Non-Hodgkin's lymphomas (NHL).
This synthesis of the literature on radiotherapy for non-Hodgkin's lymphomas is based on 158 scientific articles, including 16 randomized studies, 18 prospective studies, and 90 retrospective studies. These studies involve 14,137 patients. Non-Hodgkin's lymphomas are highly radiosensitive, and local recurrence following radiotherapy is unusual. Radiotherapy probably cures approximately 50% of both low-grade and high-grade malignant NHL at stage I. Involved field is apparently sufficient, however, higher doses are required for high-grade malignant lymphomas. Chemotherapy is recommended for stage II. Consolidation radiotherapy after chemotherapy may increase the number of complete remissions. The value of adjuvant radiotherapy has not been confirmed. Radiotherapy plays a limited role at stages III and IV. Radiotherapy is clearly indicated for extranodal localized disease in the skin and in the orbit of the eye. It is important to identify groups and subgroups in whom radiotherapy alone is sufficient, ie, the risk for distant recurrence is small. MALT lymphoma belongs to this group. Radiotherapy is often valuable in palliative situations.


Isolated noninfectious granulomas of the ovary.
Four examples of noninfectious granulomas of the ovary were studied. All four occurred in premenopausal women. One patient had a salpingo-oophorectomy for a symptomatic ovarian mass; the other three examples were incidental findings in hysterectomy and salpingo-oophorectomy specimens. None of the patients had a history of systemic granulomatous disease, nor have any of the patients developed any symptoms on follow-up, which varies from 2 to 7 years.


Solid organ transplantation: referral, management, and outcomes in HIV-infected patients.
Advances in HIV management make it difficult to deny solid organ transplantation to HIV-infected patients based on futility arguments. Preliminary studies suggest that both patient and graft survival are similar in HIV-negative and HIV-positive transplant recipients. While there has been no significant HIV disease progression, substantial interactions between immunosuppressants and antiretroviral drugs necessitate careful monitoring. The evaluation and management of HIV-infected transplant candidates and recipients require excellent communication among a multidisciplinary team, the primary HIV care provider, and the patient. Timely referral for transplant evaluation will prevent unnecessary mortality during the pre-transplant evaluation process.


[Comparison of robotic surgery documentary in gynecological cancer].
Robotic surgery is a surgical technique recently introduced, with major expansion and acceptance among the medical community is currently performed in over 1,000 hospitals around the world and in the management of gynecological cancer are being developed comprehensive programs for implementation. The objectives of this paper are to review the scientific literature on robotic surgery and its application in gynecological cancer to verify its safety, feasibility and efficacy when compared with laparoscopic surgery or surgery classical major surgical complications, infections are more common in traditional radical surgery compared with laparoscopic or robotic surgery and with these new techniques surgical and staying hospital are lesser than the former however, the disadvantages are the limited number of robot systems, their high cost and applies only in specialized centers that have with equipment and skilled surgeons. In conclusion robotic surgery represents a major scientific breakthrough and surgical management of gynecological cancer with better results to other types of conventional surgery and is likely in the coming years is become its worldwide.


Egocentric social networks, lifestyle behaviors, and body size in the Asian Community Health Initiative (CHI) cohort.
Social networks have been shown to influence lifestyle behaviors in non-Latinx white (NLW) populations. We examined their influence in Asian American, Native Hawaiian and Pacific Islander (AANHPI) women. We included 477 AANHPI women from the Asian Community Health Initiative Study who provided egocentric (degree, density, composition) and epidemiologic (size, types of ties) social network data and data on alcohol intake, physical activity, smoking, diet, and body size. We used logistic regression to evaluate associations of social network measures and dichotomous outcomes, and linear regression for continuous outcomes. In multivariable-adjusted analyses, higher degree and/or proportion of friends were significantly related to higher Western diet, higher odds of any alcohol consumption, and lower odds of physical inactivity and body mass index (BMI)≥23 kg/m2. Additionally, a higher proportion of NLW in women's networks was related to lower Asian diet but also lower waist size. Community participation was related to higher Western diet and lower Asian diet. By contrast, degree and/or proportion of relatives were positively related to BMI, waist size and to a higher odds of BMI≥23 kg/m2 and of ever smoking 100 cigarettes. Being married was related to fewer alcoholic drinks per week and higher Asian diet. A higher density of relationships with frequent contact was also associated with higher Asian diet. AANHPI women with larger proportions of friends and NLWs in their networks had more Western health behaviors and smaller body size. Norms for health behaviors and body size may be influenced by the size, composition, and structure of social networks, relevant to chronic disease prevention.


Modeling distinct sources of neural variability driving neuroprosthetic control.
Many closed-loop, continuous-control brain-machine interface (BMI) architectures rely on decoding via a linear readout of noisy population neural activity. However, recent work has found that decomposing neural population activity into correlated and uncorrelated variability reveals that improvements in cursor control coincide with the emergence of correlated neural variability. In order to address how correlated and uncorrelated neural variability arises and contributes to BMI cursor control, we simulate a neural population receiving combinations of shared inputs affecting all cells and private inputs affecting only individual cells. When simulating BMI cursor-control with different populations, we find that correlated activity generates faster, straighter cursor trajectories, yet sometimes at the cost of inaccuracies. We also find that correlated variability can be generated from either shared inputs or quickly updated private inputs. Overall, our results suggest a role for both correlated and uncorrelated neural activity in cursor control, and potential mechanisms by which correlated activity may emerge.


Use of multicriteria decision analysis to address conservation conflicts.
Conservation conflicts are increasing on a global scale and instruments for reconciling competing interests are urgently needed. Multicriteria decision analysis (MCDA) is a structured, decision-support process that can facilitate dialogue between groups with differing interests and incorporate human and environmental dimensions of conflict. MCDA is a structured and transparent method of breaking down complex problems and incorporating multiple objectives. The value of this process for addressing major challenges in conservation conflict management is that MCDA helps in setting realistic goals; entails a transparent decision-making process; and addresses mistrust, differing world views, cross-scale issues, patchy or contested information, and inflexible legislative tools. Overall we believe MCDA provides a valuable decision-support tool, particularly for increasing awareness of the effects of particular values and choices for working toward negotiated compromise, although an awareness of the effect of methodological choices and the limitations of the method is vital before applying it in conflict situations.


Preparation of Parabolic Superhydrophobic Material for Oil-Water Separation.
In order to prepare parabolic superhydrophobic materials, copper meshes were used as the substrate and ultrasonic etching and oxidative corrosion were carried out with FeCl₃ solution and H₂O₂ solution, respectively, and then the surface was modified with stearic acid (SA). The topological structure and surface wettability of the prepared mesh were characterized by fluorescence microscope, scanning electron microscopy and contact angle measurement. Finally, the as-prepared copper meshes were applied to oil-water separation. The results showed that the micro-nano-mastoid structure on the surface of the copper mesh was flaky bulges, forming a rough structure similar to a paraboloid. When the oxidative corrosion time of H₂O₂ was 1 min, it is more beneficial to increase the hydrophobicity of the surface of the copper mesh and increase the contact angle of water droplets on the surface of the membrane. Additionally, based on superhydrophobic materials of the parabolic copper mesh, the static contact angles of the water droplets, engine oil and carbon tetrachloride with the surface were approximately 153.6°, 5° and 0.1°, respectively and the sliding angle of the water droplets with the surface were approximately 4.9°. The parabolic membrane was applied to discuss the separation efficiency of different oils with deionized water and the separation efficiency was obtained as benzene > carbon tetrachloride > oil > machine oil. Therefore, based on the research, the parabolic superhydrophobic material has good efficiency of oil-water separation.


Hyperglycemia as a predictor for mortality in veterans with pneumonia.
The elderly may have multiple problems including diabetes mellitus and pneumonia. This study was undertaken to evaluate the effect of hyperglycemia on the length of stay (LOS) and mortality of elderly veterans admitted for pneumonia. Forty-seven and forty-eight patients over the age of 60 admitted for the diagnosis of pneumonia at the Lexington, Kentucky and Iron Mountain, Michigan VAMC's respectively were evaluated. The mean age at Lexington was 72 and at Iron Mountain was 73.9. At Lexington the mean LOS was 39.5 days with a standard deviation of 9.2 for those with hyperglycemia (n = 18) and 16.5 days with a standard deviation of 2.5 for those without hyperglycemia (n = 29). At Iron Mountain the mean LOS was 21.5 days with a standard deviation of 3.3 for those with hyperglycemia (n = 10) and 13.6 days with a standard deviation of 1.2 for those without (n = 38). These differences were significant at p less than .01 using the 2-sample independent t-test. At Iron Mountain 5 of 38 (13%) of the patients with normoglycemia died during the hospital stay compared to 3 of 10 (30%) those with hyperglycemia. For Lexington the figures were 4 of 29 (13%) and 6 of 18 (33%) respectively. These differences were significant at p less than .05. Age did not have any significant effect on either mortality or length of stay. Hyperglycemia appears to be a significant predictor of a longer hospital course and increased mortality in elderly veterans hospitalized for pneumonia.


FOLFOX4 versus sequential dose-dense FOLFOX7 followed by FOLFIRI in patients with resectable metastatic colorectal cancer (MIROX): a pragmatic approach to chemotherapy timing with perioperative or postoperative chemotherapy from an open-label, randomized phase III trial.
Perioperative FOLFOX4 (oxaliplatin plus 5-fluorouracil/leucovorin) chemotherapy is the current standard in patients with resectable metastases from colorectal cancer (CRC). We aimed to determine whether a sequential chemotherapy with dose-dense oxaliplatin (FOLFOX7) and irinotecan (FOLFIRI; irinotecan plus 5-fluorouracil/leucovorin) is superior to FOLFOX4. The chemotherapy timing was not imposed, and was perioperative or postoperative. In this open-label, phase III trial, patients with resectable or resected metastases were randomly assigned either to 12 cycles of FOLFOX4 (oxaliplatin 85 mg/m(2)) or 6 cycles of FOLFOX7 (oxaliplatin 130 mg/m(2)) followed by 6 cycles of FOLFIRI (irinotecan 180 mg/m(2)). Randomization was done centrally, with stratification by chemotherapy timing, type of local treatment (surgery versus radiofrequency ablation with/without surgery), and Fong's prognostic score. The primary end point was 2-year disease-free survival (DFS). A total of 284 patients were randomized, 142 in each treatment group. Chemotherapy was perioperative in 168 (59.2%) patients and postoperative in 116 (40.8%) patients. Perioperative chemotherapy was preferentially proposed for synchronous metastases, whereas postoperative chemotherapy was more frequently used for metachronous metastases. Two-year DFS was 48.5% in the FOLFOX4 group and 50.0% in the FOLFOX7-FOLFIRI group. In the multivariable analysis, more than one metastasis [hazard ratio (HR) = 2.15] and synchronous metastases (HR = 1.63) were independent prognostic factors for shorter DFS. Five-year overall survival (OS) rate was 69.5% with FOLFOX4 versus 66.6% with FOLFOX7-FOLFIRI. FOLFOX7-FOLFIRI is not superior to FOLFOX4 in patients with resectable metastatic CRC. Five-year OS rates observed in both groups are the highest ever reported in this setting, possibly reflecting the pragmatic approach to chemotherapy timing. NCT00268398.


Effects of Choto-san on hemorheological factors and vascular function in stroke-prone spontaneously hypertensive rats.
Choto-san is a formula used for the treatment of headache and vertigo. Recently it has often also been used for hypertension and dementia. One of the mechanisms involved is thought to be the improvement of blood circulation, but the details are still unclear. In this study, the effect of Chotosan was studied on nitric oxide (NO) function, hemorheological factors and endothelial function in stroke-prone spontaneously hypertensive rats (SHR-SP). Rats were given Choto-san in drinking water for eight weeks. Body weight, blood pressure, serum NO2-/NO3-, lipid peroxides, blood viscosity, erythrocyte deformability and endothelium-dependent/-independent relaxation were measured. The results indicated that Choto-san caused a decrease in blood pressure and an increase in erythrocyte deformability and NO function. Blood viscosity was not changed. Furthermore, endothelium-dependent relaxation by acetylcholine was significantly increased as compared to control. In this study, it was supposed that Choto-san had a protective effect on the endothelium. SHR-SP is a useful model for human brain stroke, and Choto-san showed a protective effect against cerebral vascular injury in the susceptible rat.


Combined Effects of Particle Size and Dough Improvers on Improving the Quality of Purple-Colored Whole Wheat Bread.
Consumers' interest in healthy products is increasing. However, the production of excellent-quality whole wheat bread (WWB) faces challenges due to the reduced gluten functionality and varied particle sizes of whole wheat flour (WWF). This study aimed to explore the enhancement of purple-colored WWB quality by controlling the particle size of WWF and using dough improvers. Six purple-colored WWFs were obtained using an ultra-centrifugal mill with different sieve openings (0.5 and 1.0 mm) and rotor speeds (6000, 10,000, and 14,000 rpm). The average particle diameter (d50) of the smaller particle size group (S) and the larger particle size group (L) based on the sieve opening ranged from 115 to 258 μm and 294 to 492 μm, respectively. Group S demonstrated higher water absorption, damaged starch, and gluten strength compared to group L. Additionally, group S exhibited a greater bread volume and height compared to group L. Among the tested dough improvers (vital wheat gluten, vitamin C, enzymes, and emulsifiers), vital wheat gluten was the most effective in improving the quality of purple-colored WWB. The improvement effect was significantly greater in group S than in group L. These findings suggest that controlling the particle size of purple-colored WWFs and utilizing dough improvers can result in superior-quality WWB.


Socioeconomic Differences in and Predictors of Home-Based Palliative Care Health Service Use in Ontario, Canada.
The use of health services may vary across people with different socioeconomic statuses, and may be determined by many factors. The purposes of this study were (i) to examine the socioeconomic differences in the propensity and intensity of use for three main home-based health services, that is, home-based palliative care physician visits, nurse visits and personal support worker (PSW) hours; and (ii) to explore the determinants of the use of home-based palliative care services. A prospective cohort study was employed. A total of 181 caregivers were interviewed biweekly over the course of the palliative care trajectory, yielding a total of 994 interviews. The propensity and intensity of health service use were examined using logistic regression and negative binomial regression, respectively. The results demonstrated that both the propensity and intensity of home-based nurse and PSW visits fell with socioeconomic status. The use of home-based palliative care services was not concentrated in high socioeconomic status groups. The common predictors of health service use in the three service categories were patient age, the Palliative Performance Scale (PPS) score and place of death. These findings may assist health service planners in the appropriate allocation of resources and service packages to meet the complex needs of palliative care populations.


Elevated maternal serum alpha-fetoprotein and amniotic fluid alpha-fetoprotein after multifetal pregnancy reduction.
Forty patients underwent fetal reduction at approximately 12 weeks' gestation for multiple pregnancy. Twenty-two had maternal serum alpha-fetoprotein (MSAFP) determinations and all but one was elevated, with a mean value of 9.41 multiples of the median (MOM). A total of 53 amniotic fluid specimens were evaluated for AFP; 25% were elevated above 2.0 MOM and one sample was positive for acetylcholinesterase. None of these elevations were associated with a neural tube defect, although two neural tube defects were detected by other means. Routine MSAFP is not recommended for patients with multifetal pregnancy reduction.


A total diet study and probabilistic assessment risk assessment of dietary mercury exposure among First Nations living on-reserve in Ontario, Canada.
Methyl Mercury (MeHg) exposure is a global environmental health concern. Indigenous peoples around the world are susceptible to MeHg exposure from often higher fish consumption compared to general populations. The objective of this study was to estimate dietary exposure to methylmercury (MeHg) among First Nations living on-reserve in the province of Ontario, Canada. A total diet study was constructed based on a 24-h recall from the First Nations Food, Nutrition, and Environment Study (FNFNES), and measured contaminant concentrations from Health Canada for market foods, and FNFNES for traditional foods. A probabilistic assessment of annual and seasonal traditional food consumptions was conducted for 1429 adult participants. Results were compared to exposures in the general Canadian population and reference values from Health Canada for adults and women of childbearing age (ages 19-50). Results indicated traditional foods to be the primary contributor to the dietary total MeHg intake (72%). The average dietary total MeHg exposure in the First Nations population in Ontario (0.039μg/kg/d) was 1.6 times higher than the general Canadian population; however, the majority (97.8%) of the population was below the reference values. Mercury concentrations in participants' hair samples (n = 744) ranged from 0.03 to 13.54µg/g, with an average of 0.64µg/g (geometric average of 0.27µg/g). Less than 1% of the population had a hair mercury value above the 6µg/g level, and 1.3% of women of child bearing age had values greater than 2µg/g. Fish species contributing to the MeHg intake included pickerel-walleye, pike, perch and trout. Only 7.9% of the population met the recommended fish consumption rate of two, 3.5oz servings per week from the American Heart Association. Therefore, consumption of lower trophic level fish can be promoted to provide the maximum nutritional benefit with minimal risk of MeHg exposure.


Surgical treatment of acute abdominal complications in hematology patients: outcomes and prognostic factors.
The decision to operate on hematology patients with abdominal emergencies can be difficult, as neutropenia and thrombocytopenia are common and the usual causes of abdominal pain are broad. We conducted a retrospective observational study including all hematology patients undergoing emergency abdominal surgery between January 1998 and January 2013. Of the fifty-eight consecutive patients included in the study, nineteen (33%) underwent an operation during the neutropenia period. In the multivariate analysis, a laparotomy after 2002 was protective (HR: 0.05; 95%CI: 0.001-0.24), whereas preoperative septic shock (HR: 8.58; 95%CI: 2.25-32.63) and use of dialysis (HR: 6.67; 95%CI: 2.11-21.07) were independently associated with hospital mortality. Surgery during neutropenia or thrombocytopenia was not associated with prognosis. In hematology patients, emergency abdominal surgery is associated with encouraging hospital survival rates. Surgery should be performed prior to septic shock, regardless of whether neutropenia or thrombocytopenia is present.


Kinematic asymmetries of the lower limbs during ergometer rowing.
Rowing injuries, particularly of the lumbar spine, are often attributed to poor technique. Rowing technique comprises a series of coordinated movements between the back, upper limbs, and lower limbs, and abnormalities in these may lead to injury. The aim of this study was to test the hypothesis that ergometer rowing is symmetrical with respect to lower limb motion and that deviations from symmetry result from rowing experience, work rate, or stroke position. Twenty-two rowers in three levels of ability participated in this study. A motion analysis system was used with an instrumented rowing ergometer, which incorporated load cells at the handle and seat. Kinematic measurements of the knees, hips, lumbar-pelvic joints, and pelvic twist, in addition to measures of handle force, seat force, stroke length, mediolateral seat drift, and mean external power, were made during an incremental step test. Elite rowers exhibited the largest handle force and mean external power (P < 0.01) and least mediolateral seat drift (P < 0.01). All groups demonstrated lower limb asymmetries, with hip asymmetries significantly greater than knee asymmetries (P < 0.01). Regression analysis indicated that both hip and knee range of motion (ROM) asymmetry was significant (P < 0.05) in predicting lumbar-pelvic flexion at the catch and maximum handle force of the stroke. However, hip ROM asymmetry showed a better relation with lumbar-pelvic flexion compared with knee ROM asymmetry, explaining a greater proportion of the variance. Bilateral asymmetries during the rowing stroke, particularly at the hips, can contribute to suboptimal kinematics of the lumbar-pelvic region. Quantification of hip ROM asymmetries may therefore be a useful tool in predicting the development of low back pain in rowers.


Cell cycle and histological effects of reinnervation in denervated forelimb stumps of larval Ambystoma.
Although nerves are a requirement for regeneration of a salamander limb, denervation of an amputated larval Ambystoma forelimb does not permanently prevent the limb from regenerating. When nerves grow back into the distal stump in sufficient numbers, regeneration occurs. In this study we examined histological and cell cycle events in denervated limb stumps of Ambystoma as they became reinnervated and began to regenerate. Prior to reinnervation and regeneration, dedifferentiated cells are present in the distal stump but are rarely synthesizing DNA or undergoing mitosis and are densely packed. About 2 days after the distal tip of the stump becomes reinnervated, the limb tip appears to "expand" as cells become less densely packed, and cell cycle activity begins. Mitotic index (MI) and labeling index (LI) increase slowly compared to MI and LI in control amputated limbs. Evidence for the localization of cycling activity is presented. In reinnervated stumps, the increase in LI precedes the increase in MI, suggesting that most of the cells are initiating cycling from the G1 phase.


Growth hormone and bone metabolism.
GH is a potent anabolic hormone for bone and calcium metabolism, not only via direct effects but also mediated through other systems. The individual effects on bone metabolism are summarized in Table 1. Some of the signs (low BMD and low serum osteocalcin) and symptoms (increased prevalence of vertebral fractures) seen in patients with GHD may be due to the lack of GH itself, others may be due to secondary hormone deficiencies or changes in body composition induced by GHD. GH treatment can reverse changes of calcium metabolism. Whether it is able to increase bone mass still needs to be determined in larger and longer studies. Some patients with established osteoporosis and vertebral fractures seem to suffer from GHD. Treatment of osteoporosis with GH has not previously been successful, but studies with more patients over several years to investigate the effects of GH treatment on vertebral fracture rates are lacking. As GH seems to reverse some signs of old age, such as muscle weakness and reduced exercise capacity, it is possible to speculate that GH could prevent the occurrence of hip fractures in elderly people.


Neo-sex Chromosomes in the Maculipennis Species Group (Dichroplus: Acrididae, Melanoplinae): The Cases of D. maculipennis and D. vittigerum.
South American melanopline grasshoppers display a disproportionate number of derived karyotypes, including many cases of neo-sex chromosome systems. This is especially true of the genus Dichroplus and its Maculipennis species group. We analyzed the karyotype and neo-sex chromosomes in mitosis and meiosis of Dichroplus maculipennis and D. vittigerum from Argentina using conventional and fluorescent cytogenetic protocols in order to elucidate the behavior and origin of these neo-XY systems in relation to the current phylogeny of this group. Our results showed that D. maculipennis (2n = 22♂/22♀; neoXY/neoXX) and D. vittigerum, whose karyotype is described here for the first time (2n = 18♂/18♀; neoXY/neoXX), show highly evolved neo-XY systems, although with significant differences between them. Furthermore, both species differ for two autosomal fixed Robertsonian fusions present in D. vittigerum. Analysis of karyotypic character state optimization strongly suggests the independent origin and evolution of neo-sex systems within this species group.


Human cytomegalovirus UL84 protein contains two nuclear export signals and shuttles between the nucleus and the cytoplasm.
Previous studies defined pUL84 of human cytomegalovirus as an essential regulatory protein with nuclear localization that was proposed to act during initiation of viral-DNA synthesis. Recently, we demonstrated that a complex domain of 282 amino acids within pUL84 functions as a nonconventional nuclear localization signal. Sequence inspection of this domain revealed the presence of motifs with homology to leucine-rich nuclear export signals. Here, we report the identification of two functional, autonomous nuclear export signals and show that pUL84 acts as a CRM-1-dependent nucleocytoplasmic shuttling protein. This suggests an unexpected cytoplasmic role for this essential viral regulatory protein.


Real-time continuous-wave terahertz line scanner based on a compact 1 × 240 InGaAs Schottky barrier diode array detector.
We demonstrate real-time continuous-wave terahertz (THz) line-scanned imaging based on a 1 × 240 InGaAs Schottky barrier diode (SBD) array detector with a scan velocity of 25 cm/s, a scan line length of 12 cm, and a pixel size of 0.5 × 0.5 mm². Foreign substances, such as a paper clip with a spatial resolution of approximately 1 mm that is hidden under a cracker, are clearly detected by this THz line-scanning system. The system consists of the SBD array detector, a 200-GHz gyrotron source, a conveyor system, and several optical components such as a high-density polyethylene cylindrical lens, metal cylindrical mirror, and THz wire-grid polarizer. Using the THz polarizer, the signal-to-noise ratio of the SBD array detector improves because the quality of the source beam is enhanced.


Verapamil in prophylaxis of paroxysmal atrioventricular nodal reentrant tachycardia.
We examined by electrophysiologic study and clinical follow-up the use of verapamil as a prophylactic agent in 13 patients with refractory paroxysmal supraventricular tachycardia due to atrioventricular (AV) node reentry. Electrophysiologic variables and initiation and maintenance of AV nodal reentry were studied by programmed electrical stimulation. Observations were made before and after intravenous administration of verapamil, 0.15 mg/kg. Twelve of the 13 patients had previously not been controlled by other antiarrhythmic agents. Before verapamil, AV nodal reentry was induced in all 13 patients. Verapamil increased AV nodal transmission time (AH interval), as well as the effective and functional refractory periods of the AV node. Reentry could not be initiated in 5 of the 13 patients after verapamil and was nonsustained in a further 3. The echo zone for atrial premature beats which initiated tachycardia decreased in 2 of the remaining 5 patients. The rate of tachycardia was also significantly decreased. Over a mean follow-up period of 16 months, 11 of the 13 patients had definite symptomatic improvement, with decrease in frequency, duration, and/or associated symptoms of their arrhythmia. Only 1 patient had side effects which necessitated withdrawal of the drug. It was concluded that verapamil is a useful agent in the management of such patients.


Short hairpin RNA-mediated silencing of bovine rotavirus NSP4 gene prevents diarrhoea in suckling mice.
While RNA interference (RNAi) has been widely used to study rotavirus gene function in vitro, the potential therapeutic role for RNAi in vivo has not been explored. To this end, we constructed two recombinant lentiviral vectors containing short hairpin RNA (shRNA) against non-structural protein-4 (NSP4) of bovine rotavirus (BRV), RNAi-351 and RNAi-492. RNAi-351 and RNAi-492 strongly suppressed the transient expression of a FLAG-tagged NSP4 fusion protein in 293T cells. In BRV-susceptible MA104 cells, RNAi-492 more potently silenced NSP4 mRNA than RNAi-351 and combination of the two shRNAs almost completely silenced viral NSP4 gene expression. While 100% of suckling mice exposed to BRV and control shRNA developed severe diarrhoea, no suckling mice exposed to BRV in the presence of RNAi-492 or a combination of RNAi-492/RNAi-351 developed severe diarrhoea, and only 20 and 3.3% developed mild diarrhoea, respectively. In addition, RNAi-492 and RNAi-351 markedly abrogated rotaviral replication in MA104 cells and significantly inhibited BRV replication in mouse pups. These results indicated that shRNAs silencing NSP4 gene had substantial antiviral properties and inhibited replication of BRV in a sequence-specific manner that may have clinical application.


Myocardial infarction and viral triggers: what do we know by now?
Myocardial infarction (MI) is an acute clinical manifestation ischaemic heart disease, which is the leading cause of death worldwide. Infections also have an important burden worldwide, with lower respiratory infections being the worldwide leading cause of death due to communicable diseases. The relationship of MI with viral respiratory infections (including influenza and SARS-CoV-2) as a trigger has been well documented with significant associations. These infections can lead to Type 1 MI, where inflammation and vascular dysfunction, as well as the increased prothrombotic environment lead to atherothrombosis. Type 2 MI may also occur due to an imbalance of oxygen/blood supply and myocardial demand (hypoxaemia, fever, and tachycardia). The data from randomized controlled trials showing a potential benefit of influenza vaccination in coronary artery disease patients should not be ignored. This can be considered a further argument for the association of viral infections (influenza in particular) and MI.


Ketoprofen alleviates diet-induced obesity and promotes white fat browning in mice via the activation of COX-2 through mTORC1-p38 signaling pathway.
The nonsteroidal anti-inflammatory drug (NSAID) ketoprofen is commonly used as a pain reliever, but its role in mediating the energy metabolism in lipids is unclear. This paper reports for the first time the critical role of ketoprofen in ameliorating white fat browning and alleviating diet-induced obesity. The effects of ketoprofen were evaluated using C57BL/6 mice fed a high fat diet and the expression levels of the target genes and proteins in the lipid metabolisms were determined by quantitative real-time PCR, immunoblot analysis, histopathology study, immunofluorescence, and molecular docking techniques. Ketoprofen induced browning in cultured 3T3-L1 white adipocytes and inguinal white adipose tissue by increasing the expression of core fat browning marker proteins as well as beige-specific genes through COX-2 activation. Ketoprofen also led to the robust activation of brown adipocytes and enhanced brown fat adipogenesis. In addition, ketoprofen elevated lipolysis, thereby increasing mitochondrial biogenesis resulting in higher fat oxidation. Furthermore, the molecular docking and mechanistic study demonstrated the recruitment of beige fat by ketoprofen via mTORC1-p38-mediated activation of the COX-2 pathway. Overall, these results indicate the unique role of ketoprofen in body weight reduction by enhancing thermogenesis, suggesting its therapeutic potential in the treatment of obesity.


Development of calcium oxalate crystals on urothelium: effect of free radicals.
The effects of free radicals on the development of crystals attached to the living epithelium have been studied using an experimental model that enables close simulation of the conditions prevailing in the kidney. The results obtained clearly demonstrate that free radical-damaged cells produce a favorable environment for crystal development. At low free radical concentrations, crystals develop on calcium-enriched zones, whereas at higher concentrations, crystals develop on areas with a destroyed monolayer of superficial cells. Evaluation of the action of some products with antioxidant action and/or crystallization-inhibitory capacity is also included. Antioxidants, such as ascorbic acid and mannitol, exerted the most remarkable effects in avoiding calcium oxalate crystal development, whereas crystal inhibitors, such as citric acid, did not produce any remarkable reduction in calcium oxalate crystallization. Phytic acid notably decreased calcium oxalate crystal development. The ability of phytic acid to diminish calcium oxalate crystallization must be attributed to the combination of its inhibitory capacity of calcium oxalate crystallization and its preventive antioxidant action.


Morphological changes in liver biopsies from patients with rheumatoid arthritis.
Oxphenisatin is known to induce liver damage and is suspected to cause or perpetuate chronic liver disease. In order to evaluate the hepatotoxic effect of long-term therapy with oxyphenisatin 26 consecutive patients with rheumatoid arthritis were investigated for the presence of liver disease. In all cases, liver biopsy, biochemical liver function tests and determination of Hepatitis-B antigen were performed. Ten patients showed no pathological changes in the liver biopsy and a further 2 had only non-specific changes. Seven patients had fatty liver, 5 passive congestion, one haemosiderosis and only one had cirrhosis of the liver. No correlation was found between the activity of rheumatoid arthritis, and duration of the disease, the drug therapy given, and the liver damage.


The effectiveness of psychoanalysis in a case study using multi-perspective methodology: Conflict in choosing a partner due to transgenerational mandate.
A case study is presented to evaluate the effectiveness of psychoanalysis and the persistence of its benefits 20 years later in a young woman with severe depression, professional inhibition, and difficulties in partner selection due to transgenerational mandate (TGM). The investigation was carried out with psychoanalytic interviews with the patient and analyst, which were evaluated by both psychoanalytic and non-psychoanalytic judges following a methodology based on one tested in Germany by Leuzinger-Bohleber et al. (2003). The psychoanalytic treatment began in the early 1980s in Monterrey, Mexico. The study concludes that the psychoanalysis was effective in assisting with the patient's character disorder and partner selection, mainly because of the therapeutic alliance, the analysis of transference and character, and the patient's increased capacity for mentalization as a result of the interpretation of the TGMs.


Extreme droughts affecting Mediterranean tree species' growth and water-use efficiency: the importance of timing.
It has been known for a long time that drought intensity is a critical variable in determining water stress of Mediterranean tree species. However, not as much attention has been paid to other drought characteristics, for example the timing of the dry periods. We investigated the impact of the timing and intensity of extreme droughts on growing season length, growth and water-use efficiency of three tree species, Pinus nigra ssp. Salzmannii J.F. Arnold, Quercus ilex ssp. ballota (Desf.) Samp. and Quercus faginea Lam. coexisting in a continental Mediterranean ecosystem. Over the study period (2009-13), intense droughts were observed at annual and seasonal scales, particularly during 2011 and 2012. In 2012, an atypically dry winter and spring was followed by an intense summer drought. Quercus faginea growth was affected more by drought timing than by drought intensity, probably because of its winter-deciduous leaf habit. Pinus nigra showed a lower decrease in secondary growth than observed in the two Quercus species in extremely dry years. Resilience to extreme droughts was different among species, with Q. faginea showing poorer recovery of growth after very dry years. The highest intra- and inter-annual plasticity in water-use efficiency was observed in P. nigra, which maintained a more water-saving strategy. Our results revealed that the timing of extreme drought events can affect tree function to a larger extent than drought intensity, especially in deciduous species. Legacy effects of drought over months and years significantly strengthened the impact of drought timing and intensity on tree function.


Use of the Moses Technology to Improve Holmium Laser Lithotripsy Outcomes: A Preclinical Study.
To evaluate in vitro and in vivo effects of Moses technology in Holmium laser and to compare it with the Regular mode in terms of lithotripsy efficiency and laser-tissue interactions. The Lumenis® Pulse™ P120H holmium laser system together with Moses D/F/L fibers were used to compare the Regular mode with the Moses modes in stone retropulsion by using a high-speed camera, and stone ablation efficiency. In addition, a porcine ureteroscopy model was used to assess stone fragmentation and dusting as well as laser-tissue interaction with the ureteral wall. After a laser pulse, in vitro stone displacement experiments showed a significant reduction in retropulsion when using the Moses mode. The stone movement was reduced by 50 times at 0.8 J and 10 Hz (p < 0.01). The pronounced reduction of retropulsion in the Moses mode was clearly observed during fragmentation setting (high energy) and dusting (low energy, high Hz). In addition, stone fragmentation tests showed that the Moses modes resulted in a significantly higher ablation volume when compared with the Regular mode (160% higher; p < 0.001). In vivo assessment also supported the reduction in retropulsion when treating stones in the porcine kidney. Histological analysis of the porcine ureter after direct lasing in the Moses mode suggested less damage than in the Regular mode. The Moses technology resulted in more efficient laser lithotripsy, in addition to significantly reduced stone retropulsion, and displayed a margin of safety that may result in a shorter procedural time and safer lithotripsy.


[Single day treatment in acute cystitis].
The effect of a single day treatment with 600 mg norfloxacin 600 mg ofloxacin or 1,920 mg trimethoprim-sulfamethoxazol was determined on 114 patients with acute cystitis. The overall clinical efficacy was excellent in 101 patients (89%), moderate in 9 patients (8%) and poor in 4 patients (3%). Recurrence was observed in 8 cases (8%) within 6 weeks after the treatment. The effectiveness rate and the recurrence rate were inferior in those caused by S. epidermidis compared with those caused by E. coli.


Health-related quality of life in children and adolescents living in the north-east of China before and after cardiac catheter interventional treatment.
The goal of the present prospective study was to assess health-related quality of life in children and adolescents with CHD before and after cardiac catheter treatment. The study enrolled 96 children/adolescents with CHD from the north-east of China who underwent cardiac catheter intervention treatment between March, 2013 and January, 2014. The health-related quality of life at 24 hours before treatment, 1 month after treatment, and 6 months after treatment was evaluated using Pediatric Quality of Life Inventory Measurement Models 4.0 (PedsQLTM 4.0) generic core scales, and the scores were further compared. Before treatment, each HRQOL domain score and the total score were obviously decreased than the post-treatment scores (1 month and 6 months). The total score and the scores in physical functioning and psychological functioning components were further increased 6 months after treatment than the scores 1 month after treatment. The present study suggests that cardiac catheter interventional treatment improves the life quality of children or adolescents with CHD as time increases after the intervention.


Regeneration of cochlear efferent nerve terminals after gentamycin damage.
Chickens recover auditory function after hair cell loss caused by ototoxic drug damage or acoustic overstimulation, indicating that mechanisms exist to reestablish appropriate neuronal connections to regenerated hair cells. However, despite similar hair cell regeneration times, hearing recovery takes substantially longer after aminoglycoside than after sound damage. We have therefore begun examining damage and regeneration of efferent nerve terminals by immunolabeling whole-mount cochleae for differentially localized synaptic proteins and by visualizing the distribution of label with confocal microscopy. In undamaged cochleae, the synaptic proteins synapsin and syntaxin show similar distribution patterns corresponding to the large cup-like terminals on short hair cells. After gentamycin administration, these terminals are disrupted as hair cells are lost, leaving smaller, more numerous synapsin-reactive structures in the sensory epithelium. Syntaxin reactivity remains associated with the extruded hair cells, indicating that the presynaptic membrane is still attached to the postsynaptic site. In contrast, after sound damage, both synapsin and syntaxin reactivity are lost from the epithelium with extruded hair cells. As regenerated hair cells differentiate after gentamycin treatment, the synapsin labeling associated with cup-like efferent endings reappears but is not completely restored even after 60 d of recovery. Thus, efferent terminals are reestablished much more slowly than after sound damage (), consistent with the prolonged loss of hearing function. This in vivo model system allows comparison of axonal reconnection after either complete loss (sound damage) or partial disruption (gentamycin treatment) of axon terminals. Elucidating the differences in recovery between these injuries can provide insights into reinnervation mechanisms.


The Surgical Treatment of Deep Infection in the Native Shoulder Joint.
The overall clinical picture surrounding native shoulder infections, and, in particular, the associated long-term functional outcomes of treatment are presently underreported. The purpose of this study is to examine the demographics, diagnostic and treatment strategies, and functional outcomes of isolated shoulder joint sepsis treated with surgical irrigation and debridement (I&D). All patients treated with I&D for native shoulder sepsis between 2007 - 2017 were identified. Those without a minimum of one-year follow-up were excluded. Functional outcomes scores, reoperations, and predictors of poor outcome were evaluated. Twenty-three patients were included in the final study population. Mean age-adjusted CCI score was 4.1 (SD = 3.4, Range = 0 - 10). Twelve patients (52.2%) were treated with open I&D, while 11 patients (47.8%) were treated arthroscopically. Nine patients (39.1%) required multiple I&Ds (mean total number of I&Ds = 1.7, SD = 1.0, Range: 1 - 4). Five patients (21.7%) had at least one documented reinfection after their initial hospitalization, with the initial recurrence of infection occurring 2 - 15 months after the index procedure. Mean ASES score at final follow-up was 55.3 (SD = 26.7, Range: 5.8 - 98.3) and mean SANE score was 53.3 (SD = 30.6, Range: 0 - 100). Stepwise multiple linear regression modeling identified intravenous drug abuse as the most significant predictor for final ASES score [F(1,18) = 6.12, p = .024, adjusted R2 = .254]. Following isolated shoulder joint sepsis, infection clearance and acceptable functional outcomes can be achieved using surgical I&D followed by a course of antibiotics, but outcomes are variable.


Experimental and Computational Study of Optimized Gas Diffusion Layer for Polymer Electrolyte Membrane Electrolyzer.
Polymer electrolyte membrane fuel cells (PEMFCs) and PEM electrolyzer are emerging technologies that produce energy with zero carbon emissions. However, the commercial feasibility of these technologies mostly relies on their efficiency, which is determined by individual parts, including the gas diffusion layer (GDL). GDL transfers fluid and charges while protecting other components form flooding and corrosion. As there is a very limited attention toward the simulation work, in this work, a novel approach was utilized that combines simulation and experimental techniques to optimize the sintering temperature of GDL. Ti64 GDL was produced through tape casting, a commercial method famous for producing precise thickness, uniform, and high-quality films and parameters such as slurry composition and rheology, casting parameters, drying, and debinding were optimized. The porosity and mechanical properties of the samples were tested experimentally at various sintering temperatures. The experimental results were compared with the simulated results achieved from the GeoDict simulation tool, showing around 96% accuracy, indicating that employing GeoDict to optimize the properties of Ti64 GDL produced via tape casting is a critical step towards the commercial feasibility of PEMFCs and electrolyzer. These findings significantly contribute to the development of sustainable energy solutions.


Characterization and expression of genes encoding three small heat shock proteins in Sesamia inferens (Lepidoptera: Noctuidae).
The pink stem borer, Sesamia inferens (Walker), is a major pest of rice and is endemic in China and other parts of Asia. Small heat shock proteins (sHSPs) encompass a diverse, widespread class of stress proteins that have not been characterized in S. inferens. In the present study, we isolated and characterized three S. inferens genes that encode members of the α-crystallin/sHSP family, namely, Sihsp21.4, Sihsp20.6, and Sihsp19.6. The three cDNAs encoded proteins of 187, 183 and 174 amino acids with calculated molecular weights of 21.4, 20.6 and 19.6 kDa, respectively. The deduced amino acid sequences of the three genes showed strong similarity to sHSPs identified in other lepidopteran insects. Sihsp21.4 contained an intron, but Sihsp20.6 and Sihsp19.6 lacked introns. Real-time quantitative PCR analyses revealed that Sihsp21.4 was most strongly expressed in S. inferens heads; Whereas expression of Sihsp20.6 and Sihsp19.6 was highest in eggs. The three S. inferens sHSP genes were up-regulated during low temperature stress. In summary, our results show that S. inferens sHSP genes have distinct regulatory roles in the physiology of S. inferens.


[Genital lichen in girls. General aspects and clinical course].
The authors re-examine the clinical aspects of infantile vulvar Lichen sclerosus in the light of the latest reports in the literature. A group of 40 girls was studied with a mean age of 8 years old suffering from this pathology; 8 of the subjects had reached a prepuberal age. The group received different types of therapy and maintenance during a six-month and then annual follow-up. The results are reported correlated to the type of treatment. The results obtained were also evaluated depending on the age of the subject, the onset of puberty in some during the course of the study, the age at onset of disease. It was seen that recovery was mainly linked to aging and hence the evolution of puberty rather than the type of treatment, given that every drug has a predominantly symptomatic effect. The mean recovery time was 2.5 years (namely the average interval between diagnosis and puberty). Contrary to the findings reported in the literature, lesions with an early onset (prior to adrenarche) recovered more slowly and later.


Ibrutinib in mantle cell lymphoma patients: glass half full? Evidence and opinion.
Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin's lymphoma typically marked by an aggressive clinical course and a predilection for relapse. The B-cell receptor (BCR) signaling survival pathway is chronically activated in MCL, contributing to its pathogenesis. Ibrutinib is an inhibitor of Bruton's tyrosine kinase, a vital component of this pathway. This article details the current clinical experience with ibrutinib in the treatment of patients with MCL, including completed and published clinical trials and reviews potential adverse events (AEs) and pitfalls associated with ibrutinib therapy. Although most AEs experienced by patients treated with ibrutinib are mild, some can be severe and treatment limiting and may be attributed to off-target effects. Ibrutinib is a very promising agent for patients with MCL with notable response rates. However, when used as a single agent, around one third of patients relapse in the first 2 years of treatment. Recently reported combination therapies have shown significant activity. Emerging data evaluating potential mechanisms of drug resistance and the poor clinical outcomes after treatment failure are also discussed. Further understanding of resistance and its implications not only in relapsed disease but in the frontline setting are needed. Investigation of strategies to overcome resistance remains an area of high unmet clinical need. Evaluation of the impact of shorter treatment duration, effects on minimal residual disease, and incorporation of novel combinations are also warranted.


Short-term ozone exposure upregulates P-selectin in normal human airways.
Short-term exposure to ambient levels of ozone induces neutrophilic bronchitis. To investigate the early events contributing to inflammatory cell recruitment in the airways we exposed 12 healthy nonsmoking volunteers to 0.12 ppm ozone or filtered air for 2 h on two separate occasions. Spirometry and fiberoptic bronchoscopy were performed immediately and at 1.5 h after the two exposures, respectively. Total protein, albumin, and total and differential cell counts were performed on the bronchial wash and BAL fluid. Bronchial biopsies were embedded in glycol methacrylate and immunostained for inflammatory cells, including neutrophils, mast cells, total T-cells (CD3), T-cell subset CD8, and leukocyte endothelial adhesion molecules, including VCAM-1, ICAM-1, E-selectin, and P-selectin. No significant changes were observed in FEV1, FVC, or any inflammatory indices in the bronchial wash and BAL fluid. In addition, no significant differences were seen in inflammatory cell numbers or percentages of vessels expressing VCAM-1, E-selectin, or ICAM-1 in the biopsies. The percentage of vessels expressing P-selectin increased significantly after ozone exposure: p = 0.016; median (IQR), 28.76 (26.36-36.94) versus 47.06 (38.14-56.86)%. The upregulation of P-selectin could signify an early inflammatory response to ozone such as margination and rolling of the neutrophils on the vessel wall prior to transendothelial migration.


Peripheral markers of brain damage and blood-brain barrier dysfunction.
Occurrence of brain damage is frequently associated with abnormal blood-brain barrier (BBB) function. Two brain-specific proteins, S100beta and neuron-specific enolase (NSE) are released systemically in a variety of neurological diseases, but S100beta levels sometimes rise in the absence of neuronal damage, suggesting that S100beta is a marker of BBB rather than neuronal damage. We measured both proteins in the serum of patients undergoing iatrogenic BBB disruption with intrarterial mannitol, followed by chemotherapy. Serum S100beta increased significantly after mannitol infusion (p<0.05) while NSE did not. Furthermore, in a model of intracerebral hemorrhage, S100beta increases in CSF did not lead to serum changes at a time when the BBB was intact. Modeling of S100beta release from the CNS suggested that low (<0.34 ng/ml) serum levels of S100beta are consistent with BBB opening without CNS damage, while larger increases imply synthesis and release from presumable damaged glia. Thus, S100beta in serum is an early marker of BBB openings that may precede neuronal damage and may influence therapeutic strategies. Secondary, massive elevations in S100beta are indicators of prior brain damage and bear clinical significance as predictors of poor outcome or diagnostic means to differentiate extensive damage from minor, transient impairment.


Host-adapted parasitoids in biological control: does source matter?
It has been hypothesized that the success of a biological control introduction is, in part, dependent on the ability of the control agent to become established in its new environment or to its new population of hosts through local adaptation. Despite this, few studies have investigated the influence of the recent coevolutionary history of pest species and natural enemies on the efficacy of biological control agents, especially for agents that are mass-reared for release in agriculture. We investigate the evolutionary potential of a biological control agent Aphidius ervi to adapt to a key pest species, the foxglove aphid Aulacorthum solani, through components essential to the evolution of parasitoid virulence. We explored (1) the influence of genetic variation from natural source populations on the ability to parasitize natal and non-natal host species; (2) the heritability of key traits related to parasitoid fitness; and (3) the efficacy of parasitoid host-selection lines in a greenhouse system. Source populations maintained genetic variation in the ability to utilize natal and non-natal host species; however, only some of the traits sampled suggested local adaptation of parasitoid populations. The ability to parasitize a host was found to be genetically determined and strongly heritable, irrespective of host species. The greenhouse study demonstrated the potential of parasitoid selection lines to substantially increase performance of parasitoids for target pest species. This research provides insight into novel techniques that can be used to increase the quality of biological control agents through the development of lines of natural enemies adapted to particular pest species.


OPC-aided transmission with low-complexity digital nonlinearity compensation.
Based on the dispersion-folded digital back-propagation (DBP) method, we propose a low-complexity digital nonlinearity-compensation scheme to enhance the system performance of optical phase conjugation (OPC)-aided transmission whilst preserving the low computational requirement of dispersion-folded DBP. When the transmission reach is increased, the computational efficiency of the proposed scheme becomes more apparent compared with conventional DBP while the performance penalty is negligible.


Actin-dependent, retrograde motility of surface-attached beads and aggregating pigment granules in dissociated teleost retinal pigment epithelial cells.
Teleost retinal pigment epithelial (RPE) cells contain pigment granules within apical projections which undergo actin-dependent, bi-directional motility. Dissociated RPE cells in culture attach to the substrate and extend apical projections in a radial array from the central cell body. Pigment granules within projections can be triggered to aggregate or disperse by the presence or absence of 1 mM cAMP. Aminated, fluorescent latex beads attached to the dorsal surface of apical projections and moved in the retrograde direction, towards the cell body. Bead rates on RPE cells with aggregating or fully aggregated pigment granules were 2.2 +/- 0.5 and 2.6 +/- 0.2 microm/min (mean +/- SEM), respectively, similar to rates of aggregating (retrograde) pigment granule movement (2.0 +/- 0.4 microm/min). Bead rates were slightly slower on cells with fully dispersed or dispersing pigment granules (1.5 +/- 0.1 and 1.5 +/- 0.4 microm/min). Movements of surface-attached beads and aggregating pigment granules were closely correlated in the distal portions of apical projections, but were more independent of each other in proximal regions of the projections. The actin disrupting drug, cytochalasin D (CD), reversibly halted retrograde bead movements, suggesting that motility of surface-attached particles is actin-dependent. In contrast, the microtubule depolymerizing drug, nocodazole, had no effect on retrograde bead motility. The similar characteristics and actin-dependence of retrograde bead movements and aggregating pigment granules suggest a correlation between these two processes.


A Patient-based severity measure of chronic lung disease: evaluating functional health and predicting health services use.
Prior research has consistently shown that among patients with chronic lung disease (CLD), health-related quality of life (HRQOL) is tied more to respiratory symptoms than to physiologic measures. However, traditional methods to quantify the severity of CLD have been restricted to physiologic measures (eg, FEV1, FVC, etc) that are often poor predictors of HRQOL and utilization of health services. Using a patient-based measure of symptom severity for CLD developed in the Veterans Health Study (VHS), this article evaluated the impact of the severity of CLD on patients' self-reported HRQOL and future use of health services. We used data from the VHS, a prospective study of patients receiving ambulatory care services in 4 Veterans Affairs outpatient clinics in the greater Boston area. Three hundred fifty-two (14.5%) patients were identified as having CLD through self-report of having a physician's diagnosis of chronic bronchitis, emphysema, or asthma, and either using inhaled medications or having a productive cough for most days for 3 months. Ordinary least-square regressions were used to ascertain the effects of CLD severity on functional health and health services use. Compared with peak expiratory flow rate, which explained only 10% and 2%, respectively, of the variance in the SF-36 physical component summary (PCS) and in future doctor visits, the symptom severity explained 19% and 19%, respectively, of the variance in PCS and future doctor visits, after adjusting for age, education, and household income. The symptom severity measure is a strong predictor of future functional health (at 12 months of the VHS baseline) and health services use (within 6 months following the baseline). The study findings indicate that our measure of CLD severity is an efficient and easy-to-use approach that can be readily administered in ambulatory setting. It can be used as a case-mix adjustment in evaluating health outcomes and in predicting future utilization of health services.


Commentary on Some Recent Theses Relevant to Combating Aging: August 2017.
Theses reviewed in this issue include "Engineering Cellular Input-Output for the Robust Control of Mammalian Cell-Based Therapies"; "Enzyme-Instructed Self-Assembly (EISA) Selectively Targets Cancer Cells"; "Exploration of helminth-derived immunoregulatory molecules as options for therapeutic intervention in allograft rejection and autoimmune disease"; "Expression of the Medial HOXA genes is indispensible for self-renewal in human hematopoietic stem cells"; "Gamma frequency entrainment attenuates amyloid load and modifies microglia"; and "Heterogeneous Distribution of Microvascular Blood Flow Contributes to Impaired Skeletal Muscle Oxygenation in Diabetes".


Impact of transient acquired hypermutability on the inter- and intra-species competitiveness of Pseudomonas aeruginosa.
Once acquired, hypermutation is unrelenting, and in the long-term, leads to impaired fitness due to its cumulative impact on the genome. This raises the question of why hypermutators arise so frequently in microbial ecosystems. In this work, we explore this problem by examining how the transient acquisition of hypermutability affects inter- and intra-species competitiveness, and the response to environmental insults such as antibiotic challenge. We do this by engineering Pseudomonas aeruginosa to allow the expression of an important mismatch repair gene, mutS, to be experimentally controlled over a wide dynamic range. We show that high levels of mutS expression induce genomic stasis (hypomutation), whereas lower levels of induction lead to progressively higher rates of mutation. Whole-genome sequence analyses confirmed that the mutational spectrum of the inducible hypermutator is similar to the distinctive profile associated with mutS mutants obtained from the airways of people with cystic fibrosis (CF). The acquisition of hypermutability conferred a distinct temporal fitness advantage over the wild-type P. aeruginosa progenitor strain, in both the presence and the absence of an antibiotic selection pressure. However, over a similar time-scale, acquisition of hypermutability had little impact on the population dynamics of P. aeruginosa when grown in the presence of a competing species (Staphylococcus aureus). These data indicate that in the short term, acquired hypermutability primarily confers a competitive intra-species fitness advantage.


Diurnal variation of the rat vas deferens contraction induced by stimulation of presynaptic nicotinic receptors and pineal function.
A rhythmic variation of maximal contraction induced by acetylcholine in the prostatic portion of rat vas deferens was tested. This contraction is due to the release of norepinephrine and ATP from sympathetic nerve terminals. Male Wistar rats (4 months old) were housed on a light/dark cycle (12 hr/12 hr, lights on at 6:00 A.M.). The diurnal variation of acetylcholine-induced contraction was determined on animals sacrificed every 3 hr during the day. The maximal contractile response shows a circadian (24:00 hr) and an ultradian (12:20 hr) rhythm. Otherwise, the sensitivity to acetylcholine (pD2 values) and the maximal contraction or pD2 values to norepinephrine, ATP and K+ did not change throughout the day. The blocking effect of hexamethonium on the contraction induced by field stimulation was higher at 9:00 P.M. than at 3:00 P.M., indicating a diurnal variation of the effect of endogenous released acetylcholine. When melatonin released by the pineal gland is suppressed by constant illumination or superior cervical ganglionectomy, the circadian rhythm was abolished and the period of the ultradian rhythm changed to 6:30 hr. The acetylcholine-induced contraction of vasa deferentia from animals sacrificed at 3:00 P.M. and incubated "in vitro" with melatonin (100 pg/ml) increased reaching nocturnal values. In conclusion, it seems that a functional pineal gland, most probably through the synthesis and release of melatonin, is necessary for expression (circadian) and modulation (ultradian) of the rhythmicity in the maximal acetylcholine-induced contraction in the prostatic portion of the rat vas deferens.


Evaluating the role of LPIN1 variation in insulin resistance, body weight, and human lipodystrophy in U.K. Populations.
Loss of lipin 1 activity causes lipodystrophy and insulin resistance in the fld mouse, and LPIN1 expression and common genetic variation were recently suggested to influence adiposity and insulin sensitivity in humans. We aimed to conduct a comprehensive association study to clarify the influence of common LPIN1 variation on adiposity and insulin sensitivity in U.K. populations and to examine the role of LPIN1 mutations in insulin resistance syndromes. Twenty-two single nucleotide polymorphisms tagging common LPIN1 variation were genotyped in Medical Research Council (MRC) Ely (n = 1,709) and Hertfordshire (n = 2,901) population-based cohorts. LPIN1 exons, exon/intron boundaries, and 3' untranslated region were sequenced in 158 patients with idiopathic severe insulin resistance (including 23 lipodystrophic patients) and 48 control subjects. We found no association between LPIN1 single nucleotide polymorphisms and fasting insulin but report a nominal association between rs13412852 and BMI (P = 0.042) in a meta-analysis of 8,504 samples from in-house and publicly available studies. Three rare nonsynonymous variants (A353T, R552K, and G582R) were detected in severely insulin-resistant patients. However, these did not cosegregate with disease in affected families, and Lipin1 protein expression and phosphorylation in patients with variants were indistinguishable from those in control subjects. Our data do not support a major effect of common LPIN1 variation on metabolic traits and suggest that mutations in LPIN1 are not a common cause of lipodystrophy in humans. The nominal associations with BMI and other metabolic traits in U.K. cohorts require replication in larger cohorts.


Gene therapy for articular cartilage repair.
Articular cartilage serves as the gliding surface of joints. It is susceptible to damage from trauma and from degenerative diseases. Restoration of damaged articular cartilage may be achievable through the use of cell-regulatory molecules that augment the reparative activities of the cells, inhibit the cells' degradative activities, or both. A variety of such molecules have been identified. These include insulin-like growth factor I, fibroblast growth factor 2, bone morphogenetic proteins 2, 4, and 7, and interleukin-1 receptor antagonist. It is now possible to transfer the genes encoding such molecules into articular cartilage and synovial lining cells. Although preliminary, data from in-vitro and in-vivo studies suggest that gene therapy can deliver such potentially therapeutic agents to protect existing cartilage and to build new cartilage.


Migration of human monocytes in response to procalcitonin.
Circulating serum levels of procalcitonin rise significantly during bacterial infection. Because calcitonin is known to be a monocyte chemoattractant, we investigated whether procalcitonin, a prohormone of calcitonin, also affects leukocyte migration. Prospective, controlled in vitro study. University research laboratories. Forearm venous blood polymorphonuclear neutrophils and monocytes were isolated from healthy human donors. Cell migration was assessed in a blindwell chemotaxis chamber. The distance of migration into filter micropores was measured. To biochemically confirm functional data on cell migration, effects of procalcitonin on cellular levels of cyclic adenosine monophosphate were measured by high-performance liquid chromatography. Both procalcitonin and calcitonin elicited dose-dependent migration of monocytes at concentrations from the femtomolar to the micromolar range. Neutrophils did not migrate toward procalcitonin or calcitonin, nor was their oxygen free radical release affected as measured fluorimetrically. Checkerboard analysis of monocyte locomotion revealed procalcitonin-induced migration as true chemotaxis. Pretreatment of monocytes with procalcitonin or calcitonin rapidly deactivated their migratory response to formyl-Met-Leu-Phe, and both also induced homologous deactivation of migration. Procalcitonin elevated levels of cyclic adenosine monophosphate in monocytes. In vitro procalcitonin is a monocyte chemoattractant that deactivates chemotaxis in the presence of additional inflammatory mediators. Procalcitonin stimulates cyclic adenosine monophosphate production in monocytes, suggesting that its action may be specific and comparable with calcitonin, which exerts similar functions.


Cutaneous melanoma in childhood presenting as intraparotid lymph node metastasis.
Cutaneous melanoma in childhood is a rare disease. Rendering a clinical diagnosis of melanoma in pediatric patients is confounded by the fact that pigmented lesions in pediatric patients do not conform to the ABCDE rules applicable to adult patients. Furthermore, making a histologic diagnosis of cutaneous melanoma in childhood is also difficult with no universally accepted criteria applicable to pediatric melanomas. We report the case of a 5-year-old child presenting with intraparotid lymph node metastasis who was later found to have melanoma involving periorbital region. It is proposed that careful analysis of histologic features as well as the additional information provided by immunohistochemistry should allow for a correct diagnosis in most cases of melanoma in children.


The Path to Conserved Extended Haplotypes: Megabase-Length Haplotypes at High Population Frequency.
This minireview describes the history of the conceptual development of conserved extended haplotypes (CEHs): megabase-length haplotypes that exist at high (≥0.5%) population frequency. My career began in internal medicine, shifted to pediatrics, and clinical practice changed to research. My research interest was initially in hematology: on plasma proteins, their metabolism, synthesis, and function. This narrowed to a focus on proteins of the human complement system, their role in immunity and their genetics, beginning with polymorphism and deficiency of C3. My group identified genetic polymorphisms and/or inherited deficiencies of C2, C4, C6, and C8. After defining glycine-rich beta glycoprotein as factor B (Bf) in the properdin system, we found that the genes for Bf (CFB), C2, C4A, and C4B were inherited as a single haplotypic unit which we named the "complotype." Complotypes are located within the major histocompatibility complex (MHC) between HLA-B and HLA-DRB1 and are designated (in arbitrary order) by their CFB, C2, C4A, and C4B types. Pedigree analysis revealed long stretches (several megabases) of apparently fixed DNA within the MHC that we referred to as "extended haplotypes" (later as "CEHs"). About 10 to 12 common CEHs constitute at least 25 - 30% of MHC haplotypes among European Caucasian populations. These CEHs contain virtually all the most common markers of MHC-associated diseases. In the case of type 1 diabetes, we have proposed a purely genetic and epigenetic model (with a small number of Mendelian recessive disease genes) that explains all the puzzling features of the disease, including its rising incidence.


Bradykinin-induced nociceptor sensitisation to heat depends on cox-1 and cox-2 in isolated rat skin.
Bradykinin is an important inflammatory mediator that can either activate and/or sensitise nociceptors to heat stimuli applied to the skin. Several studies have suggested that prostaglandins and thus the cyclooxygenase (cox) enzymes are important in the sensitisation process but little is known about the relative involvement of the two cox isoforms, cox-1 and cox-2. Extracellular recordings were made from C-mechanoheat-sensitive fibres in isolated rat skin-saphenous nerve preparations. Bradykinin-mediated sensitisation of heat responses in these afferents was significantly attenuated by the selective cox-1 inhibitor, SC-560, and by the selective cox-2 inhibitor, NS-398. In the same experiments, bradykinin-mediated induction of ongoing activity was reduced by SC-560 but not NS-398. In a second series of experiments, bradykinin-stimulated synthesis and release of prostaglandin E2 (PGE2) was measured in isolated skin-nerve preparations. Although the basal release of PGE2 appeared unaffected by either drug, bradykinin-stimulated PGE2 release from the skin was inhibited by both SC-560 and NS-398. Immunocytochemical evaluation revealed cox-1 immunostaining was present in large cutaneous nerve branches, small intradermal nerve bundles as well as nerve endings within the skin. Cox-1 labelling was also present in non-neuronal cell types such as mast cells. Cox-2 immunoreactivity was weak but where present was located in small nerve bundles, smaller intradermal nerve bundles and nerve endings. This study shows that both cox isoforms are present in skin and that they have an important role in mediating bradykinin-evoked heat sensitisation of C-MH sensitive fibres through cox-1 and cox-2 dependent prostaglandin synthesis.


Bicuspid Aortic Valve Stenosis and the Effect of Vitamin K2 on Calcification Using 18F-Sodium Fluoride Positron Emission Tomography/Magnetic Resonance: The BASIK2 Rationale and Trial Design.
BASIK2 is a prospective, double-blind, randomized placebo-controlled trial investigating the effect of vitamin K2 (menaquinone-7;MK7) on imaging measurements of calcification in the bicuspid aortic valve (BAV) and calcific aortic valve stenosis (CAVS). BAV is associated with early development of CAVS. Pathophysiologic mechanisms are incompletely defined, and the only treatment available is valve replacement upon progression to severe symptomatic stenosis. Matrix Gla protein (MGP) inactivity is suggested to be involved in progression. Being a vitamin K dependent protein, supplementation with MK7 is a pharmacological option for activating MGP and intervening in the progression of CAVS. Forty-four subjects with BAV and mild-moderate CAVS will be included in the study, and baseline 18F-sodiumfluoride (18F-NaF) positron emission tomography (PET)/ magnetic resonance (MR) and computed tomography (CT) assessments will be performed. Thereafter, subjects will be randomized (1:1) to MK7 (360 mcg/day) or placebo. During an 18-month follow-up period, subjects will visit the hospital every 6 months, undergoing a second 18F-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR 18F-NaF uptake (6 months minus baseline) compared to this delta change in the placebo arm. The main secondary endpoints are changes in calcium score (CT), progression of the left ventricularremodeling response and CAVS severity (echocardiography). We will also examine the association between early calcification activity (PET) and later changes in calcium score (CT).


Multiple mechanisms compensate to enhance tumor-protective CD8(+) T cell response in the long-term despite poor CD8(+) T cell priming initially: comparison between an acute versus a chronic intracellular bacterium expressing a model antigen.
We evaluated CD8(+) T cell responses against the dominant CTL epitope, OVA(257-264), expressed by an acute (Listeria monocytogenes (LM) OVA) vs a chronic pathogen (Mycobacterium bovis bacillus Calmette-Guérin (BCG) OVA) to reveal the influence on CD8(+) T cell memory and consequent protection against a challenge with OVA-expressing tumor cells. Infection with lower doses of both pathogens resulted in stronger bacterial growth but weaker T cell memory indicating that memory correlates with pathogen dose but not with bacterial expansion. The CD8(+) T cell response induced by LM-OVA was helper T cell-independent and was characterized by a rapid effector response followed by a rapid, but massive, attrition. In contrast, BCG-OVA induced a delayed and weak response that was compensated for by a longer effector phase and reduced attrition. This response was partly dependent on CD4(+) T cells. CD8(+) T cell response induced by BCG-OVA, but not LM-OVA, was highly dependent on pathogen persistence to compensate for the weak initial CD8(+) T cell priming. Despite a stronger initial T cell response with LM-OVA, BCG-OVA provided more effective tumor (B16OVA) control at both local and distal sites due to the induction of a persistently activated acquired, and a more potent innate, immunity.


Mumps outbreak in a tribal population from the Union Territory of Dadra and Nagar Haveli, India.
A cluster of parotitis cases (n = 13) were observed in a tribal population of Vansda village from the Union Territory of Dadra and Nagar Haveli, India between 20th and 22nd week of 2016. Primary information was received by the local Infectious Disease Surveillance Program team, and subsequently field investigations were carried out in the affected area. Active surveillance was conducted till twice the incubation period from onset of the last surveyed case. For the laboratory investigations, 19 serum samples were collected from 11-suspected cases and their close contacts (n = 8). All samples were transported within 12 h on icepacks to the main laboratory at Pune. Majority of the suspected mumps cases were children except four adults. Mumps infection was confirmed in 8 of 11 suspected cases with post-onset ranging from 28 to 43 days and none from the close contacts. Both mumps specific IgM and IgG antibodies were detected in nine cases (including one equivocal) and single contact (equivocal result). Overall, ten cases and eight contacts (including one equivocal) showed mumps specific IgG antibodies. Present investigation provides information about the characteristics of mumps outbreak in a tribal community that resides in the remote areas. In addition, introduction of mumps containing vaccine in the tribal population may have added advantages in the tribal health program.


Noisy Label Learning With Provable Consistency for a Wider Family of Losses.
Deep models have achieved state-of-the-art performance on a broad range of visual recognition tasks. Nevertheless, the generalization ability of deep models is seriously affected by noisy labels. Though deep learning packages have different losses, this is not transparent for users to choose consistent losses. This paper addresses the problem of how to use abundant loss functions designed for the traditional classification problem in the presence of label noise. We present a dynamic label learning (DLL) algorithm for noisy label learning and then prove that any surrogate loss function can be used for classification with noisy labels by using our proposed algorithm, with a consistency guarantee that the label noise does not ultimately hinder the search for the optimal classifier of the noise-free sample. In addition, we provide a depth theoretical analysis of our algorithm to verify the justifies' correctness and explain the powerful robustness. Finally, experimental results on synthetic and real datasets confirm the efficiency of our algorithm and the correctness of our justifies and show that our proposed algorithm significantly outperforms or is comparable to current state-of-the-art counterparts.


Hydrolysis of xylan by Aspergillus niger immobilized on non-woven fabrics.
Aspergillus niger, which produces xylan-degrading enzymes, was immobilized on non-woven fabrics. The maximum xylan hydrolysis activity (15 U/cm3-support) and the highest stability were obtained when the fungus was immobilized on non-woven fabric made of silk. The enzymatic properties of the immobilized preparation were similar to those of the free enzyme. Ten times repeated batch hydrolysis of birch-wood xylan was done over a period of 450 h. Hydrolysis of different xylan substrates such as oat spelts and rice bran by the immobilized mycelia was also investigated.


Explaining inequalities in access to treatment in lung cancer.
Geographical inequalities in lung cancer treatment and patient survival have been described. We hypothesized that lung cancer patients' access to treatment may be influenced by deprivation and the pathway to care. Case notes were reviewed for patients resident in south-east London who were registered with lung cancer at the Thames Cancer Registry in 1998. Use of surgery, chemotherapy, radiotherapy or any specific treatment and one-year survival were examined. Analyses were adjusted for age, sex, histology, stage and basis of diagnosis. Data for 695 out of 958 (73%) patients were analysed. Subjects who were initially referred to a specialist in thoracic medicine, surgery or oncology were more likely to receive active treatment (71%) than subjects who were referred to other consultants (51%) or who were admitted as emergencies (42%) (P < 0.0001). Socio-economic deprivation was associated with lower rates of treatment and this partly explained variations in survival. Subjects who were referred to specialists were more likely to receive active treatment and treatment patterns varied between first trust attended.


Are the contents of treatment outcomes in fibromyalgia trials represented in the International Classification Of Functioning, Disability, and Health?
To identify the concepts contained in treatment outcomes of randomized controlled trials (RCTs) for interventions in patients with fibromyalgia (FM) using the International Classification of Functioning, Disability, and Health (ICF) as external reference. RCTs between 1992 and 2001 were located in MEDLINE and selected according to predefined eligibility criteria. The outcome measures were extracted and the concepts within the outcome measures were identified and linked to the ICF using a content-analytical approach. Forty-two trials on FM were included. Twenty-seven different questionnaires were extracted. Of all, 79.2% (N=236) of the clinical and physiologic outcomes could be linked to 31 different ICF categories and 84.7% (N=964) of the concepts contained in the health-status questionnaire to 113 ICF categories. The ICF provides a useful external reference to identify the concepts contained in outcome measures used in RCTs in FM.


Post-irradiation lumbosacral radiculopathy associated with multiple cavernous malformations of the cauda equina: Case report and review of the literature.
Multiple radiation-induced cavernous malformations of the cauda equina are extremely rare. A review of the literature suggested that the post-irradiation lumbosacral radiculopathy in our patient was most likely associated with a diagnosis of multiple radiation-induced cavernous malformations of the cauda equina. A 76-year-old man with a remote history of abdominal radiation therapy presented with a 6-month history of progressively worsening right foot drop and balance impairment. Magnetic resonance imaging (MRI) revealed multiple enhancing areas of the cauda equina concerning for carcinomatous meningitis, however, cerebrospinal fluid (CSF) analysis was unrevealing. Intraoperative findings were consistent with multiple radiation-induced cavernous malformations of the cauda equina. Multiple radiation-induced cavernous malformations of the cauda equina may mimic carcinomatous or infectious meningitis. Clinicians should be suspicious of this diagnosis when CSF and MRI findings are inconsistent with metastatic disease or infectious meningitis in patients who present with radiculopathy and a history of radiation therapy.


Determination of plasma lipid profiles by automated gas chromatography and computerized data analysis.
Plasma or serum [ 0.1-1.0 ml] was digested with phospholipase C and total lipid extracts were prepared and silylated in the presence of tridecanoylglycerol as internal standard. The neutral lipid and free fatty acid profiles were determined by means of an automated GLC system equipped with an unheated on-column inlet, time actuated liquid injector, programmed heating, cooling and equilibration cycles, and an electronic peak area integrator. The separations were accomplished on a 50 cm x 2 mm i.d. steel column packed with 3% OV-1 on100-120 mesh Gas Chrom Q using nitrogen as a carrier gas in the temperature range 175-350 degrees C. The tube number, peak retention time and peak area were recorded on a punched paper tape, which was subsequently read into a computer via a time-share terminal. The composition of the sample was calculated in relation to the internal standard using a modification of a commercially available computer program and the results were expressed as mg or mole % and characteristic molar ratios of lipid classes. In addition to estimates for total cholesterol and triglyceride, the method provides a detailed account of individual or small groups of molecular species of various lipid classes, which is a major advantage over other automated methods of plasma lipid analyses.


Observation as an option for epithelial positive margin after partial glossectomy in stage I and II squamous cell carcinoma: analysis of 365 cases.
This study was conducted to assess local recurrence and clinical prognosis in patients diagnosed as having a positive margin in the epithelial layer after a partial glossectomy treated by close observation. A total of 365 cases of squamous cell carcinoma of the tongue diagnosed as clinical Stage I or II, treated by partial glossectomy in the National Cancer Center Hospital East between 1992 and 2006, were studied retrospectively. Pathological findings showed that 13 cases had positive margins in the epithelial layer, 4 (30.8%) of whom showed up with local recurrence in 4.4 years (3.0-5.0) on average. Lymph node recurrence was not observed and the 5-year overall survival rate was 76.2% in those 13 cases. The treatment for the recurrent cases was an additional partial glossectomy without neck dissection, which resulted in no recurrence and a survival rate of 100% after an average follow-up of 6.7 years. We suggest careful observation as one option for cases diagnosed with epithelial positive margin.


A Prospective Study of Anterior Segment Ocular Parameters in Anisometropia.
The aim of this study was to investigate the differences in anterior segment ocular parameters in anisometropia >1 D. This study included 202 eyes of 101 subjects ranging from 10 to 40 years of age with anisometropia of 1 D or more. The subjects were divided into groups according to anisomyopia, anisoastigmatism, and anisohypermetropia. After providing informed consent, each patient underwent a detailed ophthalmological examination including cycloplegic refraction, best-corrected visual acuity, cover test, axial length (AL) measurement using A-scan ultrasound biometer, keratometry, anterior chamber depth, and central corneal thickness measurement. For each participant, the eye with greater refractive error was compared to the fellow eye via paired t-tests. Correlations between parameters were studied using the Pearson correlation coefficient. The average age of subjects was 21.7 ± 9.3 years. Of 101 subjects, 31 had anisomyopia; 42 had anisohypermetropia; and 28 had anisoastigmatism. A predisposition toward greater myopia in right eyes was noted in anisomyopia (24 of 31 subjects, 77%). The inter-ocular acuity difference was significant in all three groups (p < 0.01). As the degree of anisometropia increased, there was significant positive correlation in the difference in AL in myopes (r = 0.863, p < 0.01) and hypermetropes (r = 0.669, p < 0.01) and the difference in corneal curvature in anisoastigmatism (r = 0.564, p = 0.002) and hypermetropes (r = 0.376, p = 0.014). A significant positive correlation was also present between the anterior chamber depth difference and refractive difference in hypermetropes (r = 0.359, p = 0.020). This study showed that anisomyopia is correlated only with anterior chamber differences. Anisohypermetropia is correlated with AL differences as well as corneal curvature difference and anterior chamber depth difference. The amount of anisoastigmatism correlates only with corneal curvature difference.


Development and Evaluation of Some Molecular Hybrids of N-(1-Benzylpiperidin-4-yl)-2-((5-phenyl-1,3,4-oxadiazol-2-yl)thio) as Multifunctional Agents to Combat Alzheimer's Disease.
A series of some novel compounds (SD-1-17) were designed following a molecular hybridization approach, synthesized, and biologically tested for hAChE, hBChE, hBACE-1, and Aβ aggregation inhibition potential to improve cognition and memory functions associated with Alzheimer's disease. Compounds SD-4 and SD-6 have shown multifunctional inhibitory profiles against hAChE, hBChE, and hBACE-1 enzymes in vitro. Compounds SD-4 and SD-6 have also shown anti-Aβ aggregation potential in self- and acetylcholinesterase (AChE)-induced thioflavin T assay. Both compounds have shown a significant propidium iodide (PI) displacement from the cholinesterase-peripheral active site (ChE-PAS) region with excellent blood-brain barrier (BBB) permeability and devoid of neurotoxic liabilities. Compound SD-6 ameliorates cognition and memory functions in scopolamine- and Aβ-induced behavioral rat models of Alzheimer's disease (AD). Ex vivo biochemical estimation revealed a significant decrease in malonaldehyde (MDA) and AChE levels, while a substantial increase of superoxide dismutase (SOD), catalase, glutathione (GSH), and ACh levels is seen in the hippocampal brain homogenates. The histopathological examination of brain slices also revealed no sign of neuronal or any tissue damage in the SD-6-treated experimental animals. The in silico molecular docking results of compounds SD-4 and SD-6 showed their binding with hChE-catalytic anionic site (CAS), PAS, and the catalytic dyad residues of the hBACE-1 enzymes. A 100 ns molecular dynamic simulation study of both compounds with ChE and hBACE-1 enzymes also confirmed the ligand-protein complex's stability, while quikprop analysis suggested drug-like properties of the compounds.


The New Possibility of Lymphoscintigraphy to Guide a Clinical Treatment for Lymphedema in Patient With Breast Cancer.
Lymphedema is a chronic disease that occurs frequently after breast cancer treatment. For the treatment of lymphedema, surgical approach such as vascularized lymph node transfer and super-microscopic lymphovenous anastomosis surgery is well established. Complex decongestive therapy (CDT) and sympathetic ganglion block (SGB) are two non-surgical therapeutic options. This study aimed to evaluate the effectiveness of lymphoscintigraphy in guiding the selection of the optimal non-surgical treatment in lymphedema. A total of 81 lymphedema patients who underwent lymphoscintigraphy and were treated with CDT or SGB were retrospectively evaluated. The parameters for the lymphoscintigraphic findings included the extent of dermal backflow (small extent/large extent groups), the level of lymphatic flow (trunk flow pattern/upper arm-restricted pattern/forearm-restricted pattern groups), and the visualization of lymph nodes (visualized/non-visualized groups). The change in the circumferential difference between the two sides of the body at the upper arm and forearm was used as the clinical outcome variable. Paired comparison and group comparison analysis were conducted. Of 81 patients, 41 received CDT and 40 received SGB. There were no significant differences in demographic data between the CDT and SGB groups. Both CDT and SGB had a significant therapeutic effect. Upper arm edema was more significantly reduced after SGB than after CDT in the small extent group (P = 0.004), the forearm-restricted pattern group (P = 0.002), and the non-visualized group (P = 0.018). In the other groups, SGB and CDT showed comparable therapeutic effects without statistical differences. SGB was found to have a better therapeutic effect in the lymphedema patients with specific lymphoscintigraphic findings compared with CDT. Lymphoscintigraphy may be helpful in selecting the appropriate approach to lymphedema treatment. Further well-designed prospective studies are warranted to validate the findings of this study.


Adrenergic signaling regulation of macrophage function: do we understand it yet?
Macrophages are immune cells that are widespread throughout the body and critical for maintaining tissue homeostasis. Their remarkable plasticity allows them to acquire different phenotypes, becoming able either to fight infection (M1-like, classically activated macrophages) or to promote tissue remodeling and repair (M2-like, alternatively activated macrophages). These phenotypes are induced by different cues present in the microenvironment. Among the factors that might regulate macrophage activation are mediators produced by different branches of the nervous system. The regulation exerted by the sympathetic nervous system (SNS) on macrophages (and the immune system in general) is becoming a subject of increasing interest, indeed a great number of articles have been published lately. Catecholamines (noradrenaline and adrenaline) activate α and β adrenergic receptors expressed by macrophages and shape the effector functions of these cells in contexts as diverse as the small intestine, the lung, or the adipose tissue. Activation of different subsets of receptors seems to produce antagonistic effects, with α adrenergic receptors generally associated with pro-inflammatory functions and β adrenergic receptors (particularly β2) related to the resolution of inflammation and tissue remodeling. However, exceptions to this paradigm have been reported, and the factors contributing to these apparently contradictory observations are still far from being completely understood. Additionally, macrophages per se seem to be sources of catecholamines, which is also a subject of some debate. In this review, we discuss how activation of adrenergic receptors modulates macrophage effector functions and its implications for inflammatory responses and tissue homeostasis.


Investigation, Pollution Mapping and Simulative Leakage Health Risk Assessment for Heavy Metals and Metalloids in Groundwater from a Typical Brownfield, Middle China.
Heavy metal and metalloid (Cr, Pb, Cd, Zn, Cu, Ni, As and Hg) concentrations in groundwater from 19 typical sites throughout a typical brownfield were detected. Mean concentrations of toxic metals in groundwater decreased in the order of Cr > Zn > Cu > Cd > Ni > Pb > Hg > As. Concentration of Cr6+ in groundwater was detected to further study chromium contamination. Cr6+ and Cd in groundwater were recommended as the priority pollutants because they were generally 1399-fold and 12-foldgreater than permissible limits, respectively. Owing to the fact that a waterproof curtain (WPC) in the brownfield is about to pass the warranty period, a steady two-dimensional water quality model and health risk assessment were applied to simulate and evaluate adverse effects of Cr6 + and Cd on the water quality of Xiangjiang River and the drinking-water intake of Wangcheng Waterworks. The results indicated that when groundwater in the brownfield leaked with valid curtain prevention, the water quality in Xiangjiang River and drinking-water intake downstream were temporarily unaffected. However, if there was no curtain prevention, groundwater leakage would have adverse impact on water quality of Xiangjiang River. Under the requirements of Class III surface water quality, the pollution belt for Cr6+ was 7500 m and 200 m for Cd. The non-carcinogenic risk of toxic metals in Xiangjiang River exceeded the threshold in a limited area, but did not threaten Wangcheng Waterworks. By contrast, the carcinogenic risk area for adults was at a transverse distance of 200 m and a longitudinal distance of 18,000 m, which was close to the Wangcheng Waterworks (23,000 m). Therefore, it was essential to reconstruct the WPC in the brownfield for preventing pollution diffusion.


The Current State of Surgical Ergonomics.
Work-related musculoskeletal disorders are widespread among surgeons, causing significant disability and career modification. Gender plays a role, as female surgeons have a two-fold greater risk for discomfort during certain operations due to generally smaller hand sizes and height as compared to male surgeons. There is a lack of appropriate surgical instrumentation geared toward smaller hand sizes. Maintaining a neutral position while operating, frequent changes in position, and increased awareness can contribute to decreasing the detrimental impact on surgeons' bodies from performing operations.


Low-intensity endurance exercise plus nandrolone decanoate modulates cardiac adiponectin and its receptors.
Vast adverse effects of anabolic-androgenic steroids (AASs) on athletes' cardiovascular systems have been reported. However, there is still a lack of adequate information regarding the pathways and mechanisms involved. We tested the hypothesis that adiponectin and its receptors in the heart may be affected by long-term use of AASs alongside exercising. Male Wistar rats were randomized into the control (CTL), exercise (EX), nandrolone (Nan), arachis (Arach) group which treated with arachis as vehicle, trained vehicle (EX+Arach) and trained nandrolone (EX+Nan) groups that were treated for 8 weeks. One day after the end of the protocol, animals were sacrificed and their hearts were frozen. TNF-α and adiponectin proteins of hearts were evaluated quantitatively by ELISA kits, and Western blot analysis was used for measuring adiponectin receptor protein expression. TNF-α protein increased significantly in the EX+Nan group (P<.05 vs CTL group). The AdipoR1 protein was significantly higher in the presence of nandrolone alongside exercise (P<.05 vs Nan and EX+Arach groups, P<.01 vs CTL and Arach groups). In addition, AdipoR2 protein enhanced in the EX+Nan group when compared with the other groups (P<.05 vs EX and EX+Arach groups, P<.01 vs CTL, Arach and Nan groups). Chronic nandrolone plus mild endurance exercise may be associated with imbalance in pro-/anti-inflammatory cytokines and may induce a positive modulatory effect on cardiac adiporeceptors in rat. Further studies are required before these findings can be generalized to humans.