Applying principles of motor learning and control to upper extremity rehabilitation.
The purpose of this article is to provide a brief review of the principles of motor control and learning. Different models of motor control from historical to contemporary are presented with emphasis on the Systems model. Concepts of motor learning including skill acquisition, measurement of learning, and methods to promote skill acquisition by examining the many facets of practice scheduling and use of feedback are provided. A fictional client case is introduced and threaded throughout the article to facilitate understanding of these concepts and how they can be applied to clinical practice.


Axonal transport of adenylate cyclase activity in normal and axotomized frog sciatic nerve.
Adenylate cyclase activity accumulated proximal to a constriction placed around the frog sciatic nerve. The rate of accumulation was linear between 8 and 24 h following placement of the constriction; accumulation rate declined substantially after 24 h. Accumulation of activity distal to the constriction in normal nerve was not significantly different from control for the first 72 h, but increased at 5 days. These data are interpreted as indicating that adenylate cyclase is transported from the cell body to the nerve terminals in normal frog nerve, but not in the reverse direction. Following axon transection, anterograde transport of adenylate cyclase activity declined, but a transient retrograde transport of adenylate cyclase activity appeared. In addition, adenylate cyclase activity accumulated in the proximal transected nerve stump during the period when Schwann cell proliferation and the initiation of nerve regeneration both appear. The pattern of response of adenylate cyclase activity to nerve injury suggests that the adenylate cyclase: cAMP system could play some role in peripheral nerve regeneration.


Bursts in the medial geniculate body: a comparison between anesthetized and unanesthetized states in guinea pig.
Thalamic high frequency bursts have long been described under anesthesia and during slow-wave sleep (SWS). More recently, studies in the lateral geniculate nucleus have pointed out that they are also present during waking (W). Here, we compared the bursts recorded in the medial geniculate body of guinea pigs under anesthesia or during periods of W and SWS. The tuning of single units was tested between threshold and 80 dB SPL in two conditions: (1) in restrained, undrugged, non-sleep-deprived guinea pigs (n=101 cells) and (2) under pentobarbital anesthesia (n=53 cells). Off-line analyses allowed us to distinguish single action potentials (APs) from bursts. A burst was defined as a group of APs with an interspike interval < or =4 ms, preceded by a silent period > or =100 ms. We found that auditory thalamus bursts occur in synchronized electroencephalogram states (SWS and anesthesia), but also during W. Although the burst characteristics did not differ among the three states, group data showed that the proportion of bursts within spike trains was the greatest under anesthesia. This observation resulted from two types of effects: (1) the percentage of non-bursting cells was lowest under anesthesia and (2) some cells under anesthesia exhibited up to 90% of bursts, whereas during W or SWS the highest proportion of bursts did not exceed 40%. The presence of these bursts is discussed with regards to the known fluctuations of membrane potential which occur in these various states.


Quo vadis, analytical chemistry?
This paper presents an open, personal, fresh approach to the future of Analytical Chemistry in the context of the deep changes Science and Technology are anticipated to experience. Its main aim is to challenge young analytical chemists because the future of our scientific discipline is in their hands. A description of not completely accurate overall conceptions of our discipline, both past and present, to be avoided is followed by a flexible, integral definition of Analytical Chemistry and its cornerstones (viz., aims and objectives, quality trade-offs, the third basic analytical reference, the information hierarchy, social responsibility, independent research, transfer of knowledge and technology, interfaces to other scientific-technical disciplines, and well-oriented education). Obsolete paradigms, and more accurate general and specific that can be expected to provide the framework for our discipline in the coming years are described. Finally, the three possible responses of analytical chemists to the proposed changes in our discipline are discussed.


Evaluation of ochratoxin A level in human milk in Italy.
In order to estimate the incidence of ochratoxin A (OA) in biological fluids, a study was carried out to determine the concentration of OA in breast milk of donor mothers in Italy. Out of 111 samples, 22 were contaminated in the range 0.1-12 micrograms/kg.


Ten steps for proper peripheral nerve handling during inguinal hernia surgery.
Post-inguinal pain after a hernia surgery is prevalent and can be quite frustrating for the surgeon and patient alike. There are several sources for possible post-operative inguinal pain after a successful hernia repair; however, in the setting where a recurrent inguinal hernia is not present, it is likely related to the nerves in the inguinal canal or pelvis. Chronic inguinal groin pain after hernia repairs have been reported in a high percentage of patients following inguinal hernia surgery despite being one of the most common procedures performed annually in the USA and worldwide. We present ten of the basic concepts utilized by peripheral nerve surgeons to limit nerve injury, which can easily be applied to open inguinal hernia surgery with or without mesh, starting with the firm understanding of the inguinal anatomy to addressing the nerves, meticulous placement of the mesh and the active revision of the surrounding structures and nerve position before closure. Understanding the proper handling of the inguinal nerves during hernia surgery can decrease the incidence of post-operative chronic pain by employing microsurgical concepts to day-to-day surgical procedures and prevent complications in an extensive set of patients.


Mucin-carbohydrate directed monoclonal antibody.
To raise monoclonal antibodies recognizing cancer-associated alterations of the carbohydrate structure of glycoproteins, Balb/c mice were immunized with human colonic cancer cells (LS 180 from ATCC). One of the generated hybridomas produced a monoclonal antibody that bound to the carbohydrate moiety of mucin-type glycoproteins from LS 180. The antibody did not bind to glycoproteins from another colonic cancer cell line, SW 1116, or to glycolipids from any of the colonic cancer cell lines. The antibody bound to ovine and bovine submaxillary mucins (OSM and BSM). NeuAc alpha 2----6Ga1NAc seemed to be involved in the epitope.


Null allele alpha-1 antitrypsin deficiency: case report of the total pleural covering technique for disease-associated pneumothorax.
A 44-year-old woman, who had been diagnosed as having null type alpha-1 antitrypsin (AAT) deficiency, was admitted with right recurrent pneumothorax. She had undergone right visceral pleural strengthening and pleural adhesion-preventing surgery, the total pleural covering technique (TPC), with oxidized regenerative cellulose (ORC). Three years after the operation, she developed left recurrent pneumothorax and underwent left TPC. AAT deficiency is a rare inherited disease in Japan that causes early-onset emphysema and secondary pneumothorax. In addition, null/null phenotype has the highest risk of emphysema and may require lung transplantation. For future lung transplantation, pleural adhesion should be prevented. However, pleurodesis and surgery for pneumothorax generally cause adhesion. TPC with ORC is a surgical treatment for pneumothorax that is done to strengthen visceral pleura and prevent pleural adhesions. The patient has had no recurrence of pneumothorax 3.5 years after right TPC and 6 months after left TPC.


Impact of biochemical failure on overall survival after radiation therapy for localized prostate cancer in the PSA era.
To study the impact of biochemical failure on overall survival rates during the first 10 years after definitive radiotherapy for localized prostate cancer. The analysis was performed on 936 cases treated at a single institution between 1986 and 1998 with definitive radiotherapy. The median age of treatment was 69 years (range: 46-86 years). Pretreatment PSA levels (iPSA) and biopsy Gleason scores (bGS) were available for all cases. The clinical stage was T1/T2A in 63%, T2B/C in 27%, and T3 in 10%. The median iPSA level was 9.6 ng/mL (range: 0.4-692.9 ng/mL). The iPSA was < or =10 in 53% and >10 in 47%. The bGS was < or =6 in 59% and > or =7 in 41%. Androgen deprivation (AD) was administered in 181 cases (19%) for a median duration of 6 months (range: 1-6 months). All 181 cases received AD neoadjuvantly, i.e., before and/or during the radiotherapy. No AD was delivered after the completion of radiation. The median radiation dose was 70 Gy (range: 60-78 Gy). The radiotherapy technique was conformal in 376 (40%) cases. The American Society of Therapeutic Radiology and Oncology definition of biochemical failure (bF) was used; 316 cases (34%) had failed biochemically, and 620 (66%) had not. The end point was overall survival (OS). Time to death was determined from the time of definitive radiotherapy. The median PSA follow-up was 58 months. The median follow-up times for bF vs. no-bF cases were 77 and 49 months, respectively. A multivariate analysis of factors affecting OS using the proportional hazards model was performed for all cases using the following variables: age (>65 vs. < or =65 years), race (African-American vs. Caucasian), clinical T stage (T1-2A vs. T2B-C vs. T3), bGS (< or =6 vs. 7 vs. > or =8), iPSA (continuous variable), use of AD (yes vs. no), year of therapy (continuous variable), radiation dose (continuous variable), radiation technique (conformal vs. standard), and biochemical failure (yes vs. no). The 5-year OS rate for the entire group was 89% (95% CI [confidence interval]: 86-91%). The 5-year OS rates for bF vs. no-bF patients were 89% (95% CI: 86-93%) and 89% (95% CI: 86-92%), respectively. The 10-year OS rate for the entire group was 68% (95% CI: 61-75%). The 10-year OS rates for bF vs. no-bF patients were 65% (95% CI: 56-74%) and 77% (95% CI: 69-84%), respectively. The difference between bF and no bF was not significant in predicting overall survival in univariate analysis (log-rank test, p = 0.68). On multivariate analysis, bGS (p < 0.001), T stage (p = 0.003), radiation dose (p = 0.017), year of therapy (p = 0.031), and age (p = 0.020) were independent predictors of death. iPSA levels (p = 0.33), race (p = 0.80), radiation technique (p = 0.16), and use of AD (p = 0.09) were not predictive of OS. Biochemical failure (p = 0.052) showed only a trend for independently predicting overall survival on multivariate analysis. Biochemical failure after definitive radiotherapy for localized prostate cancer is not associated with increased mortality within the first 10 years after initial therapy, although a trend toward worse outcome was observed at 10 years. Longer follow-up from initial therapy is needed to fully understand the impact of biochemical failure on overall survival. With longer follow-up, significant differences might be observed at 15 or 20 years after therapy.


Acute Effects of Tissue Flossing Around the Upper Thigh on Neuromuscular Performance: A Study Using Different Degrees of Wrapping Pressure.
It has been recently demonstrated that tissue flossing around the ankle joint can be effectively used to improve ankle range of motion, jump, and sprint ability. However, there is a lack of studies investigating the acute effects of tissue flossing applied using different wrapping pressures. To investigate the acute effects of tissue flossing and the degree of floss band pressure, around the upper thigh on knee range of motion, strength, and muscle contractile characteristics. Crossover design in 3 distinct sessions. University laboratory. A total of 19 recreationally trained volunteers (age 23.8[4.8] y) participated in this study. Active knee extension and flexion performed for 3 sets of 2 minutes (2-min rest between sets with wrapped upper thigh). Individualized wrapping pressures were applied to create conditions of high and moderate vascular occlusion, while a loose band application served as a control condition. Participants were assessed for active straight leg raise test; tensiomyography displacement and contraction time for rectus femoris, vastus medialis, and biceps femoris muscles; and maximum voluntary contractions for knee extensors and flexors for pre, after, and 30 minutes after applying the floss band. There was a statistically significant increase in maximum voluntary contractions for knee extensors and a significant shortening in rectus femoris contraction time for the moderate condition, which was associated with small to medium effects in favor of the moderate condition. There were no statistically significant changes observed between control and high conditions. The active straight leg raise test was unaffected regardless of intervention. The results of this study suggest that tissue flossing around the upper thigh might have a localized as well as pressure-sensitive response, thereby improving neuromuscular function of the knee extensors.


Human embryonic stem cells derived from abnormal blastocyst donated by polycystic kidney syndrome patient.
Human embryonic stem cell (hESC) line chHES-468 was derived from abnormal blastocyst donated by polycystic kidney syndrome (PKD) patient after preimplantation genetic diagnosis (PGD) treatment. DNA sequencing analysis confirmed that chHES-468 cell line carried a heterozygous mutation, c.10526_10527delAG, of PKD1. Characteristic tests proved that the chHES-468 cell line presented typical markers of pluripotency and had the capability to form the three germ layers both in vitro and in vivo.


CRISPR-based engineering of phages for in situ bacterial base editing.
Investigation of microbial gene function is essential to the elucidation of ecological roles and complex genetic interactions that take place in microbial communities. While microbiome studies have increased in prevalence, the lack of viable in situ editing strategies impedes experimental progress, rendering genetic knowledge and manipulation of microbial communities largely inaccessible. Here, we demonstrate the utility of phage-delivered CRISPR-Cas payloads to perform targeted genetic manipulation within a community context, deploying a fabricated ecosystem (EcoFAB) as an analog for the soil microbiome. First, we detail the engineering of two classical phages for community editing using recombination to replace nonessential genes through Cas9-based selection. We show efficient engineering of T7, then demonstrate the expression of antibiotic resistance and fluorescent genes from an engineered λ prophage within an Escherichia coli host. Next, we modify λ to express an APOBEC-1-based cytosine base editor (CBE), which we leverage to perform C-to-T point mutations guided by a modified Cas9 containing only a single active nucleolytic domain (nCas9). We strategically introduce these base substitutions to create premature stop codons in-frame, inactivating both chromosomal (lacZ) and plasmid-encoded genes (mCherry and ampicillin resistance) without perturbation of the surrounding genomic regions. Furthermore, using a multigenera synthetic soil community, we employ phage-assisted base editing to induce host-specific phenotypic alterations in a community context both in vitro and within the EcoFAB, observing editing efficiencies from 10 to 28% across the bacterial population. The concurrent use of a synthetic microbial community, soil matrix, and EcoFAB device provides a controlled and reproducible model to more closely approximate in situ editing of the soil microbiome.


Similar COVID-19 incidence to the general population in people with opioid use disorder receiving integrated outpatient clinical care.
During the COVID-19 pandemic, limited access to health care augmented COVID-19 risk in subjects with opioid use disorder (OUD). The aim of the study was to compare COVID-19 incidence in individuals with OUD receiving continuous clinical care with that of the general population. A prospective cohort study was carried out from March 2020 to March 2021 comparing COVID-19 cumulative incidence of individuals presenting an OUD receiving integrated clinical care with that of an age-reference general population, in three public outpatient treatment centers for addiction in Barcelona, Spain. Over the study period, 366 individuals received clinical care. Mean age: 48.2±8.9 years, 280 (76.5%) were men and 283 (77.3%) native Spanish. All subjects were on opioid agonist therapy. Prevalence of communicable diseases were: HIV infection in 109 (29.8%) and hepatitis C in 46 (12.6%). Psychiatric comorbidity was present in 207 (56.6%), and 119 (32.5%) had >1 chronic medical disease. a cumulative incidence of 2,732 casesx100,000 people/year (C.I.95%: 1,318-4,967). There were no differences compared to the age-general population: 2,856 casesx100,000 people/year (C.I.95%: 2,830-2,880) (p=0.81). In the bivariate analysis, hypertension (5[50.0%] vs. 53[14.9%], p=0.01) and cardiovascular chronic diseases (2 [20.0%] vs. 8 [2.2%], p=0.03) were more prevalent in patients with OUD and COVID-19. Individuals with OUD who received integrated clinical care had a COVID-19 incidence comparable to the general population. Ensuring comprehensive healthcare is essential to prevent the clinical impact of COVID-19 on individuals with OUD.


Involvement of SREBPs in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced disruption of lipid metabolism in male guinea pig.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has multiple toxic effects causing a wasting syndrome characterized by a loss of body weight accompanied by a decrease in adipose tissue weight. To elucidate the mechanism behind this syndrome, we investigated the changes in lipid metabolism 7 and 21 days after a single intraperitoneal injection of TCDD at 1 microg/kg body weight to male guinea pigs. TCDD caused the symptoms of the syndrome, body weight loss with a decrease in adipose tissue weight, while it increased the levels of triacylglycerols, total cholesterols, and free fatty acids in plasma. On day 7, TCDD decreased the levels of CCAAT/enhancer binding protein (C/EBP) alpha, peroxisome proliferator activated receptor gamma, and glucose transporter 4, adipogenesis-related factors, in adipose tissue, whereas the levels of retinoid X receptor alpha, C/EBPbeta, C/EBPdelta, and c-Myc remained unchanged. TCDD also reduced the levels of both p125 precursor and p68 active forms of sterol regulatory element binding protein (SREBP)-1 and -2, the lipogenesis-related factors, and downregulated their DNA binding activity in adipose tissue, while it raised the levels of their p68 active forms and increased their DNA binding activity in the liver. TCDD decreased mRNA and protein levels of acetyl-CoA carboxylase and HMG-CoA synthase in the liver and adipose tissue. Similar results were obtained on day 21. These results suggest that TCDD disrupts lipid metabolism through changes in the expression levels of the adipogenesis-related and lipogenesis-related proteins in the liver and adipose tissue, and SREBPs would be involved in the development of the wasting syndrome.


Periostin plays a key role in maintaining the osteogenic abilities of dental follicle stem cells in the inflammatory microenvironment.
This study aimed to explore the effect of periostin in the osteogenic abilities of dental follicle stem cells (DFSCs) and DFSC sheets in the inflammatory microenvironment. DFSCs were isolated from dental follicles and identified. A lentiviral vector was used to knock down periostin in DFSCs. 250 ng/ml lipopolysaccharide from Porphyromonas gingivalis (P.g-LPS) was used to construct the inflammatory microenvironment. Osteogenic differentiation was evaluated by alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot. The formation of extracellular matrix was assessed by qRT-PCR and immunofluorescence. The expressions of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) were measured by western blot. Knockdown of periostin inhibited osteogenic differentiation and promoted adipogenic differentiation of DFSCs. In an inflammatory microenvironment, knockdown of periostin attenuated the proliferation and osteogenic differentiation of DFSCs. Knockdown of periostin inhibited the formation of extracellular matrix collagen I (COL-I), fibronectin, and laminin in DFSC sheets, but did not affect the expression of osteogenesis-related markers alkaline phosphatase (ALP) and osteocalcin (OCN). In the inflammatory microenvironment, knocking down periostin inhibited the expression of OCN and OPG in DFSC sheets, and promoted the expression of RANKL. Periostin played a key role in maintaining the osteogenic abilities of DFSCs and DFSC sheets in the inflammatory microenvironment and might be an important molecule in the process of DFSCs coping with inflammatory microenvironment and promoting periodontal tissues regeneration.


Molecular cloning of porcine alpha 1-microglobulin/HI-30 reveals developmental and tissue-specific expression of two variant messenger ribonucleic acids.
A 1008 basepair (bp) cDNA clone encoding 335 amino acids followed by an inframe TGA translation termination codon and a 295-nucleotide 3' untranslated (UT) region has been isolated from a pig liver cDNA library. Based on the deduced amino acid and nucleotide sequence homology to a human cDNA (Kaumeyer, J.F., Polazzi, J.O. and Kotick, M.P. (1986) Nucleic Acids Res. 14, 7839-7850), the 5' amino terminus was found to code for alpha 1-microglobulin (alpha 1-M), a 183 amino acid protein belonging to the lipocalin protein superfamily (Pervaiz, S. and Brew, K. (1985) Science 228, 335-337). The 3' half encoded HI-30 which constitutes the Kunitz-type proteinase inhibitory (L-chain) domain of porcine inter-alpha-trypsin inhibitor (I alpha TI). In Northern blot hybridization, this cDNA identified two equally abundant mRNA species of approx. 1.3 kb and 1.6 kb in length. However, a 125 bp cDNA probe derived from the 3' UT region of the cDNA hybridized only to the 1.6 kb mRNA. The differences observed in the 3' UT region of these mRNAs suggest the utilization of alternative polyadenylation signals or presence of unprocessed nuclear RNA. Densitometric scanning of Northern blots indicated that alpha 1-M/HI-30 mRNA levels were higher (5-8-fold) in fetal and neonatal liver compared to that of primiparous pigs. In contrast, the RNA levels did not change significantly during pregnancy. Dot blot analysis of RNA indicated liver to be the major site of alpha 1-M/HI-30 mRNA expression with lower levels observed in the stomach. The results suggest that modulation of alpha 1-M/HI-30 gene expression could play a role during porcine growth. Increased I alpha TI L-chain mRNA levels may be particularly important in fetal and neonatal development when regulation of the inflammatory response and protection of macromolecules from proteolytic degradation is vital to survival and sustained growth.


PELE: Protein Energy Landscape Exploration. A Novel Monte Carlo Based Technique.
Combining protein structure prediction algorithms and Metropolis Monte Carlo techniques, we provide a novel method to explore all-atom energy landscapes. The core of the technique is based on a steered localized perturbation followed by side-chain sampling as well as minimization cycles. The algorithm and its application to ligand diffusion are presented here. Ligand exit pathways are successfully modeled for different systems containing ligands of various sizes: carbon monoxide in myoglobin, camphor in cytochrome P450cam, and palmitic acid in the intestinal fatty-acid-binding protein. These initial applications reveal the potential of this new technique in mapping millisecond-time-scale processes. The computational cost associated with the exploration is significantly less than that of conventional MD simulations.


Determination of 33 elements in scalp hair samples from inhabitants of a mountain village of Tonglu city, China.
Hair samples from 190 relatively healthy 20- to 98-year-old volunteers from a mountain village of Tonglu city (Zhejiang province, China) were analyzed to determine the contents of 33 chemical elements (Ag, Al, As, Au, B, Ba, Be, Ca, Cd, Co, Cr, Cs, Cu, Fe, Ga, Hg, Li, Mg, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sr, Th, Ti, Tl, U, V, Zn, and Zr) with the aim of assessing preliminary reference values. Mean values, median values, ranges and selected percentiles of all element concentrations in scalp hair are presented. By comparing data from different countries, it was determined that the mean concentrations of the majority of elements in our study clearly differed from the mean levels reported in the literature. The effects of gender and age on element concentrations were also investigated. Significant differences that were correlated with age and gender were determined for certain elements. For example, Fe exhibited a mean value of 11.26mg/kg for males and 4.37mg/kg for females. An age-dependent pattern for Fe was also apparent when the two age subgroups of 20-59 and 60-98 years were compared.


A scoping review of regenerative medicine in medical education.
Stem cell therapeutics and regenerative medicine have taken a strong foothold in biomedicine. However, most physicians are currently not adequately prepared to identify, refer, and deliver safe regenerative therapies. To understand this gap, we sought to characterize published literature on current physician training in regenerative medicine. Our scoping review describes current training strategies to bridge the gap and integrate such education into medical curricula for adequate training.


Integrated healthscape strategies: an ecological approach to evidence-based design.
This paper explores some of the premises of evidence-based design (EBD) and suggests that greater attention to and differentiation of the various purposes of research are needed, along with the development of an ecological theory that reflects the complexity of the health systems studied and more varied ways to communicate with and engage practitioners. Problems with the American healthcare system are well known. For the past 20 years, an intervention that has gained increasing attention has been the physical design of healthcare facilities-hospitals in particular. EBD has been advocated as one means of using research to examine the relationship between design and healthcare to improve patient safety and the quality of care. The concept of integrated healthscape strategies is proposed to focus not only on research "evidence" and the methods used to collect and analyze it, but also on the different purposes research serves, the role of theory, and the use of EBD research in practice.


Taxonomy and Distribution of Trichoptera in El Harrach Wadi (Northcentral Algeria) with the First Record of Hydropsyche incognita in North Africa.
Data on the caddisfly fauna of Algeria are incomplete and the available information concerns only some regions. In the present contribution, new distribution data on Trichoptera in El Harrach Wadi are given. Sampling campaigns were conducted during 20102013 at 10 sampling sites where eleven species were collected as follows: Hydropsyche fezana Navs 1935, H. incognita Pitsch 1993, H. lobata McLachlan 1884, H. maroccana Navs 1936, H. obscura Navs 1928, H. resmineda Malicky 1977, Hydropsyche sp., Cheumatopsyche sp., Diplectrona sp., Oxyethira sp., and Rhyacophila munda McLachlan 1862. The record of H. incognita Pitsch 1993a is new for Algeria and the Maghreb.


Metabolic responses to temperature change in a tropical freshwater copepod (Mesocyclops brasilianus) and their adaptive significance.
Metabolic rates of Mesocyclops brasilianus from Lake Valencia, Venezuela, were determined at several temperatures spanning the environmental range (22-28° C). The QO2's (oxygen consumption per unit weight) of all Mesocyclops stages from Lake Valencia are higher than most but not all QO2's from temperate copepod species that have been studied. The QO2 is essentially static through naupliar development and shows a sudden jump between N6 and CI, which probably results from the major change in morphology and behavior at this point in the life history. QO2 declines steadily between CI and adult stages. Acclimated copepodite and adult Mesocyclops show a decreasing metabolic rate with increasing temperature (i.e. Q10< 1.0) over the temperature range 26-28° C. This is the range of temperatures normally encountered during the daily vertical migration when the lake is thermally stratified (April-November). Since vertical migration would result in a compromise between a fully acclimated and an acute response, a nearly constant metabolic rate or a slight decline in metabolic rate in the warmer water would be expected in field populations. The results thus show that the metabolic rate of Mesocyclops is not reduced when it moves into deeper (cooler) water, as would be predicted by certain energy-based hypotheses that have been used to explain vertical migration. In contrast to the low Q10's between 26 and 28° C, copepodites and adults have very high Q10 values in the range 22-26° C. This indicates an adaptive decrease in metabolic rate which is thermally programmed to coincide with the cooler temperatures that are encountered during the mixing season (December-March), when a drastic change in ecological conditions occurs in the lake.Nauplii show evidence of the same seasonal response but without the superimposed plateau at high temperatures, which they would not need because they are weak migrators. Nauplii show a plateau at the lowest temperatures, however, which suggests that a fixed metabolic reduction occurs at the onset of mixing and metabolism is not altered thereafter with declining temperature.The change in QO2 with temperature generally supports the hypothesis that all Mesocyclops stages are adapted to hold a high, constant metabolic rate through the diel cycle but experience a seasonal reduction in metabolic rate in response to major ecological changes in the lake at the time of seasonal mixing.


Combined-modality therapy for patients with regional nodal metastases from melanoma.
To evaluate the outcome and patterns of failure for patients with nodal metastases from melanoma treated with combined-modality therapy. Between 1983 and 2003, 466 patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. Surgery was a therapeutic procedure for clinically apparent nodal disease in 434 patients (regionally advanced nodal disease). Adjuvant radiation was generally delivered with a hypofractionated regimen. Adjuvant systemic therapy was delivered to 154 patients. With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The actuarial 5-year disease-specific, disease-free, and distant metastasis-free survival rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year actuarial disease-specific and distant metastasis-free survival. Also, the number of involved lymph nodes was associated with the development of brain metastases, whereas thickness was associated with lung metastases, and primary ulceration was associated with liver metastases. The actuarial 5-year regional (in-basin) control rate for all patients was 89%, and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The risk of lymphedema was highest for those patients with groin lymph node metastases. Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of distant metastases and melanoma death remains high. A management approach to these patients that accounts for the competing risks of distant metastases, regional failure, and long-term toxicity is needed.


[Cyclosporine-induced follicular eruption].
Cyclosporine is one of the immunosuppressant agents most widely used in the prevention and treatment of organ transplant rejection and also in autoimmune diseases. Many cutaneous side effects have been described with oral cyclosporine, mainly in transplant recipients, for example, hypertrichosis, gingival hyperplasia and viral skin infections. Here, we report an unusual follicular eruption induced by this drug. A 22-year-old man presenting cystic fibrosis received a double-lung graft in January 2005. Six weeks later, he developed a subacute eruption of follicular papules, not highly pruritic, located mainly on the trunk, the extensor surfaces of the limbs and the face. Diagnosis of cyclosporine-induced follicular eruption was adopted on the basis of the histological and microbiological findings. Complete regression was obtained after switching to tacrolimus. Three similar cases were previously reported characterized by typical follicular changes different from those observed in hypertrichosis or pilar keratosis. This rare cutaneous side effect may be explained by the direct action of cyclosporine on the pilosebaceous unit: this drug is known to extend the anagen phase of the follicular cycle and to induce toxic follicular dystrophy at higher tissue concentrations. This particular toxicity is usually seen after many months of treatment. In our patient, the time to onset was shorter, probably due to occasionally excessive plasma concentrations.


Low-frequency electromagnetic fields do not alter responses of inflammatory genes and proteins in human monocytes and immune cell lines.
The effects of low frequency electromagnetic fields (LF EMF) on human health are the subject of on-going research and serious public concern. These fields potentially elicit small effects that have been proposed to have consequences, either positive or negative, for biological systems. To reveal potentially weak but biologically relevant effects, we chose to extensively examine exposure of immune cells to two different signals, namely a complex multiple waveform field, and a 50 Hz sine wave. These immune cells are highly responsive and, in vivo, modulation of cytokine expression responses can result in systemic health effects. Using time course experiments, we determined kinetics of cytokine and other inflammation-related genes in a human monocytic leukemia cell line, THP-1, and primary monocytes and macrophages. Moreover, cytokine protein levels in THP-1 monocytes were determined. Exposure to either of the two signals did not result in a significant effect on gene and protein expression in the studied immune cells. Also, additional experiments using non-immune cells showed no effects of the signals on cytokine gene expression. We therefore conclude that these LF EMF exposure conditions are not expected to significantly modulate innate immune signaling.


Facial affect recognition and schizotypal personality characteristics.
Deficits in facial affect recognition are well established in schizophrenia, yet relatively little research has examined facial affect recognition in hypothetically psychosis-prone or 'schizotypal' individuals. Those studies that have examined social cognition in psychosis-prone individuals have paid little attention to the association between facial emotion recognition and particular schizotypal personality features. The present study therefore sought to investigate relationships between facial emotion recognition and the different aspects of schizotypy. Facial affect recognition accuracy was examined in 50 psychiatrically healthy individuals assessed for level of schizotypy using the Schizotypal Personality Questionnaire. This instrument provides a multidimensional measure of schizophrenia proneness, encompassing 'cognitive-perceptual', 'interpersonal' and 'disorganized' features of schizotypy. It was hypothesized that the cognitive-perceptual and interpersonal aspects of schizotypy would be associated with difficulties identifying facial expressions of emotion during a forced-choice recognition task using a standardized series of colour photographs. As predicted, interpersonal aspects of schizotypy (particularly social anxiety) were associated with reduced accuracy on the facial affect recognition task, but there was no association between affect recognition accuracy and cognitive-perceptual features of schizotypy. These results suggest that subtle deficits in facial affect recognition in otherwise psychiatrically healthy individuals may be related to the vulnerability for interpersonal communication difficulties, as seen in schizophrenia.


Supply chain security evaluation model and index system based on a 5G information system.
Currently, the supply chain management model has been widely adopted worldwide. Internationally renowned companies such as IBM and Walmart have made significant achievements in supply chain management and have played a greater role in promoting the growth of their interests. However, while they are enjoying their own interests, they are also facing various risks in the supply chain. From the perspective of systems engineering, this paper uses complex network theory as a research tool to study supply chain networks and systematically study the important issues of supply chain network risks. This paper analyzes the new characteristics of the relationship between enterprises and suppliers in the supply chain and which indicators should be selected as the basis for evaluating suppliers from the perspective of cooperation and development, which more comprehensively reflects the characteristics of the new enterprise-supplier relationship in the supply chain environment. This highlights the evaluation of the supplier's cooperation ability and development ability. Aiming at the problem of supply chain network system identification and integrated evaluation, a supply chain security evaluation model and index system research framework model are proposed, and the intercompany business risk and supply chain in supply chain network evaluation are introduced. As a model for evaluating transition parameters, the study of supply chain risk propagation introduces the theory of dynamic propagation in complex networks, the law of evolution, and the supplier's dynamic supply chain risk model. The experimental results of this paper show that when the global reputation value is 0.5 and the local reputation value is 0.8 and 0.7, the trust degree changes with the change of the confidence factor; when the value of the confidence factor decreases, the degree of trust converges more and more to the global reputation and vice versa. It can be seen that this model has high feasibility.


Long-term opioid medication profile of European adult spinal deformity patients: minimum five years follow-up study.
There remains significant variability in the use of postoperative opioids. On one end, it is proven that appropriate pain control is a critical aspect of patient management; on the other end, past few decades have been associated with major increases in opioid-related overdoses and addiction treatment. We hypothesized that several pre- and postoperative risk factors affecting long-term opioid use could be identified. Evaluation of factors associated with minimum 5-year postoperative opioid use following adult spinal deformity surgery. Prospectively followed study group database. Adult spinal deformity patients who underwent elective spine surgery between 2009 and 2016 were included. Opioid usage or otherwise at minimum 5 years follow-up. Use of nonopioid analgesics, weak and strong opioids METHODS: Retrospective analysis of patients undergoing elective spinal deformity surgery. A total of 37 factors comprising patient characteristics, radiographic measurements, operative details, preoperative and early postoperative opioid use, and mechanical complications and revisions were analyzed. Details on identified factors were provided. A total of 265 patients (215F, 50M) from five sites were included. The mean follow-up duration was 68.4±11.7 (60-102) months. On average, 10.6±3.5 levels were fused. Preoperatively, 64 (24.2%) patients were using opioids. The rate of opioid users increased to 33.6% at 6 weeks and decreased to 21.5% at 6 months. During follow-up, there were patients who discontinued opioids, while others have started and/or restarted using opioids. As a result, 59 (22.3%) patients were still on opioids at the latest follow-up. Multivariate analyses showed that factors independently affecting opioid use at an average of 68 months postoperatively, in order of significance, were opioid use at sixth weeks, preoperative opioid use and opioid use at sixth months with the odds ratios of 2.88, 2.51, and 2.38 respectively. At these time points, factors such as age, number of comorbidities, tobacco use, the time of the last prior spine surgery and postoperative sagittal plane alignment affected opioid usage rates. Opioid usage at 6 weeks was found to be more predictive of long-term opioid use compared to preoperative use. Patients should be well informed to have realistic expectations regarding opioid use when considering adult spinal deformity surgery.


Blockade of sodium-glucose cotransporter 2 suppresses high glucose-induced angiotensinogen augmentation in renal proximal tubular cells.
Renal proximal tubular angiotensinogen (AGT) is increased by hyperglycemia (HG) in diabetes mellitus, which augments intrarenal angiotensin II formation, contributing to the development of hypertension and kidney injury. Sodium-glucose cotransporter 2 (SGLT2) is abundantly expressed in proximal tubular cells (PTCs). The present study investigated the effects of canagliflozin (CANA), a SGLT2 inhibitor, on HG-induced AGT elevation in cultured PTCs. Mouse PTCs were treated with 5-25 mM glucose. CANA (0-10 µM) was applied 1 h before glucose treatment. Glucose (10 mM) increased AGT mRNA and protein levels at 12 h (3.06 ± 0.48-fold in protein), and 1 and 10 µM CANA as well as SGLT2 shRNA attenuated the AGT augmentation. CANA did not suppress the elevated AGT levels induced by 25 mM glucose. Increased AGT expression induced by treatment with pyruvate, a glucose metabolite that does not require SGLT2 for uptake, was not attenuated by CANA. In HG-treated PTCs, intracellular reactive oxygen species levels were elevated compared with baseline (4.24 ± 0.23-fold), and these were also inhibited by CANA. Furthermore, tempol, an antioxidant, attenuated AGT upregulation in HG-treated PTCs. HG-induced AGT upregulation was not inhibited by an angiotensin II receptor antagonist, indicating that HG stimulates AGT expression in an angiotensin II-independent manner. These results indicate that enhanced glucose entry via SGLT2 into PTCs elevates intracellular reactive oxygen species generation by stimulation of glycolysis and consequent AGT augmentation. SGLT2 blockade limits HG-induced AGT stimulation, thus reducing the development of kidney injury in diabetes mellitus.


Effect of sulphonate incorporation on in vitro leucocyte adhesion to polyurethanes.
A series of poly(tetramethylene oxide)-based polyurethane block copolymers was synthesized with varying levels of sulphonate ion incorporated in the hard segment block. Static in vitro adhesion of polymorphonuclear leucocytes (PMNs) on the underivatized and propyl sulphonate-grafted polyurethanes was investigated. The effect of plasma proteins on PMN adhesion to the polymers was also examined. The number of adherent cells on the sulphonated polyurethane surfaces was significantly higher than on the underivatized polyurethane under all conditions. The adherent PMNs on sulphonated polyurethanes showed increased cell spreading compared to the underivatized base polyurethane. Increasing the level of sulphonate incorporation from 5 to 17 mol% had no effect on the extent of cell adhesion. The presence of preadsorbed proteins generally led to a decrease in the number of adherent PMNs on the surfaces. However, the presence of plasma proteins in the suspension medium had no effect on the degree of leucocyte adhesion to the sulphonated polyurethanes.


Pulmonary barotrauma in congenital diaphragmatic hernia: experimental study in lambs.
A left diaphragmatic hernia was created surgically in 20 fetal lambs between 93 and 110 days of gestation. Ten animals were alive with defects at cesarean section near term (135 to 140 days). These animals and two controls were submitted to various transpulmonary pressure gradients (inspiratory pressure minus pleural pressure). Hemodynamic and ventilatory studies were performed after the correction of the hernia. Morphometric analysis of the lung was carried out in all cases. The results showed a highly significant linear correlation between the transpulmonary pressure gradient employed and the pulmonary interstitial emphysema found at morphometry. Our data suggest that using low ventilatory pressures and not draining the pleural cavity results in less trauma to both lungs and may prevent one of the components of the pulmonary hypertension so often seen in newborns with congenital diaphragmatic hernia.


Effects of enalapril on T and B cell function in rats after myocardial infarction.
The cellular mechanisms following myocardial infarction remain poorly characterized. It is believed that an inflammatory and immunologic process may be involved and that the beneficial effects of enalapril on remodeling may, in part, work through an immune mechanism. To characterize the effect of enalapril on immune alterations in the late phase of ventricular remodeling after myocardial infarction, rats underwent left coronary artery ligation followed by 6 weeks of either enalapril or placebo treatment. Infarct sizes, heart weights, and volumes were compared. Peripheral and splenic leukocyte and lymphocyte subsets, along with T cell blastogenesis, were quantified in enalapril treated rats 6 weeks after coronary ligation and compared to untreated control rats. Additionally, antibody production to a de novo antigen, keyhole limpet hemocyanin, was assessed with and without treatment. Average infarct size was equivalent among enalapril-treated myocardial infarction rats and untreated infarct rats. There was, however, less left and right ventricular hypertrophy in the enalapril treated group. Enalapril completely prevented the 42% increase in white blood count, the 88% increase in neutrophils, and the 28% increase in lymphocyte count seen in untreated infarct rats. Both untreated and enalapril treated rats tended toward a decrease in T helper:suppressor ratio. All rats treated with enalapril, however, had a significant increase in the T helper:suppressor ratio versus untreated control rats (F = 3.6, P = .018). Blastogenesis was markedly increased in T cells from infarcted animals. This was mitigated by treatment with enalapril. Additionally, immunoglobulin G antibody production was significantly lessened in rats treated with enalapril. The results of this study suggest that alterations in immunoregulatory cell type and function occurs following myocardial infarction. The beneficial effects of the angiotensin-converting enzyme inhibitor enalapril may be, in part, due to its mitigating effects on immune cell release and activation following myocardial infarction.


3' UTR-dependent, miR-92-mediated restriction of Tis21 expression maintains asymmetric neural stem cell division to ensure proper neocortex size.
Mammalian neocortex size primarily reflects the number and mode of divisions of neural stem and progenitor cells. Cortical stem cells (apical progenitors) switching from symmetric divisions, which expand their population, to asymmetric divisions, which generate downstream neuronal progenitors (basal progenitors), start expressing Tis21, a so-called antiproliferative/prodifferentiative gene. Tis21 encodes a small (17.5 kDa), functionally poorly characterized protein and a relatively large (2 kb), highly conserved 3' UTR. Here, we show that mice lacking the Tis21 3' UTR develop a microcephalic neocortex with fewer neurons, notably in the upper layers. This reflects a progressive decrease in basal progenitors, which in turn is due to a fraction of apical progenitors prematurely switching from asymmetric self-renewing to symmetric self-consuming divisions. This switch is caused by the markedly increased Tis21 protein level resulting from lack of microRNA-, notably miR-92-, dependent restriction of Tis21 expression. Our data show that a premature onset of consumptive neural stem cell divisions can lead to microcephaly.


[The effect of Herba Erigerontis Compound on epithelial dysplasia of leukoplakia and lichen planus].
To explore the effective Chinese medicine to prevent and treat oral precancerous lesions,and study the clinical therapeutic effect of Erigerontis Compound and its cellular dynamic mechanism. Select 45 volunteers suffering from leukoplakia(LK) and lichen planus(LP)who were divided int treatment and control groups. Treatment group(TG) took Herba Erigrontis Compound capsule for 3 months, Control group(CG) received YUN ZHI Polysacchrodepepitide and vitamin A capsule The results of variation of clinical symptoms, histopathology,and proliferative cell nucleic antigen (PCNA) were observed and compared. In 79.2% case the degree of epithelia dysplasia was decreased and the TG was less than that of CG; the positive cell counts of PCNA of TG fewer than that of CG obviously;the symptom of TG lessen. All of these of TG were better than that of CG. Herba Erigerontis Compound Capsule can prevent and treat LK and LP confirmly. Its anticanceration mechanism is to affect actively the cellular dynamics.


Measurement of the temperature inside the rotor of the Airfuge and its operation at low temperature.
A method based on the slow hydrolysis of saccharose allows the temperature inside the revolving centrifuge tubes to be measured with precision. Equipment that enables the instrument to be operated at low temperature is also described.


Concurrent chemoradiotherapy with low dose weekly gemcitabine in medically inoperable muscle-invasive bladder cancer patients.
We aimed to determine the efficacy and the toxicity of low dose weekly gemcitabine with radiation therapy in medically unfit muscle-invasive bladder cancer patients. Twenty-six patients were included into the retrospective analysis. Weekly gemcitabine was administered 75 mg/m(2) with a median dose of 63 Gy radiation therapy. Clinical target volume was defined as the urinary bladder only in conformal treatment planning. Median follow-up was 51 months (range 14-118 months). Complete response rate was 62.5 %. The 5-year local progression-free survival, disease-specific survival and overall survival rates were 40.6, 59.5 and 58.5 %, respectively. Concurrent chemotherapy was continued in 80.7 % of patients without any interruption. Gemcitabine was stopped due to grade 3 thrombocytopenia (n = 1), cardiac angina (n = 1), chronic obstructive pulmonary disease exacerbation (n = 1) or patients' reluctance (n = 2). Low dose weekly gemcitabine with concurrent radiotherapy is a tolerable regimen and have comparable outcomes with platinum-based combined treatments in muscle-invasive bladder cancer. Prospective randomized trials can help in understanding the safety and efficacy of this treatment specially in medically unfit patients.


Severe exercise-induced ischemia does not identify high risk patients with normal left ventricular function and one- or two-vessel coronary artery disease.
This study was conducted to determine whether severe exercise-induced ischemia identifies high risk patients with a normal left ventricular ejection fraction and one- or two-vessel coronary artery disease. Severe ischemia during exercise radionuclide angiography has been shown to identify high risk patients among certain other patient subsets. Four hundred twenty patients with left ventricular ejection fraction > or = 50% and one- or two-vessel disease underwent exercise radionuclide angiography within 3 months of coronary angiography. Patients were treated initially with revascularization (n = 140) or medical therapy (n = 280) at the discretion of their physicians. Patients treated with revascularization were more likely to have angina by history, a positive exercise electrocardiogram, a lower exercise ejection fraction, two-vessel disease and proximal left anterior descending coronary artery disease. Two hundred sixty-four of the 280 patients given medical therapy who had complete follow-up data formed the study group. Outcome was compared between patients with (n = 56) and without (n = 208) severe exercise-induced ischemia, defined by previously published criteria (work load < or = 600 kg-m/min, ST segment depression > or = 1 mm and decrease in ejection fraction with exercise). During follow-up, there were 30 initial cardiac events (12 cardiac deaths and 18 nonfatal myocardial infarctions). There was no difference in the 5-year event-free survival rate: 91% in patients with and 87% in patients without severe ischemia (p = 0.89). There was no association between event-free survival and severe ischemia (chi 2 = 1.41, p = 0.24). The study had approximately 80% power at alpha = 0.05 to detect a 25% decrease in event-free survival in the group with severe ischemia. In addition, there was no association between severe ischemia and outcome if late revascularization was included as an event or if the total mortality rate (overall survival) was analyzed. Severe exercise-induced ischemia fails to identify a high risk subgroup among patients with normal left ventricular function and one- or two-vessel disease who are treated initially with medical therapy.


SPECT using Bremsstrahlung to quantify 90Y uptake in Baker's cysts: its application in radiation synovectomy of the knee.
The use of SPECT with Bremsstrahlung radiation has been investigated in studies on patients undergoing 90Y therapy for persistent synovitis of the knee. In particular, its value in the estimation of 90Y uptake into Baker's cysts was assessed and, to this end, realistic 'knee phantoms' were employed in order to calibrate for cysts of different size. Problems associated with the measurement of the extensive Bremsstrahlung spectrum and the estimation of cyst volume have been discussed. It is shown that, although the apparent volume of a cyst is markedly dependent on the chosen count rate threshold, volumes greater than about 30 ml can be estimated with reasonable accuracy using a threshold of 50%. The uptake of 90Y in cysts, measured on 3 occasions within the first 2 days in 10 patients, showed wide variation (0%-40%) between patients and was poorly related to the size of cysts on arthrograms and to the clinical response to therapy. In these studies, the ability to analyse SPECT slices provided a distinct advantage over planar imaging for discriminating between 90Y uptake in cysts and adjacent sites. Retention of 90Y in the total knee was also widely variable, with losses of 2%-38% observed 2 days after injection which, in general, were not fully accounted for by uptake in liver or lymph nodes. The changing distribution of 90Y colloid in the knee during the first two days, as observed in some patients, might explain part of the discrepancy.


Potency of N6-modified N-alkyl adenosine-5'-uronamides at presynaptic adenosine receptors in guinea-pig ileum.
The ability of a series of N6-modified N-alkyl-5'-uronamides to cause presynaptic inhibition of transmitter release was examined in isolated guinea-pig ileum stimulated at 0.2 Hz. These analogs inhibited the twitch responses to nerve stimulation, the majority being full agonists with their inhibitory effects being antagonised by theophylline. These analogs had no significant effects on responses of ileum to carbachol. N-ethyl 5'-uronamide substitution resulted in an up to four-fold reduction in activity of N6-substituted adenosine analogs, while stereoselectivity of the N6-substituted analogs continued to be present. 5'-Uronamide substitutions to N6-(3-pentyl)-adenosine resulted in a marked loss of activity when there were large alkyl groups at the amide or with amides of secondary amines. It was concluded that adenosine analogs interact with both the N6 and C-5' regions of the adenosine receptor in this tissue, with the interaction being less than additive.


Onabotulinum toxin A for the treatment of sialorrhea in familial dysautonomia.
Familial dysautonomia is a rare disease affecting the nervous system. Symptoms include speech and movement problems, anterior sialorrhea (drooling) due to hypersalivation as a consequence of poor oropharyngeal coordination; dysphagia and aspiration pneumonia secondary to recurrent posterior sialorrhea. The treatment for sialorrhea in this population is very challenging. Traditional drugs carry a number of side-effects that are difficult to control in this disease. We report the first documented case series of 3 patients with this condition that successfully responded to Onabotulinum toxin A injection into their salivary glands. This is an innovative, safe method for drooling control in this population.


Effects of Wii balance board exercises on balance after posterior cruciate ligament reconstruction.
To establish the effects of training on Wii balance board (WBB) after posterior cruciate ligament (PCL) reconstruction on balance. Included patient injured her posterior cruciate ligament 22 months prior to the study. Training on WBB was performed 4 weeks, 6 times per week, 30-45 min per day. Center of pressure (CoP) sway during parallel and one-leg stance, and body weight distribution in parallel stance were measured. Additionally, measurements of joint range of motion and limb circumferences were taken before and after training. After training, the body weight was almost equally distributed on both legs. Decrease in CoP sway was most significant for one-leg stance with each leg on compliant surface with eyes open and closed. The knee joint range of motion increased and limb circumferences decreased. According to the results of this single case report, we might recommend the use of WBB for balance training after PCL reconstruction. Case series with no comparison group, Level IV.


Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Prognostic factors in cancer patients infected with SARS-CoV-2: a Latin American country results.
The aim of this study was to evaluate the demographic characteristics, clinical and pathological factors, and the outcome of cancer and COVID-19 patients in Mexico. A prospective, multicentric study was performed through a digital platform to have a national registry of patients with cancer and positive SARS-CoV-2 test results through reverse transcription quantitative polymerase chain reaction (RT-qPCR). We performed the analysis through a multivariate logistic regression model and Cox proportional hazard model. From May to December 2020, 599 patients were registered with an average age of 56 years with 59.3% female; 27.2% had hypertension. The most frequent diagnoses were breast cancer (30.4%), lymphoma (14.7%), and colorectal cancer (14.0%); 72.1% of patients had active cancer and 23.5% of patients (141/599) were deceased, the majority of which were men (51.7%). This study found that the prognostic factors that reduced the odds of death were gender (OR = 0.42, p = 0.031) and oxygen saturation (OR = 0.90, p = 0.0001); meanwhile, poor ECOG (OR = 5.4, p = 0.0001), active disease (OR = 3.9, p = 0.041), dyspnea (OR = 2.5, p = 0.027), and nausea (OR = 4.0, p = 0.028) increased the odds of death. In the meantime, the factors that reduce survival time were age (HR = 1.36, p = 0.035), COPD (HR = 8.30, p = 0.004), having palliative treatment (HR = 10.70, p = 0.002), and active cancer without treatment (HR = 8.68, p = 0.008). Mortality in cancer patients with COVID-19 is determined by prognostic factors whose identification is necessary. In our cancer population, we have observed that being female, younger, non-COPD, with non-active cancer, good performance status, and high oxygen levels reduce the probability of death.


[Use of positron emission tomography in sarcoidosis].
FDG-PET, now hybrid positron emission tomography/computed tomography (PET-CT), has become an established diagnostic tool in oncology. Fluorodesoxyglucose ((18)F-FDG) is not specific for malignant lesions, as uptake of the tracer depends on its accumulation in cells with an increased glucose metabolism as it is also the case in infectious and inflammatory lesions, like sarcoidosis. Thus, FDG-PET has been proposed for internal medicine indications, one of whom is sarcoidosis. The main characteristics of FDG-PET are its better sensitivity compared to (67)Ga scintigraphy and its ability to be used as an earlier marker of therapeutic response as compared with anatomy-based and conventional scintigraphic imaging. However, FDG-PET should be used in atypical or advanced stage of the disease. Future prospective studies should be awaited before integrating FDG-PET in clinical routine for treatment outcome and disease activity assessment in sarcoidosis. New radiopharmaceutical probes are under development and will improve the performance of PET.


Social-affective functioning and learning in psychopathy.
Psychopathy is a personality construct for which impairments in multiple aspects of social and affective functioning are considered to be central. Individuals with elevated levels of psychopathic traits tend to exhibit maladaptive behaviors that are harmful to themselves and others, and seem to be limited in how they perceive and experience affective states. This chapter provides a brief overview of biopsychological theories and studies of psychopathy targeting impairments in affective processing and behavioral adaptation through learning. Also, current gaps in the literature will be discussed in addition to findings highlighting the need to routinely reexamine the validity and robustness of decades-old views on psychopathy in the light of recent multidisciplinary empirical research. The chapter ends with a short reflection on how alternative views may offer novel insights that may bring significant advances in the study of the biopsychological factors underlying psychopathy.


Malaria vaccines: into a mirror, darkly?
Recent advances in adjuvant and delivery systems, in addition to a wealth of genomic and proteomic information on parasite composition, are being harnessed to develop a malaria vaccine. To do so effectively, it might be necessary to reassess the criteria by which formulations have been selected to progress to clinical trials. Specifically, better in vitro surrogates of protective immunity, better animal models and a more complete understanding of the unique canvas presented by the immune system of individuals who have experienced multiple malaria infections are needed.


Metabolomic profile of human myocardial ischemia by nuclear magnetic resonance spectroscopy of peripheral blood serum: a translational study based on transient coronary occlusion models.
The aim of this study was to investigate the metabolomic profile of acute myocardial ischemia (MIS) using nuclear magnetic resonance spectroscopy of peripheral blood serum of swine and patients undergoing angioplasty balloon-induced transient coronary occlusion. Biochemical detection of MIS is a major challenge. The validation of novel biosignatures is of utmost importance. High-resolution nuclear magnetic resonance spectroscopy was used to profile 32 blood serum metabolites obtained (before and after controlled ischemia) from swine (n = 9) and patients (n = 20) undergoing transitory MIS in the setting of planned coronary angioplasty. Additionally, blood serum of control patients (n = 10) was sequentially profiled. Preliminary clinical validation of the developed metabolomic biosignature was undertaken in patients with spontaneous acute chest pain (n = 30). Striking differences were detected in the blood profiles of swine and patients immediately after MIS. MIS induced early increases (10 min) of circulating glucose, lactate, glutamine, glycine, glycerol, phenylalanine, tyrosine, and phosphoethanolamine; decreases in choline-containing compounds and triacylglycerols; and a change in the pattern of total, esterified, and nonesterified fatty acids. Creatine increased 2 h after ischemia. Using multivariate analyses, a biosignature was developed that accurately detected patients with MIS both in the setting of angioplasty-related MIS (area under the curve 0.94) and in patients with acute chest pain (negative predictive value 95%). This study reports, to the authors' knowledge, the first metabolic biosignature of acute MIS developed under highly controlled coronary flow restriction. Metabolic profiling of blood plasma appears to be a promising approach for the early detection of MIS in patients.


Potentially advanced malignancies detected by screening for prostate carcinoma after an interval of 4 years.
At the Rotterdam branch of the European Randomized Study of Screening for Prostate Cancer, a cohort of 19,970 men ages 55-75 years is screened at an interval of 4 years. Screening includes systematic sextant needle biopsy for men with elevated prostate-specific antigen (PSA) levels and/or positive findings on digital rectal examination or transrectal ultrasound. Detection during the second screening round of a large number of high-grade (Gleason Grade 4 or 5) malignancies and/or a large number of malignancies in general could be considered the result of a failure to identify these malignancies at an early stage, during prevalence screening. Men diagnosed during the second screening round with potentially advanced carcinoma (PAC), characterized by a biopsy Gleason score of 7 (4 + 3, or 3 + 4 with > 30% malignant involvement) or a biopsy Gleason score of 8-10, were identified. Clinical data, including PSA values on prevalence screening, biopsy history, clinical stage, and follow-up data, were retrieved for these patients. Tumor features were further analyzed in radical prostatectomy specimens. During the second screening round, 503 malignancies, including 30 (6.0%) with features of PAC on diagnostic biopsy, were detected in 11,210 patients. Curative treatment was offered to 26 patients. Prostatectomy demonstrated the presence of organ-confined disease in 11 of 12 specimens, and tumor volume ranged from 0.11-7.93 cm3 (median, 1.05 cm3). PSA failure was noted in 6 of 22 patients who were offered curative therapy. PAC is a rare finding in the second round of screening after a 4-year interval, and a substantial proportion of PAC cases detected in the second screening round represent organ-confined disease. The findings of the current study suggest that the screening protocol used is sufficiently effective for detecting > 95% of malignancies before they develop features that would make them incurable.


Impact of the Level of Adherence to the DASH Diet on Blood Pressure: A Systematic Review and Meta-Analysis.
Introduction: the objective of our study was to systematically review the current literature and perform a meta-analysis to evaluate the effect of the level of adherence to the DASH diet on blood pressure. Methods: The identification of relevant studies, data extraction and critical appraisal of the included studies were performed independently by two reviewers. A random-effects model was employed to synthesize the available evidence using the standardized mean difference (SMD) as the appropriate effect size. Results: A total of 37 and 29 articles were included in the qualitative and quantitative analysis, respectively. The pooled effect for systolic blood pressure was SMD = -0.18 (95%CI: -0.32 to -0.04; I2 = 94%; PI: -0.93 to 0.57) and for diastolic blood pressure it was SMD = -0.13 (95%CI: -0.19 to -0.06; I2 = 94%; PI: -0.42 to 0.17). Conclusions: Our findings showed that greater adherence to the DASH diet has a beneficial effect on blood pressure compared to the lowest adherence. Increased compliance with DASH diet recommendations might also have a positive effect on cardiometabolic factors and overall health status. Future studies should aim to standardize the tools of adherence to the DASH diet and utilize rigorous study designs to establish a clearer understanding of the potential benefits of the level of adherence to the DASH diet in blood pressure management.


The genomic landscape of swine influenza A viruses in Southeast Asia.
Swine are a primary source for the emergence of pandemic influenza A viruses. The intensification of swine production, along with global trade, has amplified the transmission and zoonotic risk of swine influenza A virus (swIAV). Effective surveillance is essential to uncover emerging virus strains; however gaps remain in our understanding of the swIAV genomic landscape in Southeast Asia. More than 4,000 nasal swabs were collected from pigs in Cambodia, yielding 72 IAV-positive samples by RT-qPCR and 45 genomic sequences. We unmasked the cocirculation of multiple lineages of genetically diverse swIAV of pandemic concern. Genomic analyses revealed a novel European avian-like H1N2 swIAV reassortant variant with North American triple reassortant internal genes, that emerged approximately seven years before its first detection in pigs in 2021. Using phylogeographic reconstruction, we identified south central China as the dominant source of swine viruses disseminated to other regions in China and Southeast Asia. We also identified nine distinct swIAV lineages in Cambodia, which diverged from their closest ancestors between two and 15 B.P., indicating significant undetected diversity in the region, including reverse zoonoses of human H1N1/2009 pandemic and H3N2 viruses. A similar period of cryptic circulation of swIAVs occurred in the decades before the H1N1/2009 pandemic. The hidden diversity of swIAV observed here further emphasizes the complex underlying evolutionary processes present in this region, reinforcing the importance of genomic surveillance at the human-swine interface for early warning of disease emergence to avoid future pandemics.


The midline supra-orbital approach, using a large single free bone flap. Technical note.
Surgical access to the anterior frontal region of the skull base is facilitated by the removal of a fronto-orbital bone flap. This technique was first described as a two-step procedure by Cophignon. We recently devised a simplified one-step approach in which a single bifrontal supra-orbital bone flap is removed. This report is a technical description and resume of our experiences.


Aromatase activity in the breast and other peripheral tissues and its therapeutic regulation.
Studies using [3H]androstenedione (A) demonstrated that this substrate can be aromatized to estrone (E1) in homogenates of breast carcinoma tissue and breast adipose tissue, in breast carcinoma and breast adipose stromal cells in culture, and in cultured adipose stromal cells from sites remote from the tumor. Using cultured breast carcinoma cells, it was shown that estrogen formation was stimulated by cortisol (10(-6) M) and inhibited by endogenous 5 alpha-reduced androgens: 5 alpha-androstene-dione greater than androsterone greater than dihydrotestosterone greater than epiandrosterone greater than 3 alpha- and 3 beta- androstanediol. It was also shown that 19-nortestosterone and 19-norandrostenedione (10(-6) M) inhibited E1 formation by 80%. Progesterone (10(-6) M) had no effect on aromatase activity, while the progestational agent R5020 (10(-6) M) caused a 70% inhibition. These studies emphasize that a variety of compounds can influence aromatase activity and that drugs which are used as aromatase inhibitors in patients with breast carcinoma may have multiple sites of action.


An in vivo model to compare human leukocyte infiltration in carcinoma xenografts producing different chemokines.
In this study we tested whether the pattern of cytokines expressed by human carcinomas could account for a different in vivo recruitment of leukocyte subpopulations as a part of the anti-tumor immune response. Two carcinoma cell lines, SK-OV-3 ovary carcinoma and CALU-3 lung carcinoma, were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence and ELISA for the expression and in vitro production of cytokines with chemotactic, proinflammatory and growth-stimulating activity. Although both cell lines displayed a constitutive expression of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage-CSF (GM-CSF), M-CSF, interleukin (IL-) 1 alpha and IL-8, only CALU-3 cell line expressed IL-10, RANTES (Regulated upon Activation, Normal T Expressed and Secreted) and monocyte-activating protein (MCP)-1. MCP-1 and IL-8 were detected by immunohistochemistry on sections from tumors xenografted in nude mice. To analyze whether the tumor-released cytokines modulate leukocytes in tumor infiltration, we studied the distribution of human peripheral blood leukocytes injected in the proximity of SK-OV-3 and of CALU-3 tumor xenografts. While SK-OV-3 was unable to recruit human leukocytes and appeared to be barely infiltrated by murine CD45+ cells, CALU-3 appeared to be rapidly and heavily infiltrated by human leukocytes which induced tumor necrosis within 18-24 hr.


SMAD4 is essential for generating subtypes of neurons during cerebellar development.
Cerebellum development involves the coordinated production of multiple neuronal cell types. The cerebellar primordium contains two germinative zones, the rhombic lip (RL) and the ventricular zone (VZ), which generate different types of glutamatergic and GABAergic neurons, respectively. What regulates the specification and production of glutamatergic and GABAergic neurons as well as the subtypes for each of these two broad classes remains largely unknown. Here we demonstrate with conditional genetic approaches in mice that SMAD4, a major mediator of BMP and TGFβ signaling, is required early in cerebellar development for maintaining the RL and generating subsets of RL-derived glutamatergic neurons, namely neurons of the deep cerebellar nuclei, unipolar brush cells, and the late cohort of granule cell precursors (GCPs). The early cohort of GCPs, despite being deficient for SMAD4, is still generated. In addition, the numbers of GABAergic neurons are reduced in the mutant and the distribution of Purkinje cells becomes abnormal. These studies demonstrate a temporally and spatially restricted requirement for SMAD4 in generating subtypes of cerebellar neurons.


A new thermo-desorption laser-heating setup for studying noble gas diffusion and release from materials at high temperatures.
A new heating and gas treatment line for Thermo-Desorption Spectrometry (TDS) of noble gases (He, Ne, Ar, Kr, and Xe) is presented. It was built with the primary objective to offer advanced temperature controls and capabilities while working in a cold environment. By choosing a high-power continuous wave laser as the heating source and using a proportional-integral-derivative controller system, TDS of noble gases can now be performed with fast and highly steady heating ramps (e.g., less than 1 °C deviation from the set point for ≤1 °C s-1 ramps). Sample temperature over 2000 °C can also routinely be reached, with limited heating of the sample support and the sample chamber, offering the possibility to have several samples awaiting in the ultra-high vacuum chamber. We also present the development efforts made to increase temperature homogeneity of the heated sample while limiting the contact with the sample holder. Recent results acquired with this TDS setup on krypton thermal diffusion in uranium dioxide (UO2) as a function of O2 additions are also presented as an application example.


Management of gastric lymphoma.
The management of gastric lymphoma is controversial and a wide variety of unimodality or multimodality approaches have been used. The aim of this report is to highlight the variety of treatment regimens deployed, the outcomes achieved and to present a modern management approach for this enigmatic tumour. 42 cases of primary gastric lymphoma managed at one centre over a 15-year period were reviewed. Weight loss (52%), pain (41%) and anorexia (33%) were the most common presenting symptoms. Most patients (86%) had high-grade lymphoma. Primary treatment modalities included surgery (36%), chemotherapy (40%), supportive care only (22%) and H. pylori eradication (2%). Adjuvant therapies included chemotherapy (17%), radiotherapy (7%) and combined chemoradiotherapy (5%). The overall median survival was 53 months, with a five year survival of 46%. In the curative group, the median survival was 75 months and five year survival 58%. Curative surgery or chemotherapy +/- radiotherapy were similarly effective for stage IE and IIE disease. The prognosis for gastric lymphoma is grade- and stage-dependent. With equivalent outcomes for cure in localised gastric lymphoma for surgery and chemotherapy, the latter is preferred in this unit because of gastric preservation, with surgery being reserved for failed medical management or presentations with haemorrhage, perforation or obstruction refractive to steroid therapy.


Early Stage and Locally Advanced Nasopharyngeal Carcinoma Treatment from Present to Future: Where Are We and Where Are We Going?
Nasopharyngeal carcinoma (NPC) is a rare malignancy, endemic in China, that is commonly diagnosed in locally advanced scenarios. Its pathogenesis is strongly associated with Epstein-Barr virus (EBV), an infection for which measuring EBV plasma DNA levels has helped as a prognostic factor guiding treatment options, including a stronger treatment in those with high titers. Additionally, tobacco and alcohol are often implicated in EBV-negative patients. The local disease is treated with radiotherapy alone, preferentially intensity modulated radiotherapy. For locally advanced disease, the backbone treatment is concurrent chemoradiotherapy with the ongoing research dilemma being adding adjuvant chemotherapy or induction chemotherapy. The ongoing research is focused not only on identifying patients that will benefit from adjuvant or induction chemotherapy, but also on identifying the best chemotherapeutic regimen, regimen alternatives to diminish toxicity, the role that immune checkpoint inhibitors play, and the use of molecularly guided treatment targeting patients with NPC whether driven by EBV or tobacco and alcohol. Knowing the precise oncogenesis of NPC not only offers a better understanding of the role that EBV plays in this tumor but also helps create targeted therapies that could potentially block important pathways such as the NF-κB pathway. Much is yet to be done, but the prognosis and management of NPC patients have changed drastically, offering precise treatment methods and excellent control of the disease, even in locally advanced scenarios.


Degradation of nonylphenol polyethoxylates by functionalized Fe3O4 nanoparticle-immobilized Sphingomonas sp. Y2.
In this study, the efficiency of the nonylphenol polyethoxylates (NPEOs)-degrading bacterium Sphingomonas sp. strain Y2 was evaluated, which was immobilized by a novel system composed of polydopamine (PD)-coated Fe3O4 iron nanoparticles (IONPs). The PD-IONPs, with a distinct core-shell structure, relatively uniform size, and high saturation magnetization, were prepared for Y2 immobilization. The performance of Y2 was unaffected by this novel immobilization method, exhibiting 79.5% and 99.9% of NPEOs (500ppm) degradation efficiency at day 1 and 2, respectively. Furthermore, separation and recycling were more readily achieved for immobilized cells as compared to free cells. Immobilized cells retained over 70% of the original degradation activity after 6cycles of utilization. These results suggest that Y2-PD-IONPs can be potentially used for NPEOs-contaminated wastewater bioremediation. Immobilization of Sphingomonas sp. Y2 by functionalized PD-IONPs with easy separation, recycling utilization and high efficiency.


Transposable element expression in tumors is associated with immune infiltration and increased antigenicity.
Profound global loss of DNA methylation is a hallmark of many cancers. One potential consequence of this is the reactivation of transposable elements (TEs) which could stimulate the immune system via cell-intrinsic antiviral responses. Here, we develop REdiscoverTE, a computational method for quantifying genome-wide TE expression in RNA sequencing data. Using The Cancer Genome Atlas database, we observe increased expression of over 400 TE subfamilies, of which 262 appear to result from a proximal loss of DNA methylation. The most recurrent TEs are among the evolutionarily youngest in the genome, predominantly expressed from intergenic loci, and associated with antiviral or DNA damage responses. Treatment of glioblastoma cells with a demethylation agent results in both increased TE expression and de novo presentation of TE-derived peptides on MHC class I molecules. Therapeutic reactivation of tumor-specific TEs may synergize with immunotherapy by inducing inflammation and the display of potentially immunogenic neoantigens.


Relaxation and diffusion of water protons in BDDE cross-linked hyaluronic acid hydrogels investigated by NMR spectroscopy-Comparison with physicochemical properties.
Cross-linked hyaluronic acid (HA) hydrogels are used in many biomedical applications but their characterization in order to distinguish between physicochemical properties is challenging. Longitudinal (T1) and transverse (T2) relaxation times and diffusion coefficient (D) of water protons in diepoxide 1,4-butanediol diglycidyl ether (BDDE)-cross-linked HA hydrogels were analyzed by high-field NMR spectroscopy to distinguish between different physicochemical properties. Hydrogels of different degrees of modification and cross-linking, representing a range of gel content, swelling ability, elastic and viscous behavior were studied, as well as solutions of native HA of different molecular weights. T1, T2 and D were measured for several concentrations of HA and as a function of temperature. D and T1 showed a weak concentration dependence, but did not differ between the hydrogels. T2, dominated by chemical exchange between water protons and exchangeable protons of HA, varied significantly between the different hydrogels and the temperature profiles changed dramatically between different concentrations.


Analysis of closed abdominal injury in pregnant women.
To explore the characteristics of closed abdominal injury in pregnancy women and its treatment. The clinical data of 37 pregnancy patients with closed abdominal injury treated in our hospital from June 1993 to June 2003 were collected and analyzed. All the 37 patients were treated with operation. Among them 2 early pregnancy patients with intestinal rupture and 1 patient with retroperitoneal hematoma were treated under laparoscope; in other 34 pregnancy patients laparotomy was performed. Of the 34 patients 8 used cesarean section because premature separation of placenta and enlarged womb interrupted the management of intra-abdominal organ injury. In the 37 patients 33 (89.1%) were cured, 4 (10.8%) die, postoperative complication rate was 16.2% (6/37). Two patients (5.4%) suffered from abdominal cavity infection, 3 (8.1%) from pulmonary infection, and 1 (2.7%) had multi-organ failure. For pregnancy patients with closed abdominal injury, besides obsteric diseases intra-abdominal injury should be given much attention. Accurate diagnosis and timely treatment can gain the time to save the life of both mother and fetus.


Novel Biocompatible Adhesive for Intrarenal Embedding and Endoscopic Removal of Small Residual Fragments after Minimally Invasive Stone Treatment in an Ex Vivo Porcine Kidney Model: Initial Evaluation of a Prototype.
Residual fragments related to endoscopic intracorporeal lithotripsy are a challenging problem. The impact of residual fragments remains a subject of discussion and growing evidence highlights that they have a central role in recurrent stone formation. Therefore, we developed a novel bioadhesive system for intrarenal embedding and retrieval of residual fragments after endoscopic lithotripsy in an ex vivo porcine kidney model. In a standardized setting 30 human stone fragments 1 mm or less were inserted in the lower pole of an ex vivo porcine kidney model. We assessed the extraction efficacy of flexible ureteroscopy using the bioadhesive system in 15 preparations and a conventional retrieval basket in 15. Outcomes were compared regarding the endoscopic and macroscopic stone-free rate, and overall time of retrieval. Embedding and retrieving the residual fragment-bioadhesive complex were feasible in all trial runs. We observed no adverse effects such as adhesions between the adhesive and the renal collecting system or the instruments used. The stone-free rate was 100% and 60% in the bioadhesive and conventional retrieval groups, respectively (p = 0.017). Mean retrieval time was significantly shorter at 10 minutes 33 seconds vs 36 minutes 56 seconds in the bioadhesive group vs the conventional group (p = 0.001). This novel method involving adhesive based complete removal of residual fragments from the collecting system has proved to be feasible. Our evaluation in a porcine kidney model revealed that this technology performed well. Further tests, including inpatient studies, are required to thoroughly evaluate the benefit and potential drawbacks of bioadhesive based extraction of residual fragments after intracorporeal lithotripsy.


Detection and affinity purification of beta-endorphin precursors using a monoclonal antibody.
A monoclonal antibody to porcine beta-lipotropin has been produced which binds to the N-terminal (gamma-lipotropin) portion of the molecule. The antibody can be used to detect beta-lipotropin as well as other beta-endorphin precursors (predominantly a Mr 38 000 polypeptide) using radiobinding assay or the immunoblotting technique. Purification of the peptides can be readily achieved by affinity chromatography using the monoclonal antibody covalently bound to Sepharose 4B. As the antibody recognises the N-terminal part of beta-lipotropin, it can be used to detect and purify beta-lipotropin and other beta-endorphin precursors in the presence of beta-endorphin.


Catheter ablation of scar based ventricular tachycardia - Procedural characteristics and outcomes.
Ventricular tachycardia (VT) is a major cause of morbidity in patients with cardiomyopathy. Radiofrequency ablation has emerged as the mainstay of the management of recurrent sustained VT in these patients. We describe the clinical characteristics, procedural and medium term outcomes of patients undergoing ablation of scar VT in a tertiary care center in India. This was a single-center descriptive cohort study. All patients who underwent ablation for scar related VT were included. Endpoints were immediate procedural success, procedural complications and recurrence during follow up. A total of 72 patients with scar VT underwent ablation with electroanatomic mapping. Previous myocardial infarction (MI) was the commonest etiology (69.4%) with arrhythmogenic right ventricular cardiomyopathy (ARVC) being the next common (19.4%). Acute procedural success was achieved in 69.4% patients, partial success in 9.7% and failure in 1 patient (1.4%). Outcome was labeled indeterminate in 19.4% who did not undergo post ablation VT induction. Procedural complications were seen in 4%. Follow up data was available in 95% of the patients with a mean follow up of 28.9 ± 22.8 months. At one year, freedom from VT was 83.8% and mortality was 13.2%. Overall mortality during follow up was 22.1% while VT recurrence was seen in 35.3%. Recurrence rate was higher in ARVC as compared to previous MI. Ablation of scar VT has high acute success rates. Ablation is safe with low risk of major complications. Rates of recurrence are higher in patients with ARVC as compared to post MI VT.


Simultaneous assay of pigments, carbohydrates, proteins and lipids in microalgae.
Biochemical compositional analysis of microbial biomass is a useful tool that can provide insight into the behaviour of an organism and its adaptational response to changes in its environment. To some extent, it reflects the physiological and metabolic status of the organism. Conventional methods to estimate biochemical composition often employ different sample pretreatment strategies and analytical steps for analysing each major component, such as total proteins, carbohydrates, and lipids, making it labour-, time- and sample-intensive. Such analyses when carried out individually can also result in uncertainties of estimates as different pre-treatment or extraction conditions are employed for each of the component estimations and these are not necessarily standardised for the organism, resulting in observations that are not easy to compare within the experimental set-up or between laboratories. We recently reported a method to estimate total lipids in microalgae (Chen, Vaidyanathan, Anal. Chim. Acta, 724, 67-72). Here, we propose a unified method for the simultaneous estimation of the principal biological components, proteins, carbohydrates, lipids, chlorophyll and carotenoids, in a single microalgae culture sample that incorporates the earlier published lipid assay. The proposed methodology adopts an alternative strategy for pigment assay that has a high sensitivity. The unified assay is shown to conserve sample (by 79%), time (67%), chemicals (34%) and energy (58%) when compared to the corresponding assay for each component, carried out individually on different samples. The method can also be applied to other microorganisms, especially those with recalcitrant cell walls.


Bowel "dissection" in microvillus inclusion disease.
A preterm male neonate was diagnosed as having microvillus inclusion disease based on the characteristics of histological and ultrastructural findings. The peripheral blood sample also revealed MYO5B mutation. He had been on long-term parenteral nutrition. However, a bowel segment was seen in the baby's diaper during hospitalization when he was 5 months old. Serial abdominal ultrasound demonstrated progressive dissection of the bowel wall with detached mucosa in real-time. Small intestinal epithelia were seen on the histology of the detached bowel segment. He died 2 weeks after the episode; postmortem autopsy showed diffuse detachment of mucosa of small bowels without perforation. This is the first report of an infant with microvillus inclusion disease that presented with bowel "dissection". Weakened adhesion and integrity of intestinal epithelial cells caused by MYO5B mutation was speculated to result in the dissection and detachment of the epithelia of the gastrointestinal tract.


The imidazoline preferring receptor: binding studies in bovine, rat and human brainstem.
The binding of [3H]clonidine to brainstem membrane preparations was studied in an attempt to characterize imidazoline-sensitive, catecholamine-insensitive receptors. Human samples and samples from two animal species were used. [3H]Clonidine binding was always saturable, reversible and specific with a KD value of 6-7 nM. The Bmax values were 45.5 +/- 5.5, 145 +/- 34 and 65 +/- 33 fmol/mg protein in the whole rat medulla oblongata, the nucleus reticularis lateralis region of bovine and that of human, respectively. In the whole rat brainstem we could not demonstrate the presence of [3H]clonidine binding sites that were insensitive to catecholamines. In bovine and human nucleus reticularis lateralis (NRL) preparations, the amount of specifically bound labelled clonidine that was not displaced by an excess of (-)-norepinephrine was 25 and 100%, respectively. Substances that had a structure similar to that of clonidine were able to compete with [3H]clonidine binding within the human NRL. Cirazoline was the most potent to inhibit [3H]clonidine binding although yohimbine was also able to displace binding in the human NRL but with lower apparent affinity. Competition assays with idazoxan stereoisomers clearly showed that this binding was stereospecific. Therefore the human NRL region provides the first model of an homogenous population of imidazoline-preferring, non-alpha-adrenergic membrane receptors.


The effect of chronic protozoan infection by Babesia rodhaini on leukemogenesis in mice.
The effect of chronic infection with the protozoan parasite Babesia rodhaini on the subsequent development of mouse leukemia was investigated in three different murine leukemia-lymphoma model systems: congenital lymphoma (in AKR mice), irradiation-induced lymphoma (in C57BL mice), and Rauscher-virus-induced leukemia in NMRI mice. Leukemia incidence was significantly greater than in controls in Babesia-infected (NMRI strain) mice that had been infected with an adjusted dose of Rauscher leukemia virus.


Modification by glibenclamide of the electrophysiological consequences of myocardial ischaemia in dogs and rabbits.
Glibenclamide has been shown to block ATP-dependent K+ channels in the heart and prevent the shortening of cardiac action potentials caused by hypoxia in vitro. The present study examines the ability of glibenclamide to modify the effect of acute ischaemia on monophasic action potential duration in pentobarbital-anaesthetized rabbits, and on monophasic action potential duration and ventricular fibrillation threshold in pentobarbital-anaesthetized dogs. Left ventricular endocardial monophasic action potential duration was measured using a contact electrode catheter, and ventricular fibrillation threshold was measured by the single pulse method. Ischaemia was produced in rabbits by occluding the circumflex coronary for 5 min and in dogs by occluding the left anterior descending coronary artery for 40 min. In rabbits, glibenclamide (0.3-3 mg/kg, i.v.) had no effect on baseline monophasic action potential duration, but attenuated action potential shortening during ischaemia in a dose-related manner. In dogs, monophasic action potential duration did not shorten during ischaemia in the vehicle group, but tended to increase in the glibenclamide group (0.5 mg/kg, i.v.) both before and during ischaemia (7 +/- 5% and 14 +/- 8%, respectively, NS). Likewise, ventricular effective refractory period was significantly increased by glibenclamide prior to ischaemia (5 +/- 1%). Ventricular fibrillation threshold tended to increase during 40 min of ischaemia in vehicle-treated dogs (40 +/- 29%, NS), but was unchanged during ischaemia in the glibenclamide-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)


Can urodynamic studies predict bladder behaviour changes after artificial urinary sphincter implantation?
To assess whether preoperative urodynamic studies can predict bladder behaviour changes that will necessitate bladder augmentation in patients with neuropathic incontinence after undergoing artificial urinary sphincter (AUS) implantation. We analysed 17 patients, with a mean age of 14.4 years at AUS implantation, who did not undergo bladder augmentation either before or at implantation. All patients were followed at regular intervals before and after implantation. Urodynamic studies were done at least three times before implantation and yearly thereafter. Bladder capacity and compliance were evaluated preoperatively and during the follow up, in order to determine whether these urodynamic measurements could predict the eventual need for bladder augmentation. After a mean follow up of 7.5 years bladder behaviour was unchanged in 11 patients while six required augmentation. In these six patients, normal bladder capacity and compliance decreased from 67 to 39.6% of age expected capacity (AEC) (P=0.004) and from 31.6 to 13.5 ml/cm of water (P=0.001), respectively. Four of the six had no clinical symptoms to suggest the change in bladder behaviour. The differences in the average preoperative and follow up values for both normal bladder capacity (72.4 vs 83.5% of AEC) and compliance (30 vs 33.7 ml/cm of water) were not significant in the non-augmented patients (P=0.2 and P=0.3, respectively). Preoperative normal bladder capacity and compliance were 72% of AEC and 30 ml/cm of water, respectively, in the 11 non-augmented patients and 67% and 31 ml/cm of water in the six patients with augmentation. These differences between the two groups were not significant (P=0.06; P=0.1). Preoperative urodynamic studies do not predict bladder function outcome after AUS implantation. These patients require long-term careful observation to detect any asymptomatic change in detrusor behaviour.


Modulation of linker histones during development in Tetrahymena: selective elimination of linker histone during the differentiation of new macronuclei.
Macronuclei of Tetrahymena thermophila contain a typical H1 which has been shown to be missing from micronuclei. Instead, micronuclei contain three unique polypeptides, alpha, beta, and gamma, which are associated with linker regions of micronuclear chromatin. In this report polyclonal antibodies raised against macronuclear H1 are shown to react with alpha, beta, and gamma by immunoblotting analyses. This result suggests that these polypeptides share some common structural feature(s). Also consistent with this result is the finding that both macro- and micronuclei in growing and mating cells stain positively with H1 antibodies by in situ indirect immunofluorescence. However, these analyses demonstrate that the level of linker histone is greatly reduced in the micronucleus of starved cells and in young macronuclear anlagen. These results are in agreement with earlier biochemical studies and together provide strong evidence that dramatic changes in linker histone accompany nuclear differentiation (and dedifferentiation) in Tetrahymena.


Therapeutic effect of praziquantel against Taeniasis asiatica.
Eight Japanese adult patients infected with Taenia asiatica were treated with a single 600 mg dose of praziquantel. The patients' body weights ranged from 47 to 87 kg (mean 67.1±12.7 kg). All patients expelled the strobila after taking praziquantel, and all of them were free from proglottids the day after praziquantel administration, hence all patients were considered to be cured. No side effects due to praziquantel were noted. Although the number of patients is small, our results indicate that praziquantel is a drug of choice for the treatment of taeniasis asiatica and that a single dose of 7-13 mg/kg (9.3±1.9 mg/kg) is effective.