Rotator cuff muscle function and its relation to scapular morphology in apes.
It is widely held that many differences among primate species in scapular morphology can be functionally related to differing demands on the shoulder associated with particular locomotor habits. This perspective is largely based on broad scale studies, while more narrow comparisons of scapular form often fail to follow predictions based on inferred differences in shoulder function. For example, the ratio of supraspinous fossa/infraspinous fossa size in apes is commonly viewed as an indicator of the importance of overhead use of the forelimb, yet paradoxically, the African apes, the most terrestrial of the great apes, have higher scapular fossa ratios than the more suspensory orangutan. The recent discovery of several nearly complete early hominin scapular specimens, and their apparent morphological affinities to scapulae of orangutans and gorillas rather than chimpanzees, has led to renewed interest in the comparative analysis of human and extant ape scapular form. To facilitate the functional interpretation of differences in ape scapulae, particularly in regard to relative scapular fossa size, we used electromyography (EMG) to document the activity patterns in all four rotator cuff muscles in orangutans and gibbons, comparing the results with previously published data for chimpanzees. The EMG results indicate that the distinctive contributions of each cuff muscle to locomotion are the same in the three ape species, failing to support inferences of differences in rotator cuff function based on relative scapular fossa size comparisons. It is also shown that relative scapular fossa size is not in fact a good predictor of either the relative masses or cross-sectional areas of the rotator cuff muscles in apes, and relative fossa size gives a false impression of the importance of individual cuff muscles to locomotor differences among apes. A possible explanation for the disparity between fossa and muscle size relates to the underappreciated role of the scapular spine in structural reinforcement of the blade.


Muco-cutaneous manifestations in 178 renal transplant recipients.
Mucosal membrane and skin can be affected by immunosuppressive drug(s) and immunosuppression itself. The spectrum of muco-cutaneous lesions can range from malignancy at one end to infection, iatrogenic lesions, and esthetic effects on the other end. In Razi Hospital of Guilan University of Medical Sciences, a cross-sectional study for the detection of muco-cutaneous lesions in 178 renal transplant recipients (RTRs) was conducted from the years 2001 to 2006. Biopsy and skin scraping according to the type of skin lesions were performed. A total of 31 RTRs (25%) had normal skin. Iatrogenic lesions were the most common (70%) followed by infectious lesions (57%), and miscellaneous skin lesions were exhibited by 26% of the patients. Among the iatrogenic skin lesions, gingival hyperplasia was the most common lesion (48%), followed by hypertrichosis and acne. Malignant lesions (biopsy proven) were recorded in seven patients (5%). Four patients were found to have Kaposi's sarcoma, and three patients were identified with basal cell carcinoma. Our results showed that muco-cutaneous lesions are crucial problems with RTRs. Attending physicians must pay close attention to skin care regularly and consider reduction of immunosuppression to a safe level, and patient must have self-checkups.


Application of Tunica Vaginalis Flap for Epispadias Repair in the Epispadias-Exstrophy Complex.
To describe long-term outcomes and experience with the tunica vaginalis flap (TVF) as a tissue augment for complex epispadias repair. A prospectively maintained institutional database was reviewed for patients who underwent epispadias repair with TVF from 2010 to 2021. Evaluation of patient characteristics between those who developed dehiscence or UCF and those who did not was performed via Mann-Whitney U, Kruskal-Wallis, or Fisher's exact test, as appropriate. A total of 47 male patients were identified, of whom, 1 (2.1%) had cloacal exstrophy, 38 (80.9%) had classic bladder exstrophy or a variant, and 8 (17.0%) had epispadias as their primary exstrophy-epispadias complex diagnosis. The median age at epispadias repair was 13 months (IQR 11 - 19). The overall rate of fistula or dehiscence development was 19.1% (9 patients), of whom, 7 developed urethrocutaneous fistulae, 1 dehiscence, and 1 both. Notably, 0 of the 5 patients who had undergone prior epispadias repair and 0 of the 8 patients with a diagnosis of isolated epispadias developed a UCF or dehiscence after repair with TVF. Differences in age at repair, primary EEC diagnosis, prior epispadias repair, pre-repair testosterone, fibrin sealant utilization, closure layers, stent removal time, and bladder capacity at repair were not statistically significant (P>.05) CONCLUSION: Our expanded evaluation indicates that utilization of the tunica vaginalis as an adjunct to epispadias repair may provide durable protection against fistula development in EEC patients who have undergone prior epispadias repair and in primary repair of patients with isolated epispadias.


Use of PARP inhibitors in prostate cancer: from specific to broader application.
Prostate cancer (PC) is one of the major health issues of elderly men in the word. It is showed that there were approximately 1.414 million patients with PC in 2020 worldwide, with a high mortality rate in metastatic cases. In the present choices of treatment in PC, androgen deprivation therapy has long been as a backbone of them. But the clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) were not ideal because of their poor prognosis, more effective therapeutic approaches are still necessary to further improve this problem. Poly (ADP-ribose) polymerase (PARP) inhibitors lead to the single-strand DNA breaks and/or double-strand DNA breaks, and result in synthetic lethality in cancer cells with impaired homologous recombination genes. It is estimated that approximately 20~25% of patients with mCRPC have a somatic or germinal DNA damage repair gene mutation. Furthermore, in "BRCAness" cases, which has been used to describe as tumors that have not arisen from a germline BRCA1 or BRCA2 mutation, there were also a number of studies sought to extend these promising results of PARP inhibitors. It is worth noting that an interaction between androgen receptor signaling and synthetic lethality with PARP inhibitors has been proposed. In this review, we discussed the mechanism of action and clinical research of PARP inhibitors, which may benefit population from "specific" to the "all-comer" in patients with PC when combined with novel hormonal therapies.


Oocyte mitochondrial bioenergy potential and oxidative stress: within-/between-subject, in vivo versus in vitro maturation, and age-related variations in a sheep model.
To analyze within-/between-subject, in vivo versus in vitro maturation (IVM), and age-related variations of mitochondrial (mt) bioenergy potential and oxidative status of metaphase II (MII) oocytes recovered from hormonally stimulated sheep. Prospective study. Academic basic research laboratory. Ten adult ewes. Estrus synchronization, controlled ovarian hyperstimulation (COH), ovariohysterectomy; follicular and oviductal oocyte retrieval; IVM of follicular oocytes. Mean ± SD, within-subject (CV(w)) and between-subject (CV(b)) variation coefficients of mt activity, intracellular reactive oxygen species (ROS) levels, and mt/ROS colocalization in sheep oocytes from young and aged donors and matured in vivo (in vivo MIIs) or in vitro (IVM MIIs). Within- and between-subject, in vivo versus IVM, and age-related variations of mt activity were observed in MII oocytes from hormonally stimulated donor sheep. ROS levels increased significantly in oocytes from aged donors. Mt-ROS colocalization was consistently higher in in vivo MIIs compared with IVM MIIs. Oviductal energy/antioxidant ability is influenced by COH. Oocyte energy/oxidative status is affected by within-/between-subject, in vivo versus IVM, and age-related variations. Mt/ROS colocalization is a reliable marker of in vivo MII oocytes.


Comparative effectiveness research--a proposal for a new NHMRC funding stream.
Opportunities to examine the relevance of health interventions in actual clinical scenarios need to be created.


Platelet activation and dysfunction in a large-animal model of traumatic brain injury and hemorrhage.
Traumatic brain injury (TBI) and hemorrhage are the leading causes of trauma-related mortality. Both TBI and hemorrhage are associated with coagulation disturbances, including platelet dysfunction. We hypothesized that platelet dysfunction could be detected early after injury, and that this dysfunction would be associated with early activation, as measured by circulating levels of platelet activation markers. A total of 33 swine were allocated to TBI and hypotension (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation only). Animals in the TBI/Hemorrhage group were left hypotensive, defined as mean arterial pressure of 35 mm Hg, for 2 hours. Blood samples were drawn at baseline and 3 minutes and 15 minutes following injury as well as following 2 hours of shock. Samples were analyzed for platelet aggregation using impedance aggregometry with agonists collagen, arachidonic acid, and adenosine diphosphate (ADP) and thromboelastography (TEG) and circulating levels of platelet activation markers transforming growth factor-β (TGF-β), CD40 ligand, and sP-selectin. Platelet ADP aggregation was significantly lower in the TBI/Hemorrhage group when compared with the control group 15 minutes following injury (62.4 vs. 80.4 U, p = 0.03) as well as following 2 hours of hypotension (59.9 vs. 73.5 U, p < 0.01). The latter was associated with lower TEG measured clot strength (TEG-MA, 74.1 vs. 79.4 mm, p = 0.05). No difference in collagen or arachidonic acid aggregation was observed. TGF-β levels were significantly higher in the TBI/Hemorrhage group following 2 hours of hypotension (1,764 vs. 1,252 pg/mL, p = 0.01). No differences in CD40 ligand or sP-selectin levels were observed. In this combined model of TBI and hemorrhage, a significantly lower ADP-induced platelet aggregation was detected 15 minutes following injury that was further aggravated during the 2-hour shock period. This dysfunction was associated with an increase in platelet activation marker TGF-β.


Utilization of key preventive measures for pregnancy complications and malaria among women in Jimma Zone, Ethiopia.
In Ethiopia, malaria infections and other complications during pregnancy contribute to the high burden of maternal morbidity and mortality. Preventive measures are available, however little is known about the factors influencing the uptake of maternal health services and interventions by pregnant women in Ethiopia. We analyzed data from a community-based cross-sectional survey conducted in 2016 in three rural districts of Jimma Zone, Ethiopia, with 3784 women who had a pregnancy outcome in the year preceding the survey. We used multivariable logistic regression models accounting for clustering to identify the determinants of antenatal care (ANC) attendance and insecticide-treated net (ITN) ownership and use, and the prevalence and predictors of malaria infection among pregnant women. Eighty-four percent of interviewed women reported receiving at least one ANC visit during their last pregnancy, while 47% reported attending four or more ANC visits. Common reasons for not attending ANC included women's lack of awareness of its importance (48%), distance to health facility (23%) and unavailability of transportation (14%). Important determinants of ANC attendance included higher education level and wealth status, woman's ability to make healthcare decisions, and pregnancy intendedness. An estimated 48% of women reported owning an ITN during their last pregnancy. Of these, 55% reported to have always slept under it during their last pregnancy. Analysis revealed that the odds of owning and using ITNs were respectively 2.07 (95% CI: 1.62-2.63) and 1.73 (95% CI: 1.32-2.27) times higher among women who attended at least one ANC visit. The self-reported prevalence of malaria infection during pregnancy was low (1.4%) across the three districts. We found that young, uneducated, and unemployed women presented higher odds of malaria infection during their last pregnancy. ANC and ITN uptake during pregnancy in Jimma Zone fall below the respective targets of 95 and 90% set in the Ethiopian Health Sector Transformation Plan for 2020, suggesting that more intensive programmatic efforts still need to be directed towards improving access to these health services. Reaching ANC non-users and ITN ownership and use as part of ANC services could be emphasized to address these gaps.


Human neuronal calcium sensor-1 shows the highest expression level in cerebral cortex.
Neuronal calcium sensors (NCS) are important constituents in the intracellular signaling pathways. A novel human gene, NCS-1, was identified in the present study. Among the 16 human tissues examined, NCS-1 is expressed most abundantly in the brain. Among the brain regions, the expression level of NCS-1 in cerebral cortex is the highest, which is about six times higher than the average level of the whole brain and a hundred times higher than the spinal cord. In the 12 different anatomical regions of human brain, the expression level of NCS-1 is very high in the temporal lobe, occipital pole, frontal lobe, thalamus, amygdala and hippocampus; moderate in cerebellum, putamen, caudate nucleus; low in the medulla, substantia nigra and the lowest in corpus callosum. Our results suggest that NCS-1 in human brain might be involved in a variety of brain functions such as sensory processing, motor control, emotional control, learning and memory.


Startle response to unpredictable threat in comorbid panic disorder and alcohol dependence.
Although the adverse consequences of comorbid panic disorder (PD) and alcohol dependence (AD) are well-established, relatively little is known about the mechanisms underlying their co-occurrence. Several researchers have postulated that alcohol's ability to dampen response to unpredictable threat may be an important motivational factor in comorbid PD and AD. To date, no research has examined these processes using a clinical sample and it is unclear whether individuals with PD and AD evidence different reactivity to unpredictable threat relative to individuals with PD-only. The aim of the current study was to examine differences in aversive responding during predictable and unpredictable threat-of-shock in three groups of individuals with: (1) current PD and remitted AD (PD and AD), (2) current PD but no lifetime diagnosis of AD (PD-only), and (3) no lifetime diagnoses of PD or AD (controls). Aversive responding was assessed using a well-established electromyography (EMG) startle paradigm. Results indicated that PD and AD individuals evidenced greater startle potentiation during unpredictable (but not predictable) threat relative to controls and PD-only individuals (who did not differ). These findings suggest that heightened reactivity to unpredictable threat may be an important process in PD and AD comorbidity and a possible key motivational factor underlying engagement in alcohol use.


Risk-taking behaviors engaged in by early adolescents while on school property.
This longitudinal study was guided by a Youth Resilience Framework. The study purpose was to examine the influence of protective resources, contextual factors, and risk factors in middle childhood (grades 4-6) on health-risk behaviors (e.g., smoking cigarettes, using marijuana, drinking alcohol, carrying a weapon) engaged in on school property by early adolescents (grade 7) who live in rural central Texas. Students in grades 4 to 6, a majority of whom were Mexican American (54.3%) and male (56.4%), completed surveys annually until the 7th grade. Generalized estimating equations were run to determine predictors of 7th graders' health-risk behaviors on school property. Engaging in healthy behaviors, knowing others cared about them, and having a sense of competence in middle childhood (grades 4-6) were found to be protective factors, while having a large family size and the expectation that they would not complete school were found to be risk factors for engaging in health risk behaviors in 7th grade. These findings show the influence of family and schools as environments that can offer protection from health-risk behaviors in early adolescence.


Nonoperative management of abdominal gunshot wounds.
Mandatory surgical exploration for gunshot wounds to the abdomen has been a surgical dictum for the greater part of this past century. Although nonoperative management of blunt solid organ injuries and low-energy penetrating injuries such as stab wounds is well established, the same is not true for gunshot wounds. The vast majority of patients who sustain a gunshot injury to the abdomen require immediate laparotomy to control bleeding and contain contamination. Nonoperative treatment of patients with a gunshot injury is gaining acceptance in only a highly selected subset of hemodynamically stable adult patients without peritonitis. Although the physical examination remains the cornerstone in the evaluation of patients with gunshot injury, other techniques such as computed tomography, diagnostic peritoneal lavage, and laparoscopy allow accurate determination of intra-abdominal injury. The ability to exclude internal organ injury nonoperatively avoids the potential complications of unnecessary laparotomy. Clinical data to support selective nonoperative management of certain gunshot injuries to the abdomen are accumulating, but the approach has risks and requires careful collaborative management by emergency physicians and surgeons experienced in the care of penetrating injury.


Adjusting rations for climate.
Cold conditions resulting from a combination of temperature, wind, and wetness result in increased energy required for maintenance. Constant levels of intake reduce energy available for production. Direct effects of cold include reduced rate and efficiency of growth and milk production. Indirect effects on measures of reproductive efficiency are well documented. Impacts on health and longevity are perhaps less obvious but are no doubt affected. Energy supplementation is an obvious need for cold-stressed animals. For maximum effectiveness, efforts should incorporate a systems approach and integrate the expertise of many disciplines into a logical decision-making process. The entire spectrum of animal response, not just short-term acute response, must be included in environmental management.


Leakage of mitochondrial and cytosolic GOT in isolated rat hepatocytes exposed to halothane: an immunohistochemical study.
The leakage of mitochondrial (m-) and cytosolic (s-) aspartate aminotransferases (glutamic-oxaloacetic transaminase: GOT) from isolated hepatocytes exposed to halothane was investigated immunohistochemically. In control isolated hepatocytes, a large number of cells were immunopositive (m-GOT, 85%; s-GOT, 98.5%) at various intensities. Reaction products of m-GOT-immunohistochemistry (m-GOT-I) were seen exclusively in mitochondria, while those of s-GOT (s-GOT-I) were seen in the cytoplasm. When treated with low concentrations of halothane (up to 0.75%), the number of strongly m-GOT-I-immunopositive cells was reduced to half, while that of s-GOT-I showed no noticeable change. The number of m-GOT-I-immunonegative cells showed a negligible increase, while that of s-GOT-I increased gradually. At higher concentrations of halothane (1% or more), strongly immunopositive cells in both m- and s-GOT-I almost disappeared, while immunonegative cell numbers predominantly increased. This study showed that the isolated hepatocyte system was not homogeneous with regard to the quantity of GOT isozymes, and that halothane could induce the leakage of these isozymes from hepatocytes, along with inducing ultrastructural abnormalities, even at the lowest concentration used (0.5%). Furthermore, the data appear to indicate that the sensitivity of isolated hepatocytes to halothane is dependent on the nature of the hepatocyte itself and on the nature of both types of GOT isozymes.


Association of cerebral malaria and TNF-α levels: a systematic review.
Cerebral malaria is the most severe form of infection with Plasmodium falciparum characterized by a highly inflammatory response. This systematic review aimed to investigate the association between TNF-α levels and cerebral malaria. This review followed the Preferred Reporting of Systematic Review and Meta-analyses (PRISMA) guidelines. The search was performed at PubMed, LILACS, Scopus, Web of Science, The Cochrane Library, OpenGrey and Google Scholar. We have included studies of P. falciparum-infected humans with or without cerebral malaria and TNF-α dosage level. All studies were evaluated using a risk of bias tool and the GRADE approach. Our results have identified 2338 studies, and 8 articles were eligible according to this systematic review inclusion criteria. Among the eight articles, five have evaluated TNF- α plasma dosage, while two have evaluated at the blood and one at the brain (post-Morten). Among them, only five studies showed higher TNF-α levels in the cerebral malaria group compared to the severe malaria group. Methodological problems were identified regarding sample size, randomization and blindness, but no risk of bias was detected. Although the results suggested that that TNF-α level is associated with cerebral malaria, the evidence is inconsistent and imprecise. More observational studies evaluating the average TNF-alpha are needed.


Hemorrhage in a patient with Bronchial Dieulafoy's disease and associated pulmonary fibrosis: A case report.
Bronchial Dieulafoy's disease (BDD) is a rare vascular anomaly that was first described in 1995. The main symptom is recurrent hemoptysis. It can be diagnosed through angiography, bronchoscopy, and sometimes histology and endobronchial ultrasound scan (EBUS). Treatment includes embolization and surgery. A 77-year-old male with dyspnea and CT scan revealing an interstitial pattern underwent bronchoscopy for bronchoalveolar lavage (BAL). During bronchoscopy, a protruding white non-pulsatile lesion was biopsied. The biopsy triggered a massive hemorrhage, which required an embolization procedure. Bronchial Dieulafoy's disease was diagnosed. There was no need for surgery in this case. The interstitial pattern was diagnosed as idiopathic pulmonary fibrosis. This report describes a novel case of BDD leading to bronchial hemorrhage. Considering the endoscopic differential diagnosis, including rather frequent carcinoid tumor and broncholithiasis, we highlight the need for extreme caution when considering endoscopic biopsy of protruding white lesions. Indeed, biopsy - or even contact - with a BDD lesion is frequently associated with massive hemorrhage. According to our review, BDD is the most hemorrhage-prone lesion when biopsied, associated with significant bleeding in 90% of cases and 30% mortality, compared with significant bleeding in only 2.6% of carcinoid tumors and 3.1% of broncholithiasis cases.This case of BDD is also original since associated with idiopathic pulmonary fibrosis. It is to our knowledge the first time that such an association has been reported.


The relationship of metalloproteinase gene polymorphisms and lung cancer.
We analyzed the relationship between matrix metalloproteinase (MMP)-2, -7, and -13 gene expression and polymorphisms and disease susceptibility and prognosis in patients who had undergone surgery for non-small-cell lung cancers. The study group consisted of 132 patients who had undergone radical surgery for non-small-cell lung cancers. The control group consisted of 80 healthy volunteers. We isolated deoxyribonuclease samples for use in analyzing gene polymorphisms from pathology blocks for the patient group and from blood samples for the control group. We identified MMP gene polymorphisms with polymerase chain reaction and restriction fragment length polymorphisms. Results were compared with those of the control group to evaluate disease susceptibility, correlation with other clinical parameters, and with survival and prognosis by using appropriate statistical methods. When we compared polymorphisms pertaining to MMP genes in healthy controls and lung tumor DNA, we observed a decrease in the MMP-2 (-735) polymorphism GG genotype and increases in the MMP-13 (A77G) polymorphism AG and GG genotypes (P = 0.008, P = 0.047, and P = 0.047, respectively). For the MMP-7 (-181) polymorphism, the genotype did not differ significantly for disease susceptibility. Median overall survival time was 25.5 mo in the MMP-13 AA/AG genotypes and 9.3 mo in the GG genotype. Decreases in the MMP-2 (-735) polymorphism GG genotype and increases in the MMP-13 (A77G) polymorphism AG and GG genotypes increase the risk for lung cancer. Furthermore, the presence of the MMP-13 (A77G) polymorphism GG genotype is an unfavorable prognostic factor.


Bladder-emptying methods, neurogenic lower urinary tract dysfunction and impact on quality of life in people with long-term spinal cord injury.
To describe bladder-emptying methods used by people with long-term spinal cord injury (SCI) and to determine usage differences in relation to time since injury, sex, lesion level and completeness of lesion. Furthermore, to evaluate the relationship between bladder-emptying methods and the impact of neurogenic lower urinary tract dysfunction (NLUTD) on quality of life (QoL). Cross-sectional multicenter study. Dutch community. Persons dependent on wheelchairs (N = 282) with traumatic or non-traumatic SCI for ≥10 years and age at injury of 18-35 years. Not applicable. The International Lower Urinary Tract Function Basic SCI Data Set and the Short-Form Qualiveen (SF-Qualiveen). Median time since injury was 22.0 years (IQR: 16.8-30.3). Clean intermittent catheterization (CIC) was most commonly used (42.6%). Longer time since injury was associated with fewer continent urinary diversions and more transurethral catheter use. Transurethral catheter use and continent urinary diversions were more prevalent among women. Participants with tetraplegia were more likely to use reflex voiding or a suprapubic catheter, and participants with paraplegia were more likely to use CIC. Transurethral catheter users reported the highest impact of NLUTD on quality of life (SF-Qualiveen score: 1.9; SD = 0.8). Participants with a continent urinary diversion reported the lowest impact (SF-Qualiveen score: 0.9; SD = 0.6). Higher age and indwelling catheter use versus CIC were associated with a higher impact of NLUTD on QoL. CIC is the most common bladder-emptying method in Dutch people with long-term SCI. Clinicians should be aware of the impact of NLUTD on QoL, especially for those using an indwelling catheter.


The maximum recovery potential of human tumor cells may predict clinical outcome in radiotherapy.
We studied inherent radiosensitivity/resistance (D0), ability to accumulate sublethal damage (n) and repair of potentially lethal damage (PLDR) in established human tumor cell lines as well as early passage human tumor cell lines derived from patients with known outcome following radiotherapy. Survival 24 hrs after treatment of human tumor cells with X rays in plateau phase cultures is a function of initial damage (D0, n), as well as recovery over 24 hrs (PLDR). A surviving fraction greater than .1 24 hrs following treatment with 7 Gy in plateau phase cultures is associated with tumor cell types (melanoma, osteosarcoma) with a high probability of radiotherapy failure or tumor cells derived from patients who actually failed radiotherapy. Therefore, total cellular recovery following radiation may be an important determinant or radiocurability. Accurate assays of radiotherapy outcome may need to account for all these radiobiological parameters.


Conservation and Diversity in Allosteric Fingerprints of Proteins for Evolutionary-inspired Engineering and Design.
Hand-in-hand work of physics and evolution delivered protein universe with diversity of forms, sizes, and functions. Pervasiveness and advantageous traits of allostery made it an important component of the protein function regulation, calling for thorough investigation of its structural determinants and evolution. Learning directly from nature, we explored here allosteric communication in several major folds and repeat proteins, including α/β and β-barrels, β-propellers, Ig-like fold, ankyrin and α/β leucine-rich repeat proteins, which provide structural platforms for many different enzymatic and signalling functions. We obtained a picture of conserved allosteric communication characteristic in different fold types, modifications of the structure-driven signalling patterns via sequence-determined divergence to specific functions, as well as emergence and potential diversification of allosteric regulation in multi-domain proteins and oligomeric assemblies. Our observations will be instrumental in facilitating the engineering and de novo design of proteins with allosterically regulated functions, including development of therapeutic biologics. In particular, results described here may guide the identification of the optimal structural platforms (e.g. fold type, size, and oligomerization states) and the types of diversifications/perturbations, such as mutations, effector binding, and order-disorder transition. The tunable allosteric linkage across distant regions can be used as a pivotal component in the design/engineering of modular biological systems beyond the traditional scaffolding function.


Simultaneous operations for abdominal aortic aneurysm and liver cancer complicated by severe ischemic heart disease: report of a case.
We performed successful simultaneous operations for an abdominal aortic aneurysm (AAA) and liver cancer in a patient complicated by severe ischemic heart disease. A 59-year-old man with a history of liver dysfunction presented with acute epigastric pain. Abdominal computed tomography findings of ascites and a liver tumor indicated a diagnosis of ruptured hepatocellular carcinoma. He had a concomitant 65-mm AAA and a 48-mm right common iliac aneurysm. Elective surgery was scheduled because of his good general condition. Although triple-vessel disease was detected preoperatively, there were no graftable coronary arteries. The aneurysms were repaired first to utilize intra-aortic balloon pumping (IABP) during resection of the liver cancer, followed by left lateral segmentectomy. Perioperative hemodynamics were maintained by administering catecholamines and vasodilators, without the need for IABP. The patient was discharged on the 21st postoperative day without any complications, and no recurrence of liver cancer has been found in the 5 months since his operation.


Investigation of interaction mechanisms during co-combustion of sewage sludge and coal slime: Combustion characteristics and NO/SO2 emission behavior.
Co-combustion of sewage sludge (SS) and coal slime (CS) is a promising method to achieve resource utilization of both solid wastes. However, the emission characteristics of NO/SO2 and the interaction mechanisms between SS and CS are unclear. In this paper, the co-combustion characteristics and NO/SO2 emission behavior of SS and CS were investigated using a thermogravimetric analyzer and a tube furnace combustion system, and the interactions between SS and CS were explored. The results revealed the presence of remarkable interactions between SS and CS during the co-combustion. For the combustion characteristics, non-catalytic factors (interaction between volatiles and heat synergy) and catalytic factors (catalysis of inorganic components) controlled the combustion stage of the heavy volatiles and fixed carbon of the blends, respectively, leading to an earlier combustion process. For NO and SO2 emission characteristics, SS-CS co-combustion had significant NO in-situ reduction and self-desulphurization characteristics at 800 °C and 900 °C. The best inhibition occurred at 900 °C and 50 % CS ratio, and NO and SO2 emission amounts were reduced by 0.25 mg/g and 1.37 mg/g, respectively, compared to the theoretical values. At 1000 °C, co-combustion promoted the emissions of both NO and SO2. The interaction mechanisms suggested that the reducing atmosphere created and the reducing gases released by SS combustion promoted the reduction of CS-NO, while the char formed by CS exhibited a significant reduction of SS-NO. In addition, the effect of CS addition on the mass transfer process enhanced the sulfur fixation of inorganic components in SS, which led to the suppression of SO2 production. These findings provide a better understanding of the interactions between SS and CS during SS-CS co-combustion.


Ontogeny of heart rate response to milk infusion in infant rats as a function of level of deprivation.
The heart rate (HR) responses of infant rats aged 8, 11, 14, and 17 days were recorded during the intraoral infusion of milk. Subjects were deprived for various periods of time prior to the start of testing. The results revealed a transition from HR deceleration to HR acceleration between 8 and 14 days of age, with the magnitude of the response varying directly with the degree of deprivation. A follow-up experiment was run in order to demonstrate that the observed HR changes were not a result of the termination of infusion. Implications for a transition from infant to adult feeding systems as well as the development of a somatic-cardiac linkage are discussed.


Artificial intelligence in coronary artery calcium measurement: Barriers and solutions for implementation into daily practice.
Coronary artery calcification (CAC) measurement is a valuable predictor of cardiovascular risk. However, its measurement can be time-consuming and complex, thus driving the desire for artificial intelligence (AI)-based approaches. The aim of this review is to explore the current status of CAC volume measurement using AI-based systems for the automated prediction of cardiovascular events. We also make proposals for the implementation of these systems into clinical practice. Research to date on applying AI to CAC scoring has shown the potential for automation and risk stratification, and, overall, efficacy and a high level of agreement with categorisation by trained clinicians have been demonstrated. However, research in this field has not been uniform or directed. One contributing factor may be a lack of integration and communication between computer scientists and cardiologists. Clinicians, institutions, and organisations should work together towards applying this technology to improve processes, preserve healthcare resources, and improve patient outcomes.


Intestinal transport of pyridoxine in experimental renal failure.
Renal failure (RF) has been shown to alter intestinal transport of a number of nutrients. We studied jejunal absorption of pyridoxine (B6) in rats rendered azotemic by subtotal nephrectomy (RF group) and compared the results with those obtained in normal rats subjected to sham operation (controls) and animals pair-fed (PF) with their RF counterparts. In vivo recirculating perfusion and in vitro everted sac techniques were employed. The in vitro experiments were repeated using sera from uremic and normal individuals to assess the possible effect of uremic chemical environment. The results showed significant reduction in B6 absorption in vivo in the RF group as compared to the control and PF groups. Paradoxically, the rate of in vitro B6 absorption determined for a wide range of concentrations was increased in the RF and PF groups as compared to the control group. The observed increase in B6 absorption in vitro suggests enhanced permeability in the RF and PF groups due probably to reduced nutrient intake which was common to both groups. The disparity between the in vivo and in vitro results is indicative of some inhibitory factor(s) present in the RF animals. Sacs containing uremic serum showed significantly suppressed B6 absorption in vitro as compared to those containing normal serum. These observations suggest that the uremic chemical environment may be, in part, responsible for the observed impairment of B6 transport in RF animals despite in vitro evidence of hyperpermeability.


Design of liposomes to improve delivery of amphotericin-B in the treatment of aspergillosis.
The efficacy and toxicity of free and liposome intercalated amphotericin-B (Amp-B) in controlling Aspergillosis, caused by Aspergillus fumigatus in BALB/c mice were studied. Liposomal Amp-B had higher LD50 (8.1 mg/kg) as compared to that of the free drug (1.2 mg/kg). An improvement in the therapeutic index of the drug was observed with liposomal formulation of the drug. We also focussed on the effect of lipid composition and surface sugar in modulating the therapeutic potency of Amp-B. The most effective liposomal preparation was composed of egg phosphatidylcholine (EPC): L-alpha-phosphatidylethanolamine, dipalmitoyl (DPPE): cholesterol (Chol) in the molar ratio of 6:1:3. Amp-B intercalated into mannose grafted liposomes (LD50 = 9.3 mg/kg) was more effective as compared to the other formulation tested.


The use of diversity profiling to characterize chemical modulators of the histone deacetylases.
Target specificity and off-target liabilities are routinely monitored during the early phases of drug discovery for most kinase projects. Typically these criteria are evaluated using a profiling panel comprised of a diverse collection of in vitro kinase assays and relates compound structure to potency and selectivity. The success of these efforts has led to the design of similar panels for phosphatase, protease, and epigenetic targets. Here the implementation of an epigenetic profiling panel, comprised of eleven histone deacetylases (HDACs) and one histone acetyltransferase (HAT), was used to evaluate chemical modulators of these enzymes. HDAC inhibitors (HDACi) such as sodium butyrate and trichostatin A demonstrate diverse biological effects which have led to broad speculation about their therapeutic potential in multiple disease states. Some HDACi have demonstrated tumor suppression in vivo and recently Zolinza was the first HDACi approved by the FDA for the treatment of cutaneous T-cell lymphoma. While HDACi have demonstrated therapeutic utility, many of the first generation compounds are pan-inhibitors. Thus, use of an HDAC profiling panel will be essential in achieving isoform specificity of the next generation of inhibitors. To this end, twenty-one compounds, twelve of which are known to have activities against the HDACs, were tested to evaluate the utility of the epigenetic panel. Additionally, these compounds were tested against a larger 72 member enzyme panel comprised of kinase, phosphatase and protease activities. This effort represents the first time these compounds have been profiled with such a broad range of biochemical activities.


Cell wall invertase-deficient miniature1 kernels have altered phytohormone levels.
The Zea mays (maize) miniature1 (Mn1) locus encodes the cell wall invertase INCW2, which is localized predominantly in the basal endosperm transfer layer (BETL) of developing kernels and catalyzes conversion of sucrose into glucose and fructose. Mutations in Mn1 result in numerous changes that include a small kernel phenotype resulting from both decreased cell size and number. To explore the pleiotropic effects of this mutation, we investigated the levels of indole-3-acetic acid (IAA), abscisic acid (ABA), salicylic acid (SA), and jasmonic acid (JA) in basal regions, upper regions, and embryos of developing kernels in the inbred line W22. We measured phytohormones from 6 to 28 days after pollination (DAP) in wild type (WT) and two alleles of mn1, mn1-1 and mn1-89. IAA was the predominant hormone in kernels, with WT levels of free IAA accumulating over time to more than 2microg/g of fresh weight. Kernels of mn1-1 accumulated up to 10-fold less IAA than WT, and levels of IAA sugar conjugates were similarly reduced. Although less abundant, differences were also observed in levels of ABA, JA, and SA between WT and the mn1 alleles. SA levels were increased by as much as 10-fold in mn1-1, and mn1-89 displayed intermediate SA levels at most timepoints. These findings indicate that invertase-mediated sucrose cleavage directly or indirectly regulates the levels of key plant hormones during seed development.


Persistent liver lesions in rats after a single oral dose of polybrominated biphenyls (firemaster FF-1) and concomitant PBB tissue levels.
In a preliminary study, 12 male and 12 female weanling Sherman strain rats were given a single dose of 1000 mg polybrominated biphenyls (PBBs) FireMaster FF1 Lot 7042 kg/body weight as a 5% solution in corn oil. Three male and three female weanling rats were given corn oil. One day after dosing PBB blood levels ranged from 78 to 162 ppm and 42 days later they ranged from 1.1 to 2.99 ppm. The liver was the only organ with pathological changes. In a long-term recovery study groups of 20 male and female rats, 2 months old, were given 0 or 1000 mg PBBs/kg body weight as a single dose in peanut oil. Five rats per group killed 2, 6, 10, and 14 months after dosing had pronounced liver pathology, including hepatic porphyria in the female rats and neoplastic nodules also mainly in female rats. Chemical analyses of blood, liver, and adipose tissue for PPBs 10 and 14 months after dosing gave the following mean results. Blood levels in females were 2.9 and 2.92 ppm, respectively, and males 0.94 and 1.34 ppm, respectively. Adipose tissue levels in females were 1202 and 783 ppm and in males 713 and 866 ppm, respectively. The liver levels in females were 37 and 22 ppm and in males 60 and 63 ppm, respectively.


Follow-Up Shadow Coaching Improves Primary Care Provider-Patient Interactions and Maintains Improvements When Conducted Regularly: A Spline Model Analysis.
Shadow coaching improves provider-patient interactions, as measured by CG-CAHPS® overall provider rating (OPR) and provider communication (PC). However, these improvements erode over time. Examine whether a second coaching session (re-coaching) improves and sustains patient experience. Large, urban Federally Qualified Health Center PROGRAM: Trained providers observed patient care by colleagues and provided suggestions for improvement. Providers with OPRs<90 (0-100-point scale) were eligible. We used stratified randomization based on provider type and OPR to assign half of the 40 eligible providers to re-coaching. For OPR and PC, we fit mixed-effects regression models with random-effects for provider (level of treatment assignment) and fixed-effects for time (linear spline with knots and possible "jump" at initial coaching and re-coaching), previous OPR, patient characteristics, and sites. We observed a statistically significant medium jump among re-coached providers after re-coaching on OPR (3.7 points) and PC (3.5 points); differences of 1, 3, and ≥5-points for CAHPS measures are considered small, medium, and large. Improvements from re-coaching persisted for 12 months for OPR and 8 months for PC. Re-coaching improved patient experience more than initial coaching, suggesting the reactivation of knowledge from initial coaching. However, re-coaching gains also eroded. Coaching should occur every 6 to 12 months to maintain behaviors and scores.


When do confounding by indication and inadequate risk adjustment bias critical care studies? A simulation study.
In critical care observational studies, when clinicians administer different treatments to sicker patients, any treatment comparisons will be confounded by differences in severity of illness between patients. We sought to investigate the extent that observational studies assessing treatments are at risk of incorrectly concluding such treatments are ineffective or even harmful due to inadequate risk adjustment. We performed Monte Carlo simulations of observational studies evaluating the effect of a hypothetical treatment on mortality in critically ill patients. We set the treatment to have either no association with mortality or to have a truly beneficial effect, but more often administered to sicker patients. We varied the strength of the treatment's true effect, strength of confounding, study size, patient population, and accuracy of the severity of illness risk-adjustment (area under the receiver operator characteristics curve, AUROC). We measured rates in which studies made inaccurate conclusions about the treatment's true effect due to confounding, and the measured odds ratios for mortality for such false associations. Simulated observational studies employing adequate risk-adjustment were generally able to measure a treatment's true effect. As risk-adjustment worsened, rates of studies incorrectly concluding the treatment provided no benefit or harm increased, especially when sample size was large (n = 10,000). Even in scenarios of only low confounding, studies using the lower accuracy risk-adjustors (AUROC < 0.66) falsely concluded that a beneficial treatment was harmful. Measured odds ratios for mortality of 1.4 or higher were possible when the treatment's true beneficial effect was an odds ratio for mortality of 0.6 or 0.8. Large observational studies confounded by severity of illness have a high likelihood of obtaining incorrect results even after employing conventionally "acceptable" levels of risk-adjustment, with large effect sizes that may be construed as true associations. Reporting the AUROC of the risk-adjustment used in the analysis may facilitate an evaluation of a study's risk for confounding.


Improved infarct-related arterial patency after high dose, weight-adjusted, rapid infusion of tissue-type plasminogen activator in myocardial infarction: results of a multicenter randomized trial of two dosage regimens.
To determine whether a weight-adjusted high dose (2 mg/kg body weight over 3 h) rapid infusion of recombinant tissue-type plasminogen activator (rt-PA) was more efficacious than a weight-adjusted standard dose (1.25 mg/kg over 3 h) in achieving reperfusion in the setting of acute myocardial infarction, 175 patients were entered into a randomized multicenter trial. Eighty-four patients were entered into the high dose group, receiving 1.2 mg/kg (10% given as a bolus injection) over 1 h, followed by 0.8 mg/kg over the next 2 h. Ninety-one patients were given 0.75 mg/kg (10% given as a bolus injection) in 1 h, followed by 0.5 mg/kg administered over the next 2 h. The median dose in the group that received 2 mg/kg dose was 145 mg, compared with 100 mg in the group that received 1.25 mg/kg. The 90 min patency rate in the group that received 2 mg/kg was 84% compared with 70% in the group that received 1.25 mg/kg (p = 0.003). Sixty-four percent of the patients in each group underwent coronary angioplasty at the time of cardiac catheterization. The infarct-related artery patency rate at the end of catheterization was 91% in the group that received 2 mg/kg compared with 83% in the group that received 1.25 mg/kg (p = 0.08). Among patients with a patent infarct-related coronary artery after catheterization, the 6 month mortality rate in the group that received 2 mg/kg was 2.9% compared with 9.8% in the group that received 1.25 mg/kg (p = 0.15). The bleeding complication rate in the two groups was similar.(ABSTRACT TRUNCATED AT 250 WORDS)


Current status of chemoradiotherapy for gastric cancer in Japan.
Chemoradiotherapy (CRT) is the latest modality to be explored as a treatment for gastric cancer. Advances have been made in the United States with CRT as preoperative or postoperative adjuvant treatment. The rationale for preoperative or postoperative adjuvant CRT is to increase the curability of surgery or to prevent local recurrence, because standard surgery (D0 or D1) is not sufficient to control local relapse and improve survival where disease has become advanced. D2 is standard in Japan and D2 gastrectomy plus postoperative adjuvant chemotherapy with S-1 is currently standard for stage II and III cancer. Predominant recurrence patterns associated with these advanced disease stages are peritoneal dissemination and hematogenous metastasis. Local relapse or regional nodal recurrence is infrequent. CRT has been provided at only a limited number of institutions in Japan. The response to and safety of CRT for gastric cancer, in combination with various chemotherapeutic agents, are currently being studied in patients with unresectable or recurrent disease. Considering the high response rate, CRT seems to be an attractive option. In the near future, an examination will be made to ascertain whether neoadjuvant CRT in combination with extensive surgery has survival benefits in the treatment of locally advanced disease. Prior to this, a phase I/II study should be conducted in patients with unresectable or recurrent disease.


Lipopolysaccharides, cytokines, and nitric oxide affect secretion of prostaglandins and leukotrienes by bovine mammary gland during experimentally induced mastitis in vivo and in vitro.
The aim of the study was to determine the effects of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF), interleukin-1-alpha (IL-1α), and nitric oxide donor (NONOate) on both in vivo and in vitro secretion of prostaglandin (PG)E2, PGF2α, leukotriene (LT)B4, and LTC4 by the bovine mammary gland. In the first experiment, tissues isolated from the teat cavity and lactiferous sinus were treated in vitro with LPS (10 ng/mL), TNF (10 ng/mL), IL-1α (10 ng/mL), NONOate (10(-4) M), and the combination of TNF + IL-1α + NONOate for 4 or 8 h. PGE2 or PGF2α secretion was stimulated by all treatments (P < 0.05) excepting NONOate alone, which did not stimulate PGF2α secretion. Moreover, all factors increased LTB4 and LTC4 secretion (P < 0.05). In the second experiment, mastitis was experimentally mimicked in vivo by repeated (12 h apart) intramammary infusions (5 mL) of (1) sterile saline; (2) 250-μg LPS; (3) 1-μg/mL TNF; (4) 1-μg/mL IL-1α; (5) 12.8-μg/mL NONOate; and (6) TNF + IL-1α + NONOate into 2 udder quarters. All infused factors changed PGE2, 13,14-dihydro,15-keto-PGF2α, and LT concentrations in blood plasma collected from the caudal vena cava, the caudal superficial epigastric (milk) vein, the jugular vein, and the abdominal aorta (P < 0.05). In summary, LPS and other inflammatory mastitis mediators modulate PG and LT secretion by bovine mammary gland in both in vivo and in vitro studies.


Investigation of nuclear envelope structure and passive permeability.
We present an experimental approach by the help of which structure and passive permeability of the nuclear envelope (NE) can be investigated thoroughly, by combining imaging, fluorescent, and electrophysiological techniques. A mature Xenopus laevis oocyte features a large nucleus offering an excellent system for these investigations. Using the emerging technique of atomic force microscopy, NE structure and the conformational state of nuclear pore complexes (NPCs), known to rule NPC and inevitably NE permeability, can be visualised at high resolution and under near physiological conditions. Passive NE permeability to macromolecules can be determined by the long-established confocal laser scanning microscopy, applying fluorescent macromolecules (dextran). Passive NE permeability to small molecules, which has long remained confounded by the lack of an appropriate technique, can finally be investigated following development of a proper technique designated the "nuclear hourglass" technique. The experimental approach presented here thus opens unique perspectives towards understanding the correlation between NE structure and passive permeability. This chapter describes in detail the protocols for performing such investigations.


Inhibitory control impairment in social disinhibition following severe traumatic brain injury: An experimental study using social and nonsocial go/no-go task.
Inhibitory control impairment is highly prevalent following traumatic brain injury (TBI). There have not been any empirical investigations into whether this could explain social disinhibition following severe TBI. Further, social context may be important in studying social disinhibition. Therefore, the objectives of this research study were to investigate the role of inhibitory control impairment in social disinhibition following severe TBI, using a social and a nonsocial task. This was a between-group comparative study. Twenty-six adult participants with severe TBI and 27 sex, age, and education-matched controls participated. Social disinhibition was assessed using the Frontal Systems Behavior Scale and the Social Disinhibition Interview. Inhibitory control was assessed using a social and a nonsocial go/no-go task. Two-way mixed analyses of covariance were used to test study hypotheses. Overall, participants were slower, F(1, 43) = 9.841, p = .003, ηp² = .245, and made more errors of commission on no-go trials, F(1, 44) = 11.560, p = .001, ηp² = .208, on the social go/no-go task. When categorized based on disinhibition level (high vs. low), the high disinhibition group made more errors on the social task, F(1, 41) = 4.095, p = .050, ηp² = .091, than the low disinhibition group, and more errors on the social, compared to nonsocial task, task-group interaction, F(1, 41) = 7.233, p = .010, ηp² = .150. Social disinhibition appears to be associated with inhibitory control impairment, although this is only evident when a social task is used. No relationship between social disinhibition and response speed was found. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Phase II pilot study of single-agent etirinotecan pegol (NKTR-102) in bevacizumab-resistant high grade glioma.
Patients with recurrence of high-grade glioma (HGG) after bevacizumab (BEV) have an extremely poor prognosis. Etirinotecan pegol (EP) is the first long-acting topoisomerase-I inhibitor designed to concentrate in and provide continuous tumor exposure throughout the entire chemotherapy cycle. Here we report results of a Phase 2, single arm, open-label trial evaluating EP in HGG patients who progressed after BEV. Patients age >18 with histologically proven anaplastic astrocytoma or glioblastoma (GB) who previously received standard chemo-radiation and recurred after BEV were eligible. A predicted life expectancy >6 weeks and KPS ≥ 50 were required. The primary endpoint was PFS at 6-weeks. Secondary endpoint was overall survival from first EP infusion. Response was assessed by RANO criteria. Single agent EP was administered IV every 3 weeks at 145 mg/m2. Patients did not receive BEV while on EP. 20 patients (90 % GB) were enrolled with a median age of 50 and median KPS of 70. Three patients with GB (16.7 % of GB) had partial MRI responses. 6-week PFS was 55 %. Median and 6-month PFS were 2.2 months (95 % CI 1.4-3.4 months) and 11.2 % (95 % CI 1.9-28.9 %) respectively. Median overall survival from first EP infusion was 4.5 months (95 % CI 2.4-5.9). Only one patient had grade 3 toxicity (diarrhea with dehydration) attributable to EP. Hematologic toxicity was mild. Three patients had confirmed partial responses according to RANO criteria. These clinical data combined with a favorable safety profile warrant further clinical investigation of this agent in HGG.


Protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity by the antioxidant ascorbic acid.
Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 2 X 8 mg/kg retro-orbital) to BALB/cBy mice reduced [3H]mazindol binding to striatal membranes by 50%. Reactive oxygen derivatives have been suggested to be involved in MPTP neurotoxicity; therefore we examined the effects of ascorbic acid (an antioxidant). Ascorbic acid (100 mg/kg) given 20 min prior to MPTP administration appreciably prevented the reduction of [3H]mazindol binding. The involvement of oxidative processes in the mechanism of MPTP neurotoxicity may suggest a relationship to the etiology of Parkinson's disease, and the possible benefit of treatment with ascorbic acid.


Integral and peripheral protein composition of the apical and basolateral membrane domains in MDCK cells.
Selective biotinylation of the apical or basolateral domains of confluent MDCK monolayers grown on polycarbonate filters with a water soluble biotin analog, sulfo-NHS-biotin, was employed to reveal strikingly distinct patterns of endogenous "peripheral" and "integral" membrane proteins. "Peripheral" proteins were found to be approximately fivefold more abundant with this procedure than "integral" membrane proteins, both on the apical and on the basolateral surface. The distinct apical and basal patterns were shown to depend upon the integrity of the monolayer; when the tight junctions were disrupted by preincubation in calcium-depleted medium, the patterns appeared practically indistinguishable. Two-dimensional gel electrophoresis demonstrated that only a very small percentage of the biotinylated proteins were found in similar amounts on both apical and basolateral domains. These results indicate that the sorting mechanisms that segregate apical and basolateral epithelial proteins are very strict. The simple procedure described here has clear advantages over other methods available to label apical and basal epithelial surface domains, namely, higher accessibility of the biotin probe to the basolateral membrane, possibility of purifying biotinylated proteins via immobilized streptavidin and minimal exposure of the researcher to isotopes. It should be very useful in characterizing the apical and basolateral protein compositions of other epithelial cells and in studies on the development of epithelial cell polarity.


Prophylaxis of gonococcal and chlamydial ophthalmia neonatorum. A comparison of silver nitrate and tetracycline.
We evaluated the use of silver nitrate drops and tetracycline ointment for the prophylaxis of ophthalmia neonatorum in a controlled trial involving 2732 newborns in Nairobi, Kenya. The overall rates of prevalence of intrapartum maternal gonococcal and chlamydial infection were 6.4 and 8.9 percent, respectively. After prophylaxis with silver nitrate, the incidence rates of gonococcal, chlamydial, and nongonococcal, nonchlamydial ophthalmia neonatorum were 0.4, 0.7, and 6.2 percent, respectively, whereas after prophylaxis with tetracycline, the rates were 0.1, 0.5, and 4.5 percent. The attack rates of gonococcal ophthalmia neonatorum in newborns exposed to Neisseria gonorrhoeae at birth were 7.0 percent in those receiving silver nitrate and 3.0 percent in those receiving tetracycline (95 percent confidence interval for the difference in rates, -3.4 to 11.4 percent). As compared with historical controls, the incidence of gonococcal ophthalmia neonatorum decreased 83 percent among infants treated with silver nitrate and 93 percent among those treated with tetracycline. Failure of prophylaxis was associated with postpartum maternal endometritis (P = 0.05). Among newborns exposed to maternal infection with Chlamydia trachomatis, chlamydial conjunctivitis developed in 10.1 percent given silver nitrate and in 7.2 percent given tetracycline (95 percent confidence interval for the difference in rates, -4.7 to 10.5 percent), yielding reductions in the incidence of chlamydial ophthalmia of 68 and 77 percent, respectively, as compared with the historical controls. We conclude that tetracycline is as effective as silver nitrate in preventing gonococcal ophthalmia neonatorum.


The kinetics of transport inhibition by noncompetitive inhibitors.
A new analysis of the conventional carrier model shows that noncompetitive inhibitors can give rise to either competitive, noncompetitive or uncompetitive kinetics; the true mechanism and also the relative affinity of the inhibitor on each surface of the membrane can be decided from the patterns of inhibition observed in different transport experiments. The principles governing the kinetics of inhibition apply to both reversible and irreversible inhibitors, for in either case the substrate may increase or decrease inhibition or be without effect. Ambiguity arises if the noncompetitive inhibitor acts on only one side of the membrane and if the substrate, in the course of being transported, alters the steady-state distribution of the carrier between inner and outer forms. In facilitated transport systems only equilibrium exchange should give rise to noncompetitive kinetics, whatever the location of the inhibitor. In active systems even the interpretation of exchange in the final steadystate is complicated if the energy-coupling mechanism produces a large displacement in the distribution of the free carrier or the substrate complex: the inhibition could be competitive or uncompetitive, depending on the location of the inhibitor. The actual mechanism is revealed in the uncoupled system.


Modified tubular electrode in a multi-commutated flow system: determination of acetaminophen in blood serum and pharmaceutical formulations.
This work describes the construction of a Nafion coated glassy carbon tubular electrode and its use, coupled to a multi-commutated flow system, for the voltammetric determination of acetaminophen in serum and pharmaceutical formulations. The modification of the electrode enhanced the analytical signal intensity and, simultaneously, prevented the electrode surface fouling. The multi-commutated system conferred high versatility to the manifold, allowing it to be easily adjusted to each determination without the need to introduce any physical reconfiguration. The on line enzymatic hydrolysis of acetaminophen, giving rise to 4-aminophenol, allowed the problem of interferences resulting from the oxidation of the matrix serum constituents to be overcome. The method presented a linear range up to 5.0 x 10(-4) mol l(-1) with a detection limit of 1.7 x 10(-5) mol l(-1), a sampling rate of 24 determinations per hour and a repeatability (expressed in relative standard deviation) always lower than 3%. The method was applied to serum samples and pharmaceutical formulations and no statistically significant difference between the results obtained by the proposed method and by the reference methods was found, for a confidence level of 95%.


Recruitment of phosphatase PP2A by RACK1 adaptor protein deactivates transcription factor IRF3 and limits type I interferon signaling.
The transcription factor IRF3 is a central regulator of type I interferon (IFN) signaling. The mechanisms underlying deactivation of IRF3 are poorly understood although many studies suggest that IRF3 activity is terminated through degradation after viral infection. Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3 pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection. After challenge with LPS, poly(I:C), or low-titer SeV, activated IRF3 was dephosphorylated and returned to resting state without being degraded, although high-titer SeV infection triggered the degradation of IRF3. Furthermore, PP2A-deficient macrophages showed enhanced type I IFN signaling upon LPS, poly(I:C), and SeV challenge and protected mice from lethal vesicular stomatitis virus infection. Therefore, dephosphorylation of IRF3 is a deactivation mechanism that contributes to termination of IRF3-type I IFN signaling.


A novel textual track-data-based approach for estimating individual infection risk of COVID-19.
With the recurrence of infectious diseases caused by coronaviruses, which pose a significant threat to human health, there is an unprecedented urgency to devise an effective method to identify and assess who is most at risk of contracting these diseases. China has successfully controlled the spread of COVID-19 through the disclosure of track data belonging to diagnosed patients. This paper proposes a novel textual track-data-based approach for individual infection risk measurement. The proposed approach is divided into three steps. First, track features are extracted from track data to build a general portrait of COVID-19 patients. Then, based on the extracted track features, we construct an infection risk indicator system to calculate the infection risk index (IRI). Finally, individuals are divided into different infection risk categories based on the IRI values. By doing so, the proposed approach can determine the risk of an individual contracting COVID-19, which facilitates the identification of high-risk populations. Thus, the proposed approach can be used for risk prevention and control of COVID-19. In the empirical analysis, we comprehensively collected 9455 pieces of track data from 20 January 2020 to 30 July 2020, covering 32 provinces/provincial municipalities in China. The empirical results show that the Chinese COVID-19 patients have six key features that indicate infection risk: place, region, close-contact person, contact manner, travel mode, and symptom. The IRI values for all 9455 patients vary from 0 to 43.19. Individuals are classified into the following five infection risk categories: low, moderate-low, moderate, moderate-high, and high risk.


Case for diagnosis. Eyelid edema and erythematous papules disseminated on the face.
Lupus miliaris disseminatus faciei or acne agminata is a chronic inflammatory disorder of the skin, considered an intriguing entity due to its pathogenesis, which is still largely speculative. It has been linked to tuberculosis, sarcoidosis, rosacea, and other granulomatous diseases, but it is considered an independent entity.


What--and why--the pediatric surgeon should know about twin-to-twin transfusion syndrome.
Abstract Endoscopic laser ablation of placental vessels is the most commonly performed fetal operation today. Herein, we review the pathophysiology of twin-to-twin transfusion syndrome and the challenges of its treatment. Pediatric surgeons, with their knowledge of fetal and congenital pathology, and their technical expertise with minimally invasive surgery, can be of great benefit to the patient and the medical team.


Intrinsic properties and synaptic connectivity of Phox2b-expressing neurons in rat rostral parvocellular reticular formation.
The paired-like homeobox 2b gene (Phox2b) is critical for the development of the autonomic nervous system. We have previously demonstrated the distinct characteristics of Phox2b-expressing (Phox2b+) neurons in the reticular formation dorsal to the trigeminal motor nucleus (RdV), which are likely related to jaw movement regulation. In this study, we focused on Phox2b+ neurons in the rostral parvocellular reticular formation (rPCRt), a critical region for controlling orofacial functions, using 2-11-day-old Phox2b-EYFP rats. Most Phox2b+ rPCRt neurons were glutamatergic, but not GABAergic or glycinergic. Approximately 65 % of Phox2b+ rPCRt neurons fired at a low frequency, and approximately 24 % of Phox2b+ rPCRt neurons fired spontaneously, as opposed to Phox2b+ RdV neurons. Stimulation of the RdV evoked inward postsynaptic currents in more than 50 % of Phox2b+ rPCRt neurons, while only one Phox2b+ rPCRt neuron responded to stimulation of the nucleus of the solitary tract. Five of the 10 Phox2b+ neurons sent their axons that ramified within the trigeminal motor nucleus (MoV). Of these, the axons of the two neurons terminated within both the MoV and rPCRt. Our findings suggest that Phox2b+ rPCRt neurons have distinct electrophysiological and synaptic properties that may be involved in the motor control of feeding behavior.


Irreversible shock in rats after injection of microspheres into the renal artery.
After injection of microspheres into both renal arteries of rats, an irreversible shock syndrome develops, resulting in death within 4-12 h. Ligation of both renal pedicles after injection of microspheres prevents the shock. It is presumed that kininogenases released from the kidneys participate in the pathogenesis of the shock syndrome.


The renal function and blood pressure effects of dilevalol in the normotensive and hypertensive elderly.
Dilevalol, the R-R optical isomer of labetalol, is a nonselective beta adrenergic blocking drug with selective beta-2 agonist properties. In a double-blind, crossover study the renal function effects of dilevalol were compared to placebo in 12 normotensive elderly volunteers before and after single dose administration. In addition, chronic treatment (greater than 4 weeks) effects of dilevalol were determined in eight elderly patients with mild to moderate essential hypertension. Renal function was determined by plasma disappearance curves from single injections of 99mTc-DTPA and 131I-orthohippurate. In both study populations renal function tests commenced two hours after dosing at expected peak plasma levels of dilevalol. Normotensive volunteers had an acute decrease in glomerular filtration rate of 10.3 ml/min, which was significant (P less than 0.05), while hypertensive patients had no change in glomerular filtration rate. There were no significant changes in other parameters of renal function measured. In the hypertensive elderly dilevalol treatment resulted in significant reductions, 18 and 19 mmHg respectively, of systolic (P less than 0.01) and diastolic (P less than 0.001) blood pressure. Heart rate was reduced by 5 beats per minute, and the change was not statistically significant. Dilevalol appears to be an excellent agent for treatment of hypertension in the elderly hypertensive patient, and does not change renal function when administered chronically to the hypertensive patient. Small but significant decrements in glomerular filtration rate occur with acute administration to normotensive volunteers.


Ellipsoidal particles at fluid interfaces.
For partially wetting, ellipsoidal colloids trapped at a fluid interface, their effective, interface-mediated interactions of capillary and fluctuation-induced type are analyzed. For contact angles different from 90( degrees ) , static interface deformations arise which lead to anisotropic capillary forces that are substantial already for micrometer-sized particles. The capillary problem is solved using an efficient perturbative treatment which allows a fast determination of the capillary interaction for all distances between and orientations of two particles. Besides static capillary forces, fluctuation-induced forces caused by thermally excited capillary waves arise at fluid interfaces. For the specific choice of a spatially fixed three-phase contact line, the asymptotic behavior of the fluctuation-induced force is determined analytically for both the close-distance and the long-distance regime and compared to numerical solutions.


Applicability of Willems methods and Demirjian's four teeth method for dental age estimation: Cross sectional study on Tunisian sub-adults.
This study aims to evaluate and compare the applicability of three dental methods for age estimation, including Demirjian's four teeth, Willems I, and Willems II methods in a sample of Tunisian children. Panoramic radiographs of 500 children (241 females, 259 males) aged between 5 and 15 years were examined. The mean absolute error (MAE) was performed to assess the accuracy of age estimation. Independent samples t-test was employed to compare the differences, the chronological age minus dental age (CA-DA), between sexes for the three methods. All of the three methods underestimated the chronological age on the average, and almost for all age groups. The discrepancy between the chronological age and the estimated age was most frequently observed for ages above 8 years for all methods. In our study, the Demirjian's four teeth method underestimated the chronological age by 0.45 years for males and 0.32 years for females, with no significant difference (p=0.124). Whereas the Willems I method is indicted for underestimating the chronological age by 0.40 years for males, and by 0.69 years for females. Willems II method underestimated age by 0.91, and 0.64 years for males and females, respectively. It is established that the Demirjian's four teeth method was more accurate in estimating the dental age than the Willems I and II methods, with a mean absolute error of 0.76 years for males and 0.79 years for females (MAE=1.10, and 0.98 years for the Willems I/1.02, and 0.92 years for the Willems II). According to the results, it is highly recommended that the Demirjian's four teeth method should be applied when estimating the dental age in Tunisian males and females. In forensic cases, when the sex is unknown or doubted, the Willems II method could be appropriate.


Unsteady mhd flow of tangent hyperbolic liquid past a vertical porous plate plate.
The analysis in this communication addresses the unsteady MHD flow of tangent hyperbolic liquid through a vertical plate. The model on mass and heat transport is set up with Joule heating, heat generation, viscous dissipation, thermal radiation, chemical reaction and Soret-Dufour in the form of partial differential equations (PDEs). The PDEs are simplified into a dimensionless PDEs by utilizing a suitable quantities. The simplified equations are solved by utilizing the spectral relaxation method (SRM). The outcomes shows that increase in the Weissenberg and the magnetic field degenerates the velocity profile. The thermal radiation is found to elevate the velocity and temperature profiles as its values increases. The impact of Soret and Dufour on the flow is found to alternate each other. The computational outcomes for concentration, temperature and velocity are illustrated graphically for all encountered flow parameters. The present outcomes are compared with previous outcomes and are found to correlate.


The creation of a White Coat Ceremony.
Historically, the White Coat Ceremony has had a medical school connotation. While not exclusive to the discipline of medicine, the White Coat Ceremony is a recently adopted ritual embraced by a variety of health care professions. The white coat serves as a symbol of achievement into one's professional program. The purpose of this article is to provide an overview of the White Coat Ceremony as an emblematic transition into professional nursing education, to provide context of the use of symbolic ceremony in nursing, to describe the details of a White Coat Ceremony currently in place in a nursing college, and to discuss suggestions for replication. A survey to elicit student responses to the ceremonial event was achieved through an IRB study. Results obtained through a student survey were strongly favorable to the personal meaning as to participating in a White Coat Ceremony. The authors endorse the use of such a ceremony in professional nursing education settings.


Pathogenesis of keratoconus: NRF2-antioxidant, extracellular matrix and cellular dysfunctions.
Keratoconus (KC) is a degenerative disease associated with cell and extracellular matrix (ECM) loss that causes gradual thinning and steepening of the cornea and loss of vision. Collagen cross linking with ultraviolet light treatment can strengthen the ECM and delay weakening of the cornea, but severe cases require corneal transplantation. KC is multifactorial and multigenic, but its pathophysiology is still an enigma. Multiple approaches are being pursued to elucidate the molecular changes that underlie the corneal phenotype to identify relevant genes for tailored candidate searches and to develop potential biomarkers and targets for therapeutic interventions. Recent proteomic and transcriptomic studies suggest dysregulations in oxidative stress, NRF2-regulated antioxidant programs, WNT-signaling, TGF-β, ECM and matrix metalloproteinases. This review aims to provide a broad update on the transcriptomic and proteomic studies of KC with a focus on findings that relate to oxidative stress, and dysregulations in cellular and extracellular matrix functions.


Masting, seed dispersal and seed predation in the cycad Macrozamia communis.
Little is known about the adaptive value of mast seeding, a common phenomenon in temperate trees and shrubs. Masting is likely to affect both seed dispersal and seed predation. In systems where similar taxa of animals are involved in these two processes, the consequences of mast seeding are likely to be particularly complicated. This study examined the effects of mast seeding in a cycad, Macrozamia communis, on the dispersal of seeds, the pattern of dispersion of seeds and post-dispersal predation on seeds. Dispersal of seeds by possums was poorer from source plants in a masting population than from source plants in an adjacent, non-masting population. This resulted in fewer seeds per seeding female plant in the masting plot being dispersed to favourable sites. We conclude that this is caused by the feeding behaviour and movements of possums in the masting site. The abundance of seeds in this site did not satiate the post-dispersal predators, native rats. In fact, more seeds in this site were eaten than in the nonmasting site. We suggest that the mast seeding observed in M. communis may not be adaptive, but is more likely a consequence of other factors which synchromize flowering within local populations.


A multiple mediation analysis of the association between asynchronous use of music and running performance.
The purpose of this study was to examine if the effects of asynchronous use of music on running performance are directly and/or indirectly carried through psychological, psychophysical, and psychophysiological benefits. Following a standardized music selection procedure, 20 healthy undergraduate students (10 males, 10 females) completed a 30-min treadmill run at perceived moderate intensity while listening to music (135-140 beats per minute) or under a no-music condition in a randomized order. Participants' affective valence, arousal, perceived exertion, heart rate during the run, and running distance were measured in both trials. A mediation analysis was conducted for 40 data collected from the 20 participants under two conditions (no music; music) with a parallel mediation model in which affective valence, arousal, heart rate, and perceived exertion were specified as mediators. A significant indirect effect of affective valence was observed for running distance. The present finding supports the notion that the relationship between asynchronous use of music and running distance is mediated by psychological benefits.


Anatomy and assessment of a modified technique during totally robotic distal gastrectomy: A retrospective cohort study.
Robotic surgery has potential benefits in the management of gastric cancer patients. This study compares the outcomes between totally robotic distal gastrectomy (TRDG) with modified port placement and arm positioning technique and conventional totally laparoscopic distal gastrectomy (CTLDG). Fifty-two patients were enrolled into the study following a retrospective review of an in-patient database between January 2019 and June 2021. Patients who underwent gastric resection with the modified robotic technique were recruited into the study. Patients who did not receive treatment using the modified technique were excluded from the study. Data on demographic, clinical data and surgical outcomes were collected, analyzed, and presented. All statistical analyses were done using IBM SPSS statistical software. Nineteen patients were in the TRDG group, and their mean age was 60.42 ± 11.53 years. There were no differences in demographic characteristics (all p > 0.05); nonetheless, laparoscopic patients had a significantly higher preoperative albumin level (p = 0.000). The operative time was longer in the TRDG group (223min), but the difference was insignificant. The reconstruction time was significantly shorter for the laparoscopic group (p = 0.000). Except for a significantly higher value of postoperative albumin level (p-value = 0.005) in the robotic group, there were no significant differences in all other surgical outcomes between the two groups. One (5.3%) patient had a severe complication in the robotic group compared to four (12.1%) in the laparoscopic group. Nevertheless, the differences in complications were statistically insignificant. The modified approach is a safe and feasible in totally robotic distal gastrectomy for the treatment of gastric cancer patients.


Corneal epithelial dendritic cells in patients with multiple sclerosis: An in vivo confocal microscopy study.
To evaluate density and morphology of corneal epithelial dendritic cells (DCs) in patients with multiple sclerosis (MS) using in vivo confocal microscopy (IVCM). This was a single-center cross-sectional comparative study. All MS patients were clinically scored using the Expanded Disability Status Scale (EDSS) score. Patients underwent ophthalmological examination and then cornea was analyzed by IVCM Heidelberg Retina Tomograph (HRT 3) in combination with Rostock Cornea Module and CCD camera. Five sectors (central, nasal, temporal, inferior, superior and central area) were analyzed in both patient eyes, then for each sector one image was selected and analyzed by using the manual cell counting system offered with the software and ImageJ program. DCs density (cell/mm2) and DCs size (µm2) were considered for the analyses. Difference between the two groups and correlation between DCs, MS type, EDSS score, optic neuritis and ongoing therapy were analyzed. We enrolled 46 consecutive patients: 23 with MS (age 47.87 ± 7.22 years (mean ± standard deviation) and 21 healthy subjects (age 46.0 ± 12.6 years) from July 2017 to July 2018. MS patients showed a lower DCs density when compared with healthy subjects (p < 0.05). Moreover, we found a direct correlation (r:0.48, p < 0.05) between DCs density and ongoing disease-modifying therapy. IVCM was able to show a difference in corneal DCs density between MS patients and healthy subjects, providing an insight to the underlying changes of the clinical manifestations of MS. Further studies are needed to provide evidence of possible clinical implications.


Classification of Presbyopia by Severity.
There are close to two billion individuals globally living with presbyopia. In spite of its ubiquitous and progressive nature, there is no widely accepted, formal guideline or consensus statement on the classification of presbyopia by degree of severity. A panel of leading eye care professionals representing both optometrists and ophthalmologists convened virtually to discuss and document their combined assessments from the body of literature and clinical practice expertise in this commentary. In light of emerging therapies, classifying presbyopia by mild, moderate, or advanced severity may help provide consistency of diagnosis among eye care providers and may aid in managing patient expectations with different treatment options.


Sports dentistry and the olympic games.
This paper will provide a review of dental services from previous Olympic Games, and will outline components of an ideal dental program for future event organizers.


Abdominal wall endometriosis in the cesarean section surgical scar: a potential diagnostic pitfall.
The abdominal wall is an uncommon site of extrapelvic endometriosis. It usually develops in a previous surgical scar and should be considered in the differential diagnosis of any abdominal swelling. Classical symptoms of endometriosis may resemble abdominal wall lesions such as an incisional hernia, hematoma, granuloma, abscess or various soft tissue tumors; therefore, a definitive preoperative diagnosis is not always easy to determine in every case. The aim of this article is to review the clinical findings, imaging results and histopathology of those of our patients who have had cesarean scar endometriosis. Patients diagnosed with abdominal wall endometriosis in their surgical scars from February 2008 to March 2010 were documented. The age, parity, symptoms, previous surgeries, initial diagnosis, diagnostic modalities, definitive operation, postoperative complications, histopathological evaluations and recurrences were recorded and analyzed. There were 18 patients with a mean age of 34.5 ± 9.6 years. All (100%) had a gradually growing nodular abdominal mass in or adjacent to their cesarean incision scars. This was often associated with pain (83.3%), either noncyclical (26.6%) or cyclical (73.3%) in nature. Ultrasonography (100%), computerized tomography with intravenous contrast (22.2%) and/or magnetic resonance imaging (66.6%) were performed on the patients. All patients underwent surgery and their masses were completely excised. The mean diameter of the removed masses was 3.9 ± 1.4 cm. The final pathological diagnosis for each case was abdominal wall endometriosis. Biannual follow-up examinations for two years revealed that each patient had a complete and uneventful recovery without recurrence. Abdominal wall endometriosis should be considered in the differential diagnosis of masses located at cesarean section incision scars, which should be excised for definitive diagnosis and treatment.


Genetic and functional characterization of a yet-unclassified rhizobial Dtr (DNA-transfer-and-replication) region from a ubiquitous plasmid conjugal system present in Sinorhizobium meliloti, in Sinorhizobium medicae, and in other nonrhizobial Gram-negative bacteria.
Rhizobia are Gram-negative bacteria that live in soils and associate with leguminous plants to establish nitrogen-fixing symbioses. The ability of these bacteria to undergo horizontal gene transfer (HGT) is thought to be one of the main features to explain both the origin of their symbiotic life-style and the plasticity and dynamics of their genomes. In our laboratory we have previously characterized at the species level the non-pSym plasmid mobilome in Sinorhizobium meliloti, the symbiont of Medicago spp., and have found a high incidence of conjugal activity in many plasmids (Pistorio et al., 2008). In this work we characterized the Dtr (DNA-transfer-and-replication) region of one of those plasmids, pSmeLPU88b. This mobilization region was found to represent a previously unclassified Dtr type in rhizobia (hereafter type-IV), highly ubiquitous in S. meliloti and found in other genera of Gram-negative bacteria as well; including Agrobacterium, Ochrobactrum, and Chelativorans. The oriT of the type-IV Dtr described here could be located by function within a DNA fragment of 278 bp, between the divergent genes parA and mobC. The phylogenetic analysis of the cognate relaxase MobZ indicated that this protein groups close to the previously defined MOB(P3) and MOB(P4) type of enzymes, but is located in a separate and novel cluster that we have designated MOB(P0). Noteworthy, MOB(P0) and MOB(P4) relaxases were frequently associated with plasmids present in rhizospheric soil bacteria. A comparison of the nod-gene locations with the phylogenetic topology of the rhizobial relaxases revealed that the symbiotic genes are found on diverse plasmids bearing any of the four Dtr types, thus indicating that pSym plasmids are not specifically associated with any particular mobilization system. Finally, we demonstrated that the type-IV Dtr promoted the mobilization of plasmids from S. meliloti to Sinorhizobium medicae as well as from these rhizobia to other bacteria by means of their own helper functions. The results present an as-yet-unclassified and seemingly ubiquitous conjugal system that provides a mechanistic support for the HGT between sympatric rhizobia of Medicago roots, and between other soil and rhizospheric bacteria.


Coding external causes of injuries: problems and solutions.
Complete and accurate information about hospitalised injuries is essential for injury risk and outcome research, though the accuracy and reliability of hospital data for injury surveillance are often questioned. To ascertain clinical coders' views of the reasons for a lack of specificity in external cause code usage and ways to improve external cause coding, a nationwide survey of coders was conducted in Australia in 2006. Four hundred and two coders participated in the questionnaire. The results of this study show that discharge summaries and doctors' notes were the poorest source of information regarding external causes, place of injury occurrence, and activity at the time of injury. Coders viewed missing external cause information and missing documentation as having the greatest impact on the quality of external cause coding. A large majority of coders suggested that improving clinical documentation in the emergency department and introducing a centralised structured form for external cause information would improve the quality of external cause coding. Clinical coders are a valuable source of information regarding problems with, and solutions to the collection of high quality data and this research has highlighted several areas where improvements can be made and further research is needed.


New cancer biomarkers deriving from NCI early detection research.
Cancer is not a single disease but an accumulation of several events, genetic and epigenetic, arising in a single cell over a long time interval. A high priority in the cancer field is to identify these events. This can be achieved by characterizing cancer-associated genes and their protein products. Identifying the molecular alterations that distinguish any particular cancer cell from a normal cell will ultimately help to define the nature and predict the pathologic behavior of that cancer cell. It will also indicate the responsiveness to treatment of that particular tumor. Understanding the profile of molecular changes in any particular cancer will be extremely useful as it will become possible to correlate the resulting phenotype of that cancer with molecular events. Achieving these goals and knowledge will provide an opportunity for discovering new biomarkers for early cancer detection and developing prevention approaches. This will also help us identify new targets for therapeutic development. Advancement in technology includes methods and tools that enable research including, but not limited to, instrumentation, techniques, devices, and analysis tools (e.g., computer software). Resources such as databases, reagents, and tissue repositories are different than technologies. The identification and definition of the molecular profiles of cancer will require the development and dissemination of high-throughput molecular analysis technologies, as well as elucidation of all of the molecular species embedded in the genome of cancer and normal cells. The main challenge in cancer control and prevention is to detect the cancer early. This could then enable effective interventions and therapies contributing to reduction in mortality and morbidity. At a specific time, biomarkers serve as molecular signposts of the physiologic state of a cell. These signposts are the result of genes, their products (proteins) and other organic chemicals made by the cell. Biomarkers could prove to be vital for the identification of early cancer and subjects at risk of developing cancer as a normal cell progresses through the complex process of transformation to a cancerous state. This chapter discusses ongoing research in genetic and proteomic approaches to identify molecular signatures such as protein profiles, microsatellite instability, hypermethylation, and single nucleotide polymorphisms. Other topics covered here include the use of genomics and proteomics as high-throughput technology platforms to facilitate biomarker-aided detection of early cancer. Other areas covered include issues surrounding the analysis, validation, and predictive value of biomarkers using such technologies. Recent advances in noninvasive techniques, such as buccal cell isolates serving as viable sources of biomarkers, complementary to traditional sources such as serum or plasma, are also presented. The review also brings attention to the efforts of the Early Detection Research Network (EDRN) at the National Cancer Institute (NCI), in bringing together scientific expertise from leading national and international institutions, to identify and validate biomarkers for the detection of precancerous and cancerous cells in determining risk for developing cancer. The network's serious determined efforts in linking discovery to process development, resulting in early detection tests and clinical assessment, are also discussed.


Retracted: A Novel of New 7D Hyperchaotic System with Self-Excited Attractors and Its Hybrid Synchronization.
[This retracts the article DOI: 10.1155/2021/3081345.].


Predicting siRNA efficacy based on multiple selective siRNA representations and their combination at score level.
Small interfering RNAs (siRNAs) may induce to targeted gene knockdown, and the gene silencing effectiveness relies on the efficacy of the siRNA. Therefore, the task of this paper is to construct an effective siRNA prediction method. In our work, we try to describe siRNA from both quantitative and qualitative aspects. For quantitative analyses, we form four groups of effective features, including nucleotide frequencies, thermodynamic stability profile, thermodynamic of siRNA-mRNA interaction, and mRNA related features, as a new mixed representation, in which thermodynamic of siRNA-mRNA interaction is introduced to siRNA efficacy prediction for the first time to our best knowledge. And then an F-score based feature selection is employed to investigate the contribution of each feature and remove the weak relevant features. Meanwhile, we encode the siRNA sequence and existed empirical design rules as a qualitative siRNA representation. These two kinds of siRNA representations are combined to predict siRNA efficacy by supported Vector Regression (SVR) at score level. The experimental results indicate that our method may select the features with powerful discriminative ability and make the two kinds of siRNA representations work at full capacity. The prediction results also demonstrate that our method can outperform other popular siRNA efficacy prediction algorithms.


Evolution of primary tumors induced in adult mice by MSV-H and MSV-H producer tumor cells.
The oncogenic activity of both MSV-H and MSV-H-producer tumor cells (3T3 + MSV-H) in adult mice was investigated and compared. A higher incidence of tumors was observed with MSV-H tumor cells, especially with very small tumor cell doses. No regression was observed in any of the induced tumors.


Current metabolomics: technological advances.
Metabolomics, the global quantitative assessment of metabolites in a biological system, has played a pivotal role in various fields of science in the post-genomic era. Metabolites are the result of the interaction of the system's genome with its environment and are not merely the end product of gene expression, but also form part of the regulatory system in an integrated manner. Therefore, metabolomics is often considered a powerful tool to provide an instantaneous snapshot of the physiology of a cell. The power of metabolomics lies on the acquisition of analytical data in which metabolites in a cellular system are quantified, and the extraction of the most meaningful elements of the data by using various data analysis tool. In this review, we discuss the latest development of analytical techniques and data analyses methods in metabolomics study.


Identification of the novel HLA allele, HLA-C*04:01:01:129, in an individual from northeast India.
The novel allele HLA-C*04:01:01:129 as compared to HLA-C*04:01:01:01 displays polymorphism at two positions; gDNA 2905 (C → T) and 2910 (T → A).


Falling through the cracks: Evaluating the role of nonacute surgical liaison personnel during COVID-19-A narrative review.
In March 2020, in response to the COVID-19 pandemic, the New Zealand government instituted a 4-level alert system, which resulted in the rapid dissolution of nonurgent surgical services to minimize occupational exposure to both patients and staff, with the primary health sector bearing most of the diverted caseload. Consequently, the study authors sought to collate information around the establishment of a supportive nonacute surgical liaison role in a public hospital surgical department, with an interest in establishing this role in New Zealand. The narrative review conducted systematically in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases searched included Pubmed, MEDLINE, Embase, and Cochrane Controlled Register of Trials. A deductive analysis was applied using a demand management model developed by the Institute for Innovation and Improvement at Waitematā District Health Board. All included studies were rated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool. Collation of 19 studies resulted in 3 key findings: first, that a surgical liaison could be utilized at the primary care to specialist interface to improve communication and workflow between services. Second, a liaison could be utilized directly communicating with patients as a means of increasing engagement and self-management. Finally, this service can be offered through multiple modalities including a noncontact telehealth service. Evidence of nonacute surgical liaisons both internationally and specifically within New Zealand has been collated to provide evidence for its application.