Studies on pineal melatonin levels in a diurnal species, the eastern chipmunk (Tamias striatus): effects of light at night, propranolol administration or superior cervical ganglionectomy.
Five experiments were carried out on the control of melatonin levels in the pineal gland of a diurnal species, the Eastern chipmunk (Tamias striatus). We confirmed that the exposure of chipmunks of fluorescent white light of 3,981-4,304 lux during the normal dark period does not prevent the rise in pineal melatonin levels normally associated with darkness. Also, the administration of propranolol (20 mg/kg) at 8 p.m. did not block the rise in pineal melatonin in animals exposed to either dark or light at night. Similarly, if chipmunks received propranolol 4 hours into the dark phase, pineal melatonin levels were not depressed 2 hours later. When animals were superior cervical ganglionectomized, however, the pineal content of melatonin remained low regardless of whether animals were exposed to darkness or light at night. The exposure of chipmunks acutely to light at midnight (4 hours after darkness onset) had only a slight depressive effect on pineal melatonin 30 min later; by comparison, when chipmunks were acutely exposed to light at 3 a.m. (7 hours after darkness onset) daytime pineal melatonin levels were reached within 15 min after light onset. These findings in a diurnal species, The Eastern chipmunk, differ markedly when compared to previously reported observations on nocturnal laboratory rodents.


Bortezomib inhibits NLRP3 inflammasome activation and NF-κB pathway to reduce psoriatic inflammation.
The abnormal activation of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in the pathogenesis of psoriasis. Accordingly, the inhibition of NLRP3 inflammasome may be an effective strategy for psoriasis treatment. However, the NLRP3 inflammasome inhibitors are not available in the clinic. Repurposing FDA-approved drugs is a highly attractive way for identifying new drugs. Here, proteasome inhibitor bortezomib, a marketed drug for treating multiple myeloma, was found to specifically inhibit NLRP3 inflammasome activation at nanomolar concentrations. Mechanistically, bortezomib did not inhibit reactive oxygen species generation, ion efflux, NLRP3 oligomerization, and NLRP3-ASC interactions. Bortezomib reduced ASC oligomerization and ASC speck formation. In addition, bortezomib inhibited the activity of the core subunit β5i in the immunoproteasome and reduced β5i binding to NLRP3. Bortezomib reduced the production of interleukin-1β and attenuated the severity of skin lesions in the imiquimod-induced psoriatic mouse model. Thus, bortezomib is a potential therapeutic drug for psoriasis. Our study also revealed that β5i may be an indirect target for regulating NLRP3 inflammasome activation and treating psoriasis and other NLRP3 inflammasome-related diseases.


Registered Dietitian Nutritionists' Role in Hospital in Home.
Hospital in Home (HIH) involves the delivery of acute care services in a patient's home. There is currently a paucity of published information regarding nutrition care in HIH. The registered dietitian nutritionist (RDN) contributes to HIH by providing personalized medical nutrition therapy and collaborating with the HIH interdisciplinary team for optimal health care delivery. Tips for utilizing RDN services are also discussed. As HIH becomes more widely adopted within the Veterans Health Administration and other health care systems, it is crucial to consider the value and expertise of the RDN for guiding nutrition care in the HIH setting.


The relationship between Group relative deprivation and aggressive collective action online toward deprivation-related Provocateurs within the Group: the mediating role of hostile feelings.
Aggressive collective action online has many negative impacts on the online environment and can even lead to political violence or social panic in the offline world. Although the effect of relative deprivation on aggression toward the compared object is well known, the influence of relative deprivation on aggressive collective action online toward deprivation-related provocateurs within the group has been ignored. Thus, this study attempted to explore the effect, as well as the mediating mechanism underlying it. We found that group relative deprivation manipulated by an employment problem scenario (with the triggering event as a covariable) can enhance aggressive collective action online toward deprivation-related provocateurs within the group, with hostile feelings mediating the effect. These results support and develop the relative deprivation theory, frustration-aggression theory, stress and coping theory, and deepen the understanding of the relationship between relative deprivation and aggression. The findings also suggest that colleges should focus more on graduate employment problems and decreasing the relative deprivation experienced by undergraduate students in efforts to prevent aggressive collective action online.


Fatigue, Physical Disability and Self-Efficacy as Predictors of the Acceptance of Illness and Health-Related Quality of Life in Patients with Multiple Sclerosis.
Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system that leads to permanent disability and many neurological symptoms, making everyday functioning difficult. The predictors of the acceptance of illness and the health-related quality of life in people with MS include the degree of disability, neurological symptoms and psychosocial factors, such as personal resources. The aim of our study is to determine the relationships among disability, fatigue, self-efficacy, acceptance of illness and quality of life. The study group consisted of 137 people diagnosed with multiple sclerosis-73 women and 64 men. EDSS, GNDS, LSES, AIS and MSIS-29 were used in the present study. The results show that all tested variables were significantly correlated with each other. Disability and fatigue were significant predictors of both the physical and psychological aspects of patients' quality of life. Self-efficacy was a significant predictor of both the acceptance of illness and the psychological aspect of patients' quality of life. Based on the current research study, it can be concluded that factors of a biomedical nature explain other aspects of struggling with the disease, rather than psychological resources.


Chronic atrophic gastritis and risk of N-nitroso compounds carcinogenesis.
Chronic atrophic gastritis is considered a precancerous condition for carcinoma of the stomach. To evaluate the correlation between progressive alterations in the mucosa and gastric juice microenvironmental factors, retained involved on N-nitroso compounds carcinogenesis, detailed analyses of biochemical and microbiological parameters such as pH, total viable counts (TVC), nitrate reductase positive bacterial counts (NRPBC), nitrite (NO2-) and thiocyanate (SNC-) levels, were carried out on 56 fasting gastric juices samples obtained at endoscopy from 28 patients with chronic atrophic gastritis (CAG), 14 with gastric cancers (GC), and 14 normal controls (NC). The mean values of pH, nitrite, TVC, and NRPBC were significantly lower in the juices of NC than in those of CAG and GC patients. Furthermore, the mean levels of the same parameters were higher in GC than in CAG juices. No significant difference was found in the three groups for SCN- level which principally resulted influenced by smoke habit. The 28 patients with CAG were subdivided into two groups (Group A = Diffuse chronic atrophic gastritis--DCAG; Group B = Multifocal chronic atrophic gastritis--MCAG) according to the involvement of gastric corpus and fundus besides antrum by a process of mucosal atrophy. The mean levels of pH, nitrite, TVC, and NRPBC were significantly higher in MCAG than in normal controls but statistically lower in reference to DCAG and cancers. In these two groups no difference was found for the same variables. The percentage of contaminated juices was higher for DCAG and cancers in respect to MCAG but no difference was found between DCAG and neoplastic stomachs. The results of this study suggest that the DCAG could be considered as the chronic atrophic gastritis type more exposed to the risk of N-nitroso compounds carcinogenesis.


Boosted regression tree model-based assessment of the impacts of meteorological drivers of hand, foot and mouth disease in Guangdong, China.
Hand, foot and mouth disease (HFMD) is a common childhood infection and has become a major public health issue in China. Considerable research has focused on the role of meteorological factors in HFMD development. Nonlinear relationship, delayed effects and collinearity problems are key issues for achieving robust and accurate estimations in this kind of weather-health relationship explorations. The current study was designed to address these issues and assess the impact of meteorological factors on HFMD in Guangdong, China. Case-based HFMD surveillance data and daily meteorological data collected between 2010 and 2012 was obtained from China CDC and the National Meteorological Information Center, respectively. After a preliminary variable selection, for each dataset boosted regression tree (BRT) models were applied to determine the optimal lag for meteorological factors at which the variance of HFMD cases was most explained, and to assess the impacts of these meteorological factors at the optimal lag. Variance of HFMD cases was explained most by meteorological factors about 1 week ago. Younger children and those from the Pearl-River Delta Region were more sensitive to weather changes. Temperature had the largest contribution to HFMD epidemics (28.99-71.93%), followed by precipitation (6.52-16.11%), humidity (3.92-17.66%), wind speed (3.84-11.37%) and sunshine (6.21-10.36%). Temperature between 10°C and 25°C, as well as humidity between 70% and 90%, had a facilitating effect on the epidemic of HFMD. Sunshine duration above 9h and wind speed below 2.5m/s also contributed to an elevated risk of HFMD. The positive relationship between HFMD and precipitation reversed when the daily amount of rainfall exceeded 25 mm. This study indicated significantly facilitating effects of five meteorological factors within some range on the epidemic of HFMD. Results from the current study were particularly important for developing early warning and response system on HFMD in the context of global climate change.


A Randomized, Double-Blind, Placebo-Controlled Study of an Anthocyanin-Rich Functional Ingredient on Cognitive Function and Eye Dryness in Late Adulthood Volunteers: Roles of Epigenetic and Gut Microbiome Modulations.
Due to the rising demand for supplements targeting cognitive enhancement and dry eye together with the health benefits of anthocyanins, we have developed a functional soup containing an anthocyanin-rich functional ingredient, or "Anthaplex," and assessed the effects on cognitive function and eye dryness together with the possible mechanisms. A total of 69 male and female health volunteers were randomized and divided into placebo, D2, and D4 groups. All subjects consumed 120 mL of placebo or functional soup containing "Anthaplex" either at 2 or 4 g per serving per day within 5 min in the morning for eight weeks. The cognitive function, working memory, dry eye, AChE, MAO, MAO-A, MAO-B, and GABA-T activities, BDNF, HAC, HDAC, and DNMT activities, pH, and amount of lactic acid-producing bacteria, particularly Lactobacillus and Bifidobacterium spp. in feces, were determined before intervention and after eight weeks of consumption. Subjects who consumed the "Anthaplex" soup had improved cognitive function, working memory, eye dryness, histone acetylation, ACh E suppression, and BDNF with increased Bifidobacterium spp. but decreased pH in feces. These data suggest that "Anthaplex" improves cognitive function and eye dryness via the modulations of the histone acetylation process, gut microbiome, and cholinergic function.


Effectiveness of the computerized balance rehabilitation after hip fracture surgery: A study protocol of a prospective and open-label clinical trial.
Although balance problems in older populations are directly correlated with hip fractures, the overall physical gain afforded by balance rehabilitation itself has not yet been fully investigated. Here we describe a protocol for an open-label clinical trial to evaluate the effectiveness of computer-based balance-specific exercise (BSE) on the performance and balance of elderly women who underwent hip fracture surgery (HFS). Elderly female patients (≥65 years old) who underwent surgery for femoral neck, intertrochanteric, or subtrochanteric fracture regardless of surgery type will be included. The BSE will be conducted using a computed posturographic system for a 2-week intervention period following HFS. The primary outcome of this study is Berg balance scale score. All functional outcomes will be measured at 1 and 3 weeks and at 3 and 6 months after the surgical intervention. The data will be analyzed using the intention-to-treat principle.


Dissociative states in multiple personality disorder: a quantitative study.
Multiple personality disorder (MPD) patients may experience themselves as several discrete alter personalities who do not share consciousness or memories with one another. In this study, we asked whether MPD patients are different from controls in their ability to learn and remember, and their ability to compartmentalize information. MPD patients were not found to differ from controls in overall memory level. Learning of information by MPD patients in disparate personality states did not result in greater compartmentalization than that of which control subjects were capable. However, there were qualitative differences between the cognitive performance of patients and that of controls attempting to role-play alter personalities. Our results suggest that simple confabulation is not an adequate model for the MPD syndrome, and we consider a possible role for state-dependent learning in the phenomenology of MPD.


Tailored Graphene Micropatterns by Wafer-Scale Direct Transfer for Flexible Chemical Sensor Platform.
2D materials, such as graphene, exhibit great potential as functional materials for numerous novel applications due to their excellent properties. The grafting of conventional micropatterning techniques on new types of electronic devices is required to fully utilize the unique nature of graphene. However, the conventional lithography and polymer-supported transfer methods often induce the contamination and damage of the graphene surface due to polymer residues and harsh wet-transfer conditions. Herein, a novel strategy to obtain micropatterned graphene on polymer substrates using a direct curing process is demonstrated. Employing this method, entirely flexible, transparent, well-defined self-activated graphene sensor arrays, capable of gas discrimination without external heating, are fabricated on 4 in. wafer-scale substrates. Finite element method simulations show the potential of this patterning technique to maximize the performance of the sensor devices when the active channels of the 2D material are suspended and nanoscaled. This study contributes considerably to the development of flexible functional electronic devices based on 2D materials.


[Evaluation of an information document about patients and transfusion].
To evaluate the understanding of written information contained in the information sheet for patients intended to receive an homologous transfusion and to know their opinion about this document. A prospective cohort survey carried out by people unrelated to clinical units and transfusion services. A document divided in two parts, the first one summarized, the second detailed, was distributed to transfused adult patients. The patients were hospitalized in the general surgery and orthopedic wards of two hospitals and in the hematology and oncology wards of two different hospitals. A questionnaire was filled out in the presence of the inquirer. Sixty one subjects have been enrolled, among them 53 considered the information as adequate; 53 as comforting and neutral. 53 patients considered a written information as essential and 52 estimated that both part of the information sheet (summarized and detailed) were mandatory. Conversely, a more in depth investigation revealed there was a gap between patients statements and their true understanding. The value of a written information for the patients is confirmed by the study. In addition, patients were not generally worried by this information. The partition of the document has been appreciated. It is noteworthy that a gap exist between the patient's perception of the information and their actual level of understanding.


Radiation-induced atherosclerotic plaque progression in a hypercholesterolemic rabbit: a prospective vulnerable plaque model?
Human observations provide rich soil for making hypotheses, but good animal models are essential for understanding the disease and to test treatment modalities. Currently, there is no standard animal model of vulnerable plaque; therefore, the purpose of this study is to develop a pathophysiologically relevant vulnerable plaque model. New Zealand White rabbits were fed with 1% hypercholesterolemic (HC) diet for 7 days, followed by balloon denudation of both the iliac arteries, and continued on 1% HC diet. Four weeks later, in 12 rabbits one of the iliac arteries was radiated (192-Ir, 15 Gy), and in five rabbits both the iliac arteries were sham treated. Following that, rabbits were fed with 0.15% HC diet. Four weeks later, arteries were processed for histomorphometry or immunohistochemistry. Serum cholesterol levels were similar in all the groups. In radiated arteries, plaque area was significantly larger (32% larger then in sham). Macrophage-positive area in radiated arteries was 2.4 times greater than the macrophage-positive area in the nonradiated arteries. The area positive for macrophages is also positive for metalloproteinases (MMP)-1. The extent of alpha-actin positive area was significantly less (2.3-fold) in radiated arteries. The atherosclerotic plaque developed in the current model is predominantly composed of macrophages expressing metalloproteinases with few smooth muscle cells (SMC)--a characteristic of vulnerable plaque. The animal model presented in this study can elucidate at least part of the mechanism of plaque vulnerability and could be used to test treatment modalities to test plaque stability.


Conservation of Gbx genes from EHG homeobox in bivalve molluscs.
Homeobox-containing genes encode a set of transcription factors that have been shown to control spatial patterning mechanisms in bilaterian organism development. The homeobox gene Gbx, included in the EHGbox cluster, is implicated in the development of the nervous system. In this study, we surveyed five different families of Bivalvia for the presence of Gbx genes by means of PCR with degenerate primers. We were able to recover seven Gbx gene fragments from five bivalve species: Solen marginatus, Mimachlamys varia, Venerupis pullastra, Ostrea edulis and Mytilus galloprovincialis (the derived amino acid sequence were designated Sma-Gbx, Cva-Gbx, Vpu-Gbx, Oed-Gbx and Mga-Gbx, respectively). These genes are orthologous to various Gbx genes present in bilaterian genomes. The Gbx genes in four Bivalvia families, namely Solenidae, Veneridae, Ostreidae and Mytilidae, are newly reported here and we also showed additional information of the Gbx genes of Pectinidae. The phylogenetic analyses by neighbour-joining, UPGMA, maximum parsimony and Bayesian analysis clearly indicated that the Gbx sequences formed a well supported clade and assigned these Gbx genes to the Gbx family. These data permit to confirm that the homeodomain of the Gbx family is highly conserved among these five distinct families of bivalve molluscs.


Tricuspid valve thrombus: a case report associated with gonadotropin-releasing hormone analogue therapy and review of the literature.
A 35-year-old woman with a previously repaired atrial septal defect was referred for preoperative evaluation before laparoscopic surgery. The patient was asymptomatic, and a transesophageal echocardiographic examination revealed a probable thrombus attached to the tricuspid valve. The patient's history included therapy with a gonadotropin-releasing hormone analogue and deep venous thrombosis five months earlier. The tricuspid valve thrombus disappeared after anticoagulant therapy. Warfarin was initiated for prophylaxis. During the follow-up, the patient was event-free during laparoscopic surgery and pregnancy (when warfarin was switched to acetylsalicylic acid) and gave birth to a healthy term baby. Because etiological investigations revealed no reason for the tricuspid valve thrombus, it was considered to be related to the procoagulant state induced by hormonal treatment. The patient was scheduled for close follow-up.


Muscle quality determined by computed tomography predicts short-term and long-term survival after liver transplantation.
Sarcopenia, the loss of muscle mass and quality, contributes to worse clinical outcome in patients with end-stage liver disease, but its impact on short- and long-term survival remains insufficiently understood. The aim of this study was to evaluate the development of computed tomography (CT) muscle parameters and their impact on short-term and long-term survival after liver transplantation. This retrospective study included patients with liver transplantation between 2011 and 2015 and a pre-transplant CT scan. Clinical characteristics, CT muscle mass and density were assessed pre-transplant, and in available CT scans at short-term (11 months) and long-term follow-up (56 months). Overall, 93/152 (61%) patients (109 male, 55 ± 10 years) suffered from sarcopenia pre-transplant. In short- (n = 50) and long-term follow-up (n = 52) the muscle mass (- 2.65 cm2/m2 95% CI [- 4.52, - 0.77], p = 0.007; - 2.96 cm2/m2 [- 4.7, - 1.23], p = 0.001, respectively), and muscle density (- 3 HU [- 6, - 1], p = 0.007; - 2 HU [- 4, 0], p = 0.069) decreased. Myosteatosis was associated with a higher post-transplant mortality (survival probability: 3 months 72% vs. 95%, 1 year 63% vs. 90%, 5 years 54% vs. 84%, p = 0.001), while muscle mass was not. In conclusion, muscle mass and quality did not improve after transplant. Muscle quality predicts short- and long-term survival and could help to identify a patient's risk profile.


Parathyroid gland responsiveness to acute hypocalcemia in dialysis osteomalacia.
The majority of chronic hemodialysis patients have elevated serum iPTH levels and bone disease characterized by osteitis fibrosa. However, a small group of patients develop osteomalacic bone disease associated with normal or slightly elevated iPTH values and a tendency to hypercalcemia which occurs either spontaneously or after treatment with small doses of vitamin D sterols. To examine the causes of the relatively low iPTH levels, we evaluated the change in serum iPTH levels that occurred in response to acute hypocalcemia, produced by dialysis using a low calcium dialysate, in 11 patients with osteomalacia and 8 control hemodialysis patients. Dialysis against a dialysate free of calcium for 60 to 90 min led to a fall in serum calcium to 7.5 +/- 0.2 and 7.2 +/- 0.2 mg/dl in the osteomalacic and control patients, respectively. Serum iPTH rose in controls from 1380 +/- 287 to 1960 +/- 287 pg/ml (P less than 0.01), whereas in patients with osteomalacia it rose from 360 +/- 58 to 507 +/- 104 pg/ml (P less than 0.05), a value only slightly above normal for this PTH assay. These data suggest that the relatively low basal levels of serum iPTH do not arise as a consequence of physiologic suppression of parathyroid gland function. This reduction in parathyroid function could contribute to the pathogenesis of low turnover osteomalacia.


Computational model for analyzing the evolutionary patterns of the neuraminidase gene of influenza A/H1N1.
In this study, we performed computer simulations to evaluate the changes of selection potentials of codons in influenza A/H1N1 from 1999 to 2009. We artificially generated the sequences by using the transition matrices of positively selected codons over time, and their similarities against the database of influenzavirus A genus were determined by BLAST search. This is the first approach to predict the evolutionary direction of influenza A virus (H1N1) by simulating the codon substitutions over time. We observed that the BLAST results showed the high similarities with pandemic influenza A/H1N1 in 2009, suggesting that the classical human-origin influenza A/H1N1 isolated before 2009 might contain some selection potentials of swine-origin viruses. Computer simulations using the time series codon substitution patterns resulted dramatic changes of BLAST results in influenza A/H1N1, providing a possibility of developing a method for predicting the viral evolution in silico.


Predictive Model and Precaution for Oral Mucositis During Chemo-Radiotherapy in Nasopharyngeal Carcinoma Patients.
To explore risk factors for severe acute oral mucositis of nasopharyngeal carcinoma (NPC) patients receiving chemo-radiotherapy, build predictive models and determine preventive measures. Two hundred and seventy NPC patients receiving radical chemo-radiotherapy were included. Oral mucosa structure was contoured by oral cavity contour (OCC) and mucosa surface contour (MSC) methods. Oral mucositis during treatment was prospectively evaluated and divided into severe mucositis group (grade ≥ 3) and non-severe mucositis group (grade < 3) according to RTOG Acute Reaction Scoring System. Nineteen clinical features and nineteen dosimetric parameters were included in analysis, least absolute shrinkage and selection operator (LASSO) logistic regression model was used to construct a risk score (RS) system. Two predictive models were built based on the two delineation methods. MSC based model is more simplified one, it includes body mass index (BMI) classification before radiation, retropharyngeal lymph node (RLN) area irradiation status and MSC V55%, RS = -1.480 + (0.021 × BMI classification before RT) + (0.126 × RLN irradiation) + (0.052 × MSC V55%). The cut-off of MSC based RS is -1.011, with an area under curve (AUC) of 0.737 (95%CI: 0.672-0.801), a specificity of 0.595 and a sensitivity of 0.786. OCC based model involved more variables, RS= -4.805+ (0.152 × BMI classification before RT) + (0.080 × RT Technique) + (0.097 × Concurrent Nimotuzumab) + (0.163 × RLN irradiation) + (0.028 × OCC V15%) + (0.120 × OCC V60%). The cut-off of OCC based RS is -0.950, with an AUC of 0.767 (95%CI: 0.702-0.831), a specificity of 0.602 and a sensitivity of 0.819. Analysis in testing set shown higher AUC of MSC based model than that of OCC based model (AUC: 0.782 vs 0.553). Analysis in entire set shown AUC in these two method-based models were close (AUC: 0.744 vs 0.717). We constructed two risk score predictive models for severe oral mucositis based on clinical features and dosimetric parameters of nasopharyngeal carcinoma patients receiving chemo-radiotherapy. These models might help to discriminate high risk population in clinical practice that susceptible to severe oral mucositis and individualize treatment plan to prevent it.


Breast cancer cells inhibit spontaneous and bisphosphonate-induced osteoclast apoptosis.
Breast cancer metastasizes to bone where it stimulates formation of bone-resorbing osteoclasts. Bisphosphonates constitute an important treatment for osteolytic metastases. The goal of this study was to assess the effects of soluble factors produced by breast cancer cells on osteoclast survival and responsiveness to bisphosphonates. Osteoclasts derived from the murine monocytic cell line RAW264.7 or from primary mouse bone marrow were cultured for 24-48 h untreated, with 10% conditioned media (CM) from human (MDA-MB-231) or mouse (4T1) metastatic breast carcinoma cells, or with a pro-survival factor RANKL. Cancer-derived factors maintained osteoclast survival at the levels comparable to those observed with RANKL. Alendronate (10⁻⁴M) or pamidronate (10⁻⁷M) induced osteoclast apoptosis in untreated and, to a smaller extent, in RANKL-treated cultures, resulting in a significant decrease in osteoclast number and size, induction of caspase-3 cleavage and up-regulation of BIM. In the presence of cancer-derived factors, bisphosphonates were ineffective in inducing osteoclast apoptosis, resulting in only modest decrease in osteoclast numbers and not in size. MDA-MB-231 CM prevented bisphosphonate-induced cleavage of caspase-3 and up-regulation of BIM. MCSF-neutralizing antibody attenuated the effect of MDA-MB-231 CM by ~50%, but could not fully restore osteoclast responsiveness to alendronate. Inhibition of phospholipase C (PLC)-γ interfered with MDA-MB-231-induced down-regulation of BIM and prevented anti-apoptotic action of cancer-derived factors on osteoclasts. Our data suggest that factors produced by the metastatic breast cancer cells promote osteoclast survival and block the apoptotic effect of bisphosphonates in MCSF and PLC-dependent manner, potentially compromising bisphosphonate effectiveness in the bone metastasis setting.


Reduced metabolic disease risk profile by voluntary wheel running accompanying juvenile Western diet in rats bred for high and low voluntary exercise.
Metabolic disease risk is influenced by genetics and modifiable factors, such as physical activity and diet. Beginning at 6 weeks of age, rats selectively bred for high (HVR) versus low voluntary running distance (LVR) behaviors were housed in a complex design with or without voluntary running wheels being fed either a standard or Western (WD, 42% kcal from fat and added sucrose) diet for 8 weeks. Upon intervention completion, percent body fat, leptin, insulin, and mediobasal hypothalamic mRNAs related to appetite control were assessed. Wheel access led to differences in body weight, food intake, and serum leptin and insulin. Intriguingly, percent body fat, leptin, and insulin did not differ between HVR and LVR lines in response to the two levels of voluntary running, regardless of diet, after the 8 wk. experiment despite HVR eating more calories than LVR regardless of diet and voluntarily running 5-7 times further in wheels than LVR. In response to WD, we observed increases in Cart and Lepr mediobasal hypothalamic mRNA in HVR, but no differences in LVR. Npy mRNA was intrinsically greater in LVR than HVR, while wheel access led to greater Pomc and Cart mRNA in LVR versus HVR. These data suggest that despite greater consumption of WD, HVR animals respond similarly to WD as LVR as a result, in part, of their increased wheel running behavior. Furthermore, high physical activity in HVR may offset the deleterious effects of a WD on adiposity despite greater energy intake in this group.


Oral manifestation of disseminated Mycobacterium avium intracellulare in a patient with AIDS.
The acquired immune deficiency syndrome (AIDS) is characterized by a selective suppression of the immune system that renders patients susceptible to infection by a variety of opportunistic organisms. Among these is Mycobacterium avium intracellulare. AIDS victims often have oral manifestations of Kaposi's sarcoma and candidiasis. This article reports an unusual oral presentation of disseminated infection with Mycobacterium avium intracellulare in a patient with AIDS.


Keeping a reflective practice diary: a practical guide.
Reflective practice aims to enhance client care via the professional development and growing expertise of practitioners. This paper offers practical guidelines for writing diaries that may form the basis for reflective practice, while acknowledging the skills that practitioners already use to examine their nursing actions and interactions. There is an emphasis on the outcomes of reflection as well as the reflections themselves, as this is seen as important if professional development is to be recognized and clients benefit. Time constraints that may make frequent formal reflection difficult are recognized by the format that allows deeper reflection where time permits and as skills develop. While ideas presented have been influenced by the literature on reflection, the paper owes as much to the continuing education students of the Homerton School of Health Studies who studied the reflective practice module during 1996. Without listening to their discussions, becoming aware of their difficulties and sharing their growing ability to reflect on practice, this article would not have been possible.


Advance supply of emergency contraception: a randomized trial in adolescent mothers.
To examine whether the advanced provision of emergency contraception (AEC) to parenting youth would increase emergency contraception (EC) utilization, and whether AEC would impact the rates of unprotected sex and contraception use. Subjects were randomized to receive either information about EC or information and an actual supply of AEC. Subjects were interviewed at baseline, 6 and 12-month follow-up. Urban non-medical case management office. 160 adolescent mothers (ages 13 to 20) who were receiving case management services. Advance supply of emergency contraception. Emergency contraception use, sexual activity, unprotected intercourse, contraceptive methods and use. Parenting teens who received AEC were much more likely to have used it than the control group at the 6-month interview (83% vs. 11%) and the 12-month interview (64% vs. 17%). Teens in the AEC treatment group were more likely to have unprotected sex at the 12-month follow-up interview (69% vs. 45%). There was no difference in condom use between the groups at either the 6-month, or the 12-month follow-up interviews. Advance provision of emergency contraception in parenting teens increases the likelihood of its use, and does not affect the use of condoms, or hormonal methods of birth control. Parenting teens who receive AEC may be more likely to have unprotected sex.


Characterization of proteins of human papilloma viruses (HPV) and antibody response to HPV 1.
The serological characterization of virus isolates from verrucae vulgares and plantar warts revealed that HPV 1 and HPV 4 are present in about 50% of these warts with HPV 1 being more prevalent, especially in plantar warts. Parallel to the high incidence of HPV 1 infections, about 50% of non-selected young adults contained antibodies against HPV 1. Only HPV 4 particles, however, reacted with serum from a patient with epidermodysplasia verruciformis when tested by immuno-electron microscopy. An examination of HPV 1 proteins indicated that the major structural proteins VP2 and VP3 are trypsin sensitive. Tryptic degradation leads to distinct polypeptides with molecular weights between 37,000 and 23,000 which may be correlated to minor protein components of HPV 1 preparations. HPV 1 histone-like proteins, which co-migrate with purified cellular histones in SDS gel electrophoresis were analyzed in an acetic acid urea system. It was shown that H3- and H4-like proteins differ from cellular histones. The reason for this difference and its meaning are discussed.


Some observations on reticular fibers in the media of the major cerebral arteries. A comparative study of patients without vascular diseases and those with ruptured berry aneurysms.
In spite of the large number of papers about the changes in the cerebral arterial wall occurring under various conditions, no systematic study can be found in the literature on the reticular fibers surrounding the smooth muscle cells of the media. The histologic examination of the major cerebral arteries of 70 individuals without vascular diseases revealed a dense network of fine reticular fibers in the media showing a rather uniform distribution. This pattern did not change significantly from birth up to the age of 50 years and was independent of intimal proliferation with aging. Contrary to this, all the major cerebral arteries of 35 patients who died from rupture of berry aneurysms under the age of 50 contained a considerably smaller amount of reticular fibers, predominantly in the outer part of the media. It is concluded that people having few reticular fibers in their arterial wall are susceptible to develop aneurysms, and the partial lack of these fibers may play an important role in the development of cerebral aneurysms.


Intraoperative malposition of pedicle probe or screws: a potential cause of the acceleration of degeneration in superior adjacent intervertebral disc.
Adjacent segment degeneration (ASD) is considered as a long-term complication of spinal fusion procedure. Numerous clinical studies have reported some factors related with ASD, but few could address the reason why the incidence of caudal ASD is significantly lower than that of cranial ASD. Because the pedicle of vertebral arch is closer to the superior endplate of vertebrea and its cranial intervertebral disc, there might be some possibilities of malpositions of pedicle probe or screws into the superior vertebral endplate or disc during the procedure of posterior intervertebral fusion. A number of evidences have showed that puncture of intervertebral disc will result in disc degeneration. Thus the authors put forward the hypothesis that intraoperative malposition of pedicle probe or screws might be a cause of ASD at cranial segments.


Asn-linked N-acetylglucosamine of the amylin receptor 2 extracellular domain enhances peptide ligand affinity.
The calcitonin receptor (CTR) has a large extracellular domain (ECD) with multiple N-glycosylation sites. An asparagine (Asn)-linked N-acetylglucosamine (GlcNAc) of CTR ECD N130 was previously reported to enhance peptide hormone binding affinity for CTR ECD. CTR forms a complex with an accessory protein RAMP, and the RAMP:CTR complex gains affinity for peptide hormone amylin as the amylin receptor (AMY). Although N-glycosylation of AMY ECD was reported to enhance peptide hormone affinity, it remains underexplored which N-glycosites of AMY ECD are responsible for peptide affinity enhancement and it is unclear whether an Asn-linked GlcNAc of the N-glycosites plays a critical role. Here, I investigated the role of the Asn-linked GlcNAc of CTR N130 in the affinity of an antagonistic amylin analog (AC413) for AMY2 ECD (the RAMP2 ECD:CTR ECD complex). I used Endo H-treated CTR ECD in which N-glycans were trimmed to an Asn-linked GlcNAc on each of the N-glycosites. I incubated Endo H-treated CTR ECD with excess of glycan-free RAMP2 ECD to produce the RAMP2 ECD:CTR ECD complex. Using this coincubation system, I found that the RAMP2 ECD complex with Endo H-treated CTR ECD with N130D mutation showed a fourfold decrease in AC413 affinity compared with the RAMP2 ECD complex with Endo H-treated CTR ECD WT. In contrast, RAMP2 ECD N-glycosylation did not affect peptide binding affinity. These results indicate that the Asn-linked GlcNAc of CTR N130 is an important peptide affinity enhancer for AMY2 ECD and reveals a significant role of the Asn-linked GlcNAc in AMY2 function.


Effect of excitatory amino acids on microtubule-associated proteins in cultured cortical and spinal neurones.
The effect of excitatory amino acid stimulation on the cytoskeleton of cultured spinal cord and cortical neurons was monitored with antibodies against microtubule-associated proteins tau and MAP2. In unstimulated cultures tau-1 immunoreactivity was restricted to axon-like processes. Stimulation with glutamate (0.1-1 mM) or N-methyl-D-aspartate (NMDA) (0.1 mM) resulted in a dramatic increase in the intensity of tau labelling in axons and the appearance of staining within a proportion of neuronal cell bodies and dendrites. Quisqualate or kainate stimulation resulted only in an increase in tau immunoreactivity within axons. The NMDA mediated events were calcium dependent and the effects of all excitatory amino acids could be blocked by specific antagonists. In contrast, following stimulation with excitatory amino acids, MAP2-immunoreactivity was associated with filaments which formed a complex network within the cell body. This suggests that the different excitatory amino acid receptor subtypes can have differential effects on the neuronal cytoskeleton.


Time course of glutathione S-transferase elevation in Walker mammary carcinoma cells following chlorambucil exposure.
Resistance of Walker 256 rat mammary carcinoma cells to chlorambucil has been shown to be accompanied by a specific increase in the A2-2 subunit of glutathione S-transferase (GST) (Buller et al., Mol Pharmacol 31: 575-578, 1987). Analysis of the time course of GST activity following chlorambucil exposure revealed a 7.5- and 3-fold elevation on day 7 post-treatment in Walker-sensitive (WS) and Walker-resistant (WR) cells, respectively. Flow activated cell sorting (FACS) analyses using antibodies specific for rat liver cytosolic GST supported these results and demonstrated the heterogeneous response of WS cells to chlorambucil exposure. The range of GST levels in drug-treated cells was very broad as compared to that of untreated cells. Transcripts for each class of GST (alpha, mu and pi) were quantified for days 1-9 post-treatment from densitometric scans of RNA slot blots. Elevations in GST alpha RNA preceded increases in GST activity (day 7) in both WS and WR cells. Because fluctuations in GSTA1-1 transcripts were not observed, it was concluded that the increased expression of the alpha class must be attributed to increases in GSTA2-2 transcripts. Amplification of the GST genes in drug-treated cells was not present. These results support the role of GSTA2-2 in the detoxification of chlorambucil. The time course of the cellular response to chlorambucil suggests that the elevation of GSTA2-2 transcripts following alkylating agent exposure may represent only one component of a series of events which collectively confer protection and lead to the establishment of drug resistance.


Cancer and the emotions in 18th-century literature.
This essay argues that the emotional rhetoric of today's breast cancer discourse-with its emphasis on stoicism and 'positive thinking' in the cancer patient, and its use of sympathetic feeling to encourage charitable giving-has its roots in the long 18th century. While cancer had long been connected with the emotions, 18th-century literature saw it associated with both 'positive' and 'negative' feelings, and metaphors describing jealousy, love and other sentiments as 'like a cancer' were used to highlight the danger of allowing feelings-even benevolent or pleasurable feelings-to flourish unchecked. As the century wore on, breast cancer in particular became an important literary device for exploring the dangers of feeling in women, with writers of both moralising treatises and sentimental novels connecting the growth or development of cancer with the indulgence of feeling, and portraying emotional self-control as the only possible form of resistance against the disease. If, as Barbara Ehrenreich suggests, today's discourse of 'positive thinking' has been mobilised to make patients with breast cancer more accepting of their diagnosis and more cooperative with punitive treatment regimens, then 18th-century fictional exhortations to stay cheerful served similarly conservative political and economic purposes, encouraging continued female submission to male prerogatives inside and outside the household.


Assessment of myocardial ischemic memory using speckle tracking echocardiography.
The aim of this study was to evaluate which regional myocardial parameters derived from speckle tracking echocardiography could demonstrate myocardial ischemic memory in a brief ischemia-reperfusion dog model. Myocardial ischemic memory imaging, denoting the visualization of abnormalities provoked by ischemia and sustained even after restoration of perfusion, can convey important clinical information. We previously reported that post-systolic shortening (PSS) remains in the risk area after recovery from brief ischemia. However, it is still unclear whether abnormalities in other regional deformation parameters persist after relief from brief ischemia. Echocardiographic data were chronologically acquired from 11 dogs during 2 min of coronary occlusion followed by reperfusion. Regional systolic and diastolic deformation parameters, including parameters related to PSS, were measured from radial and circumferential strain and from strain rate analyzed in the risk and normal areas. Strain imaging diastolic index (SI-DI), which had been proposed as a parameter for assessing ischemic memory, was also calculated. Peak systolic strain, end-systolic strain, and peak systolic strain rate decreased in the risk area during occlusion but recovered to the baseline level immediately after reperfusion. Strain rate during early diastole decreased during occlusion; however, the decrease did not persist after reperfusion. Post-systolic strain index (PSI) and time-to-peak strain index, which are parameters of PSS, increased during occlusion. These increases persisted until 10 to 20 min after reperfusion (circumferential PSI: 0.02 ± 0.04 [baseline] vs. 0.08 ± 0.04 [20 min], p < 0.05). SI-DI did not show a significant change during occlusion because of a large variation. Although abnormalities of PSS-related parameters alone persisted after recovery from 2-min occlusion, abnormalities of other deformation parameters, such as strain rate during early diastole, did not. These data suggest that assessment of PSS by speckle tracking echocardiography is useful for detecting myocardial ischemic memory.


Heterotransplantation of human gastric carcinomas into nude mice.
A total of 33 specimens of human gastric carcinoma were used for transplantation into nude mice. Initital tumor "take" was accomplished in 15 of the 33 tumors, and the transplantability rate was 45.5%. Transplantability correlated with histologic type, but not with clinical stage or Borrmann's classification. The transplantability rate of differentiated carcinomas, such as well-differentiated tubular adenocarcinoma, moderately differentiated tubular adenocarcinoma, and papillary adenocarcinoma was greater than that of poorly differentiated tumors, such as poorly differentiated adenocarcinoma and mucinous adenocarcinoma. The growth patterns of transplanted tumors were divided into 3 types: rapid, slow, and persistent. There were no specific relationships between growth pattern and histologic type. All histologic types, except signet ring cell carcinoma, could be transplanted serially. Tumor growth became rapid after serial transfer. However, the original histology of these tumors was unchanged. No invasion or metastases were encountered. Intraperitoneal injection of a tumor cell suspension, prepared from subcutaneous transplants of a poorly differentiated adenocarcinoma of Borrmann type III, grew in an ascites form, with invasion and metastasis. Ascitic fluid accumulated within 3--6 weeks after injection. Subsequently, intravenous injection of ascites fluid produced metastases in nude mice. The histology of the subcutaneous tumor was similar to that of the original tumor from the patient.


Embryotoxicity of mixtures of weathered crude oil collected from the Gulf of Mexico and Corexit 9500 in mallard ducks (Anas platyrhynchos).
Dispersants are applied to marine crude oil spills to enhance microbial degradation and reduce impacts of crude oils on ecosystems. In summer 2010, the dispersant Corexit 9500 was applied to crude oil in the Gulf of Mexico. The co-occurrence of the Deepwater Horizon oil spill with nesting efforts of birds in the Gulf region may have resulted in exposure of adult birds, and subsequently bird eggs, to combinations of crude oil and Corexit 9500. The objective of this study was to examine the embryotoxicity of 50:1 and 10:1 mixtures of weathered crude oil collected from the Gulf of Mexico and Corexit 9500 applied to mallard duck eggs. Combinations of weathered crude oil and Corexit 9500 were applied to eggshells of mallard ducks via paintbrush in varying masses ranging from 0.1 to 59.9 mg and 0.1 to 44.9 mg for 50:1 and 10:1 mixtures, respectively. Conservatively derived median lethal applications for 50:1 and 10:1 mixtures of weathered crude oil and Corexit 9500 were 21.3±4.9 mg/egg (321.8 μg/g egg) and 33.1±11.8 mg/egg (517.0 μg/g egg), respectively. Spleen mass of hatchlings exposed to the 50:1 mixture was the only physiological measure significantly different from controls of both mixtures. Results indicated that decreasing ratios of dispersant relative to weathered crude oil decreased toxicity to mallard embryos. In comparison to treatments of eggs with weathered crude oil alone, toxicity increased when the oil to dispersant ratio was 50:1, but decreased with the mixture that contained more dispersant (10:1).


Ligasure versus cold knife tonsillectomy.
To assess parameters related to ligasure tonsillectomy (LT) versus cold knife tonsillectomy (CKT) procedure. Prospective randomized study. A prospective study was conducted on 200 consecutive adult patients undergoing tonsillectomy. Indications included chronic tonsillitis and obstructive sleep apnea syndrome. Patients undergoing adenoidectomy, or any procedure together with tonsillectomy, and patients with peritonsillar abscess history or bleeding disorders were excluded. Patients were randomly assigned to either the LT or CKT group. Intraoperative bleeding, operative time, postoperative pain using a visual analogue scale, and complication rates were evaluated. The LT and CDT groups consisted of 108 and 92 individuals, respectively. In the LT group, there was no measurable intraoperative bleeding, whereas mean bleeding for CKT group was 125 mL. The mean operative time was 15 +/- 1.43 minutes for the LT group and 21 +/- 1.09 minutes for the CKT group (P < .001). The overall mean pain score for the LT group was 3.63, whereas for the CKT group it was 5.09 (P < .001). Primary hemorrhage occurred in one subject of the CKT group. Secondary postoperative hemorrhage was noticed two subjects of the LT group and two subjects of the CKT group. In 21 subjects of the LT group, limited peritonsillar edema was noticed. No other complication occurred in both groups. LT procedure provides sufficient hemostasis, lower postoperative pain, and reduced operative time, as well as safety against Creutzfeld Jakob disease transmission.


Compromised NMDA/Glutamate Receptor Expression in Dopaminergic Neurons Impairs Instrumental Learning, But Not Pavlovian Goal Tracking or Sign Tracking
Two theories regarding the role for dopamine neurons in learning include the concepts that their activity serves as a (1) mechanism that confers incentive salience onto rewards and associated cues and/or (2) contingency teaching signal reflecting reward prediction error. While both theories are provocative, the causal role for dopamine cell activity in either mechanism remains controversial. In this study mice that either fully or partially lacked NMDARs in dopamine neurons exclusively, as well as appropriate controls, were evaluated for reward-related learning; this experimental design allowed for a test of the premise that NMDA/glutamate receptor (NMDAR)-mediated mechanisms in dopamine neurons, including NMDA-dependent regulation of phasic discharge activity of these cells, modulate either the instrumental learning processes or the likelihood of pavlovian cues to become highly motivating incentive stimuli that directly attract behavior. Loss of NMDARs in dopamine neurons did not significantly affect baseline dopamine utilization in the striatum, novelty evoked locomotor behavior, or consumption of a freely available, palatable food solution. On the other hand, animals lacking NMDARs in dopamine cells exhibited a selective reduction in reinforced lever responses that emerged over the course of instrumental learning. Loss of receptor expression did not, however, influence the likelihood of an animal acquiring a pavlovian conditional response associated with attribution of incentive salience to reward-paired cues (sign tracking). These data support the view that reductions in NMDAR signaling in dopamine neurons affect instrumental reward-related learning but do not lend support to hypotheses that suggest that the behavioral significance of this signaling includes incentive salience attribution.


Occurrence, distribution and seasonal variation of organophosphate flame retardants and plasticizers in urban surface water in Beijing, China.
The occurrence, spatial distribution and seasonal variation of 14 organophosphate esters (OPEs) were investigated in urban surface water (river and lake water) from July 2013 to June 2014 in Beijing, China. Sewage influent and effluent samples, as well as rainwater and road runoff samples were also analyzed as the potential sources of OPEs in surface water. Tris(2-chloro-1-methylethyl) phosphate (TCPP) and tris(2-chloroethyl) phosphate (TCEP) were the most abundant OPEs with the average concentrations of 291 ng L(-1) and 219 ng L(-1), respectively. Relatively high concentrations of OPEs were detected in rivers located at southern and eastern urban of Beijing, which was probably attributed to the treated and untreated sewage discharge. Besides, higher levels of OPEs were observed in urban surface water in the summer, and the wet deposition (rainfall) was confirmed to be an important factor for this observation. Risk assessment showed low or medium risk of OPEs for the organisms (algae, crustacean and fish).


Biotransformation and metabolic profile of American ginseng saponins with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry.
American ginseng is a widely used natural product. Ginseng products are usually taken orally, and human intestinal microflora may metabolize ginsenosides. Existing publications report the metabolite fates of ginsenosides. However, investigations on the comprehensive metabolic profile of American ginseng extract are absent because of the chemical complexity and limitation of analytical methods. In this work, we studied the biotransformation and metabolic profile of American ginseng extract by human intestinal microflora. Human fecal microflora was prepared from a healthy Chinese man and then anaerobically incubated with American ginseng sample at 37 °C for 24 h. A rapid and simple liquid-liquid extraction method was used for sample pretreatment. A highly sensitive and selective liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) method was used to characterize ginsenosides and related metabolites in the reaction samples. The LC-Q-TOF-MS provides superior data quality and advanced analytical capabilities for profiling, identifying, and characterizing complex metabolites in matrix-based biological samples. A total of 25 metabolites were detected, 13 of which were undoubtedly assigned by comparison with reference compounds, and 12 others were tentatively identified. The three most abundant metabolites are 20S-ginsenoside Rg3, ginsenoside F2 and compound K. The main metabolic pathways of ginseng saponins are deglycosylation reactions by intestinal microflora through stepwise cleavage of sugar moieties. Subsequent dehydration reactions also occur. Protopanaxadiol- and oleanane-type triterpenoids are easy to metabolize. The intestinal microbiota may play an important role in mediating the metabolism bioactivity of American ginseng.


Convalescent plasma anti-SARS-CoV-2 spike protein ectodomain and receptor-binding domain IgG correlate with virus neutralization.
The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the urgent need for assays that detect protective levels of neutralizing antibodies. We studied the relationship among anti-spike ectodomain (anti-ECD), anti-receptor-binding domain (anti-RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by 2 in vitro assays using convalescent plasma samples from 68 patients with COVID-19. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers and in vitro VN titers. The probability of a VN titer of ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment, was ≥80% when anti-RBD or anti-ECD titers were ≥1:1350. Of all donors, 37% lacked VN titers of ≥160. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease VN or IgG titers. Analysis of 2814 asymptomatic adults found 73 individuals with anti-ECD IgG titers of ≥1:50 and strong positive correlation with anti-RBD and VN titers. Fourteen of these individuals had VN titers of ≥1:160, and all of them had anti-RBD titers of ≥1:1350. We conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titers of ≥1:1350 may provide critical information about protection against COVID-19 disease.


Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer.
Experimental data suggest that exposure to ultraviolet radiation may indirectly induce DNA double-strand breaks. To investigate the contribution of the non-homologous end-joining repair pathway in basal and squamous cell carcinomas. Levels of Ku70 and Ku80 proteins were determined by immunohistochemical analysis and Ku70-Ku80 heterodimer-binding activity by electrophoretic mobility shift assay. Matched pathological normal margins and skin from healthy people were used as controls. A significant increase in Ku70 and Ku80 protein levels was found for both tumour types as compared with normal skin (p<0.001). Squamous cell carcinoma showed increased immunostaining as compared with basal cell tumours (p<0.02). A direct correlation was found between Ku70 and Ku80 protein levels and expression of the proliferation markers Ki-67/MIB-1 (p<0.02 and p<0.002, respectively) in basal cell carcinoma. DNA binding activity was increased in basal cell carcinoma samples as compared with matched skin histopathologically negative for cancer (p<0.006). In squamous cell carcinomas, however, the difference was significant only with normal skin (p<0.02) and not with matched pathologically normal margins. Overall, an up regulation of the Ku70 and Ku80 protein levels seems to correlate only with tumour proliferation rate. As non-homologous end joining is an error-prone mechanism, its up regulation may ultimately increase genomic instability, contributing to tumour progression.


Cytokine array after cyclosporine treatment in rats.
Long-term treatment with cyclosporine (CsA) results in chronic nephrotoxicity, which is known to be mediated by several cytokines including transforming growth factor-betal. Cytokines are known to play an important role in innate immunity, apoptosis, angiogenesis, cell growth, and differentiation. They are known to be involved in most disease processes, including cancer, cardiac disease, and nephrotoxicity. To evaluate changes of cytokines in a rat model of CsA-induced chronic nephrotoxicity, we performed a cytokine array. Experiments were performed on two groups of rats; normal control group and CsA-treated group. Cytokine array in rat serum was performed using Cytokine Antibody Array I kit from RayBiotech. Serum creatinine, urine creatinine, and creatinine clearance increased in the CsA-treated group. Among the several cytokines, the expressions of the lipopolysaccharide-induced CXC chemokine (LIX), monocyte chemoattractant protein 1 (MCP-1), nerve growth factor (beta-NGF), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the CsA-treated group were increased above that of cytokines in the control group. The density of the LIX in controls was 0.62, and in the CsA-treated group was 1.24. The density of the MCP-1 in controls was 0.68, and in CsA-treated, 1.43. The density of the beta-NGF in controls was 0.62, and that in CsA-treated, 1.24. The density of the TIMP-1 in controls 1.13, and in CsA-treated, 1.40. Our data suggested that among several cytokines elevated levels of the LIX, MCP-1, beta-NGF, and TIMP-1 are the contributing factors to CsA-induced nephropathy.


The importance of the perianal connective tissue in the surgical anatomy and function of the anus.
The anatomy of the perianal connective tissue has been reviewed. The most important element is the conjoined longitudinal coat, the axis of the connective-tissue system. Fibers of the longitudinal coat penetrate the internal and external sphincter, interlacing with each other as well as the perimysium and endomysium and forming a fibroelastic network. The fibers and bundles of the internal and external sphincters lie in the meshes of this network with innumerable attachments to it. The fibroelastic network continues through the perianal fat to the pelvic wall and is connected to the lower levator fascia and the perianal skin, insuring the firm anchoring of the anus. During sphincter contraction the fibroelastic network moves together with the sphincters. Thus, the sphincter function is the integration of the contraction of the muscle fibers attached to the web. The elastic elements of the network pull the anal canal slightly apart, but the muscle tone overcomes this and keeps the anus closed. Surmounting the elasticity of the web causes the muscle function to be elastic as well. Surgical procedures such as stretching, transecting the sphincters, whether sharply or gradually, can lead to scar formation with loss of elasticity or mobility in that part of the sphincter and secondary impairment of function.


Inhibition of 4-nitroquinoline 1-oxide induced unscheduled DNA synthesis in primary cultures of rat urothelial cells by dicumarol and pyrophosphate.
Primary cultures of rat urothelial cells were exposed to hydroxyurea, [3H]thymidine, and 4-nitroquinoline 1-oxide (NQO) or N-hydroxy-4-aminoquinoline 1-oxide (HAQO) in a serum-free media for 2 h; unscheduled DNA synthesis (UDS) was measured by autoradiography. Both NQO and HAQO produced unscheduled DNA synthesis. Dicumarol, an inhibitor of NQO nitroreductase, inhibited the activity of NQO and, to a lesser extent, HAQO. Pyrophosphate, an inhibitor of seryl-AMP synthetase, inhibited the activity of both compounds. Neither dicumarol nor pyrophosphate, under similar experimental conditions, inhibited the activity of N-hydroxy-N-2-acetylaminofluorene (N-OH-AAF). These results support the idea that nitro-reductase and seryl-AMP synthetase may be involved in the activation of NQO.


Implications of Mycoplasma hemofelis Bacterial Load on the Hematological Parameters of Naturally Infected Cats.
Mycoplasma hemofelis is the most pathogenic hemoplasma species that affect cats. M. hemofelis may cause an acute infection that leads to hemolytic anaemia. The objective of this study was to detect and to quantify the load of M. hemofelis in cats by conventional polymerase chain reaction (PCR) and by quantitative PCR (qPCR) and to describe the possible hematological changes. M. hemofelis DNA was detected in 28.6% of the randomly selected cats (42 of 147) attended at the Veterinary Hospital of the Federal University of Mato Grosso, Brazil. The agreement between conventional PCR and qPCR was substantive (k 0.6). Females were twice as likely to acquire infection as males (odds ratio, 2.31). There was no statistically significant association (P > .05) and little/no correlation between the hematological parameters and the average of bacterial load. The results indicate that M. hemofelis infection is not related to clinical signs and bacterial blood load in cats. The agreement between conventional and quantitative PCR made it possible to detect infection by M. hemofelis in a larger number of cats.


The tumor area occupied by Tbet+ cells in deeply invading cervical cancer predicts clinical outcome.
Deep invasion of the normal surrounding tissue by primary cervical cancers is a prognostic parameter for postoperative radiotherapy and relatively worse survival. However, patients with tumor-specific immunity in the blood at the time of surgery displayed a much better disease free survival. Here we analyzed if this was due to a more tumor-rejecting immune population in the tumor. Tumor sections from a group of 58 patients with deep normal tissue-invading cervical tumors were stained for the presence of immune cells (CD45), IFNγ-producing cells (Tbet) and regulatory T cells (Foxp3) by immunohistochemistry. The slides were scanned and both the tumor area and the infiltration of the differently stained immune cells were objectively quantified using computer software. We found that an increased percentage of tumor occupied by CD45+ cells was strongly associated with an enhanced tumor-infiltration by Tbet+ cells and Foxp3+ cells. Furthermore, the area occupied by CD45+ immune cells, Tbet+ cells but not Foxp3+ cells within the tumor were, in addition to the lymph node status of patients, associated with a longer disease free survival and disease specific survival. Moreover, interaction analyses between these immune parameters and lymph node status indicated an independent prognostic effect of tumor infiltrating Tbet+ cells. This was confirmed in a multivariate Cox analysis. The area occupied by a preferentially type I oriented CD45+ cell infiltrate forms an independent prognostic factor for recurrence-free and disease-specific survival on top of the patient's lymph node status.


Upper limb use differs among people with varied upper limb impairment levels early post-stroke: a single-site, cross-sectional, observational study.
Background: There is limited knowledge on the upper limb (UL) use early post-stroke by impairment levels.Objectives: To 1) To characterize paretic UL use in people with different UL impairment levels early post-stroke during and outside therapy; 2) compare UL use in people early post-stroke to age-matched controls.Methods: A prospective cross-sectional study of inpatients with first-time stroke ≤4-weeks (n=60, 61±12 years) categorized by Fugl-Meyer UL score for impairment subgroups: mild (51-66), moderate (23-50) and severe (0-22) was conducted. Age-matched, community-dwelling individuals without a history of stroke were recruited (n=30, 60±11 years). Bilateral wrist-worn accelerometers measured the duration of paretic UL use and use the ratio of paretic/non-paretic and non-dominant/dominant UL.Results: Sixty-three percent of stroke participants with mild impairment used their paretic UL >6 h/day (median (IQR): 6.7(3.3); use ratio 0.9(0.3)). Those with moderate impairment demonstrated wide variation of use; 13.3% achieving >6 h use/day (median (IQR): 4.5(3.8); use ratio 0.5(0.2)). People with severe impairment demonstrated limited use. None achieved >6 h/day of use (median (IQR): 1.7(0.7); use ratio 0.3(0.2)). Paretic UL use and use ratio were greater during therapy compared to outside therapy in moderate and severe groups (p<.002). Age-matched controls used their non-dominant UL for 8.7(3.0) hours, significantly more than all stroke participants (p<.002).Conclusions: Patterns of UL use differed by severity of impairment. Moderate and severe groups used their paretic UL more during therapy, inferring that it is possible to increase paretic use despite motor impairment. Future research stratifying by impairment across multinational sites is warranted to generalize findings.


Positive allosteric modulators of the α7 nicotinic acetylcholine receptor: SAR investigation around PNU-120596.
The α7 nicotinic acetylcholine receptor is a calcium permeable, ligand-gated ion channel that modulates synaptic transmission in the hippocampus, thalamus, and cerebral cortex. Previously disclosed work described PNU-120596 that acts as a powerful positive allosteric modulator of the α7 nicotinic acetylcholine receptor. The initial structure-activity relationships around PNU-120596 were gleaned from screening a large thiazole library. Independent systematic examination of the aryl and heteroaryl groups resulted in compounds with enhanced potency and improved physico-chemical properties culminating in the identification of 16 (PHA-758454). In the presence of acetylcholine, 16 enhanced evoked currents in rat hippocampal neurons. In a rat model of impaired sensory gating, treatment with 16 led to a reversal of the gating deficit in a dose-dependent manner. These results demonstrate that aryl heteroaryl ureas, like compound 16, may be useful tools for continued exploration of the unique biology of the α7 nicotinic acetylcholine receptor.


Incidence of Ct scan-detected pulmonary embolism in patients with oncogene-addicted, advanced lung adenocarcinoma.
Patients with stage IIIB-IV lung adenocarcinoma are at high-risk for pulmonary embolism (PE). In these patients, EGFR and KRAS mutations as well as EML4/ALK rearrangements are recognized as "drivers" and as targets for therapy. Data on the incidence of PE in oncogene-addicted lung cancer patients are limited. The aims of this study were to evaluate the incidence of CT scan-detected PE in patients with stage IIIB-IV lung adenocarcinoma and to assess the potential correlation between the presence of these oncogenes and the PE risk. Baseline staging or re-staging chest contrast-enhanced CT scans of patients with stage IIIB-IV lung adenocarcinoma were retrospectively reviewed and adjudicated for the presence of PE. Data on the oncogene drivers (EGFR, KRAS or EML4/ALK) of the same patients were collected. A total of 173 patients with lung adenocarcinoma were included in the study. 24.8% of patients were EGFR mutated (31/125), 21.6% were KRAS mutated (27/125) and 13.6% hadan EML4/ALK rearrangement (17/125). 41 patients had a CT-detected PE (23.7%). A PE was observed in 5 patients with EGFR mutation (16.2%), in 5 patients with KRAS mutation (18.5%), in 8 patients with ELM4/ALK mutation (47.1%). The presence of ELM4/ALK rearrangement was associated with an increased risk of PE [HR:2.06 (95%CI 1.08- 3.55)]. Risk of PE was not found to be associated with EGFR or KRAS mutations. Patients with advanced lung adenocarcinoma were at high risk for PE. The presence of EML4/ALK rearrangement was associated with an increased PE risk.


2,3-Dibromo-6-meth-oxy-4-[(phenethyl-amino)-methyl-idene]cyclo-hexa-2,5-dien-1-one methanol monosolvate.
In the title compound, C(16)H(15)Br(2)NO(2)·CH(4)O, the mean planes of the substituted cyclo-hexa-2,5-dien-1-one and phenyl rings are almost parallel [dihedral angle = 7.84 (4)°]. The crystal packing is stabilized by N-H⋯O hydrogen bonds generating infinite [101] chains. The methanol solvent mol-ecules are connected with the main species by O-H⋯O inter-actions.


Stark spectroscopy of the light-harvesting complex II in different oligomerisation states.
The electric field-induced absorption changes (Stark effect) of light-harvesting complex II (LHCII) in different oligomerisation states-monomeric, trimeric and aggregated-have been probed at 77 K. All the chlorophyll (Chl) a molecules exhibit electro-optic properties in the Q(y) absorption region characterized by a change in dipole moment /Deltamu-->/ =0.6+/-0.06D/f and polarizability, Tr(Deltaalpha;) approximately 55+/-5 A(3)/f(2) upon electronic excitation, which are similar to those of unbound monomeric Chl a, indicating the absence of strong delocalization of the excitations which would be expected in the presence of strong excitonic interactions. The Stark effect in the Chl b absorption region is significantly bigger with /Deltamu-->/ values of the order of 2.0+/-0.2 D/f and it is attributed to strong interactions with neoxanthin molecules. Clear oligomerisation-dependent differences are observed in the carotenoid region, mainly due to the appearance of a new xanthophyll absorption band at 509 in the spectra of trimers and oligomers. It is ascribed to some lutein molecules, in agreement with previous experimental observations. The electro-optic properties of these lutein molecules are significantly different from those of the other xanthophylls in LHCII, which do not exhibit such a big change in dipole moment upon electronic excitation (/Deltamu-->/ =14.6+/-2.0 D/f). Upon aggregation of LHCII some extra absorption appears on the red side of the main Chl a Q(y) absorption band. In contrast to an earlier suggestion [J. Phys. Chem., A 103 (1999) 2422], no indications are found for the charge-transfer character of the corresponding band. The assignments of the S(2) electronic transitions of neoxanthin and lutein in LHCII and possible origins of the Stark effect are discussed.


Multisite phosphorylation of the epidermal growth factor receptor. Use of site-directed mutagenesis to examine the role of serine/threonine phosphorylation.
The major sites of serine and threonine phosphorylation of the human epidermal growth factor (EGF) receptor observed in intact cells are Thr654, Thr669, Ser1046, and Ser1047. Phosphorylation of the EGF receptor is increased at these sites in cells treated with platelet-derived growth factor or phorbol ester. This increase in EGF receptor phosphorylation is associated with an inhibition of the high affinity binding of EGF to cell surface receptors and an inhibition of the receptor tyrosine protein kinase activity. In order to test the hypothesis that the phosphorylation of the EGF receptor is mechanistically related to the modulation of EGF receptor function, we replaced the major sites of serine and threonine phosphorylation with alanine residues. EGF receptors containing single point mutations or multiple mutations were expressed in Chinese hamster ovary cells. Analysis of the regulation of the EGF receptor tyrosine protein kinase activity demonstrated that phorbol ester caused an inhibition of the tyrosine phosphorylation of wild-type receptors and receptors lacking Thr669, Ser1046, or Ser1047. In contrast, the inhibition of EGF receptor tyrosine phosphorylation caused by phorbol ester was not observed for any of the mutated EGF receptors that lacked Thr654. These data are consistent with the hypothesis that the phosphorylation of the EGF receptor at Thr654 is required for the inhibition of the receptor tyrosine protein kinase activity caused by phorbol ester. Investigation of the apparent affinity of the EGF receptor demonstrated that treatment with phorbol ester caused an inhibition of the high affinity binding of 125I-EGF to cells expressing wild-type EGF receptors and each of the mutated EGF receptors examined. We conclude that the regulation of the apparent affinity of the EGF receptor is independent of the major sites of serine and threonine phosphorylation of the EGF receptor.


Adsorption behavior of lysozyme and Tween 80 at hydrophilic and hydrophobic silica-water interfaces.
Nonionic surfactants such as Tween 80 are used commercially to minimize protein loss through adsorption and aggregation and preserve native structure and activity. However, the specific mechanisms underlying Tween action in this context are not well understood. Here, we describe the interaction of the well-characterized, globular protein lysozyme with Tween 80 at solid-water interfaces. Hydrophilic and silanized, hydrophobic silica surfaces were used as substrates for protein and surfactant adsorption, which was monitored in situ, with ellipsometry. The method of lysozyme and Tween introduction to the surfaces was varied in order to identify the separate roles of protein, surfactant, and the protein-surfactant complex in the observed interfacial behavior. At the hydrophobic surface, the presence of Tween in the protein solution resulted in a reduction in amount of protein adsorbed, while lysozyme adsorption at the hydrophilic surface was entirely unaffected by the presence of Tween. In addition, while a Tween pre-coat prevented lysozyme adsorption on the hydrophobic surface, such a pre-coat was completely ineffective in reducing adsorption on the hydrophilic surface. These observations were attributed to surface-dependent differences in Tween binding strength and emphasize the importance of the direct interaction between surfactant and solid surface relative to surfactant-protein association in solution in the modulation of protein adsorption by Tween 80.


Only estrogen receptor "positive" is not enough to predict the prognosis of breast cancer.
Beginning in 2018, biomarkers including estrogen receptor (ER) status were incorporated in the 8th AJCC staging system. ER expression levels were not considered in these changes. We hypothesized that the levels of ER expression could affect the prognosis of breast cancer. A retrospective review was conducted to identify all female patients with invasive breast cancer between 2003 and 2012. ER negative (group I), weakly ER-positive (group II), and strongly ER-positive (group III) were defined as Allred total scores of 0-2, 3-5, and 6-8, respectively. We examined a multigene panel, designated the BCT score, which is a newly developed prognostic model for predicting the risk of a distant metastasis. Among the 4949 patients enrolled in this study, 1310 (26.5%), 361 (7.3%), and 3277 (66.2%) were categorized as group I, II, and III, respectively. Median F/U duration was 57.8 months. Compared to group III, patients in group II were younger, had larger tumors, and were also more likely to have PR-negative tumors, HER-2 amplification, high Ki-67, and high nuclear grade. Between group II and III, there was a significant difference in OS (P = 0.0764, 0.909, and 0.010, respectively). After adjusting for additional factors that may affect OS, the HR for OS showed higher in group II than in group III. The baseline median BCT score indicated that lower ER expression was associated with significantly higher BCT score (P < 0.0001) and significantly more likely to have high risk group (P < 0.0001) relative to higher levels of ER expression group. ER expression levels affect the prognosis of breast cancer. The risk for patients with weakly ER-positive breast cancer should not be underestimated.


Inositol 1,4,5-trisphosphate- and arachidonic acid-induced calcium mobilization in T and B lymphocytes.
Inositol triphosphate (IP3) formation and increase in intracytoplasmic calcium are mediators of signal transduction in lymphocytes. It has been proposed that IP3 induces Ca2+ release from intracellular stores. It is in order to study the relationship between these two events that we have analyzed the effect of IP3 addition on Ca2+ mobilization in permeabilized resting T and B lymphocytes, EBV-B lymphocytes, and HTLV1-T lymphocytes. IP3 induces a rapid and significant release of Ca2+ from the endoplasmic reticulum in a dose-dependent manner. Ca2+ release is more sensitive to IP3 addition in cycling cells (EBV-B lymphocytes and HTLV1-T lymphocytes) than in resting T and B lymphocytes. Arachidonic acid (AA) induces Ca2+ release from the endoplasmic reticulum (ER) in a manner similar to that of IP3. Neither component has an effect on Ca2+ accumulated in mitochondria, and they have no additive effects suggesting that they act on a similar Ca2+ pool. These results directly demonstrate that in T and B human lymphocytes IP3 mobilizes Ca2+ from ER as in other cellular systems and that other potential second messengers, namely AA, could play a significant role in the internal mobilization of calcium during T and B lymphocyte activation.


Treatment of verrucous carcinoma in penis with topical aminolevulinic acid photodynamic therapy: An effective and safe treatment method.
Verrucous carcinoma of the penis is a rare disease characterized by verrucous lesions. The traditional treatment methods for verrucous carcinoma result in loss of sexual function are not satisfactory. The purpose of this study was to evaluate the safety and effect of topical aminolevulinic acid photodynamic therapy in the treatment of verrucous carcinoma in penis. In this study, four male patients, average age of (47 ± 7.58) years old, with penile verrucous carcinoma were treated with topical aminolevulinic acid photodynamic therapy (ALA-PDT) combined with curettage. First, the lesions were removed under local anesthesia. Then, the first session of PDT was performed right away. Ten percent 5-ALA cream was applied to surface of the lesions with occlusive dressing for a 3-h incubation period and the lesions were irradiated for 10 min by using a 635-nm laser beam of 177 mW/cm2 intensity. The ALA-PDT was repeated after 1 and 3 weeks and two other treatments applied if necessary. Three patients were cured by this treatment, with one case relapsed at 3 months. There was no other recurrence at 5 years off treatments. The satisfaction rate of patients was 75% at 3 months after treatments. Topical PDT can be an effective and successful treatment modality for verrucous carcinoma in penis.


Left truncation results in substantial bias of the relation between time-dependent exposures and adverse events.
To assess the impact of random left truncation of data on the estimation of time-dependent exposure effects. A simulation study was conducted in which the relation between exposure and outcome was based on an immediate exposure effect, a first-time exposure effect, or a cumulative exposure effect. The individual probability of truncation, the moment of truncation, the exposure rate, and the incidence rate of the outcome were varied in different simulations. All observations before the moment of left truncation were omitted from the analysis. Random left truncation did not bias estimates of immediate exposure effects, but resulted in an overestimation of a cumulative exposure effect and underestimation of a first-time exposure effect. The magnitude of bias in estimation of cumulative exposure effects depends on a combination of exposure rate, probability of truncation, and proportion of follow-up time left truncated. In case of a cumulative or first-time exposure, left truncation can result in substantial bias in pharmacoepidemiologic studies. The potential for this bias likely differs between databases, which may lead to heterogeneity in estimated exposure effects between studies.


Interpatient Heterogeneity in Drug Response and Protein Biomarker Expression of Recurrent Ovarian Cancer.
Recurrent ovarian-cancer patients face low 5-year survival rates despite chemotherapy. A variety of guideline-recommended second-line therapies are available, but they frequently result in trial-and-error treatment. Alterations and adjustments are common in the treatment of recurrent ovarian cancer. The drug response of 30 lesions obtained from 22 relapsed ovarian cancer patients to different chemotherapeutic and molecular agents was analyzed with the patient-derived ovarian-cancer spheroid model. The profile of druggable biomarkers was immunohistochemically assessed. The second-line combination therapy of carboplatin with gemcitabine was significantly superior to the combination of carboplatin with PEGylated liposomal doxorubicin (p < 0.0001) or paclitaxel (p = 0.0007). Except for treosulfan, all nonplatinum treatments tested showed a lesser effect on tumor spheroids compared to that of platinum-based therapies. Treosulfan showed the highest efficacy of all nonplatinum agents, with significant advantage over vinorelbine (p < 0.0001) and topotecan (p < 0.0001), the next best agents. The comparative testing of a variety of treatment options in the ovarian-cancer spheroid model resulted in the identification of more effective regimens for 30% of patients compared to guideline-recommended therapies. Recurrent cancers obtained from different patients revealed profound interpatient heterogeneity in the expression pattern of druggable protein biomarkers. In contrast, different lesions obtained from the same patient revealed a similar drug response and biomarker expression profile. Biological heterogeneity observed in recurrent ovarian cancers might explain the strong differences in the clinical drug response of these patients. Preclinical drug testing and biomarker profiling in the ovarian-cancer spheroid model might help in optimizing treatment management for individual patients.


Inhibition of ROCK activity allows InlF-mediated invasion and increased virulence of Listeria monocytogenes.
Listeria monocytogenes is an intracellular bacterial pathogen that causes life-threatening disease. The mechanisms used by L. monocytogenes to invade non-professional phagocytic cells are not fully understood. In addition to the requirement of bacterial determinants, host cell conditions profoundly influence infection. Here, we have shown that inhibition of the RhoA/ROCK pathway by pharmacological inhibitors or RNA interference results in increased L. monocytogenes invasion of murine fibroblasts and hepatocytes. InlF, a member of the internalin multigene family with no known function, was identified as a L. monocytogenes-specific factor mediating increased host cell binding and entry. Conversely, activation of RhoA/ROCK activity resulted in decreased L. monocytogenes adhesion and invasion. Furthermore, virulence of wild-type bacteria during infection of mice was significantly increased upon inhibition of ROCK activity, whereas colonization and virulence of an inlF deletion mutant was not affected, thus supporting a role for InlF as a functional virulence determinant in vivo under specific conditions. In addition, inhibition of ROCK activity in human-derived cells enhanced either bacterial adhesion or adhesion and entry in an InlF-independent manner, further suggesting a host species or cell type-specific role for InlF and that additional bacterial determinants are involved in mediating ROCK-regulated invasion of human cells.


Prevalence of Chronic Neck Pain, Low Back Pain, and Knee Pain and Their Related Factors in Community-Dwelling Adults in Iran: A Population-based National Study.
Chronic musculoskeletal pain (CMP) is increasing in prevalence rapidly. Over the past 2 decades low back pain has been ranked globally as the primary cause of years lived with disability. The primary objective of this study was to investigate the prevalence of chronic neck pain (CNP), chronic low back pain (CLBP), and chronic knee pain (CKP) and their related risk factors in the national Iranian population. We analyzed data obtained through a cross-sectional, population-based survey of 7889 Iranians who were aged between 30 and 70 years. The prevalence of CNP, CLBP, and CKP was 15.34%, 27.18%, and 29.97%, respectively. Female sex, aging, body mass index≥25, Lur or Arab ethnicity, illiteracy, passive smoking, positive osteoporosis history, and low or high physical activity levels were risk factors for CLBP, CNP, and CKP after adjustment for potential confounders. For example, in participants with a body mass index≥30, odds ratios for CNP, CLBP, and CKP adjusted for age, sex, ethnicity, living area, education, employment status, smoking, and physical activity levels were 1.26 (95% confidence interval [CI], 1.04-1.52), 1.37 (95% CI, 1.17-1.59), and 1.64 (95% CI, 1.41-1.91), respectively. This is the first study investigating the prevalence of CNP, CLBP, and CKP in the national population of Iran. It shows some modifiable risk factors for CMP, and suggests that affordable planning for these risk factors can be valuable in preventing CMP globally. However, this is a cross-sectional study and future longitudinal studies in this field are necessary.


Catalytic reductions of nitroaromatic compounds over heterogeneous catalysts with rhenium sub-nanostructures.
Nitroaromatic compounds (NACs) are key contaminants of anthropogenic origin and pose a severe threat to human and animal lives. Although the catalytic activities of Re nanostructures (NSs) are significantly higher than those of other heterogeneous catalysts containing NSs, few studies have been reported on the application of Re-based nanocatalysts for NAC hydrogenation. Accordingly, herein, catalytic reductions of nitrobenzene (NB), 4-nitrophenol (4-NP), 2-nitroaniline (2-NA), 4-nitroaniline (4-NA), and 2,4,6-trinitrophenol (2,4,6-TNP) over new Re-based heterogeneous catalysts were proposed. The catalytic materials were designed to enable effective syntheses and stabilisation of particularly small Re structures over them. Accordingly, catalytic hydrogenations of NACs under mild conditions were significantly enhanced by Re sub-nanostructures (Re-sub-NSs). The highest pseudo-first-order rate constants for NB, 4-NP, 2-NA, 4-NA, and 2,4,6-TNP reductions over the catalyst acquired by stabilising Re using bis(3-aminopropyl)amine (BAPA), which led to Re-sub-NSs with Re concentrations of 16.7 wt%, were 0.210, 0.130, 0.100, 0.180, and 0.090 min-1, respectively.


Peptide growth factor control of olfactory neurogenesis and neuron survival in vitro: roles of EGF and TGF-beta s.
The olfactory epithelium (OE) is unique in the mammalian nervous system as a site of continual neurogenesis. Though many studies have described this process in vivo and olfactory neurogenesis can be demonstrated in vitro, the specific factors that modulate this process have not been defined. Noting the common ectodermal origin and structural similarity between the OE and epidermis, peptide factors known to modulate epidermal differentiation were tested in OE cultures. Our results demonstrate that EGF acts as a mitogen for the basal cells that give rise to olfactory neurons and that transforming growth factor-beta s (TGF-beta s) promote neurogenesis. Using a neutralizing antibody, we show that it is likely that the endogenous neurogenic factor is TGF-beta 2, or a very closely related factor.


Morphology and functions of erythrocyte membranes in pregnant women after exacerbation of herpesvirus infection.
Herpesvirus infection is associated with an increase of LPO and of the membrane lipid and lipid-protein layers microviscosity in erythrocyte membranes of pregnant patients. This results in modification of the erythrocyte stromal protein composition. Erythrocyte deformability increases sharply under these conditions, this leading to disorders in tissue metabolism in the organs of pregnant patients.


Propionibacterium acnes postoperative shoulder arthritis: an emerging clinical entity.
The purpose of this study, which involved 276 patients, was to report the importance of Propionibacterium acnes in shoulder infections. The proportion of patients with shoulder infection who had infection due to P. acnes was significantly greater than the proportion of patients with lower limb infection who had infection due to P. acnes (9 of 16 patients vs. 1 of 233 patients; P < .001). This bacterium requires a prolonged incubation period and should not be considered to be a contaminant.


Copper salt-dependent hydroxyl radical formation. Damage to proteins acting as antioxidants.
Cupric ions (Cu2+) and ferric ions (Fe3+) added to hydrogen peroxide generate hydroxyl radicals (OH) capable of degrading deoxyribose with the formation of thiobarbituric acid-reactive products. This damage can be inhibited by catalase, OH radical scavengers and specific metal ion chelators. All proteins tested nonspecifically inhibited copper-dependent damage but have little effect on the iron-dependent reaction. Copper ions appear to bind to the proteins which prevents formation of OH radicals in free solution. However, OH radicals are still generated at a site-specific location on the protein molecule. Protein damage is detected as fluorescent changes in amino acid residues.


Anatomically reduced fixation should always be considered when treating B and C proximal epiphyseal humeral fractures.
Proximal humeral fractures are commonly observed in elderly patients. Management of these injuries is controversial. Literature comparing locking plate fixation, arthroplasty, and conservative treatments show no clear advantages for any of these management strategies. Thus far, no study has considered anatomically reduced fractures obtained after locking plate treatment. To clarify the best surgical procedure in middle-aged patients, we considered outcomes and major complications leading to surgical revision following an anatomically reduced fracture fixed with locking plate and reverse shoulder arthroplasty (RSA) in the treatment of type B/C fractures in patients between 50 and 75 years of age. This is a retrospective study including 59 patients between 50 and 75 years of age with type B/C proximal humeral fracture treated with RSA or with locking plate fixation (resulting in an anatomical reduction) between January 2010 and December 2018. Preoperative radiographs and computed tomography (CT) were evaluated in all patients. Clinical and radiologic follow-up was performed using range of motion (ROM), the Constant-Murley Score (CMS), the Oxford Shoulder Score (OSS), the Simple Shoulder Test (SST), the Subjective Shoulder Value (SSV), and visual analog scale (VAS). Major complications were considered. In the plate fixation group, ROM, CMS, SST, and VAS were higher than in the RSA group. Lower complication rates compared with the literature were observed in both groups. Anatomically reduced fracture fixed with plate and screw could outperform RSA in terms of outcome. In second-level centers where traumatology is performed by surgeons with great expertise in upper limb trauma, the choice between plate fixation and reverse arthroplasty should be made during surgery. Anatomically reduced fractures showed better outcomes compared with RSA in type B/C fractures. Surgeons should always try to perform a reduction of the fracture in order to understand if a plate fixation could be feasible. If it is impossible to perform an anatomical reduction, we suggest to consider RSA. This is a retrospective observational study.


Multiparametric Prediction Models for Coronavirus Disease 2019 Vaccine Selection: Results of a Comparative Population-Based Cohort Study.
An understanding vaccine-dependent effects on protective and sustained humoral immune response is crucial to planning future vaccination strategies against coronavirus disease 2019 (COVID-19). In this multicenter, population-based, cohort study including 4601 individuals after primary vaccination against COVID-19 ≥ 4 months earlier we compared factors associated with residual antibody levels against severe acute respiratory syndrome coronavirus-2 receptor-binding domain (RBD) across different vaccination strategies (BNT162b2, mRNA-1273, or ChAdOx1). Our main model including 3787 individuals (2 × BNT162b2, n = 2271; 2 × mRNA-1273, n = 251; 2 × ChAdOx1, n = 1265), predicted significantly lower levels of anti-RBD antibodies after 6 months in individuals vaccinated with ChAdOx1 (392.7 binding antibody units per milliliter [BAU/mL]) compared with those vaccinated with BNT162b2 (1179.5 BAU/mL) or mRNA-1273 (2098.2 BAU/mL). Vaccine-dependent association of antibody levels was found for age with a significant predicted difference in BAU/ml per year for BNT162b2 (-21.5; 95% confidence interval [CI], -24.7 to -18.3) and no significant association for mRNA-1273 (-4.0; 95% CI, -20.0 to 12.1) or ChAdOx1 (1.7; 95% CI, .2 to 3.1). The predicted decrease over time since full immunization was highest in mRNA-1273 (-23.4; 95% CI, -31.4 to -15.4) compared with BNT162b2 (-5.9; 95% CI, -7 to -4.8). Our study revealed population-based evidence of vaccine-dependent effects of age and time since full immunization on humoral immune response. Findings underline the importance of individualized vaccine selection, especially in elderly individuals.


Kidney Damage in Long COVID: Studies in Experimental Mice.
Signs and symptoms involving multiple organ systems which persist for weeks or months to years after the initial SARS-CoV-2 infection (also known as PASC or long COVID) are common complications of individuals with COVID-19. We recently reported pathophysiological changes in various organs post-acute infection of mice with mouse hepatitis virus-1 (MHV-1, a coronavirus) (7 days) and after long-term post-infection (12 months). One of the organs severely affected in this animal model is the kidney, which correlated well with human studies showing kidney injury post-SARS-CoV-2 infection. Our long-term post-infection pathological observation in kidneys includes the development of edema and inflammation of the renal parenchyma, severe acute tubular necrosis, and infiltration of macrophages and lymphocytes, in addition to changes observed in both acute and long-term post-infection, which include tubular epithelial cell degenerative changes, peritubular vessel congestion, proximal and distal tubular necrosis, hemorrhage in the interstitial tissue, and vacuolation of renal tubules. These findings strongly suggest the possible development of renal fibrosis, in particular in the long-term post-infection. Accordingly, we investigated whether the signaling system that is known to initiate the above-mentioned changes in kidneys in other conditions is also activated in long-term post-MHV-1 infection. We found increased TGF-β1, FGF23, NGAL, IL-18, HIF1-α, TLR2, YKL-40, and B2M mRNA levels in long-term post-MHV-1 infection, but not EGFR, TNFR1, BCL3, and WFDC2. However, only neutrophil gelatinase-associated lipocalin (NGAL) increased in acute infection (7 days). Immunoblot studies showed an elevation in protein levels of HIF1-α, TLR-2, and EGFR in long-term post-MHV-1 infection, while KIM-1 and MMP-7 protein levels are increased in acute infection. Treatment with a synthetic peptide, SPIKENET (SPK), which inhibits spike protein binding, reduced NGAL mRNA in acute infection, and decreased TGF-β1, BCL3 mRNA, EGFR, HIF1-α, and TLR-2 protein levels long-term post-MHV-1 infection. These findings suggest that fibrotic events may initiate early in SARS-CoV-2 infection, leading to pronounced kidney fibrosis in long COVID. Targeting these factors therapeutically may prevent acute or long-COVID-associated kidney complications.