Short intense psychological stress induced by skydiving does not impair intestinal barrier function.
Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function. Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018. Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes. These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor.


Incidence and risk factors of surgical site infection following cervical laminoplasty: A retrospective clinical study.
There are many debates regarding the risk factors of surgical site infection (SSI) following posterior cervical surgery in previous studies. And, till now there is no such a study to examine cervical laminoplasty surgery. From January 2011 through October 2021, a total of 405 patients who were treated with unilateral open-door laminoplasty surgeries were enrolled in this study. We divided the patients into the SSI group and the non-SSI group and compared their patient-specific and procedure-specific factors. Univariate and multiple logistic regression analysis were performed to determine the risk factors. Of the 405 patients, 20 patients had SSI. The rate of SSI found to be 4.93%. There were significant differences between groups in the thicker subcutaneous fat thickness (FT) (p < 0.001), the higher ratio of subcutaneous FT to muscle thickness (MT) (p < 0.001), the higher preoperative Japanese Orthopaedic Association (JOA) Scores (p < 0.003), the decreased preoperative serum albumin (p < 0.001), the more postoperative drainage (p < 0.05) and the longer time of draining (p < 0.001). Logistic regression analysis of these differences showed that the higher ratio of subcutaneous FT/MT, the higher preoperative JOA scores, the decreased preoperative serum albumin and the longer time of draining were significantly related to SSI (p < 0.05). The higher ratio of subcutaneous FT/MT, the higher preoperative JOA scores, the decreased preoperative serum albumin and the longer time of draining are identified as the independent risk factors of SSI in cervical laminoplasty. Identification of these risk factors could be useful in reducing the SSI incidence and patients counselling.


Source Areas for the Early Immigration of Sogatella furcifera (Homoptera: Delphacidae) at Xiushan in the Middle Reach of Yangtze River of China.
The spatiotemporal distribution of source areas for the early immigration of the white-backed planthopper, Sogatella furcifera (Horvάth), at Xiushan in the middle reach of Yangtze River of China, was analyzed with HYSPLIT (Hybrid Single-Particle Lagrangian Integrated Trajectory) and ArcGIS 10.0. The analysis was based on light trap data collected during April-July in 2000-2012. The synoptic meteorology backgrounds during the immigration periods were analyzed by GrADS (Grid Analysis and Display System). The light trap catches of S. furcifera varied monthly and annually. S. furcifera started immigration in Xiushan in early April to early May, whereas the main immigration period was in July. The distribution of the source areas varied monthly, and the core was moved from the south to the north gradually. The main source areas of S. furcifera in May were in southwestern Guangxi and northern Vietnam. The source areas of S. furcifera in June were located in southwestern Guangxi and western Hunan. Additionally, some of the pests were from southeastern Yunnan. The source areas in July were in northwestern Guangxi, southwestern Guizhou, eastern Yunnan, and the transitional parts of Guangxi, Guizhou, and Yunnan. The sum frequencies of southwest and south winds on the 850 hPa isobaric surface of Xiushan of May-July in heavy occurrence years were more than the light occurrence years. The key meteorological factors were suggested to be vertical perturbation, precipitation, and wind shear during S. furcifera immigration periods.


Drought stress amelioration in tomato (Solanum lycopersicum L.) seedlings by biostimulant as regenerative agent.
Drought adversely affects many physiological and biochemical events of crops. This research was conducted to investigate the possible effects of biostimulants containing plant growth-promoting rhizobacteria (PGPR) on plant growth parameters, chlorophyll content, membrane permeability (MP), leaf relative water content (LRWC), hydrogen peroxide (H2O2), proline, malondialdehyde (MDA), hormone content, and antioxidant enzymes (catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD)) activity of tomato (Solanum lycopersicum L.) seedlings under different irrigation levels. This study was carried out under controlled greenhouse conditions with two irrigation levels (D0: 100% of field capacity and D1: 50% of field capacity) and three biostimulant doses (B0: 0, B1: 4 L ha-1, and B2: 6 L ha-1). The results of the study show that drought stress negatively influenced the growth and physiological characteristics of tomato seedlings while biostimulant applications ameliorated these parameters. Water deficit conditions (50% of field capacity) caused decrease in indole acetic acid (IAA), gibberellic acid (GA), salicylic acid (SA), cytokine, zeatin, and jasmonic acid content of tomato seedlings by ratios of 83%, 93%, 82%, 89%, 50%, and 57%, respectively, and shoot fresh weight, root fresh weight, shoot dry weight, root dry weight, plant height, stem diameter, and leaf area decreased by 43%, 19%, 39%, 29%, 20%, 18%, and 50%, respectively, compared to the control (B0D0). In addition, 21%, 16%, 21%, and 17% reductions occurred in LRWC, chlorophyll a, chlorophyll b, and total chlorophyll contents with drought compared to the control, respectively. Biostimulant applications restored the plant growth, and the most effective dose was 4 L ha-1 under drought condition. Amendment of biostimulant into the soil also enhanced organic matter and the total N, P, Ca, and Cu content of the experiment soil. In conclusion, 4 L ha-1 biostimulant amendment might be a promising approach to mitigate the adverse effects of drought stress on tomato.


Effect of diluting propofol on the incidence of pain on injection and venous sequelae.
The effect of diluting propofol in 5% dextrose on the incidence of i.v. injection pain was studied in 100 adult patients. Severe injection pain occurred in 32% (16 patients) who received undiluted propofol, compared with 10% (five patients) who received dilute propofol. We concluded that the dilution of propofol significantly reduced the incidence of severe pain during injection without increasing postoperative venous sequelae.


Cholinomimetic teratogens. III. Interaction with amino acids known as neurotransmitters.
The amino acids gamma-aminobutyric acid, taurocholate, guanidine, glycine, and beta-alanine, known to have putative functions as neurotransmitters, when given as supplement to carbachol or decamethonium, greatly reduced the incidence of malformations produced in chicken embryos by these depolarizing cholinomimetic teratogens. In combination with the nondepolarizing teratogens neostigmine and pyridostigmine similarly beneficial effects occurred only by supplementation with gamma-aminobutyric acid.


Adaptive Sparse Gaussian Process.
Adaptive learning is necessary for nonstationary environments where the learning machine needs to forget past data distribution. Efficient algorithms require a compact model update to not grow in computational burden with the incoming data and with the lowest possible computational cost for online parameter updating. Existing solutions only partially cover these needs. Here, we propose the first adaptive sparse Gaussian process (GP) able to address all these issues. We first reformulate a variational sparse GP (VSGP) algorithm to make it adaptive through a forgetting factor. Next, to make the model inference as simple as possible, we propose updating a single inducing point of the SGP model together with the remaining model parameters every time a new sample arrives. As a result, the algorithm presents a fast convergence of the inference process, which allows an efficient model update (with a single inference iteration) even in highly nonstationary environments. Experimental results demonstrate the capabilities of the proposed algorithm and its good performance in modeling the predictive posterior in mean and confidence interval estimation compared to state-of-the-art approaches.


Organic acid production by Basidiomycetes. 3. Cultural conditions for L-malic acid production.
Cultural conditions were examined for the purpose of increasing yields of l-malic acid by the Basidiomycetes Schizophyllum commune and Merulius tremellosus, which have the ability to produce this acid as a main product in CaCO(3)-containing medium in shaken culture. The most favorable nitrogen sources selected were 0.3% (NH(4))(2)SO(4) and 0.18% NH(4)Cl. Effective combinations of inorganic salts in the medium were 0.1% KH(2)PO(4), 0.05% MgSO(4).7H(2)O, and 0.05% KCl, and suitable concentrations of glucose were 5 to 10%. Several nonionic surface-active agents promoted the filamentous mycelial growth of these strains and increased acid production. In particular, Tween 80 in 0.3% concentration markedly stimulated malic acid production by S. commune, and yields greater than 50% based on available glucose, were obtained after 10 to 14 days. Acid production by M. tremellosus was stimulated most with 0.5% Carbowax 4000 (polyethylene glycol), and the resultant yields were more than 40%.


Effect of ibuprofen on blood pressure control by propranolol and bendrofluazide.
The effect of 1600 mg/day ibuprofen in two groups of patients with hypertension controlled by either propranolol or bendrofluazide was studied in a double-blind, double-placebo, randomized crossover trial. No significant difference in blood pressure was found at the end of the crossover period in either group, suggesting that the routine co-administration of ibuprofen does not attenuate the anti-hypertensive effect of thiazide diuretics or propranolol. Significant weight gain, attributable to fluid retention, had occurred in the bendrofluazide-treatment group by the end of the drug-free washout period. No significant change in mean weight occurred in the crossover stages in either group, although substantial weight gain was noted during ibuprofen treatment in two patients given bendrofluazide and one given propranolol. Biochemical variables were unaffected by ibuprofen throughout the crossover period. This study suggests that ibuprofen may be administered routinely to patients receiving thiazides or propranolol without loss of control of the anti-hypertensive action of these drugs but it is recommended that individuals are monitored for possible weight gain or an increase in diastolic blood pressure.


Interdisciplinary Orthopedic Management of Pediatric Patella Dislocation and Instability: An Educational Case Series.
Pediatric patellar instability and/or dislocation is a challenging diagnosis category that requires an interdisciplinary team consisting of orthopedic surgeons and physical therapists for optimized patient outcomes. This educational case series outlines core concepts for three patients with unique patellar dislocation presentations. Case 1 is a 16-year-old male who presented with a history of five knee traumatic patellar dislocations with self-reduction and underwent knee arthroscopic surgery with debridement and microfracture of the patella chondral defect, arthroscopic lateral release to improve the patellar tilt, and medial patellofemoral ligament (MPFL) reconstruction. Case 2 is a 15-year-old female who presented with chronic knee pain and patella instability who underwent knee arthroscopic surgery with abrasion arthroplasty, microfracture of the patella, lateral release, tibial tubercle osteotomy medializing osteotomy, and MPFL reconstruction. Case 3 is a 14-year-old male who presented after a single episode of lateral patella dislocation and underwent open reduction and fixation of the lateral femoral condyle osteochondral fracture, a Grammont patellar medialization procedure, and MPFL reconstruction. All three patients received postoperative physical therapy (PT) to improve function and outcomes. These cases represent important concepts of patellar containment, risk factors for recurrent instability, associated pathology, and appropriate surgical care and postoperative rehabilitation. Furthermore, this case series highlights management decisions and pathways for three patients with different symptoms related to patellar instability, subsequent surgical correction, and postoperative physical therapy. Overall, interdisciplinary care of common pediatric orthopedic conditions can help improve patient outcomes and satisfaction. By understanding the biomechanics and decision-making surgical parameters regarding patellofemoral instability, clinicians can provide patients with better care.


Influence of pharmacological doses of calcitonin on serum osteocalcin concentration in patients with Paget's disease of the bone.
The effect of continuous infusion of calcitonin on serum osteocalcin concentration was studied in 14 patients with Paget's disease. In all patients serum osteocalcin was initially increased. Within 24 h calcitonin gradually reduced serum osteocalcin, a marker of osteoblastic activity. This means that inhibition of the function of the osteoclasts by calcitonin results in an inhibition of the osteoblasts within 24 h in patients with Paget's disease.


Critical Analysis of Radiographic and Patient Reported Outcomes Following Anterior/Posterior Staged vs. Same Day Surgery in Patients Undergoing Identical Corrective Surgery for Adult Spinal Deformity.
Retrospective cohort study of a prospectively collected multi-center adult spinal deformity (ASD) database. To compare staged procedures to same-day interventions and identify the optimal time interval between staged surgeries for treatment of ASD. Surgical intervention for ASD is invasive and complex procedure that surgeons often elect to perform on different days (staging). Yet, there remains a paucity of literature on the timing and effects of the interval between stages. ASD patients with two-year (2Y) data undergoing an anterior/posterior (A/P) fusion to the ilium were included. Propensity score matching (PSM) was performed for number of levels fused, number of interbody devices, surgical approaches, number of osteotomies/three-column osteotomy (3CO), frailty, Oswestry Disability Index (ODI), Charlson Comorbidity Index (CCI), revisions, sagittal vertical axis (SVA), pelvic incidence-lumbar lordosis (PI-LL), and UIV to create balanced cohorts of Same-Day and Staged surgical patients. Staged patients were stratified by intervening time-period between surgeries, using quartiles. 176 PSM patients were included. Median interval between A/P staged procedures was 3 days. Staged patients had greater operative time and lower ICU stays postop (P<0.05). At 2Y, staged compared to same day showed a greater improvement in T1 slope - cervical lordosis (TS-CL), C2 sacral slope (C2SS), and SRS-Schwab SVA (P<0.05). Staged patients had higher rates of minimal clinically-important difference (MCID) for 1Y SRS-Appearance and 2Y physical component summary (PCS) scores. Assessing different intervals of staging, patients at the 75th percentile interval showed greater improvement in 1Y SRS Pain and Total postop as well as SRS Activity, Pain, Satisfaction, and Total scores (P<0.05) compared to patients in lower quartiles. Compared to the 25th percentile, patients reaching the 50th percentile interval were associated with increased odds of improvement in Global Alignment and Proportion (GAP) score proportionality (9.3[1.6-53.2], P=0.01). This investigation is among the first to compare multicenter staged and same day surgery anterior/posterior adult spinal deformity patients fused to ilium using propensity-matching. Staged procedures resulted in significant improvement radiographically, reduced ICU admissions, and superior patient reported outcomes compared to same day procedures. An interval of at least three days between staged procedures is associated with superior outcomes in terms of GAP score proportionality.


Simultaneous detection of mastitis pathogens, Staphylococcus aureus, Streptococcus uberis, and Streptococcus agalactiae by multiplex real-time polymerase chain reaction.
The objective of this study was to develop a multiplex real-time polymerase chain reaction (PCR) method for simultaneous detection of Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus uberis directly from milk. A genetic marker specific for Staph. aureus was used for primers and dual-labeled probe design. The target for Strep. agalactiae primers and dual-labeled probe was selected from the cfb gene encoding the Christie-Atkins-Munch-Petersen factor. The plasminogen activator gene was the target for primers and dual-labeled probe design for Strep. uberis. Quarter milk samples (n = 192) were analyzed by the multiplex real-time PCR assay and conventional microbiological methods. An additional 57 quarter milk samples were analyzed in a separate real-time PCR assay for Strep. agalactiae only. Using an overnight enrichment step, the real-time PCR technique correctly identified 96.4% of all quarter milk samples; 91.7% of Staph. aureus, 98.2% of Strep. agalactiae, and 100% of Strep. uberis. Results of conventional microbiological methods were used to determine the sensitivity and specificity of the multiplex real-time PCR procedure. The sensitivity of the procedure to correctly identify Staph. aureus, Strep. agalactiae, and Strep. uberis directly from milk was 95.5%, and the specificity was 99.6%. Results of this study indicate that the multiplex real-time PCR procedure has the potential to be a valuable diagnostic technique for simultaneous identification of Staph. aureus, Strep. agalactiae, and Strep. uberis directly from quarter milk samples.


Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.
Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.


Biological parameters of interbreeding subspecies of Meccus phyllosomus (Hemiptera: Reduviidae: Triatominae) in western Mexico.
Understanding the biological parameters of some triatomine subspecies of Meccus phyllosomus (Burmeister) is a crucial first step in estimating the epidemiological importance of this group. Biological parameters related to egg eclosion, egg-to-adult development time, number of blood meals to moult, percentage of females at the end of the cycle, number of laid eggs, and the accumulative mortality for each instar of three M. phyllosomus subspecies [Meccus phyllosomus pallidipennis (Stål), Meccus phyllosomus longipennis (Usinger), and Meccus phyllosomus picturatus (Usinger)] as well as their laboratory hybrids were evaluated and compared. No significant differences (P > 0.05) were recorded among the experimental hybrids (M. p. longipennis × M. p. pallidipennis, M. p. longipennis × M. p. picturatus, M. p. pallidipennis × M. p. picturatus) and reciprocal cohorts. In five of the six studied parameters (egg eclosion, egg-to-adult development time, number of blood meals to moult, number of laid eggs and accumulative mortality), with the exception of the non-significant percentage of females obtained among all the studied cohorts, at least one of the parental cohorts in each set of crosses exhibited better fitness results than by those of their hybrid descendants. The lack of hybrid fitness in our study indicates the maintenance of reproductive isolation of parental genotypes. Moreover, the results lead us to propose that an incipient speciation process by distance is currently developing among the three studied subspecies, increasing the differences between them that modify the transmission efficiency of Trypanosoma cruzi to human beings in Mexico.


[Efficacy and Safety of a Fixed Combination of Perindopril Arginine and Amlodipine in Patients With Hypertension Uncontrolled by Treatment With Angiotensin II Receptor Blockers in Real Clinical Practice. Results of the PREVOSHODSTVO (SUPERIORITY) Program].
The article presents preliminary results of a subanalysis of PREVOSHODSTVO (SUPERIORITY) phase IV study. Aim of this subanalysis was to assess efficacy and tolerability of a fixed-dose perindopril/amlodipine combination (FDPAC) in patients with arterial hypertension (AP) uncontrolled on previous treatment with angiotensin receptor blockers (ARBs). We included in this analysis 125 patients (70.4% women, mean age 57.2+/-10.0 years), final analysis of efficacy was performed on 124 patients. Before inclusion in the study 47 patients received ARB either as monotherapy (n=47), or components of free-dose (n=49) and fixed-dose (n=28) dual combinations with other antihypertensive drugs. Dose. of FDPAC was determined by physician. Duration of observation period was 24 weeks. After 2weeks significant reduction of blood pressure (BP) (from 159.9+/-8.8/93.8+/-6.8 to 143.9+/-10.7/86.4+/-6.5 mm Hg, p<0.001) was noted. At final visit mean BP was 125.1+/-7.1/78.1+/-4.7 mm Hg. Number of patients with target BP (< 140/90 mm Hg) was 24, 75 and 97% after 1, 3, and 6 months, respectively. Visit-to-visit systolic BP variability by the end of the observation period decreased to 3.8+/-2.3 mm Hg. In patients, whose hypertension was not controlled by treatment with ARBs the fixed-dose combination of perindopril/amlodipine provided high percentage of achievement of target BP and reduction of long-term BP variability.


Effects of extracts of leaves from Sparattosperma leucanthum on hyperuricemia and gouty arthritis.
The species Sparattosperma leucanthum (Vell.) K. Schum is used in Brazilian folk medicine to treat rheumatism, throat ulcers, stomatitis, syphilis, bladder stones and as blood cleanser. The aim of this study was to evaluate the potential, in vitro and in vivo, of the extracts of leaves from Sparattosperma leucanthum to treat hyperuricemia and inflammation in the gouty arthritis model. Ethyl acetate extract (SLE), methanolic extract (SLM) and aqueous extract (SLW) were evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with oxonate-induced hyperuricemia in mice which was used to evaluate anti-hyperuricemic activity and liver xanthine oxidase (XOD) inhibition. Anti-inflammatory activity was also investigated on MSU crystal-induced paw edema model. Sparattosperma leucanthum crude extracts showed expressive results on urate-lowering activity in blood. SLW at the dose of 125 mg/kg has proved to be active in reducing hyperuricemia and was capable to inhibit the hepatic xanthine oxidase enzyme (XOD). SLM showed anti-hyperuricemic activity on all doses tested; however, this extract showed activity on the XOD only at the dose of 500 mg/kg. SLE, at the three evaluated doses, has proved to be active in reducing hyperuricemia in vivo and was able to inhibit XO activity in vitro at the concentration of 100 µg/mL. This extract was also able to inhibit XOD activity in vivo at the doses of 250 mg/kg and 500 mg/kg. SLE (125 and 250 mg/kg) and SLW (500 mg/kg) showed significant anti-inflammatory activity on monosodium urate crystal-induced paw edema model. The ethyl acetate, methanolic and aqueous extracts of Sparattosperma leucanthum showed significant results on evaluated models and therefore may be important agents for the treatment of gouty arthritis and hyperuricemia.


[Cranial acupuncture in the treatment of spasticity. Clinical results].
Hospitals in communist China perfected a new acupuncture technique about 3 yrs ago, whereby needles are placed in the scalp to stimulate the cortical centres below. This method is particularly indicated in subjects with neurological damage. Results observed in 45 subjects with cerebral vasculopathy at the neurological clinic of Pisa University and the reflexotherapy service of the University of Turin were encouraging and suggest that clinical experimentation should be attempted on a wider scale.


Live-birth rate in euthyroid women with recurrent miscarriage and thyroid peroxidase antibodies.
Thyroid autoimmunity with normal thyroid function is associated with recurrent miscarriage (RM), but the association with live birth is less clear. Therefore, we determined the association between thyroid peroxidase antibodies (TPO-Ab) and live-birth rate (LBR) in a retrospective cohort of euthyroid women with unexplained RM. We included 202 women of which 28 were TPO-Ab positive (13.9%) and 174 were TPO-Ab negative. TPO-Ab positive women (n = 10) without levothyroxine treatment had a lower LBR (29%) compared to TPO-Ab negative women (51%) (HR 0.23, 0.07-0.72, p = 0.012). The LBR in women with TPO-Ab receiving levothyroxine was not different compared women without TPO-Ab (60% versus 51%, p = 0.50). In conclusion, TPO-Ab are associated with a lower LBR in euthyroid women with unexplained RM and these women may benefit from treatment with levothyroxine.


Immunohistochemical analysis of inflammatory cells in benign and precancerous lesions and carcinoma of the prostate.
Inflammation is an important cause of tumorigenesis in various types of malignancy. Mediators derived from inflammatory cells are associated with cancer proliferation, angiogenesis, and DNA damage. In the present study, we immunohistochemically examined the infiltration patterns of inflammatory cells in benign glands including glandular hyperplasia, and in prostatic intraepithelial neoplasia and adenocarcinoma. Formalin-fixed, paraffin-embedded tissues were obtained from 100 patients with prostate cancer. All patients underwent radical prostatectomy. We assessed the number of infiltrating T cells (CD3(+)), B cells (CD20(+), CD79alpha(+)), and macrophages (CD68(+), CD204(+)) in benign and malignant prostate tumors. CD68(+) macrophages infiltrated benign glands to a higher extent than those of adenocarcinoma. In contrast, the number of CD204(+) cells was higher in malignant glands than in benign glands. There was no significant difference in the number of infiltrating T cells between benign and malignant tumors; however, the number of infiltrating B cells was significantly reduced in malignant glands. Inflammation of the prostate may act on prostate carcinomas; particularly that involving M2 macrophage infiltration may play a significant role in prostate carcinogenesis.


A sensitive assay for maleimide groups.
A sensitive spectrophotometric assay has been developed for maleimide groups incorporated into proteins. The assay involves the reaction of maleimide with an excess of cysteine and quantitation of the remaining cysteine using an enzymatic assay that is based on the stoichiometric conversion of an inactive disulfide form of papain to the active enzyme. The restored enzymatic activity is then measured using a chromogenic substrate. The amount of maleimide is calculated as the difference between the amounts of initial cysteine and assayed remaining cysteine. The limits of detection of this assay are about 0.1 nmol maleimide in a final assay volume of 1.2 mL. This assay is about 100-fold more sensitive than a similar assay using Ellman's reagent.


Perinatal cardiopulmonary adaptation to the thin air of the Alto Andino by a native Altiplano dweller, the llama.
Most mammals have a poor tolerance to hypoxia, and prolonged O2 restriction can lead to organ injury, particularly during fetal and early postnatal life. Nevertheless, the llama (Lama Glama) has evolved efficient mechanisms to adapt to acute and chronic perinatal hypoxia. One striking adaptation is the marked peripheral vasoconstriction measured in the llama fetus in response to acute hypoxia, which allows efficient redistribution of cardiac output toward the fetal heart and adrenal glands. This strong peripheral vasoconstrictor tone is triggered by a carotid body reflex and critically depends on α-adrenergic signaling. A second adaptation is the ability of the llama fetus to protect its brain against hypoxic damage. During hypoxia, in the llama fetus there is no significant increase in brain blood flow. Instead, there is a fall in brain O2 consumption and temperature, together with a decrease of Na+-K+-ATPase activity and Na+ channels expression, protecting against seizures and neuronal death. Finally, the newborn llama does not develop pulmonary hypertension in response to chronic hypoxia. In addition to maintaining basal pulmonary arterial pressure at normal levels the pulmonary arterial pressor response to acute hypoxia is lower in highland than in lowland llamas. The protection against hypoxic pulmonary arterial hypertension and pulmonary contractile hyperreactivity is partly due to increased hemoxygenase-carbon monoxide signaling and decreased Ca2+ sensitization in the newborn llama pulmonary vasculature. These three striking physiological adaptations of the llama allow this species to live and thrive under the chronic influence of the hypobaric hypoxia of life at high altitude.


Generation of stable nulliplex autopolyploid lines of Arabidopsis thaliana using CRISPR/Cas9 genome editing.
RNA-guided endonuclease-mediated targeted mutagenesis using the clustered regularly interspersed short palindromic repeats (CRISPR)/Cas9 system has been successful at targeting specific loci for modification in plants. While polyploidy is an evolutionary mechanism enabling plant adaptation, the analysis of gene function in polyploid plants has been limited due to challenges associated with generating polyploid knockout mutants for all gene copies in polyploid plant lines. This study investigated whether CRISPR/Cas9 mediated targeted mutagenesis can generate nulliplex tetraploid mutant lines in Arabidopsis thaliana, while also comparing the relative efficiency of targeted mutagenesis in tetraploid (4x) versus diploid (2x) backgrounds. Using CRISPR/Cas9 genome editing to generate knockout alleles of the TTG1 gene, we demonstrate that homozygous nulliplex mutants can be directly generated in tetraploid Arabidopsis thaliana plants. CRISPR/Cas9 genome editing now provides a route to more efficient generation of polyploid mutants for improving understanding of genome dosage effects in plants.


Clinical comparison of tenosynovial giant cell tumors, synovial chondromatosis, and synovial sarcoma: analysis and report of 53 cases.
Tenosynovial giant cell tumors (TGCTs), synovial chondromatosis (SC), and synovial sarcoma (SS) exhibit similarities in clinical features and histochemical characteristics, and differential diagnosis remains challenging in clinical practice. Data were collected from the pathology database of Shanghai Ninth People's Hospital regarding patients who underwent surgery from 2010 to 2019 with histologically confirmed TGCTs, SC, and SS. Demographic and clinicopathological data of these patients were reviewed. Immunohistochemistry staining of 14 different markers was performed. Correlation analyses of the prognoses were evaluated. A total of 26 patients with TGCTs (8 diffuse TGCTs and 18 localized TGCTs), 16 with SC, and 11 with SS were identified. Pain was the main symptom of patients with both TGCTs and SC, while a palpable mass was the most common symptom for patients with SS. In addition to clinical features, we identified vital risk factors for disease recurrence. The mean follow-up periods were 51, 39, and 14 months for TGCTs, SC, and SS, respectively. Younger patients with diffuse TGCTs or patients with a higher neutrophil/lymphocyte ratio (NLR) displayed a significantly higher frequency of recurrence. We also plotted receiver operating characteristic (ROC) curve analysis for age and NLR. The area under the ROC curve (AUC) was calculated and demonstrated the ability to distinguish recurrent from nonrecurrent cases. In addition, higher CD163 expression was linked to recurrent diffuse TGCT cases. These data indicated possible characteristics of different aspects of TGCTs, SC, and SS. Further clarification and understanding of these factors will help with differential clinical diagnosis and recurrent risk assessment.


Regulation of the Candida albicans Hypha-Inducing Transcription Factor Ume6 by the CDK1 Cyclins Cln3 and Hgc1.
The ability to switch between proliferation as yeast cells and development into hyphae is a hallmark of Candida albicans. The switch to hyphal morphogenesis depends on external inducing conditions, but its efficiency is augmented in stationary-phase cells. Ume6, a transcription factor that is itself transcriptionally induced under hypha-promoting conditions, is both necessary and sufficient for hyphal morphogenesis. We found that Ume6 is regulated posttranslationally by the cell cycle kinase Cdc28/Cdk1, which reduces Ume6 activity via different mechanisms using different cyclins. Together with the cyclin Hgc1, Cdk1 promotes degradation of Ume6 via the SCFCDC4 ubiquitin ligase. Since HGC1 is a key transcriptional target of Ume6, this results in a negative-feedback loop between Hgc1 and Ume6. In addition, we found that Cln3, a G1 cyclin that is essential for cell cycle progression and yeast proliferation, suppresses hyphal morphogenesis and that Cln3 suppresses Ume6 activity both in the heterologous Saccharomyces cerevisiae system and in C. albicans itself. This activity of Cln3 may provide the basis for the antagonistic relationship between yeast proliferation and hyphal development in C. albicans. IMPORTANCE The yeast to hypha (mold) morphogenetic switch of Candida albicans plays a role in its virulence and constitutes a diagnostic trait for this organism, the most prevalent systemic fungal pathogen in industrialized countries. It has long been known that hyphae are most efficiently induced from stationary cultures. Here, a molecular basis for this observation is provided. The G1 cyclin Cln3, an essential promoter of yeast proliferation, was found to suppress hyphal induction. Suppression of hyphal induction is achieved by inhibition of the activity of the central activator of hyphal morphogenesis, the transcription factor Ume6. Thus, levels of Cln3 control the switch between proliferation of C. albicans as individual yeast cells and development into extended hyphae, a switch that may preface the proliferation/differentiation switch in multicellular organisms.


Real-Time Algorithm for Detrended Cross-Correlation Analysis of Long-Range Coupled Processes.
Assessing power-law cross-correlations between a pair - or among a set - of processes is of great significance in diverse fields of analyses ranging from neuroscience to financial markets. In most cases such analyses are computationally expensive and thus carried out offline once the entire signal is obtained. However, many applications - such as mental state monitoring or financial forecasting - call for fast algorithms capable of estimating scale-free coupling in real time. Detrended cross-correlation analysis (DCCA), a generalization of the detrended fluctuation analysis (DFA) to the bivariate domain, has been introduced as a method designed to quantify power-law cross-correlations between a pair of non-stationary signals. Later, in analogy with the Pearson cross-correlation coefficient, DCCA was adapted to the detrended cross-correlation coefficient (DCCC), however as of now no online algorithms were provided for either of these analysis techniques. Here we introduce a new formula for obtaining the scaling functions in real time for DCCA. Moreover, the formula can be generalized via matrix notation to obtain the scaling relationship between not only a pair of signals, but also all possible pairs among a set of signals at the same time. This includes parallel estimation of the DFA scaling function of each individual process as well, thus allowing also for real-time acquisition of DCCC. The proposed algorithm matches its offline variants in precision, while being substantially more efficient in terms of execution time. We demonstrate that the method can be utilized for mental state monitoring on multi-channel electroencephalographic recordings obtained in eyes-closed and eyes-open resting conditions.


[An immunohistochemical study of the expression of transcription factor Oct3/4 in mouse spermatogenesis].
The expression of POU-domain transcription factor Oct3/4 in the testis of adult mice has been studied using indirect immunofluorescence with highly specific antibodies. The protein is shown to be expressed in germ cells of seminiferous epithelium in a stage specific manner. The protein synthesis is initiated in mid-pachytene spermatocytes, increases to reach its peak during meiotic division. The Oct3/4 level remains augmented in early spermatids, but gradually declines during their further developmental advancement. These findings imply that Oct3/4 may have a regulatory function providing for the control of meiosis and/or terminal differentiation of spermatogenic cells.


Metal-organic framework-derived porous ternary ZnCo2O4 nanoplate arrays grown on carbon cloth for simultaneous electrochemical determination of ascorbic acid, dopamine, and uric acid.
Metal-organic frameworks derived from ternary metal oxide directly grown on the conductive substrate have attracted great interest in electrochemical sensing. In this work, metal-organic framework-derived ternary ZnCo2O4 nanoplate arrays that were grown on carbon cloth (ZnCo2O4 NA/CC) are fabricated and applied for the electrochemical determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA). Field emission scanning electron microscope (FESEM) reveals that a network-like CC substrate is covered with considerable nanoplate arrays, presenting a large specific area. X-ray photoelectron spectroscopy (XPS) demonstrates the nanoplate arrays to be composed of ZnCo2O4. Benefiting from the unique array morphology and ternary element composition, the ZnCo2O4 NA/CC shows desirable performances for simultaneous detection of AA, DA, and UA. The individual detection limits are 7.14 μM for AA, 0.25 μM for DA, and 0.33 μM for UA. Additionally, the ZnCo2O4 NA/CC is successfully applied for the quantitative determination of AA, DA, and UA in spiked serum samples, showing its great application potential.


Dendritic cells derived from BCG-infected precursors induce Th2-like immune response.
Human monocytes can differentiate into dendritic cells (DCs) according to the nature of environmental signals. We tested here whether the infection with the live tuberculosis vaccine bacillus Calmette-Guerin (BCG), which is known to be limited in preventing pulmonary tuberculosis, modulates monocyte and DC differentiation. We found that monocytes infected with BCG differentiate into CD1a- DCs (BCG-DCs) in the presence of granulocyte macrophage-colony stimulating factor and interleukin (IL)-4 and acquired a mature phenotype in the absence of maturation stimuli. In addition, BCG-DCs produced proinflammatory cytokines (tumor necrosis factor alpha, IL-1beta, IL-6) and IL-10 but not IL-12. BCG-DCs were able to stimulate allogeneic T lymphocytes to a similar degree as DCs generated in the absence of infection. However, BCG-DCs induced IL-4 production when cocultured with human cord-blood mononuclear cells. The induction of IL-4 production by DCs generated by BCG-infected monocytes could explain the failure of the BCG vaccine to prevent pulmonary tuberculosis.


Effect of omeprazole on the pharmacokinetics of paricalcitol in healthy subjects.
Paricalcitol capsules are indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease (CKD). Proton pump inhibitors are prescribed to CKD patients to treat gastroesophageal reflux. This was a single dose, crossover study evaluating the effect of omeprazole, change in gastric pH as a result thereof, on the pharmacokinetics (PK) of paricalcitol. Twenty-six healthy subjects were administered paricalcitol capsules (16 microg) alone (regimen A), and following a single dose of OMP (40 mg) (regimen B), with a washout of at least 7 days. Plasma samples for paricalcitol concentrations were collected for 48 h post-paricalcitol dose. The plasma paricalcitol concentrations were measured using an LC-MS/MS assay (LOQ=0.02 ng/ml) and paricalcitol pharmacokinetic parameters were estimated using non-compartmental methods. The point estimates and the corresponding 90% confidence intervals for Cmax and AUC0-infinity to evaluate paricalcitol-omeprazole interaction were 1.032 [0.920-1.158] and 1.041 [0.951-1.139], respectively. No significant differences in Tmax (regimen A: 2.9 h vs regimen B: 2.6 h) or t1/2 (6.83 h vs 6.6 h) between the regimens were observed. Hence, the co-administration of omeprazole does not affect the PK of paricalcitol. Both regimens were well tolerated and no apparent differences among the regimens with respect to safety were observed.


Wernicke-Korsakoff Syndrome as a Consequence of Hyperemesis Gravidarum: A Case Report.
Wernicke-Korsakoff syndrome (WKS) is caused by severe thiamine (vitamin B1) deficiency and can lead to chronic deficits. In this case, a 22-year-old pregnant patient at 10 1/7 weeks of gestation presented to the emergency department with malaise, asthenia, headache, weakness, vomiting, and weight loss of 12 kg. Pancreatitis and hepatic steatosis were considered but ruled out, and cholecystolithiasis was confirmed by ultrasound. After significant neurological deterioration, the patient underwent a cranial MRI that revealed suggestive findings in the thalamus consistent with WKS. WKS is a rare complication of hyperemesis gravidarum and should be included in the differential diagnosis of persistent vomiting in order to initiate early and appropriate treatment.


Three-dimensional printing: The potential technology widely used in medical fields.
Three-dimensional (3D) printing technology is one of the hottest research fields nowadays, which has influenced the treatment methods in the medical industry. In order to explore the progress of 3D printing technology in medical applications, the authors conducted English retrieval with the keywords "three-dimensionalprinting," "bioprinting," and "3D printing" in PubMed, and extracted information related to this exploration. This review firstly introduces the 3D printing materials, types of technology, and printing procedures in medical fields, then elaborates the current applications of 3D printing in medical devices, in vitro anatomical models, organ printing, implants, tissue engineering scaffolds, and the leap from 3D medical printing to four-dimensional (4D) medical printing, finally put forward the shortage of the medical 3D/4D printing and possible solutions of them.


A gene of Acinetobacter calcoaceticus BD413 encodes a periplasmic peptidyl-prolyl cis-trans isomerase of the cyclophilin sub-class that is not essential for growth.
Downstream of the Acinetobacter calcoaceticus estA gene, encoding a cell-bound esterase, an open reading frame (orf) was identified, which may encode a protein with a mass of 20.4 kDa. This protein shows extensive similarity to both prokaryotic and eukaryotic peptidyl-prolyl cis-trans isomerases (PPIases) of the cyclophilin sub-class, especially to the periplasmic rotamase (RotA) of Escherichia coli. A putative signal sequence suggests that the product of the Acinetobacter gene, we termed rotA, is located outside the cytoplasm. Transcription of the gene is initiated from a promoter, just upstream of the rotA orf. The observation that two A. calcoaceticus rotA deletion mutants display no apparent mutant phenotype, suggests that this PPIase is not essential for growth of the organism. These mutants, to our knowledge, are the first prokaryotic PPIase mutants reported.


Both ATP and an energized inner membrane are required to import a purified precursor protein into mitochondria.
We have investigated the energy requirement of mitochondrial protein import with a simplified system containing only isolated yeast mitochondria, energy sources and a purified precursor protein. This precursor was a fusion protein composed of 22 residues of the cytochrome oxidase subunit IV pre-sequence fused to mouse dihydrofolate reductase. Import of this protein required not only an energized inner membrane, but also ATP. ATP could be replaced by GTP, but not by CTP, TTP or non-hydrolyzable ATP analogs. Added ATP did not increase the membrane potential of respiring mitochondria; it supported import even if the proton-translocating mitochondrial ATPase and the entry of ATP into the matrix were blocked. We conclude that ATP exerts its effect on mitochondrial protein import outside the inner membrane.


Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin.
Galectin-9, a beta-galactoside binding lectin, has recently been isolated from murine embryonic kidney. In this study, its biological functions and expression in embryonic, newborn, and adult mice tissues were investigated. By Northern blot analyses, it was found widely distributed and its expression was developmentally regulated. In situ hybridization studies revealed an accentuated expression of galectin-9 in liver and thymus of embryonic mice. In postnatal mice, antigalectin-9 immunoreactivity was observed in various tissues, including thymic epithelial cells. The high expression of galectin-9 in the thymus led us to investigate its role in the clonal deletion of thymocytes. Fusion proteins were generated, which retained lactose-binding activity like the endogenous galectin-9. Galectin-9, at 2.5 microM concentration, induced apoptosis in approximately 30% of the thymocytes, as assessed by terminal deoxytransferase-mediated dUTP nick end labeling method. The apoptotic effect was dose dependent and lactose inhibitable. At higher concentrations, it induced homotypic aggregation of the thymocytes. Electron microscopy revealed approximately 60% of the thymocytes undergoing apoptosis in the presence of galectin-9. By immunofluorescence microscopy, some of the thymocytes undergoing apoptosis had plasmalemmal bound galectin-9. Galectin-9 failed to induce apoptosis in hepatocytes. Taken together, these findings indicate that galectin-9, a developmentally regulated lectin, plays a role in thymocyte-epithelial interactions relevant to the biology of the thymus.


A preliminary report on cephradine.
Plasma cephradine levels were measured after parenteral and oral administration to healthy adults. Plasma cephradine contrations of 7 - 15 mug/ml were measured after 0.5 g had been administered by mouth, and concentrations of 12 - 57 mug/ml were measured after parenteral administration; they fell to 3 mug/ml within 240 minutes except after intramuscular administration. The results of an open clinical trial conducted among 10 patients suffering from urinary tract infections were satisfactory.


How to avoid and prevent coercion in nursing homes: a qualitative study.
In many Western countries, studies have demonstrated extensive use of coercion in nursing homes, especially towards patients suffering from dementia. This article examines what kinds of strategies or alternative interventions nursing staff in Norway used when patients resist care and treatment and what conditions the staff considered as necessary to succeed in avoiding the use of coercion. The data are based on interdisciplinary focus group interviews with nursing home staff. The study revealed that the nursing home staff usually spent a lot of time trying a wide range of approaches to avoid the use of coercion. The most common strategies were deflecting and persuasive strategies, limiting choices by conscious use of language, different kinds of flexibility and one-to-one care. According to the staff, their opportunities to use alternative strategies effectively are greatly affected by the nursing home's resources, by the organization of care and by the staff's competence.


[Two cases of myelitis associated with Sjögren syndrome without xerosis: characteristic MRI findings].
We report two cases of myelitis associated with Sjögren syndrome without xerosis. Case 1: A 30-year old woman developed dysesthesia on both upper extremities and weakness of the right arm. A T2-weighted MRI examination showed a high-intensity signal and a swollen lesion between the first and seventh cervical vertebral levels. She was diagnosed as having primary Sjögren syndrome based on the positive finding of a Saxon test, typical salivary gland scintigraphy findings, and an elevated anti-SS-A antibody titer. We suspected that her myelitis was associated with Sjögren syndrome and treated her using steroid therapy. Although her symptoms were alleviated, her myelitis relapsed at the same location after the cessation of steroid therapy. Case 2: A 31-year-old woman developed dysesthesia on her neck and both upper extremities and exhibited tonic spasm. A T2-weighted MRI examination showed a high-intensity signal and a swollen lesion between the first and sixth cervical vertebral levels. She was diagnosed as having primary Sjögren syndrome based on the positive findings of a Rose Bengal test, a Schirmer's test, and a Saxon test as well as typical salivary gland scintigraphy findings and elevated titers of anti-SS-A and anti-SS-B antibodies. We suspected that her myelitis was associated with Sjögren syndrome and treated her using steroid therapy. Her symptoms improved after steroid therapy. Based on these two cases, we concluded that MRI findings for myelitis associated with Sjögren syndrome are characterized by a swollen lesion of more than three vertebral segments in length, and the relapse tends to occur at the same location.


Properties of human erythrocyte catalases after crosslinking with bifunctional reagents. Symmetry of the quaternary structure.
Normal erythrocyte catalase, the enzyme present in the blood of Swiss acatalasemic heterozygotes, and their hybrid produced in vitro, were studied after crosslinking with bifunctional reagents. On theoretical grounds [cf. Hajdu, J., Bartha, F. & Friedrich, P. (1976) Eur. J. Biochem. 68, 373--383] it is inferred from the dodecylsulphate gel electrophoretic patterns obtained after treating catalase with diimidates of various chain lengths that the enzyme is an isologous tetramer (D2 symmetry). The minimal distances between crosslinkable primary amino groups across the three domains of bonding are different. Reaction with diimidates causes a moderate loss of enzyme activity in all three enzyme types due to amidination rather than crosslink formation. On the other hand, crosslinking stabilizes the enzyme against urea and heat inactivation. This is most prominent with heterozygote acatalasemic catalase. Crosslinking markedly prevents the development of peroxidase activity that can be elicited in catalases by urea treatment. The role of the quaternary structure of the protein in the relationship between catalase and peroxidase activities is discussed.


Heterogeneity in soil water and light environments and dispersal limitation: what facilitates tree species coexistence in a temperate forest?
In the present study, we analysed the habitat association of tree species in an old-growth temperate forest across all life stages to test theories on the coexistence of tree species in forest communities. An inventory for trees was implemented at a 6-ha plot in Ogawa Forest Reserve for adults, juveniles, saplings and seedlings. Volumetric soil water content (SMC) and light levels were measured in 10-m grids. Relationships between the actual number of stems and environmental variables were determined for 35 major tree species, and the spatial correlations within and among species were analysed. The light level had no statistically significant effect on distribution of saplings and seedlings of any species. In contrast, most species had specific optimal values along the SMC gradient. The optimal values were almost identical in earlier life stages, but were more variable in later life stages among species. However, no effective niche partitioning among the species was apparent even at the adult stage. Furthermore, results of spatial analyses suggest that dispersal limitation was not sufficient to mitigate competition between species. This might result from well-scattered seed distribution via wind and bird dispersal, as well as conspecific density-dependent mortality of seeds and seedlings. Thus, both niche partitioning and dispersal limitation appeared less important for facilitating coexistence of species within this forest than expected in tropical forests. The tree species assembly in this temperate forest might be controlled through a neutral process at the spatial scale tested in this study.


Multicriteria Decision Model and Thermal Pretreatment of Hotel Food Waste for Robust Output to Biogas: Case Study from City of Jaipur, India.
The anaerobic batch test (45 days at 37°C) was performed to describe the effect of thermal pretreatment at moderate temperatures (60, 80, and 100°C) over durations of 10 and 20 minutes on the enhancement of biogas production using hotel food waste from city of Jaipur, India. The results showed that the total cumulative biogas production with thermal pretreatment (100°C, 10 minutes) was 41% higher than the control. Also, this alternative gets first rank using multicriteria decision making model, VIKOR. This outcome was obtained due to the enhancement of degradation of organic compounds such as protein and volatile solids that occurred in the linear trend. Modified Gompertz and Logistic models were used to study the effect of different pretreatment parameters on lag time and biogas yield. Scanning electron microscopy and Fourier transform infrared spectroscopy were also employed to investigate the effect of thermal pretreatment on the physiochemical properties of food waste.


Extensive rostral mandibulectomy for treatment of ameloblastoma in a horse.
To report long-term outcome in a mare that had extensive rostral mandibulectomy to remove an ameloblastoma. Clinical report. A 21-year-old mare. An ameloblastoma, located in the rostral aspect of the mandible, was removed by complete en-bloc resection of the tumor, removing most of the mandibular symphysis. The day after surgery, the remaining mandibular symphysis (<5 mm) fractured causing marked instability of the hemi-mandibles. Partial wound dehiscence occurred 5 days after surgery; however, the mare was able to eat well and the incision healed within 2 weeks. At 18 months, there was bony fusion of the hemi-mandibles and mild protrusion of the tongue. Extensive rostral mandibulectomy (up to the caudal edge of the mandibular symphysis) can apparently be performed in a horse without internal or external stabilization, and yield a cosmetic and functional outcome.


The deubiquitinase USP7 uses a distinct ubiquitin-like domain to deubiquitinate NF-ĸB subunits.
The transcription factor NF-ĸB is a master regulator of the innate immune response and plays a central role in inflammatory diseases by mediating the expression of pro-inflammatory cytokines. Ubiquitination-triggered proteasomal degradation of DNA-bound NF-ĸB strongly limits the expression of its target genes. Conversely, USP7 (deubiquitinase ubiquitin-specific peptidase 7) opposes the activities of E3 ligases, stabilizes DNA-bound NF-ĸB, and thereby promotes NF-ĸB-mediated transcription. Using gene expression and synthetic peptide arrays on membrane support and overlay analyses, we found here that inhibiting USP7 increases NF-ĸB ubiquitination and degradation, prevents Toll-like receptor-induced pro-inflammatory cytokine expression, and represents an effective strategy for controlling inflammation. However, the broad regulatory roles of USP7 in cell death pathways, chromatin, and DNA damage responses limit the use of catalytic inhibitors of USP7 as anti-inflammatory agents. To this end, we identified an NF-ĸB-binding site in USP7, ubiquitin-like domain 2, that selectively mediates interactions of USP7 with NF-ĸB subunits but is dispensable for interactions with other proteins. Moreover, we found that the amino acids 757LDEL760 in USP7 critically contribute to the interaction with the p65 subunit of NF-ĸB. Our findings support the notion that USP7 activity could be potentially targeted in a substrate-selective manner through the development of noncatalytic inhibitors of this deubiquitinase to abrogate NF-ĸB activity.


Sleep related movement and behavior disorders.
Movement and behavior disorders developing during sleep or in the transitional state from sleep to wakefulness are mostly unfamiliar to Japanese neurologists, primarily because these disorders are objects of basic research. In addition, the patients with sleep related movement and behavior disorders (SRMBD) show no signs and symptoms in our consulting rooms, and cannot be identified without polysomnography (PSG) attended by trained sleep technologists. Although attended PSG is not widely available in Japan, some kinds of SRMBD ought to be clinical targets for neurologists, and they are the scope of this review.


Persistent Cardiac Magnetic Resonance Imaging Findings in a Cohort of Adolescents with Post-Coronavirus Disease 2019 mRNA Vaccine Myopericarditis.
We describe the evolution of cardiac magnetic resonance imaging findings in 16 patients, aged 12-17 years, with myopericarditis after the second dose of the Pfizer mRNA coronavirus disease 2019 vaccine. Although all patients showed rapid clinical improvement, many had persistent cardiac magnetic resonance imaging findings at 3- to 8-month follow-up.


[Juvenile cerebral infarction with familial hyperlipoproteinemia (a)--case report].
A 34-year-old male with a history of angina pectoris suddenly developed weakness in the right upper and lower limbs, and consulted our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) suggested cerebral infarction. Cerebral angiography revealed stenosis at the M1 portion of the left middle cerebral artery. Hypertension, diabetes, tobacco or hyperlipidemia were not considered as risk factors for cerebral infarction. The lipoprotein (a) [Lp(a)] level was high. In the present case, medication with a nicotinic acid agent, niceritrol, for hyperlipoproteinemia and low density lipoprotein (LDL) apheresis were performed. Concerning family history, the patient's mother and younger sister had hyperlipoproteinemia. Recent studies have reported that increased Lp(a) levels are an independent risk factor even in cerebral infarction and coronary artery disease. Measurement of Lp(a) levels and treatment for increased Lp (a) levels may be important.


Stigma experienced by caregivers of patients with severe mental disorders: A nationwide multicentric study.
Stigma is very common among caregivers of patients with severe mental disorder; however, there is lack of national level data from India. To assess affiliate stigma and its correlates among caregivers of patients with severe mental disorders. For this, caregivers of patients with schizophrenia ( N = 707), bipolar disorder ( N = 344) and recurrent depressive disorder ( N = 352) were assessed on Stigma scale for Caregivers of People with Mental Illness and General Health Questionnaire. Caregivers of patients with schizophrenia reported significantly higher stigma than patients with bipolar disorder and recurrent depressive disorder. Caregiver of patients with bipolar disorder reported significantly greater stigma than the caregivers of patients with recurrent depressive disorder. Higher caregiver stigma in all the diagnostic groups was associated with higher psychological morbidity in caregivers. Higher stigma in caregivers of schizophrenia was seen when the patient had younger age of onset and longer duration of treatment. In the bipolar disorder group, higher stigma in caregivers was seen when patient had higher residual manic symptoms. This study suggests that caregivers of patients with schizophrenia experience higher stigma than the caregivers of patients with bipolar disorder and recurrent depressive disorder. Higher stigma is associated with higher psychological morbidity in the caregivers. Therefore, the clinicians managing patients with severe mental disorders must focus on stigma and psychological distress among the caregivers and plan intervention strategies to reduce stigma.


Camptodactyly, with muscular hypoplasia, skeletal dysplasia, and abnormal palmar creases: Tel Hashomer camptodactyly syndrome.
A syndrome characterized by camptodactyly, distinct facial features, multiple musculoskeletal defects, and unique dermatoglyphic changes is described in two sisters born of consanguineous parents. In 1972 this same constellation of findings was first reported in two sibs from a different ethnic origin. This heritable disorder of connective tissue termed the Tel Hashomer camptodactyly syndrome is thought to be transmitted as an autosomal recessive trait. The basic defect is unknown.


Comparison Between Vancomycin and Gentamicin for Intraoperative Presoaking of Hamstring Graft in Primary Anterior Cruciate Ligament Reconstruction.
Introduction Postoperative infection is an uncommon complication with grave consequences following anterior cruciate ligament reconstruction (ACLR). Presoaking of the hamstring graft with antibiotics results in a lower rate of infection. The purpose of the current study was to compare the efficacy of two commonly used antibiotics, vancomycin and gentamicin, in reducing infection rates following anterior cruciate ligament reconstruction. Methods The retrospective study included a total of 578 patients who underwent arthroscopic anterior cruciate ligament reconstruction between June 2015 and October 2021. The timeline was categorized as the period between June 2015 to October 2018 (Vancomycin presoaking of hamstring graft) and November 2018 to October 2021 (Gentamicin presoaking of hamstring graft). All patients were examined for the development of infection, causative organism, and treatment received. Patients with intravenous drug abuse, alcoholism, steroid use, revision cases, and a prior history of infection in the knee were excluded from the study. Fisher's exact test was used for comparison of categorical data, and Poisson regression analysis was carried out to calculate incidence rate ratios after adjusting for confounding variables. Results Presoaking of hamstring grafts with vancomycin was carried out in 224 patients, and gentamicin was used in 354 patients. In total, three patients in the vancomycin and four patients in the gentamicin groups developed an intraarticular infection, and the difference in infection rate between the two groups was not statistically significant (p=0.919). Coagulase-negative Staphylococcus aureus was isolated in four cases, Enterobacter cloacae in one, and no organism was seen in two cases. The groups were comparable in terms of age (p=0.563), smoking (p=0.84), sex (p=0.359), and operative time (p=0.09). Conclusion Presoaking of hamstring autografts with gentamicin intraoperatively is a good alternative to vancomycin in the prevention of infection following arthroscopic anterior cruciate ligament reconstruction.


From Smallpox to Big Data: The Next 100 Years of Epidemiologic Methods.
For more than a century, epidemiology has seen major shifts in both focus and methodology. Taking into consideration the explosion of "big data," the advent of more sophisticated data collection and analytical tools, and the increased interest in evidence-based solutions, we present a framework that summarizes 3 fundamental domains of epidemiologic methods that are relevant for the understanding of both historical contributions and future directions in public health. First, the manner in which populations and their follow-up are defined is expanding, with greater interest in online populations whose definition does not fit the usual classification by person, place, and time. Second, traditional data collection methods, such as population-based surveillance and individual interviews, have been supplemented with advances in measurement. From biomarkers to mobile health, innovations in the measurement of exposures and diseases enable refined accuracy of data collection. Lastly, the comparison of populations is at the heart of epidemiologic methodology. Risk factor epidemiology, prediction methods, and causal inference strategies are areas in which the field is continuing to make significant contributions to public health. The framework presented herein articulates the multifaceted ways in which epidemiologic methods make such contributions and can continue to do so as we embark upon the next 100 years.


Depletion of intracellular Ca2+ stores activates a Ca(2+)-selective channel in vascular endothelium.
The present study was designed to identify the channel responsible for Ca2+ influx after depletion of intracellular Ca2+ stores. Different maneuvers that deplete intracellular Ca2+ stores activated a Ca(2+)-selective channel. Superfusion of single bovine aortic endothelial cells with 50 nmol/l bradykinin, 10 mumol/l ATP, or 10 mumol/l 2,5-di(tert-butyl)-1,4-benzohydroquinone produced activation of channels of the same amplitude in cell-attached patches. Channel activity declined within the first minute after patch excision. The channel showed strong inward rectification and a reversal potential of 0 mV in symmetrical sodium sulfate (Na2SO4) solution. Under these conditions, the conductance was 5 pS in the inward direction. Addition of 10 mmol/l Ca2+ to the extracellular solution shifted the reversal potential to +30 +/- 5 mV, and the conductance for inward current was 11 pS. The reversal potential was used to calculate an ion permeability ratio of Ca2+/Na+ > 10:1.


Ribosomal vaccines: preparation of subcellular fractions.
Methods for isolation and analysis of subcellular bacterial fractions intended to be used in the preparation of ribosomal vaccines are described. Cultivation conditions in fermentors for obtaining maximal growth curve slopes are studied; cultivation is stopped before the end of the exponential growth phase in order to collect biomasses having a high viability rate, which is essential for the quality of the subcellular fractions isolated thereafter. Extraction methods for ribosomes and ribosomal RNA, as well as two proceedings for preparing adjuvant proteoglycans from Klebsiella pneumoniae membranes, are described. The analytical methods used for the control of these preparations and the results obtained for the various fractions are given.


[Principles of classifying and naming enzymes].
Common principles of enzyme classification, nomenclature and code recommended by the Committee on Enzyme of International Union of Biochemistry are described.


In vitro activity of glufosfamide in childhood acute leukemia.
Glufosfamide is a new agent for cancer chemotherapy. The objective of the study was the comparison of the in vitro drug resistance profile of glufosfamide with other oxazaphosphorines in 106 samples of childhood acute leukemia by means of the MTT assay. The following drugs were tested: glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide, mafosfamide cyclohexylamine salt, prednisolone, vincristine, L-asparaginase, daunorubicin and cytarabine. In the group of initial Acute Lymphoblastic Leukemia (ALL) samples, equivalent cytotoxicity values for glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide and mafosfamide were 5.95, 9.92, 4.60 and 3.90 microg/ml, respectively. In comparison to initial ALL samples, the relative resistance for glufosfamide and 4-HOO-ifosfamide in relapsed ALL samples were 1.9 (p=0.049) and 1.3 (ns), and in initial Acute Myeloblastic Leukemia (AML) samples, respectively, 31 (p<0.001) and 5 (p=0.001). All oxazaphosphorines showed highly significant cross-resistance. In conclusion, in vitro activity of glufosfamide is comparable to ifosfamide. Glufosfamide shows high activity against lymphoblasts both on diagnosis and on relapse, however it cannot circumvent resistance to other oxazaphosphorines.


Open lung biopsy in patients with non-Hodgkin's lymphoma and pulmonary infiltrates.
Patients with non-Hodgkin's lymphoma (NHL) are at increased risk for pulmonary infection with opportunistic pathogens associated with diminished cell mediated immunity. Open lung biopsy (OLB) frequently is recommended for diagnosis of pulmonary infiltrates in patients with NHL, but its usefulness for patient management and outcome has not been evaluated for patients with NHL. We reviewed the results of 20 consecutive OLB in 19 patients with previously diagnosed non-Hodgkin's lymphoma at Stanford University Medical Center during a nine-year period. Fifteen patients had known active lymphoma at time of OLB, and no patient had granulocytopenia. Ten of the 20 OLBs yielded specific diagnoses. A greater proportion of patients with stage I or II disease had specific diagnoses than patients with more advanced NHL. Five of 14 patients considered to have had a life threatening illness at the time of OLB had specific diagnoses from OLB vs five of six patients considered clinically stable. Chest roentgenograms that had discrete masses or nodules correlated with ability to establish a specific diagnosis by OLB. For patients in whom the results of OLB were nonspecific, management appeared unaffected by the OLB. The OLB in NHL appeared most useful for detecting recurrent NHL in clinically stable patients with discrete nodules or masses on chest roentgenogram. Pneumocystis pneumonia was the only infection identified by OLB.


Lack of association between the 5-HTTLPR and positive screening for mental disorders among children exposed to urban violence and maltreatment.
To ascertain whether genetic variations in the serotonin transporter gene (5-HTTLPR 44-bp insertion/deletion polymorphism) influence an increase in depressive and anxiety symptoms in children and adolescents exposed to high levels of violence. Saliva samples were collected from a group of children who were working on the streets and from their siblings who did not work on the streets. DNA was extracted from the saliva samples and analyzed for 5-HTTLPR polymorphism genotypes. One hundred and seventy-seven children between the ages of 7 and 14 years were analyzed (114 child workers and 63 siblings). Data on socioeconomic conditions, mental symptoms, and presence and severity of maltreatment and urban violence were collected using a sociodemographic inventory and clinical instruments. There was no positive correlation between the 5-HTTLPR polymorphism and presence of mental symptoms in our sample, although the children were exposed to high levels of abuse, neglect, and urban violence. Despite previous studies that associated adult psychiatric disorders with the 5-HTTLPR polymorphism and a history of childhood maltreatment, no such association was found in this sample of children at risk.


What are the perceived learning needs of Australian general practice registrars for quality prescribing?
Little is known about the perceived learning needs of Australian general practice (GP) registrars in relation to the quality use of medicines (QUM) or the difficulties experienced when learning to prescribe. This study aimed to address this gap. GP registrars' perceived learning needs were investigated through an online national survey, interviews and focus groups. Medical educators' perceptions were canvassed in semi-structured interviews in order to gain a broader perspective of the registrars' needs. Qualitative data analysis was informed by a systematic framework method involving a number of stages. Survey data were analysed descriptively. The two most commonly attended QUM educational activities took place in the workplace and through regional training providers. Outside of these structured educational activities, registrars learned to prescribe mainly through social and situated means. Difficulties encountered by GP registrars included the transition from hospital prescribing to prescribing in the GP context, judging how well they were prescribing and identifying appropriate and efficient sources of information at the point of care. GP registrars learn to prescribe primarily and opportunistically in the workplace. Despite many resources being expended on the provision of guidelines, decision-support systems and training, GP registrars expressed difficulties related to QUM. Ways of easing the transition into GP and of managing the information 'overload' related to medicines (and prescribing) in an evidence-guided, efficient and timely manner are needed. GP registrars should be provided with explicit feedback about the process and outcomes of prescribing decisions, including the use of audits, in order to improve their ability to judge their own prescribing.


Fine needle aspiration cytology of pleomorphic adenoma. An analysis of 212 cases.
To assess the value of fine needle aspiration cytology (FNAC) in the diagnosis of pleomorphic adenoma and to determine the cytologic variations responsible for diagnostic errors. We retrospectively studied 212 cases cytologically diagnosed as pleomorphic adenoma. In 184 a histologic diagnosis was available. Fourteen cases of histologically proven pleomorphic adenomas with a previously erroneous cytologic diagnosis were also reviewed. This study was based on those cases with a histologic diagnosis. The sensitivity and specificity of the cytologic diagnosis of pleomorphic adenoma in our series were 92.6% and 98.4%, respectively. In relation to malignancy, the series showed six false negative and three false positive diagnoses. In those cases correctly diagnosed on aspiration (175), a typical cytologic appearance, with no diagnostic difficulties, was observed in 118 cases (67.4%); the remainder showed cytologic variations. Cellular atypia (20.6%), cystic transformation (7%) and the presence of a cylindromatous pattern (5%) resembling adenoid cystic carcinoma were the most common cytologic variations observed and responsible for the majority of the errors. The cytologic variations in FNAC of pleomorphic adenoma must be considered in order to avoid important errors in the preoperative management of and surgical approach to salivary gland lesions.


Erythropoietin for patients with malignant disease.
Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoietin (EPO) and red blood cell transfusions. The aim of this systematic review was to assess the effect of erythropoietin to either prevent or treat anaemia in cancer patients. We searched the Central Register of Controlled Trials, MEDLINE (01/1985 to 12/2001), EMBASE (01/1985 to 12/2001), other databases and reference lists of articles. We also contacted experts in the field and pharmaceutical companies. Randomised controlled trials comparing the use of recombinant human erythropoietin (plus transfusion if needed) with red blood cell transfusions alone for the treatment or prevention of anaemia in cancer patients. Two reviewers independently assessed trial quality and extracted data. All authors from included studies were contacted for additional information. Twenty seven trials with 3,287 adults were included. Use of erythropoietin significantly reduced the relative risk of red blood cell transfusions (RR 0.67; 95% CI 0.62 to 0.73, 25 trials, n = 3,069). On average participants in the erythropoietin group received one unit of blood less than the control group (WMD -1.00; 95% CI-1.31 to -0.70, 13 trials, n = 2,056). For participants with baseline haemoglobin below 10 g/dL haematological response was observed more often in participants receiving EPO (RR 3.60; 95% CI 3.07 to 4.23, 14 trials, n = 2,347). There was inconclusive evidence whether EPO improves tumour response (fixed effect RR 1.36; 95% CI 1.07 to 1.72, seven trials, n = 1,150; random effects: RR 1.21; 95% CI 0.92 to 1.59) and overall survival (adjusted data: HR 0.81; 95% CI 0.67 to 0.99; unadjusted data: HR 0.84; 95% CI 0.69 to 1.02, 19 trials, n = 2,865). There were no statistically significant adverse effects. Evidence was inconclusive with respect to quality of life and fatigue. There is consistent evidence that the administration of erythropoietin reduces the risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline haemoglobin below 10 g/dL there is strong evidence that erythropoietin improves haematological response. There is inconclusive evidence whether erythropoietin improves tumour response and overall survival. Research on side effects is inconclusive.


[Defecography in internal invagination of the rectum].
Rectal invagination has been considered an important cause of defecation difficulties and blockade (obstructed defecation). In the present study defecographies performed on 15 patients, with previous diagnosis of rectal invagination have been reviewed. Six patients had an intra-rectal (IR) invagination, three had an intra-anal (IA) invagination, while two patients did not show a typical rectal invagination. In the present series there is a suspected radiologic recurrence of the invagination. Three patients show a tendency to rectal stenosis. Anorectal angles at rest and under straining appears higher than the ones in normal subjects, after rectopexy, anorectal angles do not appear to be significantly changed and the pelvic floor is not significantly raising post-operatively. 7 out of 10 women had a rectocele preoperatively and 4 out 9 postoperatively. In 8 patients it was possible to compare a pre to a post-operative defecography. All patients but one displayed a reduction in the ability in emptying the rectum. The fact that rectal emptying is impaired may suggest that some autonomic denervation might occur following rectal mobilization.


Psychological distress and coping styles of caregivers of patients with amyotrophic lateral sclerosis: a longitudinal study.
Objectives: To assess psychological distress levels over time in caregivers of patients in the early stage of amyotrophic lateral sclerosis (ALS) and to investigate the association between caregivers' coping styles and psychological distress over time. Methods: Fifty-four caregivers were followed in a RCT of patients in the early stage of ALS. Questionnaires were administered at baseline, 4, 7, and 10 months. Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS) and task-, emotion-, and avoidance-oriented coping styles were identified with the short version of the Coping Inventory for Stressful Situations (CISS-21). Analyses were performed using linear mixed models. Results: Caregivers' psychological distress increased by 0.24 points on the HADS per month (p = 0.01). An emotion-oriented coping style was positively associated with psychological distress in caregivers (b = 0.90, p < 0.01), but did not influence the development of psychological distress over time. The avoidance-oriented coping style and the task-oriented coping style were not significantly related to psychological distress. Conclusion: Feelings of distress increase in ALS caregivers during the course of the disease of the patient. Emotion-oriented coping is related to psychological distress; however, emotional coping and distress might represent overlapping constructs. Focusing on one coping style in the care for ALS caregivers may be too simplistic for the complex situations they face, as it ignores the fact that people may require different coping strategies in different situations.


Fibrin glue mediated delivery of bone anabolic reagents to enhance healing of tendon to bone.
Tendon graft healing in bone tunnels for the fixation of intra-articular ligament reconstructions may limit clinical outcome by delaying healing. This study assesses the effects of hydrogel-mediated delivery of bone anabolic growth factors in a validated model of tendon-to-bone tunnel healing. Forty-five Wistar rats were randomly allocated into three groups (BMP2-treated, GSK126-treated, and placebo). All animals underwent a tendon-to-bone tunnel reconstruction. Healing was evaluated at 4 weeks by biomechanical assessment, micro-computed tomography (bone mineral density, bone volume, cross sectional area of bone tunnels), and traditional histology. Adverse events associated with the hydrogel-mediated delivery of drugs were not observed. Results of our biomechanical assessment demonstrated favorable trends in animals treated with bone anabolic factors for energy absorption (P = 0.116) and elongation (P = 0.054), while results for force to failure (P = 0.691) and stiffness (P = 0.404) did not show discernible differences. Cross sectional areas for BMP2-treated animals were reduced, but neither BMP2 nor GSK126 administration altered bone mineral density (P = 0.492) or bone volume in the bone tunnel. These results suggest a novel and positive effect of bone anabolic factors on tendon-to-bone tunnel healing. Histological evaluation confirmed absence of collagen fibers crossing the soft tissue-bone interface indicating immature graft integration as expected at this time point. Our study indicates that hydrogel-mediated delivery of BMP2 and GSK126 appears to be safe and has the potential to enhance tendon-to-bone tunnel healing in ligament reconstructions.


Creation of double-outlet left ventricles for left ventricular outflow obstructions: initial clinical results in six patients.
Operations for supravalvular, valvular, and subvalvular stenoses are frequently complicated by aortic insufficiency, recurrence, or aortic valve prosthetic malfunction. Without surgery, increasing left ventricular pressures, myocardial hypertrophy, congestive failure, and sudden death are common. Following an extended series of bovine experiments, we have created double-outlet left ventricles in 6 patients. All but one had been operated on previously for combined supravalvular, valvular, or subvalvular aortic stenosis or idiopathic hypertrophic subaortic stenosis. All left ventricular-ascending aortic gradients were markedly decreased and the deranged left ventricular physiologic indices returned toward normal following operation and discharge from the hospital. None of these patients is receiving Coumadin, and none has exhibited any deleterious effects from the fractionation of left ventricular output, cephalad and caudad. Our current prosthesis is a composite consisting of a special LTI carbon inlet tube with a left ventricular apical sewing ring and graft extension anastomosed to a Hancock prosthesis of appropriate size. The procedure is simple, reproducible, effective, and has much to recommend. Special conduits are now being fabricated for future use. In certain instances, this approach may have advantages over conventional primary aortic valvotomy in infants or valve replacement in adults.


Unraveling Anaerobic Metabolisms in a Hypersaline Sediment.
The knowledge on the microbial diversity inhabiting hypersaline sediments is still limited. In particular, existing data about anaerobic hypersaline archaea and bacteria are scarce and refer to a limited number of genera. The approach to obtain existing information has been almost exclusively attempting to grow every organism in axenic culture on the selected electron acceptor with a variety of electron donors. Here, a different approach has been used to interrogate the microbial community of submerged hypersaline sediment of Salitral Negro, Argentina, aiming at enriching consortia performing anaerobic respiration of different electron acceptor compounds, in which ecological associations can maximize the possibilities of successful growth. Growth of consortia was demonstrated on all offered electron acceptors, including fumarate, nitrate, sulfate, thiosulfate, dimethyl sulfoxide, and a polarized electrode. Halorubrum and Haloarcula representatives are here shown for the first time growing on lactate, using fumarate or a polarized electrode as the electron acceptor; in addition, they are shown also growing in sulfate-reducing consortia. Halorubrum representatives are for the first time shown to be growing in nitrate-reducing consortia, probably thanks to reduction of N2O produced by other consortium members. Fumarate respiration is indeed shown for the first time supporting growth of Halanaeroarchaeum and Halorhabdus belonging to the archaea, as well as growth of Halanaerobium, Halanaerobaculum, Sporohalobacter, and Acetohalobium belonging to the bacteria. Finally, evidence is presented suggesting growth of nanohaloarchaea in anaerobic conditions.


Toxicity of ferric oxide and benzo[a]pyrene alone or in combination in respiratory tract of Sprague Dawley rats.
The association of small quantities of ferric oxide with Benzo[a]Pyrene (BaP) appears to increase in vivo the toxic effect of BaP. The effect of Fe2O3 may be mediated by the recruitment of alveolar macrophages. These cells would contribute to the production of toxic and carcinogenic BaP metabolites and would stimulate development of tumors by producing cellular mediators of inflammation. In order to understand the mechanism of the synergic effect, we have instillated male Sprague Dawley rats 3 weeks of age with a single dose: Fe2O3 (3 mg) or BaP (3 mg)/combination Fe2O3-BaP (3 mg-3 mg) in 200 microliters of physiological saline solution. Control group of identical size (treated with physiological saline solutions and untreated) were used for this study. Animals were sacrificed 48 hours after instillation and a bronchoalveolar lavage (BAL) was performed. With each BAL we have obtained protein measurement, cells were stained with May-Grünwald-Giemsa method and slides were studied with polarised light. The malonaldehyde (MDA) was measured by High Performance Liquid Chromatography. The PMN elastase determination was performed by IMAC (immuno-activation) technology. An automated kinetic method for measuring cathepsins B and L was carried out using a fluorogenic substrate: Z-Phe-Arg-AMC, a specific inhibitor E64 and AMC as an internal standard. After a quantitative Dot-Blot of the samples of BAL, an immunodetection of alpha(1)-antitrypsin (alpha(1)AT) was performed. The inhibitory capacity of alpha(1)AT was determined by an enzymatic reaction with porcine pancreatic elastase. We have observed an increased MDA level for rats intoxicated with Fe2O3 (123%), BaP (31%) and Fe2O3 + BaP (56%). The levels of PMN elastase and cathepsin B and L were increased: Fe2O3 (51-58%), BaP (52-27%). This effect was not seen for rats intoxicated by Fe2O3 + BaP. The free alpha(1)AT was decreased with the three toxics (Fe2O3: 44%--BaP: 42%--Fe2O3: 41%). The inhibitory capacity of alpha(1)AT was lower in groups of rats instilled with toxics.


[A Case of Double Lung and Gastric Cancer Involving Para-Aortic Lymph Node Metastasis with Difficult Preoperative Diagnosis].
A man in his 60s was admitted to our hospital with anemia. An endoscopic examination revealed advanced gastric cancer. CT revealed peri-gastric and para-aortic lymphadenopathy, and a nodular shadow(20mm)in the lower lobe of the right lung. PET-CT revealed abnormal uptake in the para-aortic lymph node and stomach wall and the nodular shadow in the right lung. A bronchoscopy revealed pulmonary adenocarcinoma. From the above, he was diagnosed with gastric cancer(cT4a, cN2, cM1, cStage IV )and lung cancer(cT2a, cN0, cM0, cStage I B). Because of gastric bleeding, we decided to operate on the gastric cancer before the lung cancer. First, total gastrectomy, splenectomy, and cholecystectomy were performed and then dissection of lymph node No. 16was performed. Histopathological examination indicated that lymph node No. 16was common to lung cancer, so the final diagnosis was gastric cancer(pT4a, pN0, cM0, fStage II A)and lung cancer(cT2a, cN0, pM1, fStage IV ). In this case, lymphadenectomy of No. 16in the first and pathological diagnosis during surgery could help us avoid splenectomy and cholecystectomy, and could reduce invasion.


Use of transrectal ultrasound for high dose rate interstitial brachytherapy for patients of carcinoma of uterine cervix.
Transrectal ultrasound (TRUS) has been widely used for guiding prostate implants, but not much for interstitial brachytherapy (IBT) of cervix cancer. The aim of our study is to report our experience with TRUS guided high dose rate (HDR) IBT in patients with carcinoma of uterine cervix. During the year 2005-2006, 25 patients of cervical cancer not suitable for intracavitary radiotherapy (ICRT), were enrolled in this prospective study. We used B-K Medical USG machine (Falcon 2101) equipped with a TRUS probe (8658) having a transducer of 7.5 MHz for IBT. Post procedure, a CT scan was done for verification of needle position and treatment planning. Two weekly sessions of HDR IBT of 8-10 Gy each were given after pelvic external beam radiation therapy. A total of 40 IBT procedures were performed in 25 patients. Average duration of implant procedure was 50 minutes. There was no uterine perforation in any of 11 patients in whom central tandem was used. CT scan did not show needle perforation of bladder/rectum in any of the patients. During perioperative period, only 1 procedure (2.5%) was associated with hematuria which stopped within 6 hours. Severe late toxicity was observed in 3 (12%) patients. Overall pelvic control rate was 64%. Our experience suggests that TRUS is a practical and effective imaging device for guiding the IBT procedure of cervical cancer patients. It helps in accurate placements of needles thus avoiding the injury to normal pelvic structures.


Phosphorylation of the NF2 tumor suppressor in Schwann cells is mediated by Cdc42-Pak and requires paxillin binding.
Mutations in the Neurofibromatosis type 2 tumor suppressor gene that encodes Schwannomin causes formation of benign schwannomas. Schwannoma cells lose their characteristic bipolar shape and become rounded with excessive ruffling membranes. Schwannomin is phosphorylated at serine 518 (S518) by p21 activated kinase (Pak). Unphosphorylated schwannomin is associated with growth inhibition but little is known about the function of the phosphorylated form, or the molecular events leading to its phosphorylation. Here, we report in SCs that schwannomin S518 phosphorylation requires binding to paxillin and targeting to the plasma membrane. Phospho-S518-schwannomin is enriched in the peripheral-most aspects of membrane specializations where paxillin, activated Pak, Cdc42 but not Rac are highly expressed. Schwannomin and Pak phosphorylation levels are not reduced in response to lowering Rac-GTP levels with NSC23766. Expression of schwannomin S518A/D-GFP variants each distinctively altered Schwann cell shape and polarity. These results are consistent with tight spatial regulation of S518 phosphorylation at the plasma membrane in a paxillin and Cdc42-Pak dependent manner that leads to local reorganization of the SC cytoskeleton.


Dietary PUFAs attenuate NLRP3 inflammasome activation via enhancing macrophage autophagy.
Dietary PUFAs reduce atherosclerosis and macrophage inflammation, but how nucleotide-binding oligomerization domain leucine-rich repeat-containing receptor protein (NLRP3) inflammasome activation and autophagy influence PUFA-mediated atheroprotection is poorly understood. We fed Ldlr-/- mice diets containing 10% (calories) palm oil (PO) and 0.2% cholesterol, supplemented with an additional 10% of calories as PO, fish oil (FO), echium oil (EO, containing 18:4 n-3), or borage oil (BO, containing 18:3 n-6). Inflammasome activation, autophagic flux, and mitochondrial function were measured in peritoneal macrophages, blood monocytes, or liver from diet-fed mice. Compared with PO, dietary PUFAs (FO, EO, or BO) markedly inhibited inflammasome activation, shown by 1) less macrophage IL-1β secretion and caspase-1 cleavage in response to NLRP3 inflammasome activators, 2) less IL-1β secretion and caspase-1 cleavage from liver or hepatocytes in response to lipopolysaccharide (LPS), and 3) attenuated caspase-1 activity in blood monocytes. Furthermore, PUFA-enriched diets increased LC3-II expression in macrophage, aorta, and liver samples and reduced numbers of dysfunctional mitochondria in macrophages in response to LPS and palmitate, suggesting enhanced autophagic activation. Dietary PUFAs did not attenuate NLRP3 inflammasome activation in atg5-deficient macrophages, indicating that autophagic activation is critical for the PUFA-mediated inflammasome inactivation. In conclusion, dietary PUFAs reduce atherosclerosis, in part, by activation of macrophage autophagy and attenuation of NLRP3 inflammasome activation.


Smiles for success: restoring functional dentition one mouth at a time.
Edentulism is the outcome of a multifactorial process involving biological factors and patient-related factors. Prosthodontics serves as a solution. Tooth replacement through prosthetic devices may be prohibitive for the underserved population due to barriers such as cost and lack of transportation. A community service project was developed as a response strategy to address these concerns in Fort Wayne, Indiana. With the help of Indiana University Purdue University (IPFW) Dental Laboratory Technology students and local dental professionals, the Smiles for Success: Restoring Functional Dentition One Mouth at a Time project assisted the underserved of Fort Wayne. Success was accomplished through the repair or reline of existing dentures, as well as the creation of new partial and complete oral prosthetic appliances. Working within the existing healthcare framework of an inner city clinic and local health fair for the underserved, the project completed work on 29 dentures and restored 22 patients to functioning dentitions. While the prosthetic appliances bring about new and restored smiles, it leads to a lifetime of new opportunities and improved health.


Mononuclear leukocytes, expression of HLA class II antigens and intercellular adhesion molecule 1 in focal segmental glomerulosclerosis.
Immunophenotyping of infiltrating glomerular and interstitial mononuclear leukocytes performed in renal tissues of 15 patients with focal segmental glomerulosclerosis (FSGS) was compared to 15 normal kidneys in order to investigate a possible role for cell-mediated immunity (CMI) in FSGS. In addition, distribution of HLA class II (-DQ, -DR, -DP and -DY) antigens and of the intercellular adhesion molecule 1 (ICAM-1) as well as the expression of well-defined renal antigens along the human nephron was analyzed. In comparison to normal kidneys, a reduction in HLA class II antigens of ICAM-1 and of renal antigens defined by the monoclonal antibodies TN8-TN10 was observed in sclerotic glomeruli. Furthermore, an increased number of T lymphocytes was found in glomeruli of FSGS with slight predominance of the CD8+ subset. Interstitial inflammation was present in all FSGS cases except 1 with T lymphocytes and monocytes/macrophages constituting the predominant infiltrating cell types. In contrast to the glomerular T cells, the number of interstitial CD4+ cells was greater than the number of CD8+ cells in almost all cases. As a sign of activation, most interstitial inflammatory cells carried HLA class II antigens and some of them also expressed ICAM-1. Proximal tubular epithelial cells often presented an abnormal expression of HLA-DQ and HLA-DP antigens associated with aberrant expression of ICAM-1 and TN8. The number of interstitial mononuclear leukocytes was correlated to serum creatinine levels at the time of renal biopsy. The present results provide further support for the involvement of CMI in the pathogenesis of FSGS.


[Prevention of risks to children on the basis of early intervention and interdisciplinary cooperation in the example of the model project "a good start to life"].
Infants and toddlers are at high risk of neglect and maltreatment, as they are especially dependent on the care and the safeguard of their parents. Child protection can only succeed if early and preventive support for families at risk and their infants is provided. The project "A good start to life" helps to promote parental sensitive behaviour and care giving competence of parents in precarious life settings and in high risk situations and is aimed to prevent child neglect and abuse at an early age. A relevant prerequisite for child protection is interdisciplinary networking between the involved systems. The main focus of the project is the establishment of collaboration and network structures between the infant and youth welfare system and the health-care system and their services in eight communities in four states in Germany by using so-called round tables as communication platforms. Preliminary results of the round tables are reported in this article together with the results of the evaluation process.