONJ in osteoporosis appears to be comparable to that in the general population. It is likely that ONJ results from direct toxicity to cells of bone and soft tissue from high potency bisphosphonates, probably acting through their effects on the mevalonate pathway. The bone in ONJ lesions does not appear to be 'frozen', rather there is very active resorption present, probably stimulated by local infection. This is likely to result in the local release at high concentrations of bisphosphonates. Management focuses on prevention, treatment of infection and cessation of bisphosphonates. The role of surgery is unclear.


Trends in mortality inequalities in an urban area: the influence of immigration.
Nearly 20% of the population in Barcelona is foreign-born and this percentage rises to up to 40% in some neighborhoods. Consequently, migration health patterns may play an important role in trends in socioeconomic geographical inequalities in mortality. The objective of this study was to analyze the trend in socioeconomic inequalities in mortality between neighborhoods in Barcelona during the period 2001-2012 in the foreign-born and Spanish-born population. Repeated cross-sectional design of the population aged 25-64 years in Barcelona between 2001 and 2012. Hierarchical data consisted of yearly mortality linked-population. The variables analyzed were age, sex, education, and country of birth (Spanish-born, foreign-born), neighborhood of residence, and the socioeconomic level of the neighborhoods using quartiles of unemployment rates. Age-standardized mortality rates were estimated, and mixed Poisson regressions were applied using generalized linear mixed models, including two random effects to consider the intracorrelation within neighborhoods and across years. The number of foreign-born residents aged 25-64 increased notably in disadvantaged neighborhoods. Approximately 9% of premature deaths occurred in foreign-born individuals. Premature mortality rates were higher in disadvantaged neighborhoods and in the Spanish-born population in all periods. Despite the stabilized socioeconomic inequalities in mortality in the Spanish-born population, no inequalities were found between neighborhoods in foreign-born men and women. Evidence of the 'healthy migrant' effect in mortality and socioeconomic inequalities in mortality was found in Barcelona, which seems to alter the distribution of mortality through time and space, related to the low levels of premature mortality and the selective residence of immigrants in socioeconomically disadvantaged neighborhoods.


Crural repair permits morbidly obese patients with not large hiatal hernia to choose laparoscopic adjustable banding as a bariatric surgical treatment.
Hiatal hernia, present radiologically in about 50% of patients desiring bariatric surgery, has been thought a contraindication to laparoscopic adjustable gastric banding (LAGB). Posited was the notion that adding crural repair to LAGB would enable this procedure to be offered to patients desiring bariatric surgery who had hiatal hernias. After obtaining IRB approval, charts of all patients who underwent simultaneous crural repair and LAGB from June 2003 to January 2006 were reviewed. All patients were evaluated with the DeMeester score and the GERD-HQRL score pre- and postoperatively. Statistical analyses included the Mann-Whitney U test and the Chi-squared test. Twenty-one patients underwent laparoscopic procedure with crural repair; none required conversion to an open procedure. There were no mortalities. Two complications, a wound infection at the level of the port, and a case postoperative dysphagia resolved with therapy. Eighty-six percent of the patients ceased regular intake of heartburn medicines, P<.01. Median percent excess weight loss was 45% at 1 year and 55% at 2 years. The modified DeMeester score fell to 0-2 postoperatively (P<.01). Two years after the procedure, symptoms were less, as assessed by GERD-HQRL scores (P<.01). Crural repair permits LAGB to be safely and effectively performed in patients with hiatal hernia.


Visualization of the intestinal tract by amniography in a fetus with esophageal atresia.
In pregnancies complicated by hydramnios, amniography can be used for the detection of fetal gastrointestinal obstruction. A case is presented in which the appearance of contrast material in the fetal gastrointestinal tract was noted in an infant who proved to have esophageal atresia and tracheoesophageal fistula. Presumably, the contrast reached the intestinal tract by aspiration and passage through the fistula.


Measles blindness.
Measles remains a major problem in developing countries, where it affects an estimated 30 million children a year and causes up to one million deaths annually. Measles blindness is the single leading cause of blindness among children in low income countries, accounting for an estimated 15,000 to 60,000 cases of blindness per year. There is a close synergism between measles and vitamin A deficiency that can result in xerophthalmia, with corneal ulceration, keratomalacia, and subsequent corneal scarring or phthisis bulbi. High-dose oral vitamin A supplementation is recommended for all children with measles in developing countries. Higher measles immunization coverage to interrupt measles transmission and interventions aimed at improving vitamin A nutriture of children are the main strategies to prevent measles blindness.


Fatty acid metabolism in symptomatic patients with mitral valve prolapse but without coronary artery disease--comparison with 201Tl myocardial perfusion scintigraphy.
Using 123I-omega-heptadecanoic acid (HDA) and 201Tl, respectively, myocardial fatty acid metabolism and perfusion were studied in 51 symptomatic patients with mitral valve prolapse (MVP) as diagnosed by ventriculography, and no evidence of coronary artery disease. Twelve subjects with normal coronary arteries and normal ventriculogram served as a control group for the evaluation of elimination kinetics of HDA. In the control group, the mean elimination half-life was 26.1 +/- 3.6 min, whereas the patients with MVP had a mean value of 25.0 +/- 6.4 min. In patients with MVP, a high incidence concerning abnormalities of accumulation and/or elimination of HDA occurred, namely accumulation defects in 31% and both prolonged and shortened elimination half-lives in 16% and 29%, respectively. Myocardial perfusion scintigraphy using 201Tl showed abnormalities in 76%. Correlations were found between decreased uptake of HDA and prolonged elimination half-life as well as defects by 201Tl, presumably due to ischemia based on small-vessel disease or abnormalities of cellular metabolism.


Expression of p53 protein in malignant melanoma: clinicopathological and prognostic implications.
In the present study, we investigated the expression of the tumour suppressor protein p53 in 113 primary and 43 metastatic malignant melanomas by immunohistochemistry, and correlated the findings with clinicopathological parameters such as histological melanoma subtype, thickness of primary melanomas (Breslow thickness) and patient outcome. In primary melanomas, the polyclonal anti-p53 antibody CM-1 detected immunoreactivity in 70% of the lesions, predominantly in the cytoplasm. Signals were observed in this cellular compartment in 57% of the melanomas, whereas in 32% nuclear p53 over-expression was detected. Immunohistochemistry, using the monoclonal antibody DO-1, revealed lower staining frequencies. However, both antibodies showed congruent results in approximately 80% of the cases. Overall, immunoreactivity was observed in 73% of superficial spreading melanomas, but only in 52% of lentigo maligna melanomas. This difference (P < 0.001) was mainly due to a lower frequency of cytoplasmic immunoreactivity (P < 0.002). There was no difference with respect to cytoplasmic and nuclear immunoreactivity between thin (< 1 mm thickness) and thicker primary melanomas. Staining frequencies detected in metastatic lesions seemed to be lower than in primary tumours. In 103 primary melanomas, follow-up data for at least 5 years were available. In 71% (54 of 76) of the primary melanomas which did not recur, and in 78% (21 of 27) of tumours with subsequent metastases, p53 over-expression was detected by CM-1. However, this difference was not statistically significant. The results of the present study indicate that immunoreactivity to anti-p53 antibodies is a common observation in malignant melanomas, with staining signals predominantly found in the cytoplasm of cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Squamous cell carcinoma of the skin. Accuracy of clinical diagnosis and outcome of follow-up in Australia.
The accuracy of the clinical diagnosis of 1292 non-melanotic skin tumours that were submitted to a private pathology service in 1980-1981 was determined. The clinical diagnosis that was written on the pathology slip which was submitted with the tumour was correlated with the histological diagnosis and the type of medical practitioner submitting the lesion. The clinical diagnosis was most accurate in the case of basal cell carcinoma; dermatologists most often reached this diagnosis correctly. For squamous cell carcinoma, although most frequently the lesions were diagnosed correctly clinically by dermatologists, their clinical diagnosis was confirmed in only 51% of cases. On average, 36% of squamous cell carcinomas were diagnosed clinically as basal cell carcinomas. The clinical course of 299 patients with a total of 305 squamous cell carcinomas that were selected from the squamous cell carcinomas that were submitted in 1980-1981 was traced. Four tumours (1.6%) which occurred in sun-exposed areas of the body metastasized, and 18 (7.5%) recurred locally. We conclude that those non-melanotic skin tumours which have the most potential to metastasize (squamous cell carcinomas) are those which are most poorly diagnosed clinically. It is recommended that patients with non-melanotic skin cancers should undergo biopsy as a routine to confirm the clinical diagnosis. Those who have a squamous cell carcinoma removed should be followed up for at least two years after the initial treatment.


Evaluation of the outcomes of corneal collagen cross-linking in progressive keratoconic eyes.
Corneal collagen cross-linking (CXL) is gaining popularity as a treatment in arresting the progression of keratoconus. It is a relatively new therapy using ultraviolet-A (UVA) with a photosensitizer to increase corneal stiffness. The purpose of this study was to evaluate visual, keratometric and topographic outcomes after corneal CXL in progressive keratoconic eyes. In this prospective nonrandomized clinical study, 140 eyes of 110 patients with progressive keratoconus were treated by combined riboflavin/UVA CXL. Mean sphere, mean cylinder uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refractive spherical equivalent, corneal topography, pachymetry, and endothelial cell morphology were examined preoperatively and 12-24 months postoperatively. The preoperative mean sphere was -3.33 ± 3.13 diopter (D) and decreased to -3.09 ± 3.09 D (P = 0.007). The preoperative mean cylinder was -4.05 ± 2.29 D and changed to -3.79 ± 2.23 D (P = 0.011). UDVA changed from 0.95 ± 0.64 logarithm of the minimum angle of resolution (logMAR) to 0.85 ± 0.59 logMAR (P = 0.003). Thirty-five eyes (25%) gained one or more lines of preoperative UDVA, 87 eyes (62.1%) did not change and 18 eyes (12.8%) lost one or more lines of the preoperative UDVA. CDVA in 80% of the patients remained stable (no lines lost). Statistical analysis of keratometry, pachymetry, and endothelial cell count did not show the significant difference after surgery. Our study showed improvement in visual and refractive results of the corneal CXL and confirmed that CXL is the safe and effective procedure.


Genome-Scale Metabolic Model Analysis of Metabolic Differences between Lauren Diffuse and Intestinal Subtypes in Gastric Cancer.
Gastric cancer (GC) is one of the most lethal cancers worldwide; it has a high mortality rate, particularly in East Asia. Recently, genetic events (e.g., mutations and copy number alterations) and molecular signaling associated with histologically different GC subtypes (diffuse and intestinal) have been elucidated. However, metabolic differences among the histological GC subtypes have not been studied systematically. In this study, we utilized transcriptome-based genome-scale metabolic models (GEMs) to identify differential metabolic pathways between Lauren diffuse and intestinal subtypes. We found that diverse metabolic pathways, including cholesterol homeostasis, xenobiotic metabolism, fatty acid metabolism, the MTORC1 pathway, and glycolysis, were dysregulated between the diffuse and intestinal subtypes. Our study provides an overview of the metabolic differences between the two subtypes, possibly leading to an understanding of metabolism in GC heterogeneity.


Diet and men's fertility: does diet affect sperm quality?
Male contribution to a couple's fecundity is important, and identifying the dietary factors that can influence male fertility potential is of high importance. Despite this importance, there are currently no clear clinical guidelines for male patients seeking fertility treatment. In this review, we present the most up-to-date evidence about diet and male fertility in humans. We focus on the dietary factors necessary for production of healthy functioning sperm with high fertility potential. Based on this review, men may be encouraged to use antioxidant supplements and to follow dietary patterns favoring the consumption of seafood, poultry, nuts, whole grains, fruits, and vegetables. Evidence is strongest for recommending the use of antioxidant supplements to men in couples undergoing infertility treatment-although the specific antioxidants and doses remain unclear-and increasing consumption of omega-3 fatty acids from fish and nuts.


In vitro activity of cefteram against predominantly enteropathogenic and glucose nonfermentative gram-negatives.
Cefteram (T-2525), the free acid of the orally active cephalosporin ester cefteram pivoxil, was tested in vitro against 355 gram-negative clinical isolates of enteropathogenic and nonfermentative species. The compound was several times more active (w/w) against isolates belonging to the enteropathogenic Enterobacteriaceae and Vibrionaceae than against those belonging to the nonfermentative rods (excluding Pseudomonas aeruginosa).


The glycosaminoglycan of recombinant human soluble thrombomodulin affects antithrombotic activity in a rat model of tissue factor-induced disseminated intravascular coagulation.
Previous studies on recombinant human soluble thrombomodulin (rsTM) from Chinese hamster ovary cells revealed that rsTM was expressed as two proteins that differed functionally in vitro due to the presence (rsTM beta) or absence (rsTM alpha) of chondroitin-4-sulfate. The current study evaluates the in vivo behavior of rsTM in rats and in a rat model of tissue factor-induced disseminated intravascular coagulation (DIC). rsTM beta was more potent than rsTM alpha for prolongation of the activated partial thromboplastin time (APTT) and their in vivo half-lives determined by ELISA were 20 min for rsTM beta and 5.0 h for rsTM alpha. Injection of a tissue factor suspension (5 mg/kg) resulted in DIC as judged by decreased platelet counts and fibrinogen concentrations, prolonged APTT, and increased fibrin and fibrinogen degradation products (FDP) levels. A bolus injection of either rsTM (0.2 mg/kg) 1 min before induction of DIC essentially neutralized effects on platelets, fibrinogen, and FDP levels, and had only a moderate effect on APTT prolongation. The dose of anticoagulant to inhibit the drop in platelet counts by 50% (ED50) was 0.2 mg/kg rsTM alpha, 0.07 mg/kg rsTM beta, and 7 U/kg heparin. The effect of increasing concentrations of rsTM and heparin on bleeding times were compared in experiments involving incision of the rat tail. Doubling of the bleeding times occurred at 5 mg/kg rsTM alpha, 3 mg/kg rsTM beta or 90 U/kg heparin. These values represent a 25-fold increase over the ED50 for rsTM alpha, 43-fold for rsTM beta and 13-fold for heparin.(ABSTRACT TRUNCATED AT 250 WORDS)


Preliminary evaluation of anti-pyretic and anti-ulcerogenic activities of Sida cordifolia methanolic extract.
The anti-pyretic and anti-ulcerogenic properties of methanolic extract of Sida cordifolia aerial parts (MESC) were investigated in rats. Oral dose of 500 mg/kg MESC significantly reduced pyrexia induced by TAB vaccine. MESC exhibited significant anti-ulcerogenic effect against aspirin and ethanol induced damage. Both these properties were comparable to the reference drugs.


New cell line. Epithelial cell line and subline established from premalignant mouse mammary tissue.
A cell line and subline with epithelial characteristics were established from mouse mammary hyperplastic alveolar nodules (HAN). The cells do not grow in suspension cultures in vitro or form tumors in vivo. The cells do produce significant amounts of C-type and A-type virus and low amounts of plasminogen activator.


Expanding the tetrahydroquinoline pharmacophore.
Tetrahydroquinoline is a privileged scaffold with a large number of biological applications. The tetrahydroquinoline pharmacophore has been expanded to yield 34 compounds. Biological screening of these compounds led to the identification of tetrahydroquinoline as neurotropic agents not reported earlier.


A tale of two approaches: how metagenomics and proteomics are shaping the future of encephalitis diagnostics.
We highlight how metagenomics and proteomics-based approaches are being applied to the problem of diagnosis in idiopathic encephalitis. Low cost, high-throughput next-generation sequencing platforms have enabled unbiased sequencing of biological samples. Rapid sequence-based computational algorithms then determine the source of all the nonhost (e.g., pathogen-derived) nucleic acids in a sample. This approach recently identified a case of neuroleptospirosis, resulting in a patient's dramatic clinical improvement with intravenous penicillin. Metagenomics also enabled the discovery of a neuroinvasive astrovirus in several patients. With regard to autoimmune encephalitis, advances in high throughput and efficient phage display of human peptides resulted in the discovery of autoantibodies against tripartite motif family members in a patient with paraneoplastic encephalitis. A complementary assay using ribosomes to display full-length human proteins identified additional autoantibody targets. Metagenomics and proteomics represent promising avenues of research to improve upon the diagnostic yield of current assays for infectious and autoimmune encephalitis, respectively.


[Challenge prevention. From curative to preventive medicine-strategic and operational challenges].
The potentials of preventive medicine to reduce the costs of illness have been inadequately exploited to date. Even if there is still massive dissent regarding the legal setup of a prevention law, prevention should play a significantly higher role in practice. Clinicians and practitioners could use preventive medicine as another differentiating factor in the increasingly competitive healthcare field. Prevention as a new strategic business segment allows a directed reaction to the demands of the payment system and opens up enormous value-added potential at the same time. Those who seize the chance to integrate prevention into their medical services portfolio and into the structure and processes of their respective hospitals will develop an important competitive advantage for the future.


A simple and rapid method for the detection of lymphocytotoxic antibodies using cell panels frozen on Terasaki plates.
A 40 cell panel of lymphocytes selected for HLA-A,B and DR antigens, frozen in Terasaki microtest trays can be used routinely to identify the presence of specific HLA antibodies within two hours. Blind testing using well defined HLA typing sera showed that specificities could be identified to a high degree of significance using this method. The method has proved successful for screening for T cell, including HLA-A,B and B cell, including HLA-DR antibodies. The method is particularly useful for the routine tissue typing laboratory as the frozen panel can be used without the need for complicated and time-consuming cell washing procedures which have been the downfall of previously published methods.


Brains--a computer advisor system to aid in CT scan interpretation and cerebral disease diagnosis.
This paper describes a prototype system to aid in the radiological interpretation of CT scan images of patients with cerebral disease. The system is able to provide guidance, both on diagnosis and the need for enhancement.


Understanding How Gender Transformative Interventions Affect Adolescent Sexuality: A Cross-Cultural Perspective.
Early adolescence is a critical period for developing healthy sexual and reproductive health (SRH) knowledge, attitudes, and behaviors. However, a gap exists in interventions targeting very young adolescents that encompass the multilevel influences impacting healthy sexuality. This examination of two SRH programs in Indonesia and the Democratic Republic of Congo will elucidate facilitators and barriers to improving young adolescent sexuality. The Growing Up Great! (GUG) intervention in the Democratic Republic of Congo and Semangat Dunia Remaja or Teen Aspirations intervention in three districts in Indonesia were evaluated using the Global Early Adolescent Study survey. Adolescents were interviewed in 2017 and one year later in Kinshasa (n = 2,519). In Indonesia, baseline in 2018 was follow-up in 2020 in Bandar Lampung (n = 948), Denpasar (n = 1,156), and Semarang (n = 1,231). Outcomes included SRH knowledge and communication, awareness of SRH services, and attitudes about sexuality. Analysis followed a difference-in-difference approach to compare changes in each outcome over time between interventions and controls. Both interventions improved pregnancy and HIV knowledge, while Semangat Dunia Remaja or Teen Aspirations also improved SRH communication. Results differed by site in Indonesia, with Semarang, the site that adhered most closely to intervention design, observed the most improvements. Differential effects were also seen by gender, especially in Kinshasa where girls advanced in SRH communication and knowledge but not boys. Girls in Semarang shifted normative SRH attitudes, and boys in Denpasar improved knowledge. Interventions targeting very young adolescents can improve SRH knowledge, communication, and attitudes, though impact depends on context and implementation. Future programs should incorporate the community and environment influencing adolescent experiences with sexuality.


Bioactive compound from Aspergillus terreusDMTMGK004 synergistically contributes towards potential anti-pathogenicity.
This study focused on the evaluation of fungal compound for their anti-pathogenic potential against respiratory pathogens. Soil samples were collected from various geographical regions in Madurai, fungal strain was isolated and identified as Aspergillus terreusDMTMGK004 (MGK004). Secondary metabolites were extracted and evaluated for antioxidant potential. It exhibited significantly high anti-proliferative property against gastric adenocarcinoma (AGS) cell lines. Antimicrobial activity against Gram positive (Streptococcus pneumoniae) and Gram negative (Klebsiella pneumoniae and Haemophilus influenzae) respiratory pathogens were analysed and the minimum inhibitory concentration (MIC) values were determined. Furthermore, the time-killing assay illustrated that the metabolite eliminates 50% of the vegetative cells within few hours of the treatment. From the spectral data, the major functional groups present in the compound were determined as carbonyl group and phenolic hydroxyl group which contribute towards its bioactivity. The compound significantly depreciates the production of extracellular polysaccharides which results in the weakening of biofilm architecture and resistance towards serum killing and phagocytosis. It also induced cell membrane damage which leads to protein and nucleic acid leakage. Hence, the results of the present study could provide a better insinuation towards the formulation of new drug targeting respiratory pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: The ubiquitous fungi Aspergillus terreus is well known for its secondary metabolite production. The fungus was evaluated for production of antagonistic molecule to reduce the growth of infectious agents causing respiratory infections. It exhibited the biological means of antioxidant, anti-proliferative and anti-pathogenic compound production. The compound exhibits killing effect against respiratory pathogens within two hours. It induced cell membrane damage leading to protein and nucleic acid leakage. It significantly reduced the production of extracellular polysaccharides. The results provide needed information to design innovative strategies for targeting pathogenic factors of the respiratory pathogens instead of killing it precisely.


Effects of a new diuretic on cerebrospinal fluid pressure in patients with supratentorial tumors.
The effect of a new, powerful diuretic on biochemical parameters, urine output, central venous pressure, blood pressure, and cerebrospinal fluid pressure in patients with supratentorial intracerebral tumors who showed signs and symptoms of increased intracranial pressure was tested. When compared to an untreated control group and to the steady-state data of each patient, CSF pressure was significantly reduced using a dose of 240 mg of the diuretic. The 120 mg dosage did not produce significant results. Normalization of increased cerebrospinal fluid pressure was not completely obtained using either dose. Used alone, this substance is not suitable for treatment of increased intracranial pressure due to brain edema in patients with intra-cerebral tumors. It might, however, be useful in combination with other medications.


Use of catch-up vaccinations in the second year of life (2YL) platform to close immunity gaps: A secondary DHS analysis in Pakistan, Philippines, and South Africa.
Immunity gaps caused by COVID-19-related disruptions highlight the importance of catch-up vaccination. Number of countries offering vaccines in second year of life (2YL) has increased, but use of 2YL for catch-up vaccination has been variable. We assessed pre-pandemic use of 2YL for catch-up vaccination in three countries (Pakistan, the Philippines, and South Africa), based on existence of a 2YL platform (demonstrated by offering second dose of measles-containing vaccine (MCV2) in 2YL), proportion of card availability, and geographical variety. We conducted a secondary data analysis of immunization data from Demographic and Health Surveys (DHS) in Pakistan (2017-2018), the Philippines (2017), and South Africa (2016). We conducted time-to-event analyses for pentavalent vaccine (diphtheria-tetanus-pertussis-Hepatitis B-Haemophilus influenzae type b [Hib]) and MCV and calculated use of 2YL and MCV visits for catch-up vaccination. Among 24-35-month-olds with documented dates, coverage of third dose of pentavalent vaccine increased in 2YL by 2%, 3%, and 1% in Pakistan, Philippines, and South Africa, respectively. MCV1 coverage increased in 2YL by 5% in Pakistan, 10% in the Philippines, and 3% in South Africa. In Pakistan, among 124 children eligible for catch-up vaccination of pentavalent vaccine at time of a documented MCV visit, 45% received a catch-up dose. In the Philippines, among 381 eligible children, 38% received a pentavalent dose during an MCV visit. In South Africa, 50 children were eligible for a pentavalent vaccine dose before their MCV1 visit, but only 20% received it; none with MCV2. Small to modest vaccine coverage improvements occurred in all three countries through catch-up vaccination in 2YL but many missed opportunities for vaccination continue to occur. Using the 2YL platform can increase coverage and close immunity gaps, but immunization programmes need to change policies, practices, and monitor catch-up vaccination to maximize the potential.


Using unmanned aerial systems and deep learning for agriculture mapping in Dubai.
As part of the sustainable future vision, sustainable agriculture has become an essential pillar of the food security strategies formulated by the Dubai Government. Therefore, the Dubai Emirate began relying on new technology to increase productivity and efficiency. Agriculture applications also depend on accurate land monitoring for timely food security control and support actions. However, traditional monitoring requires field surveys to be performed by experts, which is costly, slow, and rare. Agriculture monitoring systems must be furnished with sustainable land use monitoring solutions, starting with remote sensing using drone surveys for affordable, efficient, and time-sensitive agriculture mapping. Hence, the Dubai Municipality is currently using Unmanned Aerial Vehicles (UAVs) to map the farming areas all over the Emirate, support locating lands conducive to cultivation, and create an accurate agriculture database contributing to the decision-making process in determining areas suitable for crop growth. This study used a novel object detection method coupled with geospatial analysis as an integrated workflow to detect individual crops. The UAV flights were executed using a Trimble UX5 (HP) over twelve communities across the Dubai Emirate for six months. Detection methods were applied to high-resolution drone images, consisting of RGB and near-infrared (NIR) bands. Advanced geoprocessing tools were also used to analyze, evaluate, and enhance the results. The performance of detection of the selected deep learning models are discussed (vegetation cover accuracy = 85.4%, F1-scores for date palms and ghaf trees = 96.03% and 94.54% respectively, with respect to visual interpretation ground truth); moreover, sample images from the datasets are used for demonstrations. The main aim is to offer specialists a solution for measuring and assessing living green vegetation cover derived from the processed images that is integrated. The results provide insight into using UAS and deep learning algorithms as a solution for sustainable agricultural mapping on a large scale.


End-tidal carbon dioxide concentration, carbon dioxide production, heart rate, and blood pressure as indicators of induced hyperthermia.
In 4 spontaneously breathing, barbiturate-anesthetized dogs, hyperthermia was induced with 2,4-dinitrophenol while rectal temperature, heart rate, mean blood pressure, end-tidal carbon dioxide, and carbon dioxide production (milliliters per minute) were measured continuously. The latter was determined with a pneumotachygraph (to obtain respired volume) and an infrared carbon dioxide analyzer that measured inspired and expired carbon dioxide concentration. Of the five physiologic measurements, the increase in carbon dioxide production preceded the increase in rectal temperature by more than 120 seconds. End-tidal carbon dioxide was an unreliable indicator in the spontaneously breathing animal of approaching hyperthermia during spontaneous breathing due to a transient tachypnea, which decreased end-tidal carbon dioxide. The carbon dioxide production (milliliters per minute) increased immediately and reached three to five times the control value. Blood pressure and heart rate were insensitive indicators of approaching hyperthermia.


Activity scheduling as a core component of effective care management for late-life depression.
Activity scheduling is an established component of evidenced-based treatment for late-life depression in primary care. We examined participant records from the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial to identify activity scheduling strategies used in the context of successful depression care management (CM), associations of activity scheduling with self-reported activity engagement, and depression outcomes. This study used observational mixed methods analysis of 4335 CM session notes from 597 participants in the intervention arm of the IMPACT trial. Grounded theory was used to identify 17 distinct activity categories from CM notes. Logistic regression was used to evaluate associations between activity scheduling, activity engagement, and depression outcomes at 12 months. All relevant institutional review boards approved the research protocol. Seventeen distinct activity categories were generated. Most patients worked on at least one social and one solitary activity during their course of treatment. Common activity categories included physical activity (32%), medication management (22%), active-non-physical (19%), and passive (14%) activities. We found significant, positive associations between activity scheduling, self-reported engagement in activities at 12 months, and depression outcomes at 12 months. Older primary care patients in CM for depression worked on a wide range of activities. Consistent with depression theory that has placed emphasis on social activities, the data indicate a benefit for intentional social engagement versus passive social and solitary activities. Care managers should encourage patients to balance instrumental activities (e.g., attending to medical problems) with social activities targeting direct interpersonal engagement.


Effective enhancement of hydroxyvalerate content of PHBV in Cupriavidus necator and its characterization.
This study investigated the effects of using a combination of substrates (fructose, propanol, citric acid, acetic acid, propionic acid and beef extract) on the synthesis of poly (3-hydroxybutyrate-co-3-hydroxyvalerate), which is also known as PHBV. The results of batch PHBV optimization by RSM, indicated that PHB was synthesized only when fructose was used as the sole carbon source. Fructose in combination with propanol and beef extract, exhibited better PHBV production performance, as compared to that of propionic acid which was used in previous studies. GC, (1)H and (13)C NMR spectroscopy revealed that the best copolymer composition was 54.1 mol% of 3-hydroxyvalerate (3HV) which was obtained in a basal medium combined with 0.3% (v/v) propanol and 0.0172% (w/v) beef extract. This is the first report on the production of PHBV with HV content of 54.1% by a wild-type Cupriavidus necator. The Fourier Transform Infrared Spectroscopy (FTIR) spectra of the PHAs indicated absorption bands at 1723, 1274, 1373, 1453, 2932cm(-1) corresponding to CO, CO stretching, CH3, -CH2 and -CH groups, respectively. This study showed that the recovered PHBV biopolymer from the optimized culture to have a melting temperature of 103.6°C, melting enthalpy of 55.67J/g and crystallization temperature of 76.1°C.


Improved disinfection performance for 280 nm LEDs over 254 nm low-pressure UV lamps in community wastewater.
Ultraviolet (UV) disinfection has been incorporated into both drinking water and wastewater treatment processes for several decades; however, it comes with negative environmental consequences such as high energy demands and the use of mercury. Understanding how to scale and build climate responsive technologies is key in fulfilling the intersection of UN Sustainable Development Goals 6 and 13. One technology that addresses the drawbacks of conventional wastewater UV disinfection systems, while providing a climate responsive solution, is UV light emitting diodes (LEDs). The objective of this study was to compare performance of bench-scale 280 nm UV LEDs to bench-scale low pressure (LP) lamps and full-scale UV treated wastewater samples. Results from the study demonstrated that the UV LED system provides a robust treatment that outperformed LP systems at the bench-scale. A comparison of relative energy consumptions of the UV LED system at 20 mJ cm-2 and LP system at 30 and 40 mJ cm-2 was completed. Based on current projections for wall plug efficiencies (WPE) of UV LED it is expected that the energy consumption of LED reactors will be on par or lower compared to the LP systems by 2025. This study determined that, at a WPE of 20%, the equivalent UV LED system would lead to a 24.6% and 43.4% reduction in power consumption for the 30 and 40 mJ cm-2 scenarios, respectively.


Impact of modified short-term fasting and its combination with a fasting supportive diet during chemotherapy on the incidence and severity of chemotherapy-induced toxicities in cancer patients - a controlled cross-over pilot study.
This pilot trial aimed to investigate whether modified short-term fasting (mSTF) reduces the incidence of chemotherapy-induced toxicities and whether an initial ketogenic diet (KD) as fasting supportive diet reduces fasting-related discomfort and improves the compliance. In this controlled cross-over trial, gynaecologic cancer patients undergoing chemotherapy with a minimum of 4 cycles fasted for 96 h during half of their chemotherapy cycles and consumed a normocaloric diet during the other chemotherapy cycles. The caloric intake during mSTF was restricted to 25% of each patient's daily requirement. In addition, half of the patients should eat a 6-day normocaloric KD prior to each mSTF period to investigate a KD's hunger-suppression effect. Chemotherapy-induced toxicities, fasting-related discomfort, body composition, quality of life, laboratory values, and compliance were assessed at each chemotherapy. Thirty patients aged 30-74 years (median 54 years) completed the study. During mSTF the frequency and severity score of stomatitis [- 0.16 ± 0.06; 95% CI -0.28 - (- 0.03); P = 0.013], headaches [- 1.80 ± 0.55; 95% CI -2.89 - (- 0.71); P = 0.002], weakness [- 1.99 ± 0.87; 95% CI -3.72 - (- 0.26); P = 0.024] and the total toxicities' score were significantly reduced [- 10.36 ± 4.44; 95% CI -19.22 - (- 1.50); P = 0.023]. We also observed significantly fewer chemotherapy postponements post-mSTF, reflecting improved tolerance of chemotherapy [- 0.80 ± 0.37; 95% CI -1.53 - (- 0.06); P = 0.034]. A significant reduction in mean body weight by - 0.79 ± 1.47 kg during mSTF was not compensated and remained until study's conclusion (P < 0.005). On average, Insulin [- 169.4 ± 44.1; 95% CI -257.1 - (- 81.8); P < 0.001] and Insulin-like growth factor 1 levels [- 33.3 ± 5.4; 95% CI -44.1 - (- 22.5); P < 0.001] dropped significantly during fasting. The KD as a fasting supportive diet neither reduced fasting-related discomfort nor improved compliance of our fasting regimen. MSTF is safe and feasible in gynaecologic cancer patients. Our results indicate that mSTF during chemotherapy can reduce chemotherapy-induced toxicities and enhance the tolerance of chemotherapy. Larger clinical trials are required to recommend mSTF for cancer patients. germanctr.de: DRKS00011610, registered 30 January, 2017.


IgE against food and respiratory allergens in healthy and allergic mothers and their children.
IgE against mixtures of common food or respiratory allergens were determined by ELISA in healthy (n = 38) and allergic (n = 62) mothers and their children. Significantly higher level of IgE against respiratory allergens was found in sera of allergic mothers and in cord blood of their children. No correlation between antibody level in maternal and newborn's sera was found; this argues against the transfer of IgE from mother to fetus and points rather to offspring's intrauterine sensitization. Specific IgE level in cord blood was higher in children who developed later allergy than in children who did not. Specific IgE level in colostrum was low both in healthy and allergic mothers; there was no correlation between high concentration of IgE against respiratory allergens in sera of allergic mothers and their colostrum, which does not support the idea of IgE transport from blood to mammary gland. Only slightly increased colostral IgE was detected in allergic mothers whose children manifested allergy later. Allergy of the mother and high level of anti-allergen IgE in her serum and in cord blood are the main predictive factors of future occurrence of allergy in the offspring. A combination of several predictive factors could have higher prognostic value.


Channeling of a beta-oxidation intermediate on the large subunit of the fatty acid oxidation complex from Escherichia coli.
The kinetic properties of the fatty acid oxidation complex from Escherichia coli were studied with the aim of elucidating the functional consequence of having enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase associated with a multifunctional polypeptide. The kinetic parameters of individual enzymes were determined and used in model calculations based on a published theory (Storer, A. C., and Cornish-Bowden, A. (1974) Biochem. J. 141, 205-209) to predict the kinetic behavior of a system of functionally unlinked enzymes. The validity of the theory for making these calculations was proven by demonstrating a good agreement between the calculated and observed rates of intermediate and product formation for the conversion of 2-decenoyl-CoA to 3-ketodecanoyl-CoA catalyzed by a mixture of bovine liver enoyl-CoA hydratase and pig heart L-3-hydroxyacyl-CoA dehydrogenase. The conversion of 2-decenoyl-CoA to 3-ketodecanoyl-CoA catalyzed by the sequential action of the hydratase and dehydrogenase of the complex from E. coli was determined by measuring the rate of NADH formation. Stopped-flow measurements showed the rate of NADH formation to be linear without any lag period. When the initial velocity of the hydratase was 10.2 microM min-1, that of the overall reaction was 8.41 microM min-1. In contrast, the results calculated by use of the Storer and Cornish-Bowden equation for a system of unlinked enzymes predicted the overall reaction to exhibit a lag time of 30 s and to result in the accumulation of 2.1 microM 3-hydroxydecanoyl-CoA before reaching a velocity corresponding to 82.5% of that of the hydratase reaction. The high initial rate and the unusual kinetic properties of the overall reaction observed in the present study are best explained by a channeling mechanism on the large subunit of the E. coli fatty acid oxidation complex. When the apparent degree of channeling is corrected for the percentage of the dehydrogenase active sites saturated with NAD+, more than 90% of the intermediate appears to be transferred directly from the active site of enoyl-CoA hydratase to that of 3-hydroxyacyl-CoA dehydrogenase.


Allogeneic hematopoietic stem cell transplantation for patients with relapsed/refractory systemic anaplastic large cell lymphoma. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.
Information regarding the curative role of allogeneic stem cell transplantation (allo-HCT) in systemic anaplastic large cell lymphoma (sALCL) is scarce. We analyzed the results of allo-HCT in patients with relapsed/refractory sALCL with special emphasis on the role of brentuximab vedotin (BV) as a bridge to allo-HCT. Forty-four patients (24 females, median age 38 years) with sALCL were included. Twenty-three patients (52%) received BV before allo-HCT; BV-treated patients were more heavily pretreated (≥3 lines of therapy in 74% vs. 38%, p = 0.04). Twenty-three patients (52%) were in complete remission (CR) at allo-HCT. Three-year nonrelapse mortality and incidence of relapse (IR) after allo-HCT were 7% and 40%, respectively. With a median follow-up of 39 (12-69) months for survivors, 3-year progression-free survival (PFS) and overall survival were 53% and 74%, respectively. Univariate analysis showed that heavily pretreated patients and those not in CR had a higher IR and a lower PFS. The use of BV before transplant did not impact on any of the outcomes. Allo-HCT is a curative therapeutic strategy in a significant proportion of patients with relapsed/refractory sALCL; BV does not seem to modify transplant-related outcomes but might be able to render more patients candidates for this curative treatment.


Composite branch construction by dual autozooidal budding modes in hornerids (Bryozoa: Cyclostomatida).
Horneridae (Cyclostomatida: Cancellata) is a family of marine bryozoans that forms tree-like colonies bearing functionally unilaminate branches. Colony development in this clade is not well understood. We used micro-computed tomography and scanning electron microscopy to trace zooidal budding in Hornera from the ancestrula onwards. Results show that hornerid branches are constructed by dual zooidal budding modes occurring synchronously at two separate budding sites at the growing tips. Frontal autozooids bud from a multizooidal budding lamina. Lateral autozooids bud from discrete abfrontal budding loci by "exomural budding," a previously undescribed form of frontal budding centered on hypostegal pores in interzooidal grooves on the colonial body wall. These two budding modes are integrated during primary branch morphogenesis, forming composite, developmentally bilaminate, branches. Patterns of exomural budding vary among hornerid taxa, and future studies of Cancellata taxonomy and phylogeny may benefit from morphological concepts presented here.


213Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate cancer cell line and shows anti-cancer activity in a xenograft animal model.
A novel alpha-particle emitting ((213)Bi) plasminogen activator inhibitor type 2 construct, which targets the membrane-bound urokinase plasminogen activator on prostate cancer cells, was prepared and evaluated in vitro and in a xenograft animal model. The PC3 prostate cancer cell line expresses urokinase plasminogen activator which binds to its receptor on the cell membrane; plasminogen activator inhibitor type 2 is bound to urokinase plasminogen activator/urokinase plasminogen activator receptor to form stable complexes. In vitro, the cytotoxicity of (213)Bi-plasminogen activator inhibitor type 2 against prostate cancer cells was tested using the MTS assay and apoptosis was documented using terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labelling (TUNEL) assay. In vivo, antiproliferative effects for tumours and prostate cancer lymph node metastasis were carried out in an athymic nude mouse model with a subcutaneous xenograft of PC3 cells. (213)Bi-plasminogen activator inhibitor type 2 was specifically cytotoxic to PC3 cells in a concentration-dependent fashion, causing the cells to undergo apoptosis. A single local or i.p. injection of (213)Bi-plasminogen activator inhibitor type 2 was able to completely regress the growth of tumours and lymph node metastases 2 days post subcutaneous inoculation, and obvious tumour regression was achieved in the therapy groups compared with control groups with (213)Bi-plasminogen activator inhibitor type 2 when the tumours measured 30-40 mm(3) and 85-100 mm(3). All control animals and one of five (20%) mice treated with 3 mCi kg(-1) (213)Bi-plasminogen activator inhibitor type 2 developed metastases in the lymph nodes while no lymphatic spread of cancer was found in the 6 mCi kg(-1) treated groups at 2 days and 2 weeks post-cell inoculation. These results demonstrate that this novel (213)Bi-plasminogen activator inhibitor type 2 conjugate selectively targets prostate cancer in vitro and in vivo, and could be considered for further development for the therapy of prostate cancer, especially for the control of micro-metastases or in minimal residual disease.


The interaction of versican with its binding partners.
Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within the extracellular matrix (ECM). Versican, like other members of its family, has unique N- and C-terminal globular regions, each with multiple motifs. A large glycosaminoglycan-binding region lies between them. This review will begin by outlining these structures, in the context of ECM proteoglycans. The diverse binding partners afforded to versican by virtue of its modular design will then be examined. These include ECM components, such as hyaluronan, type I collagen, tenascin-R, fibulin-1, and -2, fibrillin-1, fibronectin, P- and L-selectins, and chemokines. Versican also binds to the cell surface proteins CD44, integrin beta 1, epidermal growth factor receptor, and P-selectin glycoprotein ligand-1. These multiple interactors play important roles in cell behaviour, and the roles of versican in modulating such processes are discussed.


Participation of prostaglandins in pathogenesis of aspirin-sensitive asthma.
Recent evidence suggests that the induction of bronchoconstriction in aspirin-sensitive patients by analgesics is due to the inhibition of PG biosynthesis in their respiratory tract. PGEs might play the main defensive role in the bronchi of aspirin-sensitive asthmatics. Removal of this potent bronchodilator by PG synthetase inhibitors leaves the effects of spasmogens unopposed, and possibly promotes the release of histamine from its stores.