[Corticosteriod regulation of Na, K-ATPase and ion transport in diverse zones of rat kidney].
Effect of corticosteroids on the activity of transport Na, K-ATP-ase and on the content of Na and potassium ions in various zones of the kidneys in rats with removed adrenal glands was studied. Adrenalectomy diminished the activity of Na, K-ATP-ase and Na level considerably; the greatest changes were observed in the medullary and the papillary zones of the kidneys. Aldosterone administration increased the Na content in the medullary and papillary zones, but failed to influence the enzymatic activity. DOCA injections caused an increase in the enzymatic activity and normalized the Na content in the medullary and papillary zones of the kidneys. Hydrocortisone therapy restored the Na, K-ATP-ase activity in the cortical and the medullary zones. On the basis of the data obtained a conclusion was drawn that both minerals and glucocorticoids took part in the regulation of the transport processes through the membranes of the renal tubules, but influenced different areas of the nephron.


Calsarcin-2 May Play a Compensatory Role in the Development of Obese Sarcopenia.
Although obese sarcopenia is a major public health problem with increasing prevalence worldwide, the factors that contribute to the development of obese sarcopenia are still obscure. In order to clarify this issue, a high-fat-diet-induced obese sarcopenia mouse model was utilized. After being fed with a high-fat diet for 24 weeks, decreased motor functions and muscle mass ratios were found in the C57BL/6 mice. In addition, the expression of calsarcin-2 was significantly increased in their skeletal muscle, which was determined by a microarray analysis. In order to clarify the role of calsarcin-2 in muscle, lentiviral vectors containing the calsarcin-2 gene or short hairpin RNA targeted to calsarcin-2 were used to manipulate calsarcin-2 expressions in L6 myoblasts. We found that an overexpression of calsarcin-2 facilitated L6 myoblast differentiation, whereas a calsarcin-2 knockdown delayed myoblast differentiation, as determined by the expression of myogenin. However, the calsarcin-2 knockdown showed no significant effects on myoblast proliferation. In addition, to clarify the relationship between serum calsarcin-2 and sarcopenia, the bilateral gastrocnemius muscle mass per body weight in mice and appendicular skeletal muscle mass index in humans were measured. Although calsarcin-2 facilitated myoblast differentiation, the serum calsarcin-2 concentration was negatively related to skeletal muscle mass index in mice and human subjects. Taken together, calsarcin-2 might facilitate myoblast differentiation and appear to play a compensatory role in sarcopenia.


Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer.
To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification. The Update Panel conducted a systematic literature review to identify signals for updating recommendations. The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations. The 2018 ASCO-CAP recommendations for HER2 testing are affirmed. HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines.


Age and growth of the round stingray Urotrygon rogersi, a particularly fast-growing and short-lived elasmobranch.
We examined the age and growth of Urotrygon rogersi on the Colombian coast of the Eastern Tropical Pacific Ocean by directly estimating age using vertebral centra. We verified annual deposition of growth increments with marginal increment analysis. Eight growth curves were fitted to four data sets defined on the basis of the reproductive cycle (unadjusted or adjusted for age at first band) and size variables (disc width or total length). Model performance was evaluated using Akaike's Information Criterion (AIC), AIC weights and multi-model inference criteria. A two-phase growth function with adjusted age provided the best description of growth for females (based on five parameters, DW∞ = 20.1 cm, k = 0.22 yr⁻¹) and males (based on four and five parameters, DW(∞) = 15.5 cm, k = 0.65 yr⁻¹). Median maturity of female and male U. rogersi is reached very fast (mean ± SE = 1.0 ± 0.1 year). This is the first age and growth study for a species of the genus Urotrygon and results indicate that U. rogersi attains a smaller maximum size and has a shorter lifespan and lower median age at maturity than species of closely related genera. These life history traits are in contrast with those typically reported for other elasmobranchs.


Cardiovascular effects of dopamine hydrochloride and phenylephrine hydrochloride in healthy isoflurane-anesthetized New Zealand White rabbits (Oryctolagus cuniculus).
To determine the cardiopulmonary effects of progressively increasing infusion rates of dopamine hydrochloride and phenylephrine hydrochloride in healthy adult New Zealand White rabbits anesthetized with isoflurane. 6 New Zealand White rabbits. (Oryctolagus cuniculus). Each rabbit was anesthetized on 2 occasions (≥ 2 weeks apart) with isoflurane in oxygen at 1.5 times the published isoflurane minimum alveolar concentration of 2.07%. Carotid artery and pulmonary artery catheters were placed. During each anesthetic episode, each rabbit received 5 progressively increasing doses of either dopamine (5, 10, 15, 20, or 30 μg/kg/min) or phenylephrine (0.125, 0.25, 0.5, 1.0, and 2.0 μg/kg/min). Blood gas and cardiopulmonary measurements were obtained after a 20-minute equilibration period prior to administration of the first drug dose (baseline) and after each subsequent dose administration. Dopamine increased stroke index at the highest infusion rate of 30 μg/kg/min; however, cardiac output and mean arterial blood pressure remained unchanged from baseline values. Administration of phenylephrine at a rate of 2 μg/kg/min increased mean arterial blood pressure to 62 mm Hg from the baseline value of 45 mm Hg. This was a result of an increase in systemic vascular resistance with a concomitant decrease in heart rate and no change in cardiac output. Blood lactate concentration increased with time when rabbits received either treatment. Within the dose range of 5 to 30 μg/kg/min, dopamine was not an effective treatment for isoflurane-induced hypotension in rabbits and phenylephrine was only minimally effective at a dose of 2 μg/kg/min.


Hydrolysis of monomolecular layers of synthetic sphingomyelins by sphingomyelinase of Staphylococcus aureus.
The enzymic hydrolysis of three synthetic sphingomyelins, spread as monomolecular films at the air/water interface by purified Staphylococcus aureus sphingomyelinase was studied. Each of the three sphinomyelins (DL-erythro-N-palmitoyl-, -N-stearoyl- and -N-lignoceryl-sphingosylphosphocholine) has an optimal activity-dependent surface pressure or concentration curve. The optimal surface pressure as well as the optimal surface density for hydrolysis was different for each of the three substrates. This optimum coincides with the liquid-condensed/liquid-expanded phase transition for each of the sphingomyelins. At initial surface pressures (pi 0) below the optimum, reaction rates are controlled mainly by surface density of the substrate; above the optimal pi 0, reaction rates decrease with increasing surface pressure. The difference between the three synthetic sphingomyelins are explained by the variation in the degree of asymmetry between their two paraffinic chains.


Inequalities in Income and Education Are Associated With Survival Differences After Out-of-Hospital Cardiac Arrest: Nationwide Observational Study.
Despite the acknowledged importance of socioeconomic factors as regards cardiovascular disease onset and survival, the relationship between individual-level socioeconomic factors and survival after out-of-hospital cardiac arrest is not established. Our aim was to investigate whether socioeconomic variables are associated with 30-day survival after out-of-hospital cardiac arrest. We linked data from the Swedish Registry for Cardiopulmonary Resuscitation with individual-level data on socioeconomic factors (ie, educational level and disposable income) from Statistics Sweden. Confounding and mediating variables included demographic factors, comorbidity, and Utstein resuscitation variables. Outcome was 30-day survival. Multiple modified Poisson regression was used for the main analyses. A total of 31 373 out-of-hospital cardiac arrests occurring in 2010 to 2017 were included. Crude 30-day survival rates by income quintiles were as follows: Q1 (low), 414/6277 (6.6%); Q2, 339/6276 (5.4%); Q3, 423/6275 (6.7%); Q4, 652/6273 (10.4%); and Q5 (high), 928/6272 (14.8%). In adjusted analysis, the chance of survival by income level followed a gradient-like increase, with a risk ratio of 1.86 (95% CI, 1.65-2.09) in the highest-income quintile versus the lowest. This association remained after adjusting for comorbidity, resuscitation factors, and initial rhythm. A higher educational level was associated with improved 30-day survival, with the risk ratio associated with postsecondary education ≥4 years being 1.51 (95% CI, 1.30-1.74). Survival disparities by income and educational level were observed in both men and women. In this nationwide observational study using individual-level socioeconomic data, higher income and higher educational level were associated with better 30-day survival after out-of-hospital cardiac arrest in both sexes.


Dissolved organic matter uptake by Trichodesmium in the Southwest Pacific.
The globally distributed diazotroph Trichodesmium contributes importantly to nitrogen inputs in the oligotrophic oceans. Sites of dissolved organic matter (DOM) accumulation could promote the mixotrophic nutrition of Trichodesmium when inorganic nutrients are scarce. Nano-scale secondary ion mass spectrometry (nanoSIMS) analyses of individual trichomes sampled in the South Pacific Ocean, showed significant 13C-enrichments after incubation with either 13C-labeled carbohydrates or amino acids. These results suggest that DOM could be directly taken up by Trichodesmium or primarily consumed by heterotrophic epibiont bacteria that ultimately transfer reduced DOM compounds to their host trichomes. Although the addition of carbohydrates or amino acids did not significantly affect bulk N2 fixation rates, N2 fixation was enhanced by amino acids in individual colonies of Trichodesmium. We discuss the ecological advantages of DOM use by Trichodesmium as an alternative to autotrophic nutrition in oligotrophic open ocean waters.


Expression and activation of apoptosis-related molecules involved in interferon-alpha-mediated apoptosis in human liver cancer cells.
Interferon (IFN)-alpha directly inhibits proliferation of liver cancer cells by inducing apoptosis, but the molecular mechanisms by which IFN-alpha induces apoptosis in these cells are not fully understood. We examined the effect of broad spectrum caspase inhibitor, Z-VAD-fmk, and the caspase activation in IFN-alpha-mediated apoptosis by using 4 liver cancer cell lines that were sensitive or resistant to IFN-alpha-mediated apoptosis. Involvement of apoptosis-related mitochondrial proteins and Bcl-2 family proteins in IFN-alpha-mediated apoptosis was further examined in 1 sensitive cell line (KIM-1). The Z-VAD-fmk completely or moderately inhibited IFN-alpha-mediated apoptosis in the sensitive cells. IFN-alpha induced time-dependent activation of caspase-3 in the sensitive cells, while the resistant cells showed mild or no activation. Activation of caspase-9, caspase-8, and caspase-7, and the cleavage of poly(ADP-ribose)polymerase were identified in either or both of the sensitive cell lines, but not in the resistant cells. In KIM-1 cells, the release of cytochrome c and Smac/DIABLO from mitochondria to cytosole was confirmed. Meanwhile, Bcl-xL was upregulated, and Bid activation or translocation, or conformational changes of Bax were not identified. In conclusion, our results suggest IFN-alpha-mediated apoptosis in liver cancer cells involves the mitochondrial apoptotic pathway and is induced by activating various caspases.


Benefits of intracorporeal gastrointestinal anastomosis following laparoscopic distal gastrectomy.
Laparoscopic gastrectomy has recently been gaining popularity as a treatment for cancer; however, little is known about the benefits of intracorporeal (IC) gastrointestinal anastomosis with pure laparoscopic distal gastrectomy (LDG) compared with extracorporeal (EC) anastomosis with laparoscopy-assisted distal gastrectomy (LADG). Between June 2000 and December 2011, we assessed 449 consecutive patients with early-stage gastric cancer who underwent LDG. The patients were classified into three groups according to the method of reconstruction LADG followed by EC hand-sewn anastomosis (LADG + EC) (n = 73), using any of three anastomosis methods (Billroth-I (B-I), Billroth-II (B-II) or Roux-en-Y (R-Y); LDG followed by IC B-I anastomosis (LDG + B-I) (n = 248); or LDG followed by IC R-Y anastomosis (LDG + R-Y) (n = 128)). The analyzed parameters included patient and tumor characteristics, operation details, and post-operative outcomes. The tumor location was significantly more proximal in the LDG + R-Y group than in the LDG + B-I group (P < 0.01). Mean operation time, intra-operative blood loss, and the length of post-operative hospital stay were all shortest in the LDG + B-I group (P < 0.05). Regarding post-operative morbidities, anastomosis-related complications occurred significantly less frequently in with the LDG + B-I group than in the LADG + EC group (P < 0.01), whereas there were no differences in the other parameters of patients' characteristics. Intracorporeal mechanical anastomosis by either the B-I or R-Y method following LDG has several advantages over at the LADG + EC, including small wound size, reduced invasiveness, and safe anastomosis. Although additional randomized control studies are warranted to confirm these findings, we consider that pure LDG is a useful technique for patients with early gastric cancer.


Efficacies of different ovarian hyperstimulation protocols in elderly patients with poor ovarian response.
The aim of the study was to explore which controlled ovarian hyperstimulation (COH) protocol is most suitable for elderly patients with poor ovarian response (POR) undergoing assisted reproductive technology (ART). This retrospective cohort study evaluated clinical data from 2,660 patients from January 2017 and October 2020. The patients were divided into three groups: modified Gonadotropin-releasing hormone (GnRH) agonist protocol (1,225 patients), GnRH antagonist protocol (1,038 patients), and Mild stimulation protocol (397 patients). Clinical variables and pregnancy outcomes were compared among the three groups. The GnRH agonist protocol was associated with a higher number of oocyte number (3.99±2.82 vs. 3.02±1.34 vs. 2.51±1.14, p<0.001), a higher number of transferable embryos (1.39±1.32 vs. 1.24±1.24 vs. 1.18±1.11, p = 0.035), higher cumulative live birth rate [26.53% (323/1,225) vs. 22.44% (233/1,038) vs. 21.66% (86/397), p = 0.043], lower OHSS rate [5.14% (63/1,225) vs. 3.08% (32/1,038) vs. 2.02% (8/397), p = 0.005] than GnRH antagonist protocol and Mild stimulation protocol, the Mild stimulation protocol was associated with higher miscarriage rates [30.4% (24/71) vs. 25.0% (33/192) vs. 29.6% (35/168), p = 0.014] than the other two groups. The three protocols can be used in elderly patients with POR; however, if patients require more frozen-thawed embryo transfers to achieve better cumulative live birth rates, the modified GnRH agonist protocol may be the better choice. It should be emphasized that the mild stimulation had a slightly higher miscarriage rate than the other two groups.


Effect of LHRH-PE40 on target cells via LHRH receptors.
To detect the effect and cytotoxicity of luteinizing hormone-releasing hormone-Pseudomonas aeruginosa exotoxin 40 (LHRH-PE40) on target cells using LHRH receptors (LHRHR). The affinity of LHRH-PE40 and LHRH binding to LHRHR on the membrane surface of target cells were measured by enzyme linked immunosorbent assay. Morphological observations with light microscope were used to analyze its receptor pathway, with Spiegelmer, and cytotoxicity. IC(50) values of LHRH-PE40, which caused 50% inhibition of tumor cell growth were evaluated by MTT assay. The target cells were exposed to LHRH-PE40 and its cytotoxicity was analyzed by scanning and transmission electron microscopies, agarose gel electrophoresis, and flow cytometry. LHRH-PE40 killed target cells by LHRHR pathway. The morphological changes in these cells showed decreased cell size, cytoplasmic membrane blebbing, and chromatin condensation and margination. At a certain concentration and time point, HeLa cells were also induced to undergo programmed cell death. LHRH-PE40 induced target cells apoptosis via LHRHR.


Household out-of-pocket expenditures on health care in Bangladesh according to principal component analysis (PCA).
In Bangladesh, illness results in large out-of-pocket health care expenditures for households. Identifying the components associated with health care expenditures should prove meaningful for future policy formulation in Bangladesh. Thus, the objective of the study was to investigate the overall influence of individual health care costs over data space in a probalistic way using Principal Component Analysis for expenditures incurred due to a recent illness. The study is based on secondary data of the Household Income and Expenditure Survey conducted in 2005 by the Bangladesh Bureau of Statistics. This survey is a nationally representative survey in Bangladesh and its sample includes 8,126 individuals who have incurred health care expenditures in the 30 days prior to the survey. Principal Component Analysis was used to analyze the influence of the factors of health care expenditures in Bangladesh. According to results, 58% of the information on the overall data space confirmed that the cost of medicine is greater than any other factor for health care expenditures. Drug-related health expenditures represented a large component and suggest the need for policies promoting the rational use of drugs. If such strategies are considered and implemented in operational stages, the quality of health care should improve and drug expenditures should substantially decrease.


Public health and clinical approach to proactive management of frailty in multidimensional arena.
Demographic changes have forced communities and people themselves to reshape ageing concepts and approaches and try to develop actions towards active and healthy ageing. In this context, the European Commission launched different private-public partnerships to develop new solutions and answers on questions related to this topic. The European Innovation Partnership on Active and Healthy Ageing, including topic related action groups as well reference sites committed towards a common action to facilitate active and healthy ageing, has contributed key elements for interventions, scaled up best practices and evaluated impact of their action to drive innovation across many regions in Europe over the past years. This paper describes action taken by A3 action group in the European Innovation Partnership on Active and Healthy Ageing. This paper gives an overview of how the partnership combined the view on frailty coming from public health as well as the clinical management. Within different European regions, to tackle frailty, EIPonAHA partners have conceptualized functional decline and frailty, making use of good practice models working well on community programs. The A3 Group of EIPonAHA has worked alongside a process of innovation, targeting all ageing citizens with the clear goal of involving communities in the preventive approach. Engagement needs of older people with a focus on functionally rather than disease management as primary objective is considered as an overarching concept, also embracing adherence, compliance, empowerment, health literacy, shared decision-making, and activation. Furthermore, training of staff working with ageing people across all sectors needs to be implemented and evaluated in future studies.


Bone quality and muscle strength in female athletes with lower limb stress fractures.
Lower limb stress fractures (SF) have a high prevalence in female athletes of running-related sports. The purpose of this study was to investigate bone quality, including bone microarchitecture and strength, and muscle strength in athletes diagnosed with SF. Female athletes with lower limb SF (SF subjects, n = 19, 18-45 yr, premenopausal) and healthy female athletes (NSF subjects, n = 19) matched according to age, sport, and weekly training volume were recruited. Bone microarchitecture of all participants was assessed using high-resolution peripheral quantitative computed tomography at two skeletal sites along the distal tibia of the dominant leg. Bone strength and load distribution between cortical and trabecular bone was estimated by finite element analysis. Using dual-energy x-ray absorptiometry, areal bone mineral density (aBMD) at the hip, femoral neck, and spine was measured. Muscle torque (knee extension, plantarflexion, eversion/inversion) was assessed (Biodex dynamometer) as a measure of lower leg muscle strength. SF subjects, after adjusting for body weight, had thinner tibia compared with NSF subjects as indicated by a lower tibial cross-sectional area (-7.8%, P = 0.02) and higher load carried by the cortex as indicated by finite element analysis (4.1%, P = 0.02). Further site-specific regional analysis revealed that, in the posterior region of the tibia, SF subjects had lower trabecular BMD (-19.8%, P = 0.02) and less cortical area (-5.2%, P = 0.02). The SF group exhibited reduced knee extension strength (-18.3%, P = 0.03) compared with NSF subjects. These data suggest an association of impaired bone quality, particularly in the posterior region of the distal tibia, and decreased muscle strength with lower limb SF in female athletes.


White matter architecture in major depression with anxious distress symptoms.
Comorbid anxious distress is common in Major Depressive Disorder (MDD), and associated with significantly worse clinical course and treatment response. While DSM-5 recently introduced the Anxious Distress (AD) specifier as a potentially useful symptom-based subtyping scheme for MDD, its neurobiological underpinnings remain unclear. The current study hence uniquely probed whether MDD with co-occurring AD (MDD/AD+) relates to distinct perturbations in frontolimbic white matter (WM) pathways tentatively theorized in MDD/AD+ pathophysiology. Tract-based spatial statistics (TBSS) was therefore used to analyze diffusion tensor imaging data on WM microstructure, in MDD/AD+ patients (N = 20) relative to MDD patients without AD (MDD/AD-; N = 29) and healthy controls (HC; N = 39). Using TBSS, we probed fractional anisotropy and axial/radial/mean diffusivity as proxies for WM integrity. Categorical (between-groups) and dimensional (within-patients) analyses subsequently assessed how Anxious Distress in MDD impacts frontolimbic WM connectivity. Receiver-Operating Characteristics additionally assessed classification capabilities of between-groups WM effects. Compared to MDD/AD- and HC participants, MDD/AD+ patients exhibited diminished integrity within the anterior thalamic radiation (ATR). Higher AD specifier scores within MDD patients additionally related to diminished integrity of the uncinate fasciculus and cingulum pathways. These effects were not confounded by key clinical (e.g., comorbid anxiety disorder) and sociodemographic (e.g., age/sex) factors, with altered ATR integrity moreover successfully classifying MDD/AD+ patients from MDD/AD- and HC participants (90% sensitivity | 73% specificity | 77% accuracy). These findings collectively link MDD/AD+ to distinct WM anomalies in frontolimbic tracts important to adaptive emotional functioning, and may as such provide relevant, yet preliminary, clues on MDD/AD+ pathophysiology.


Incrimination of anaerobic bacteria in the induction of experimental colitis.
Commensal bacteria may participate in the pathogenesis of bowel inflammation. We studied the role of bacteria from the rat colonic flora on transmural inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). First, bacterial translocation to the colonic wall after induction of colitis was assessed by microbiological and histological methods. Second, rats with a colonic segment excluded from fecal transit were prepared for recolonization with preselected bacteria and used to test the effects of different species on inflammation (eicosanoid release, tissue myeloperoxidase) and damage (histology). Six strains (three aerobes and three anaerobes) were identified in colonic tissue 24 h after induction of colitis. Acridine staining showed bacteria in necrotic areas of the mucosa and invading the submucosa. Rats with excluded colon and sterile culture of luminal washings showed mild inflammation and low mucosal damage in response to TNBS. Rats colonized with anaerobes showed significantly higher eicosanoid release than rats colonized with aerobes only. Moreover, submucosal-lesions were mostly observed in rats with anaerobes. Our findings suggest that colonic anaerobes play a key role in transmural inflammation.


Discovery and Functional Analysis of a Salicylic Acid Hydroxylase from Aspergillus niger.
Salicylic acid plays an important role in the plant immune response, and its degradation is therefore important for plant-pathogenic fungi. However, many nonpathogenic microorganisms can also degrade salicylic acid. In the filamentous fungus Aspergillus niger, two salicylic acid metabolic pathways have been suggested. The first pathway converts salicylic acid to catechol by a salicylate hydroxylase (ShyA). In the second pathway, salicylic acid is 3-hydroxylated to 2,3-dihydroxybenzoic acid, followed by decarboxylation to catechol by 2,3-dihydroxybenzoate decarboxylase (DhbA). A. niger cleaves the aromatic ring of catechol catalyzed by catechol 1,2-dioxygenase (CrcA) to form cis,cis-muconic acid. However, the identification and role of the genes and characterization of the enzymes involved in these pathways are lacking. In this study, we used transcriptome data of A. niger grown on salicylic acid to identify genes (shyA and crcA) involved in salicylic acid metabolism. Heterologous production in Escherichia coli followed by biochemical characterization confirmed the function of ShyA and CrcA. The combination of ShyA and CrcA demonstrated that cis,cis-muconic acid can be produced from salicylic acid. In addition, the in vivo roles of shyA, dhbA, and crcA were studied by creating A. niger deletion mutants which revealed the role of these genes in the fungal metabolism of salicylic acid.IMPORTANCE Nonrenewable petroleum sources are being depleted, and therefore, alternative sources are needed. Plant biomass is one of the most abundant renewable sources on Earth and is efficiently degraded by fungi. In order to utilize plant biomass efficiently, knowledge about the fungal metabolic pathways and the genes and enzymes involved is essential to create efficient strategies for producing valuable compounds such as cis,cis-muconic acid. cis,cis-Muconic acid is an important platform chemical that is used to synthesize nylon, polyethylene terephthalate (PET), polyurethane, resins, and lubricants. Currently, cis,cis-muconic acid is mainly produced through chemical synthesis from petroleum-based chemicals. Here, we show that two enzymes from fungi can be used to produce cis,cis-muconic acid from salicylic acid and contributes in creating alternative methods for the production of platform chemicals.


Preventive effect of the flavonoid, quercetin, on hepatic cancer in rats via oxidant/antioxidant activity: molecular and histological evidences.
The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio Experiments were designed to examine the effect of N-Nitrosodiethylamine (NDEA) as cancer-inducer compound and to confirm the preventive effect of the flavonoid quercetin on hepatocellular carcinoma in rats. Briefly, thirty six male albino rats of Wistar strain were divided into 3 groups: the 1st group was administered NDEA alone (NDEA-treated), the 2nd group was treated simultaneously with NDEA and quercetin (NDEA+Q) and the 3rd group was used as control (CON). Randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) as well as p53-specifi PCR assays were employed to determine genomic difference between treated, and control animals. Histological confirmation as well as oxidant/antioxidant status of the liver tissue was done. RAPD analysis of liver samples generated 8 monomorphic bands and 22 polymorphic bands in a total of 30-banded RAPD patterns. Cluster analysis and statistical analyses of RAPD data resulted in grouping control and NDEA+Q samples in the same group with 80% similarity cut-off value. NDEA-treated samples were clustered in a separate group. Specific PCR assay for polymorphism of P53 gene revealed a uniform pattern of allele separation in both control and NDEA+Q samples. Quercetin anticancer effect was exhibited in significant decrease of oxidative stress and significant decrease of antioxidant activity. Histopathological studies showed normal liver histology of the NDEA+Q samples. Meanwhile, several cancer-induced features were clearly observable in NDEA-treated samples. This paper demonstrated that preventive effect of quercetin on hepatocarcinoma in rats by RAPD-PCR, tracing the effect on p53 gene and by histopathological evidence. Hereby, it was proved that quercetin exerted its preventive effect via decreased oxidative stress and decreased antioxidant activity.


Treatment of stage IV carcinoma of the prostate.
Accurate diagnosis and staging of carcinoma of the prostate is essential to rational management of this disease. Once dissemination outside the periprostatic area is established, treatment is essentially limited to systemic efforts to control or suppress tumor growth and local efforts to minimize secondary effects of tumor deposits. Disseminated tumor limited to pelvic nodes constitute a possible exception to this statement since excisional and radiotherapeutic efforts to eradicate these foci may be successful. At the present time, changes in a number of objective and subjective parameters are utilized to assess the effect of therapeutic endeavors. When these are taken as a group and combined with a clinical judgement, they undoubtedly have merit. On the other hand, when utilized in a relative fashion as isolated indicators of tumor responsiveness or recurrence, their value is limited. Since most patients with disseminated carcinoma of the prostate die from their disease, critical analysis of survival data is at present likely to provide the most accurate assessment of a therapeutic endeavor. Estrogen administration or orchiectomy seem to be the systemic measures which combine relatively limited risk of morbidity with the greatest hope of initially controlling disseminated carcinoma of the prostate. Of these, evidence suggests that low dose estrogen therapy, 1 mg stilbestrol daily, provides the best opportunity for long-term control. Although length of survival does not seem to depend on the time at which the therapy is instituted, our prejudice is usually to start treatment when dissemination is recognized. The hope of providing a longer period of a better life by this practice requires evaluation. Combining local measures such as transurethral resection with systemic measures may add to patient comfort and longevity. Recurrent progression of tumor after initial hormonal measures in often difficult to recognize and accept. In patients with recurrent tumor activity, measures based on the concept of persistence of hormone dependence have produced disappointing results. More sophisticated selection techniques may identify a small group of patients in whom this approach is likely to produce desirable changes. For the most part chemotherapeutic agents hold greater promise of effective therapy in this group of patients.


Endoscopic transforaminal lumbar interbody fusion without general anesthesia: technical innovations and outcomes.
Innovations in surgical techniques and technologies have enabled spine surgeons to offer patients less morbid alternatives to traditional spine procedures. This review will explore the development of the endoscopic transforaminal lumbar interbody fusion (TLIF) without general endotracheal anesthesia (GETA) and discuss the technical refinements and innovations learned from experiences with this technique. The Awake TLIF employs several key technological innovations: (I) conscious sedation; (II) endoscopic visualization; (III) an expandable interbody device; (IV) recombinant human bone morphogenetic protein; (V) long-acting local analgesia; and (VI) percutaneous instrumentation. Technical refinements, including premedication for prophylaxis against nausea, vomiting, and epistaxis, were made as a result of early experiences with this technique. Results from the first 100 patients to undergo the Awake TLIF demonstrated durable clinical benefit beyond one year postoperatively. Operating time, blood loss, and hospital length of stay averages well below those generally seen with conventional MIS TLIF. Patients achieved a significant reduction in Oswestry Disability Index from baseline of -12.3 points (P<0.0001). In this initial 100 patient cohort, four conversions to GETA were required and four complications resulted, three of which occurred during the first 50 cases. To date, over 200 Awake TLIF cases and the first three-level procedure have been performed. Endoscopic TLIF without the use of general anesthesia is a novel but promising approach for short-segment lumbar fusion. Continued technical innovations will likely afford greater improvements in outcomes, both in the acute and long-term recovery periods.


Poly(amido amine) and rechargeable adhesive containing calcium phosphate nanoparticles for long-term dentin remineralization.
The objective of the present study was to investigate long-term dentin remineralization via the combination of poly(amido amine) (PAMAM) with a novel rechargeable adhesive containing nanoparticles of amorphous calcium phosphate (NACP). The NACP adhesive was immersed in lactic acid at pH 4 to exhaust its calcium (Ca) and phosphate (P) ion release, and then recharged with Ca and P ions. Dentin samples were pre-demineralized with 37% phosphoric acid, and then divided into four groups: (1) dentin control, (2) dentin treated with PAMAM, (3) dentin with recharged NACP adhesive, (4) dentin with PAMAM + recharged NACP adhesive. In group (2) and (4), the PAMAM-coated dentin was immersed in phosphate-buffered saline with vigorous shaking for 77 days to accelerate any detachment of the PAMAM macromolecules from the demineralized dentin. Samples were treated with a cyclic remineralization/demineralization regimen for 21 days. After 77 days of fluid flow challenge, the immersed PAMAM still retained its nucleation template function. The recharged NACP adhesive possessed sustained ion re-release and acid-neutralization capability, both of which did not decrease with repeated recharge and re-release cycles. The immersed PAMAM with the recharged NACP adhesive achieved long-term dentin remineralization, and restored dentin hardness to that of healthy dentin. The PAMAM + NACP adhesive completely remineralizes pre-demineralized dentin even after long-term fluid challenges and provides long-term remineralization to protect tooth structures. The novel PAMAM + NACP adhesive provides long-term bond protection and caries inhibition to increase the longevity of resin-based restorations.


Adolescent Hepatitis C: Prevalence, Impact, and Management Challenges.
The prevalence of Hepatitis C virus infection (HCV), a leading cause of chronic liver disease worldwide, is rising in the United States (US) and other high-income countries, especially among youth and young adults. This surge in cases is closely associated with the opioid crisis and intravenous drug use (IVDU). However, its prevalence and impact on the adolescent population have not been thoroughly studied and therefore is poorly understood. The pediatric population tends to have milder liver disease and progression when compared to adults; however, there is a risk of developing liver cirrhosis, in addition to facing decreased quality of life and stigmatization from the disease. The recent approval of direct-acting antiviral (DAA) regimens for all HCV genotypes and age greater than 3 years has revolutionized its management. Therapy has shifted from the prolonged interferon-based regimens, to shorter duration, once daily oral pills that are highly effective, curative and with fewer side effects. Therapy is now indicated for all adolescents with hepatitis C virus infection, regardless of stage of liver disease, recent IVDU, or coinfection with HIV, therefore eliminating a lifetime risk of chronic liver disease, cirrhosis and hepatocarcinoma. Nonetheless, adolescents are rarely tested or treated for hepatitis C infection, and very few adolescents complete therapy. Implementation of point of care (POC) testing of high-risk youth at drug treatment centers or other juvenile facilities may be a good strategy to increase testing, diagnosis and therapy. This review article aims to educate pediatricians and other primary care providers to help decrease the existing knowledge gap on the subject.