MDA-7 negatively regulates the beta-catenin and PI3K signaling pathways in breast and lung tumor cells.
mda-7 is a novel tumor suppressor with cytokine properties. Adenoviral mda-7 (Ad-mda7) induces apoptosis and cell death selectively in tumor cells. The molecular mechanisms underlying the anti-tumor activity of Ad-mda7 in breast and lung cancer lines were investigated. Microarray analyses implicated both the beta-catenin and the PI3K signaling pathways. Ad-mda7 treatment increased protein expression from tumor suppressor genes, including E-cadherin, APC, GSK-3beta, and PTEN, and decreased expression of proto-oncogenes involved in beta-catenin and PI3K signaling. Ad-mda7 caused a redistribution of cellular beta-catenin from the nucleus to the plasma membrane, resulting in reduced TCF/LEF transcriptional activity, and upregulated the E-cadherin-beta-catenin adhesion complex in a tumor cell-specific manner. Expression of the PI3K pathway members (p85 PI3K, FAK, ILK-1, Akt, and PLC-gamma) was downregulated and expression of the PI3K antagonist PTEN was increased. Consistent with this result, pharmacological inhibition of PI3K by wortmannin did not abrogate killing by Ad-mda7. Killing of breast cancer cells by Ad-mda7 required both MAPK and MEK1/2 signaling pathways, whereas these pathways were not essential for MDA-7-mediated killing in lung cancer cells. Thus, in breast and lung tumor cells MDA-7 protein expression modulates cell-cell adhesion and intracellular signaling via coordinate regulation of the beta-catenin and PI3K pathways.


Current state of clinical trials on xenograft.
Xenotransplantation is a worth investing branch of science, since it aims to fulfil the demand on human cells, tissues and organs. Despite decades of consistent work in preclinical assessments, clinical trials on xenotransplantation are far from reaching the targeted goal. Our study aims to track the characteristics, assess the content and summarize the plan of each trial on skin, beta-island, bone marrow, aortic valve and kidney xenografts, leading to a clear sorting of efforts made in this field. In December 2022, we searched clinicaltrial.gov for interventional clinical trials related to xenograft of skin, pancreas, bone marrow, aortic valve and kidney. A total of 14 clinical trials are included in this study. Characteristics on each trial were gathered. Linked publications were searched using Medline/PubMed and Embase/Scopus. Content of trials was reviewed and summarized. Only 14 clinical trials met our study's criteria. The majority were completed, and most of the trials' enrolment was between 11 and 50 participants. Nine trials used a xenograft of porcine origin. Six trials targeted skin xenotransplantation, four targeted β-cells, two targeted bone marrow and one trial targeted each of the kidney and aortic valve. The average length of trials was 3.38 years. Four trials were conducted in the United States and two trials in each of Brazil, Argentina and Sweden. Of all the included trials, none had any results provided and only three had published work. Phases I, III, and IV had only one trial each. A total of 501 participants were enrolled in these trials. This study sheds the light on the current state of clinical trials on xenograft. Characteristically, trials on this field are of low number, low enrolment, short duration, few related publications and no published results. Porcine organs are the most used in these trials, and skin is the most studied organ. An extension of the literature is highly needed due to the variety of conflicts mentioned. Overall, this study sheds the light on the necessity of managing research efforts, leading to the initiation of more trials targeting the field of xenotransplantation.


Study of traditional Chinese animal drugs using FT-IR and 2D-IR correlation spectroscopy.
Using FT-IR and 2D-IR correlation spectroscopy, the intensity changes and their sequence of amide I and II bands of four traditional Chinese animal drugs (Cornu Cervi Pantotrichum, Cornu Saigae Tataricae, Scorpio and Hirud) under thermal perturbation are studied, and component of Ca(3)(PO(4))(2) in the drug of Cornu Cervi Pantotrichum and sulfates components in the drug of scorpion are identified. The drug of Cornu Cervi Pantotrichum contains inorganic salt Ca(3)(PO(4))(2) and the drug of Scorpio contains sulfates. It is assigned that the bands of 604 and 561 cm(-1) belong to the component of Ca(3)(PO(4))(2), and the bands of 637 and 615 cm(-1) belong to sulfates. Organic components of these drugs respond to the thermal perturbation far stronger than that of the inorganic components. The intensities of amide I and II bands in the drugs, except for amide II band in drug Scorpio, change strongly. For the drugs of Cornu Cervi Pantotrichum, Cornu Saigae Tataricae and Hirudo, the intensity changes of amide II band occurs prior to that of amide I band. The C-N bond in the product operator(3)(4) conjugative system converts from double bond to single bond, but the C=O bond remains double bond during the heating process. On the other hand, amide II vibrations, which may involve much more of the hydrogen bonded local structures of amide groups in the system compared to the C=O dominated amide I vibration, may undergo thermally induced changes at a temperature much lower than the other mode. The traditional Chinese animal drugs can be identified rapidly and non-separately by using FT-IR and 2D-IR correlation spectroscopy.


Machine learning for dynamic and early prediction of acute kidney injury after cardiac surgery.
Acute kidney injury after cardiac surgery increases morbidity and mortality. Diagnosis relies on oliguria or increased serum creatinine, which develop 48 to 72 hours after injury. We hypothesized machine learning incorporating preoperative, operative, and intensive care unit data could dynamically predict acute kidney injury before conventional identification. Cardiac surgery patients at a tertiary hospital (2008-2019) were identified using electronic medical records in the Medical Information Mart for Intensive Care IV database. Preoperative and intraoperative parameters included demographics, Charlson Comorbidity subcategories, and operative details. Intensive care unit data included hemodynamics, medications, fluid intake/output, and laboratory results. Kidney Disease: Improving Global Outcomes creatinine criteria were used for acute kidney injury diagnosis. An ensemble machine learning model was trained for hourly predictions of future acute kidney injury within 48 hours. Performance was evaluated by area under the receiver operating characteristic curve and balanced accuracy. Within the cohort (n = 4267), there were approximately 7 million data points. Median baseline creatinine was 1.0 g/dL (interquartile range, 0.8-1.2), with 17% (735/4267) of patients having chronic kidney disease. Postoperative stage 1 acute kidney injury occurred in 50% (2129/4267), stage 2 occurred in 8% (324/4267), and stage 3 occurred in 4% (183/4267). For hourly prediction of any acute kidney injury over the next 48 hours, area under the receiver operating characteristic curve was 0.82, and balanced accuracy was 75%. For hourly prediction of stage 2 or greater acute kidney injury over the next 48 hours, area under the receiver operating characteristic curve was 0.95 and balanced accuracy was 86%. The model predicted acute kidney injury before clinical detection in 89% of cases. Ensemble machine learning models using electronic medical records data can dynamically predict acute kidney injury risk after cardiac surgery. Continuous postoperative risk assessment could facilitate interventions to limit or prevent renal injury.


Potential suitability for transplantation of hearts from human non-heart-beating donors: data review from the Gift of Life Donor Program.
Organ availability limits use of heart transplantation for treatment for end-stage heart disease. Hearts are currently obtained from donors declared brain dead (heart-beating donors [HBDs]). Although use of hearts from non-heart-beating donors (NHBDs) could reduce the shortage, they are considered unusable because of possible peri-mortem ischemic injury. To project how use of NHBD hearts could increase heart donation, we retrospectively reviewed donor databases from the Gift of Life Donor Program (GLDP), our local organ procurement organization, from 2001 through 2003. We screened the NHBD population using conservative donor criteria, assuming an acceptable hypoxic/ischemic time (time from withdrawal of care to cross-clamp) of 30 minutes. During the study period, there were 894 HBDs, 334 heart transplants and 119 NHBDs. NHBDs were similar to HBDs with respect to gender and ethnicity, but NHBDs were proportionately younger. Of 119 NHBDs, 55 did not meet the age criteria (< or =45 years) and 20 were eliminated because of incomplete data. Eighty-two NHBDs were cross-clamped within 30 minutes of care withdrawal. Twenty NHBDs met all cardiac donor criteria, and 14 of these 20 had hypoxic/ischemic times < or =30 minutes. Pro rata estimation for the 20 NHBDs with incomplete data suggested 7 potential additional donors. Based on our assumptions, 12% to 18% of NHBDs in the study period (14 to 21 of 119 total) were potential heart donors, representing a 4% to 6% increase over of the number of heart transplants performed during the same time interval.


The association between a low cerebro-umbilical ratio at 30-34 weeks gestation, increased intrapartum operative intervention and adverse perinatal outcomes.
The aim of this study was to investigate the relationship between the cerebro-umbilical ratio (CUR), measured at 30-34 weeks, and adverse intrapartum and perinatal outcomes. This was a retrospective cross-sectional cohort study of women delivering at the Mater Mothers' Hospital in Brisbane, Australia. Fetal Doppler indices for 1224 singleton pregnancies were correlated with maternal demographics and intrapartum and perinatal outcomes. Only women who attempted vaginal delivery were included in the study. Infants delivered by emergency cesarean section for fetal compromise had the lowest median CUR, 1.65 (IQR 1.17-2.12), compared to any other delivery group. The proportion of infants with a CUR ≤1 who required emergency cesarean section for fetal compromise was 33.3% compared to 9.3% of infants with a CUR >1 (adjusted OR 6.92 (95% CI 2.04-25.75), p<0.001). However, the detection rate of CUR ≤1 as a predictor for emergency cesarean delivery for fetal compromise was poor (18.9%). Detection rates increased in cohorts of infants born within two weeks of the scan or with birth weights <10th centile or <5th centile. Additionally, a CUR ≤1 was associated with lower median birth weight, higher rates of admission to the neonatal critical care unit and increased neonatal mortality. This study suggests that a CUR ≤1, measured at 30-34 weeks, is associated with a greater risk of emergency cesarean delivery for fetal compromise and a number of other adverse perinatal outcomes. The association was strongest in low birth weight babies.


The effects of auditory streaming on duplex perception.
When a formant transition and the remainder of a syllable are presented to subjects' opposite ears, most subjects perceive two simultaneous sounds: a syllable and a nonspeech chirp. It has been demonstrated that, when the remainder of the syllable (base) is kept unchanged, the identity of the perceived syllable will depend on the kind of transition presented at the opposite ear. This phenomenon, called duplex perception, has been interpreted as the result of the independent operation of two perceptual systems or modes, the phonetic and the auditory mode. In the present experiments, listeners were required to identify and discriminate such duplex syllables. In some conditions, the isolated transition was embedded in a temporal sequence of capturing transitions sent to the same ear. This streaming procedure significantly weakened the contribution of the transition to the perceived phonetic identity of the syllable. It is likely that the sequential integration of the isolated transition into a sequence of capturing transitions affected its fusion with the contralateral base. This finding contrasts with the idea that the auditory and phonetic processes are operating independently of each other. The capturing effect seems to be more consistent with the hypothesis that duplex perception occurs in the presence of conflicting cues for the segregation and the integration of the isolated transition with the base.


The differential antiemetic properties of GLP-1 receptor antagonist, exendin (9-39) in Suncus murinus (house musk shrew).
The use of glucagon-like peptide-1 (7-36) amide (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus is commonly associated with nausea and vomiting. Previous studies using Suncus murinus revealed that the GLP-1 receptor agonist, exendin-4, induces emesis via the brainstem and/or hypothalamus. The present study investigated the mechanism of exendin-4-induced emesis in more detail. Ondansetron (1 mg/kg, s.c.) and CP-99,994 (10 mg/kg, s.c) failed to reduce emesis induced by exendin-4 (3 nmol, i.c.v.), suggesting that 5-HT3 and NK1 receptors are not involved in the mechanism. In other studies, the GLP-1 receptor antagonist, exendin (9-39), antagonised emesis and c-Fos expression in the brainstem and the paraventricular hypothalamus induced by the chemotherapeutic drug cisplatin (30 mg/kg, i.p.; p < 0.05), but not the emesis induced by nicotine (5 mg/kg, s.c.; p > 0.05), or copper sulphate pentahydrate (120 mg/kg, p.o.; p > 0.05). GLP-1 receptors may therefore represent a potential target for drugs to prevent chemotherapy-induced emesis in situations where 5-HT3 and NK1 receptor antagonists fail.


Effect of a novel inducible nitric oxide synthase inhibitor, FR260330, in prevention of renal ischemia/reperfusion injury in vervet monkeys.
Cytotoxic nitric oxide (NO) is produced during ischemia/reperfusion (I/R) injury by the expression of inducible NO synthase (iNOS). Therefore, continuous iNOS inhibition might prevent early graft dysfunction. FR260330, a potent and selective inhibitor of iNOS activity, impedes the dimmerization of iNOS monomer. In this study, the effect of FR260330 in the prevention of renal I/R injury was evaluated in the model of one kidney ischemia in Vervet monkeys. A total of 18 male Vervet monkeys were randomly assigned to two equal groups (n=9). Transient (60 min) left renal ischemia was produced by simultaneous contralateral nephrectomy in treated (FR260330 20 mg/kg/day) and placebo control groups. Renal function and other biochemical parameters as well as FR260330 concentrations were studies until day 15 after I/R injury. All monkeys survived after 60 min I/R injury until sacrifice on day 15. Serum creatinine in the untreated controls increased significantly in comparison to the FR260330-treated group on days 2, 3, 4, and 7 (P<0.05). Plasma FR260330 concentration after oral administration showed that C(max) was 3.251+/-2.526 microg/ml, and T(max) was 4 hr. This study thus finds that FR260330, as a selective iNOS inhibitor, effectively prevents renal I/R injury in Vervet monkeys.


Three dimensional model for surgical planning in resection of thoracic tumors.
The computed tomography scan provides vital information about the relationship of thoracic malignancies to the surrounding structures and aids in surgical planning. However, it can be difficult to visualize the images in a two-dimensional screen to interpret the full extent of the relationship between important structures in the surgical field. We report two cases where we used a three-dimensional printed model to aid in the surgical resection of thoracic malignancies. Careful planning is necessary to resect thoracic malignancies. Although two-dimensional images of the thoracic malignancies provide vital information about the tumor and its surrounding structures, the three-dimensional printed model can provide more accurate information about the tumor and assist in surgical planning. Three-dimensional printed model provide better visualization of complex thoracic tumors, aid in counseling the patient about the surgical procedure and assisted in surgical resection of thoracic malignancy.


Taxonomic notes on the genus Cyphococcus Laing (Hemiptera: Coccomorpha: Coccidae), with description of a new species from India.
The adult female, first-instar nymph, male pupa and adult male of a new species of the genus Cyphococcus Laing (Hemiptera: Coccomorpha: Coccidae) from India, C. williamsi Joshi Rajgopal sp. n., are described and illustrated. This is the first record of the genus Cyphococcus and the subfamily Cyphococcinae from the Oriental region. Information on distribution, biology, host plants, associated coccinellid predators and hymenopteran parasitoids is given.


Antibiotic exposure and risk of Parkinson's disease in Finland: A nationwide case-control study.
Gut microbiota alterations have been found in prodromal and established Parkinson's disease (PD). Antibiotic exposure can have long-term effects on the composition of human intestinal microbiota, but a potential connection between antibiotic exposure and risk of PD has not been studied previously. To evaluate the impact of antibiotic exposure on the risk of PD in a nationwide, register-based, case-control study. We identified all patients who were diagnosed with PD in Finland during the years 1998 to 2014. Information was obtained on individual purchases of orally administered antibiotics during the years 1993 to 2014. We assessed the association between prior antibiotic exposure and PD using conditional logistic regression. The study population consisted of 13,976 PD cases and 40,697 controls. The strongest connection with PD risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416; 95% confidence interval, 1.053-1.904). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10 to 15 years before the index date, sulfonamides and trimethoprim 1 to 5 years before the index date, and antifungal medications 1 to 5 years before the index date were positively associated with PD risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics. Exposure to certain types of oral antibiotics seems to be associated with an elevated risk of PD with a delay that is consistent with the proposed duration of a prodromal period. The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD, but further studies are needed to confirm this. © 2019 International Parkinson and Movement Disorder Society.


Expression and antioxidation of Nrf2/ARE pathway in traumatic brain injury.
To explore the expression of Nrf2/ARE pathway in hindbrain tissue after the traumatic brain injury (TBI) and its anti-oxidative stress effect in the secondary nerve injury. The mice with Nrf2 gene knockout were used for the establishment of brain injury model. The experimental animals were divided into four groups: (Nrf2(+)/(+)) sham-operation group, (Nrf2(+)/(+)) brain injury group, (Nrf2(-)/(-)) sham-operation group and (Nrf2(-)/(-)) brain injury group. The specimen 24 h after cerebral trauma was selected. Then RT-PCR method was adopted to detect the expression of Nrf2 mRNA in brain; Western blotting method was adopted to detect the levels of Nrf2, HO-1 and NQO1 proteins in brain; ELISA method was adopted to detect the oxidative stress indicators: protein carbonyls, 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). The Nrf2 mRNA and protein of Nrf2(-)/(-) mice were not expressed, and the difference of the relative amount of Nrf2 mRNA between Nrf2(+)/(+) TBI group and Nrf2(+)/(+) sham-operation group was not statistically significant (P>0.05); the level of Nrf2 protein in Nrf2(+)/(+) TBI group increased significantly compared with the Nrf2(+)/(+) sham-operation group (P<0.01); in the sham-operation groups, the levels of HO-1 and NQO1 proteins of Nrf2(-)/(-) mice decreased obviously compared with the Nrf2(+)/(+) mice (P<0.01); after brain injury, the levels of HO-1 and NQO1 proteins of Nrf2(+)/(+) mice increased obviously compared with the corresponding sham-operation group (P<0.01); the levels of HO-1 and NQO1 proteins of Nrf2(-)/(-) mice in TBI group had no obvious change compared with the corresponding sham-operation group (P>0.05); there was only a little amount of expression of protein carbonyls, 4-HNE and 8-OHdG proteins in brain tissues in the Nrf2(+)/(+) and Nrf2(-)/(-) sham-operation groups, and the difference was not statistically significant (P>0.05); after brain injury, the three oxidative stress indicators were significantly up-regulated in the Nrf2(+)/(+) and Nrf2(-)/(-) groups, and the up-regulation of the latter group was more significant (P<0.01). After TBI the Nrf2/ARE pathway is activated and the activity of Nrf2 transcription regulation increases. However, the regulation dose not occur in the gene transcription level and only could increase the Nrf2 protein level, while the mRNA expression level has no obvious change. The nerve cell protective effect of Nrf2/ARE pathway in TBI achieves through inhibiting the oxidative stress injuries.


A1 and A2b adenosine receptors regulate GPX4 against ferroptosis of cardiomyocytes in myocardial infarction rat model and in vitro.
The regulation of GPX4 by A1AR and A2bAR was investigated, and whether the inhibition of A1AR and A2bAR on ferroptosis of myocardial cell is related to GPX4 was also discussed. we constructed a rat model of myocardial ischemia and reperfusion (MIR) model and hypoxia/reoxygenation (H/R) model of H9C2 cells, and MIR rats were intraperitoneally injected with A1AR and A2bAR agonists and antagonists. TTC staining, DHE, TUNEL, western blot experiments, immunohistochemistry assay were implemented to analyze the influence of A1AR and A2bAR on ferroptosis and potential role of GPX4. To further authenticate the result of non-specific agonists and antagonists, we transfected siRNA interference or overexpression vectors into cells. CCK8, flow cytometry and western blot were performed to evaluate cell proliferation and apoptosis, and the expression of GPX4 and ferroptosis-related proteins. The experimental results showed that reduced expression of A1AR, A2bAR and GPX4 was found after MIR. A1AR and A2bAR activation by agonists increased GPX4 expression and decreased production of lipid ROS, further inhibiting apoptosis of cardiomyocytes. In addition, we also analyzed the effect of A1AR and A2bAR on ferroptosis-related proteins. We found that expression of FIH1 protein increased and expression of ACSL4 and NOX1 proteins decreased. Consistent with results in vivo, cellular data also indicated that A1AR and A2bAR overexpression could increase proliferation ability of H9C2, and inhibit apoptosis and ROS production, upregulate GPX4 and FIH1, and downregulate ACSL4 and NOX1. A1AR and A2bAR could regulate GPX4, thereby affecting ferroptosis of cardiomyocytes in a rat model of MIR.


Human adenovirus 2 temperature-sensitive mutant 112 contains three mutations in the protein IIIa gene.
The temperature-sensitive (ts) mutant 112 of human adenovirus 2 is defective in the late stage of virus maturation. The region of functional mutation has been localised by marker rescue. It was observed that the ts mutation can be rescued by the left-hand part of the wild-type gene (nucleotides 12,301-12,891). By nucleotide sequencing, two mutations, both C to T (at position 12,386 and 12,741), were found in this region. The first one, in the glycine 20 codon, is silent, whereas the second changes alanine 145 to valine. A third mutation, which changed C to A (nucleotide 13,613), was identified in the right-hand part of the gene, resulting in the replacement of alanine-436 by threonine.


Examination of the parameters affecting of 222Rn emanation for some industrial and environmental samples using gamma-spectroscopy.
The present work aims to radiologically characterize five samples (monazite, zircon, scale waste originating from petroleum production, black sands and phosphate rocks) from different industrial applications and environments in the Egyptian territory. The first section of the present work discusses the measurement and analysis of 226Ra, 232Th and 40K concentrations. Moreover, the assessment of the hazard indices is given in terms of radium equivalent (Raeq), external hazard index (Hex), internal hazard index (Hin), gamma-activity index (Iγ) and alpha-activity index (Iα). The second section deliberates the 222Rn gas emanated from the samples and studies the physical parameters affecting the emanation process. The results found that the monazite sample has the highest concentration of 226Ra, 232Th and 40K; however, it reached 54435, 442105 and 583 Bq.kg-1, respectively, between the studied samples. Furthermore, black sands and phosphate rock samples exhibit the lowest concentration of 226Ra, 232Th and 40K. Results also show that the radon emanation coefficients decrease while the density of materials increases.


Secretory effect of prostaglandins on the rabbit lacrimal gland in vivo.
Fluid secretion from the cannulated excretory duct of the rabbit lacrimal gland was collected in microcapillary pipette at 10 min intervals. Secretion rate and electrolyte concentrations (Na+, K+ and Cl-) in the lacrimal fluid samples were determined before and after injections of small doses of prostaglandins (PGE1, PGE2, PGF1 alpha, PGF2 alpha, 15 epi-PGF2 alpha, PGF2 beta, PGA1 & PGA2) into the external maxillary artery. Only PGE1 had a dose-dependent stimulatory effect on the lacrimal gland secretion. The maximum secretion rate which was induced by PGE1 (25 micrograms/kg) was 7.2 +/- 0.9 microliters/10 min. Na+ concentration in the fluid secretion stimulated by PGE1 was increased; however, K+ and Cl- concentrations were not changed. Pretreatment with atropine (50 micrograms/kg, I.A.) failed to prevent the stimulatory effect of low doses of PGE1. On the other hand, the secretory responses were abolished when propanolol (3 mg/kg, I.A.) was administered prior to PGE1. The results suggest that fluid secretion of the rabbit lacrimal gland in response to PGE1 may be caused by excitation of the sympathetic ganglia and/or by direct action on beta-receptors in the acinar cells.


Intramuscular co-injection of naked DNA encoding HBV core antigen and Flt3 ligand suppresses anti-HBc antibody response.
Flt3 ligand, a recently described growth factor affecting early hematopoietic progenitor cells, can also support the expansion of dendritic cells secreting IL-12. Its potential use in a clinical setting has been suggested. Here, we studied the effect of in situ delivery of Flt3 ligand plasmid (FL) on the antibody response induced by DNA vaccine encoding wild-type hepatitis B virus core antigen (HBc/w). Intramuscular injection of FL increased the expression of DEC205 and the size of splenocytes, and immunization with HBc/w or HBc/w-transfected EL-4 cells induced strong anti-HBc antibody responses in mice. However, intramuscular injection of FL with HBc/w significantly suppressed HBc/w-induced antibody response in a dose-dependent manner. Suppression of immune response by FL injection was the most prominent when FL and HBc/w were co-injected at the same time and the same site. These results suggest that FL may inhibit humoral response induced by DNA-type vaccination, and DC locally expanded by FL may not have proper functions for induction of humoral response.


Early Lyme neuroborreliosis manifesting as brachial plexopathy and meningitis in Northwestern Ontario, Canada: A case report.
Lyme disease is a tick-borne disease caused by the spirochete B. burgdorferi, and patients often present with symptoms comparable to a viral-like illness. The diagnosis can be challenging given its wide range of manifestations and diagnostic testing can take days or longer. Here, we present a case of Lyme disease presenting as brachial plexopathy and meningitis. A 76-years-old male presented to a tertiary-care hospital with left arm weakness and neck pain. Our patient was diagnosed with Lyme neuroborreliosis and had positive serology, including enzyme immunoassay and Western blot. Our patient received 17 days of ceftriaxone (2g IV daily) followed by oral doxycycline (100mg bid). Over the subsequent year, our patient had eventual complete recovery in muscle strength and sensation, with slower improvement to the cervical neck and left arm pain. Incidence of Lyme disease is increasing in North America, and the disease has a wide range of symptoms. Lyme neuroborreliosis (LNB) is 1 presentation and can present with early or late manifestations; clinicians should maintain a high index of suspicion and begin empiric treatment in individuals with a clinical syndrome consistent with LNB. Early LNB manifestations have onset within 6 months of infection and include cranial and peripheral neuropathy, radiculitis, and aseptic meningitis; late LNB encompasses a chronic encephalomyelitis.


Effects of dexamethasone and betamethasone on in vitro cultures from human astrocytoma.
Cultures of human astrocytoma have been derived by collagenase digestion and are presumed, from their aneuploid karyotypes, to be predominantly neoplastic. Early passage cultures in proliferative phase have been cloned in the presence of dexamethasone and betamethasone, both commonly used in management of patients with brain tumours. These steroids raise both the cloning efficiency and the proliferative capacity of cells within each clone. Inhibition was detected only in very high steroid concentrations (25-50 microng/ml). Since these concentrations are unlikely to be attained in vivo it is concluded that anticipated physiological levels of these steroids enhance cell survival at low densities in culture. The significance of this in vivo is discussed.


Effect of Sanguis draconis (a dragon's blood resin) on streptozotocin- and cytokine-induced β-cell damage, in vitro and in vivo.
The study was to examine the effects of Sanguis draconis ethanol extract (SDEE) on streptozotocin (STZ)- and cytokine-induced β-cell damage. In vitro, SDEE did not cause cytotoxicity below 200 μg/ml, and can prevent STZ (5mM)-induced cell death and apoptosis below 100 μg/ml on RIN-m5F cells. SDEE inhibits IL-1β/IFN-γ-stimulated NO, TNF-α release, and iNOS expression. Furthermore, SDEE suppressed the IL-1β/IFN-γ- or STZ-induced p65 expression of NF-κB, which is associated with inhibition of IκB-α degradation. In vivo, treatment of ICR mice with STZ (100 mg/kg, i.p. single injection) resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by blood glucose and plasma insulin. The diabetogenic effects of STZ were completely prevented when mice were orally administered with SDEE for 3 weeks, however, the blood glucose and plasma insulin showed no significant change after SDEE administration alone. In addition, SDEE also can inhibit STZ-induced iNOS protein expression, pancreatic injury and lipid peroxidation. In conclusions, the molecular mechanism by which SDEE inhibits iNOS gene expression appears to involve the inhibition of NF-κB activation. These results suggest the possible therapeutic value of S. draconis and could be potentially developed into a novel drug for preventing the progression of diabetes mellitus.


Assessment of groundwater vulnerability in coastal zone using SI method and GIS: case study of Bouficha aquifer (northeast Tunisia).
Nowadays, groundwater is under stress due to contamination, over-exploitation, seawater intrusion, climate change, etc. The groundwater contamination is the major problem which can engender the total deterioration of the aquifer. The groundwater vulnerability assessment may contribute to predicate and to delimitate the areas affected by contamination or any future pollution. This research aims to zoning the potential pollution of the Bouficha shallow aquifer, located in the northeast Tunisia, using the SI model and GIS. Five parameters are presented in the SI model: depth to groundwater (D), recharge (R), aquifer media (A), topography (T), and land use (LU). The different parameters were collected from diverse sources for assess groundwater vulnerability. The net recharge map was generated using GIS-based multi-criteria analysis method based on different parameters (slope, lithology, LU, soil, and drainage density). The generated vulnerability map shows three vulnerability classes: low vulnerability (< 45), moderate vulnerability (45-64), and high vulnerability (64-84) which represent 3.14%, 76.8%, and 20.06% of the total area, respectively. The SI vulnerability represent a moderate positive correlation with the measured nitrate concentrations (R2 = 0.76). The sensitivity analysis shows that the land use parameter is the most influential parameter for groundwater vulnerability in BFC.


DeepAIR: A deep learning framework for effective integration of sequence and 3D structure to enable adaptive immune receptor analysis.
Structural docking between the adaptive immune receptors (AIRs), including T cell receptors (TCRs) and B cell receptors (BCRs), and their cognate antigens are one of the most fundamental processes in adaptive immunity. However, current methods for predicting AIR-antigen binding largely rely on sequence-derived features of AIRs, omitting the structure features that are essential for binding affinity. In this study, we present a deep learning framework, termed DeepAIR, for the accurate prediction of AIR-antigen binding by integrating both sequence and structure features of AIRs. DeepAIR achieves a Pearson's correlation of 0.813 in predicting the binding affinity of TCR, and a median area under the receiver-operating characteristic curve (AUC) of 0.904 and 0.942 in predicting the binding reactivity of TCR and BCR, respectively. Meanwhile, using TCR and BCR repertoire, DeepAIR correctly identifies every patient with nasopharyngeal carcinoma and inflammatory bowel disease in test data. Thus, DeepAIR improves the AIR-antigen binding prediction that facilitates the study of adaptive immunity.


Effectiveness of interprofessional simulation-based education programs to improve teamwork and communication for students in the healthcare profession: A systematic review and meta-analysis of randomized controlled trials.
Factors, such as the dynamic and variable structure of healthcare services, the introduction of new care models and technological developments, and requirements for patient safety, quality, and accreditation, require new content, goals, and models in the education and practice of health disciplines. Curriculum studies should be planned by today's requirements and competencies to be gained in interprofessional simulation-based education. This systematic review and meta-analysis study was conducted to evaluate the effectiveness of interprofessional simulation-based education programs for improving teamwork and communication among students in the healthcare profession. In this study, Web of Science, Cochrane Library, Springer Link, Science Direct, Ovid, PubMed, Scopus, ProQuest, EBSCOhost/CINAHL Complete, and MEDLINE databases were searched without year limitations until April 2022. Two independent researchers reviewed the studies and analyzed the data. Two researchers evaluated the methodological quality of the studies using the Cochrane Collaboration tool (RoB 2.0). This study was prepared in line with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Comprehensive Meta-Analysis (CMA) 3 software was used for meta-analysis. Eight randomized controlled trials conducted with 819 participants were included in this study. The evaluation of meta-analysis data showed that interprofessional simulation-based education programs significantly improved teamwork (Hedge's g = 0.41, p < 0.001, 95 % CI = 0.25 to 0.56) and communication (Hedge's g = 0.54, p < 0.001, 95 % CI = 0.26 to 0.82). The results of the sensitivity analysis showed that teamwork and communication were stable. Interprofessional simulation-based education programs seem to be an appropriate method for improving teamwork and communication among healthcare students. In the future, it is thought that there is a need to individualize interprofessional simulation-based education programs based on cultural differences and socio-demographic characteristics of healthcare students and to plan studies that examine long-term results. CRD42022325514 (PROSPERO).


Human embryonic stem cell derivation and directed differentiation.
Human embryonic stem cells (hESCs) are produced from normal, chromosomally aneuploid and mutant human embryos, which are available from in vitro fertilisation (IVF) for infertility or preimplantation diagnosis. These hESC lines are an important resource for functional genomics, drug screening and eventually cell and gene therapy. The methods for deriving hESCs are well established and repeatable, and are relatively successful, with a ratio of 1:10 to 1:2 hESC lines established to embryos used. hESCs can be formed from morula and blastocyst-stage embryos and from isolated inner cell mass cell (ICM) clusters. The hESCs can be formed and maintained on mouse or human somatic cells in serum-free conditions, and for several passages in cell-free cultures. The hESCs can be transfected with DNA constructs. Their gene expression profiles are being described and immunological characteristics determined. They may be grown indefinitely in culture while maintaining their original karyotype but this must be confirmed from time to time. hESCs spontaneously differentiate in the absence of the appropriate cell feeder layer, when overgrown in culture and when isolated from the ESC colony. All three major embryonic lineages are produced in differentiating attachment cultures and in unattached embryoid bodies. Cell progenitors of interest can be identified by markers, expression of reporter genes and characteristic morphology, and the culture thereafter enriched for further culture to more mature cell types. The most advanced directed differentiation pathways have been developed for neural cells and cardiac muscle cells, but many other cell types including haematopoietic progenitors, endothelial cells, lung alveoli, keratinocytes, pigmented retinal epithelium, neural crest cells and motor neurones, hepatic progenitors and cells that have some markers of gut tissue and pancreatic cells have been produced. The prospects for regenerative medicine are significant and there is much optimism for their contribution to human medicine.


Flow pattern analysis of a full-scale expanded granular sludge bed-type reactor under different organic loading rates.
The hydraulic characteristics of a lab-scale and a full-scale (275 m(3)) expanded granular sludge bed (EGSB)-type reactor under different organic loading rates varying from 10 kg COD m(-3)d(-1) to 45 kg COD m(-3)d(-1) were investigated. A modified combined model composed of two completely mixing regions and a plug flow region was sufficient for simulating the flow pattern of a full-scale EGSB-type reactor. Moreover, the outputs fitted the measured tracer distribution results well. The simplified model structure was in very good agreement with the physical structure of a full-scale EGSB-type reactor. The upflow (liquid+gas) velocity, high concentration of granular sludge, and gas hold-up effect may contribute to the generation of dead spaces (maximum of 19.5%). The bed expansion characteristics indicated that the sludge bed of the EGSB-type reactor performed as a suspended bed, in which the bed expansion was controlled between 20% and 30%, rather than the usually considered expanded bed.


The Children's Dermatology Life Quality Index (CDLQI): initial validation and practical use.
Skin disease can cause severe disability and handicap in children. Measurement of the impact of skin disease on the quality of life is required to aid clinical decision-making, for clinical research, for audit of paediatric dermatology services, and for political reasons, to aid arguments for more resources for the care of children with skin disease. Adult measures are inappropriate, as the lives of children differ markedly from those of adults. The purpose of this study was to create and initially validate a simple practical questionnaire for use in children. One hundred and sixty-nine children, aged 3-16 years, attending a paediatric dermatology clinic, wrote down, with the help of their parents, all the ways in which their skin disease affected their lives. One hundred and eleven different aspects were identified; 10 questions were composed to cover these aspects, using a structure similar to the Adult Dermatology Life Quality Index. This draft questionnaire was piloted on two series, totalling 40 children, and minor alterations were made to improve clarity. The Children's Dermatology Life Quality Index (CDLQI) questionnaire (maximum score 30) was then given to a further 233 dermatology paediatric out-patients (CDLQI mean = 5.1, SD = 4.9), 47 normal controls (mean 0.4, 0.7) and 55 control patients attending a general paediatric clinic (mean 0.7, 2.5). The CDLQI scores for eczema (mean = 7.7, 5.6, n = 47), psoriasis (5.4, 5.0, n = 25) and acne (5.7, 4.4, n = 40), were all highly significantly greater than for moles and naevi (2.3, 2.9, n = 29). The highest mean score was that for scabies (mean = 9.5, 10.5, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)


Preferred orientation and its effects on intensity-correlation measurements.
Intensity-correlation measurements allow access to nanostructural information on a range of ordered and disordered materials beyond traditional pair-correlation methods. In real space, this information can be expressed in terms of a pair-angle distribution function (PADF) which encodes three- and four-body distances and angles. To date, correlation-based techniques have not been applied to the analysis of microstructural effects, such as preferred orientation, which are typically investigated by texture analysis. Preferred orientation is regarded as a potential source of error in intensity-correlation experiments and complicates interpretation of the results. Here, the theory of preferred orientation in intensity-correlation techniques is developed, connecting it to the established theory of texture analysis. The preferred-orientation effect is found to scale with the number of crystalline domains in the beam, surpassing the nanostructural signal when the number of domains becomes large. Experimental demonstrations are presented of the orientation-dominant and nanostructure-dominant cases using PADF analysis. The results show that even minor deviations from uniform orientation produce the strongest angular correlation signals when the number of crystalline domains in the beam is large.


Psychic distress and the immune response.
This minireview surveys recent progress in the field of immunoregulation by the central nervous system. Representative findings from human and animal studies show evidence for significant immunosuppression in states of psychic distress. Mechanisms of immunomodulation are discussed in light of data implicating neuroendocrine, genetic, neuroanatomical, and learning factors. Evidence for reciprocal modulation of immune and nervous systems is considered. A simple hierarchical model proposes traits that are acted on by environment and experience to produce chronic states of mental health vs. psychic distress; these states determine baseline immunocompetence and response to afferent signals during acute immune challenge. Multidisciplinary interest in psychoneuroimmunology has accelerated the rate of inquiry into the mechanistic details of immunoregulation and has generated new appreciation for the pervasive effects of mental status on physiologic homeostasis.


Transplantation and enrichment of busulfan-resistant primordial germ cells into adult testes for efficient production of germline chimeras in songbirds†.
Zebra finch is a unique model for behavioral, neural, and genomic studies of vocal learning. Several transgenic zebra finches have been produced, although the germline transmission efficiencies are reportedly low. Recently, there have been attempts to produce germline chimeras using primordial germ cells (PGCs). However, this has been hampered by difficulties associated with the manipulation of the small eggs and the fact that the zebra finch is an altricial species that requires parental care after birth, unlike precocial chickens. Consequently, it is difficult to transplant PGCs into embryos and maintain the chimeras. Here, we developed a busulfan-mediated system for transplantation of PGCs into adult testes, to produce germline chimeras with an improved germline transmission capacity. We established microsomal glutathione-S-transferase II (MGSTII)-overexpressing PGCs that are resistant to busulfan, which induces germ cell-specific cytotoxicity, and transplanted them into testes rendered temporarily infertile by busulfan. The recipients were given a second dose of busulfan to deplete endogenous germ cells and enrich the transplanted cells, and donor cell-derived spermatogenesis was accomplished. This method requires fewer recipients due to higher survival rates, and there is no need to wait for maturation of the founders, which is required when transplanting PGCs into embryos. These results are expected to improve transgenic zebra finch production.


Pathways through the small RNA world of plants.
RNA silencing pathways in plants have diversified along with key gene families involved in small RNA biogenesis and effector steps. Evidence suggests that these pathways have distinct roles in plant biology.


Population data for 17 short tandem repeat loci on Y chromosome in northern Croatia.
Human Y-short tandem repeats (STRs) are tandem repeat arrays of two to seven base pair units on non-recombining region (NRY) of the human Y chromosome. Studies on Y-STR are interesting in both population genetics and forensics. The aim of this study was to investigate the population genetic properties of 17 STR loci on Y chromosome in the northern Croatia region. We carried out a statistical analysis of the data from previously performed genetic analysis collected during routine forensic work by the Forensic Science Centre "Ivan Vučetić". A total of 220 unrelated healthy men from northern Croatia were selected for the purpose of this study. Genomic DNA was extracted using Chelex procedure from FTA(®) cards. Y-chromosomal STRs were determined using the AmpFISTR Yfiler PCR amplification kit. The haplotype frequencies were determined by direct counting and analyzed using Arlequin 3.1 and analysis of molecular variance calculated with the Y chromosome haplotype reference database online analysis tool. A total of 210 haplotypes were identified, 200 of which were unique. Total haplotype diversity was 0.995. Locus diversity varied from 0.331 for DYS392 to 0.783 for DYS385 locus. Allele frequencies diversity was 0.662. Discrimination capacity was 95.7%. The use of European minimal haplotype set indicated the most resemblance of this population to the Croatian capital of Zagreb, with modest resemblance to Bosnia and Herzegovina, Serbia and Hungary. This article provides the first overview of the Y chromosome STR variability in northern Croatia, thus providing the referent point for any future forensic and genetic epidemiology efforts in this region.


Parametric imaging using contrast-enhanced ultrasound with Sonazoid for hepatocellular carcinoma.
To clarify the usefulness of parametric imaging using contrast-enhanced ultrasound (CE-US) with Sonazoid by comparing parametric images of hepatocellular carcinoma (HCC) with histopathological findings. Two patients with HCCs underwent CE-US with Sonazoid before surgical resection. A single focus point was set at the lower margin of the tumor, and a bolus intravenous injection of Sonazoid (0.5 ml) was administered. Images of the ideal scanning plane were displayed in real-time mode for the early vascular phase. We analyzed these images using prototype PC software. The software watches, pixel by pixel, the increase in the intensity due to the inflow of the microbubbles, and displays colors if the intensity becomes larger than a certain threshold. Parametric images were compared with histopathological findings. The level of blood flow in the tumor could be visually evaluated using a single image by expressing the detailed hemodynamics of the tumor in terms of differences in color using a time axis appropriate for each case. Parametric imaging is a very useful way of facilitating straightforward visualization of the level of blood flow within HCC and the distribution of histopathological findings in single static images.


Triazolodiazepines are potent antagonists of platelet activating factor (PAF) in vitro and in vivo.
The triazolodiazepines brotizolam, triazolam and alprazolam inhibited PAF-induced human platelet aggregation in vitro (IC50 = 0.54, 7.6 and 13.7 microM, respectively) but showed only a weak or no effect against other aggregating agents (ADP, adrenaline, collagen, serotonin, arachidonic acid). In comparison, flunitrazepam and diazepam, two diazepines without the triazole ring, showed IC50-values of 42 and 260 microM, respectively. Flunitrazepam does not possess the specificity shown by the other compounds. Brotizolam and triazolam also inhibited PAF-induced human neutrophil aggregation in vitro, with IC50-values 0.21 and 6.6 microM, respectively. In anesthetized guinea pigs, brotizolam (2.5 to 10 mg/kg p.o. or 0.1 to 0.5 mg/kg i.v.) or triazolam (20 to 100 mg/kg p.o.) inhibited dose-dependently the intrathoracic accumulation and aggregation of 111Indium labelled platelets induced by an i.v. infusion of PAF (30 ng/kg X min). Brotizolam at doses of 1 to 10 mg/kg p.o. and 0.1 to 0.5 mg/kg i.v. inhibited dose-dependently the reduction in tidal volume (bronchoconstriction), the systemic hypotension and the lethal effect due to i.v. PAF in guinea pigs. Triazolam inhibited these effects of PAF at doses of 50 to 200 mg/kg p.o. PAF-induced systemic hypotension in rats can be reversed by cumulative i.v. doses (0.05 to 1.0 mg/kg) of brotizolam. In conclusion, these results show that triazolodiazepines, like brotizolam and triazolam, are potent inhibitors of PAF-induced effects in vitro and in vivo.


Analysis of MT-ATP8 gene variants reported in patients by modeling in silico and in yeast model organism.
Defects in ATP synthase functioning due to the substitutions in its two mitochondrially encoded subunits a and 8 lead to untreatable mitochondrial diseases. Defining the character of variants in genes encoding these subunits is challenging due to their low frequency, heteroplasmy of mitochondrial DNA in patients' cells and polymorphisms of mitochondrial genome. We successfully used yeast S. cerevisiae as a model to study the effects of variants in MT-ATP6 gene and our research led to understand how eight amino acid residues substitutions impact the proton translocation through the channel formed by subunit a and c-ring of ATP synthase at the molecular level. Here we applied this approach to study the effects of the m.8403T>C variant in MT-ATP8 gene. The biochemical data from yeast mitochondria indicate that equivalent mutation is not detrimental for the yeast enzyme functioning. The structural analysis of substitutions in subunit 8 introduced by m.8403T>C and five other variants in MT-ATP8 provides indications about the role of subunit 8 in the membrane domain of ATP synthase and potential structural consequences of substitutions in this subunit.


Hair cortisol concentrations in relation to ill-being and well-being in healthy young and old females.
Hair cortisol concentration (HCC) provides a retrospective measure of long-term (i.e. over a period of months) cortisol secretion and has been shown to be elevated in relation to chronic stress conditions. However associations in healthy participants with subjective ill-being are less clear and associations with well-being have not been explored. The current study examined HCC in relation to independent comprehensive measures of ill-being (stress, depression, anxiety) and well-being (subjective happiness, life satisfaction, psychological well-being) in healthy young and old females (mean±SD: 19.5±2.2years and 78.6±6.7years respectively, total N=115). The data supported evidence of increased total cortisol secretion with increased age. No association between ill-being and HCC was found in either the young or older group of participants. A positive association between HCC and well-being was found in the older participant group which was independent of ill-being and potential confounds. These findings do not support associations between HCC and ill-being in healthy young or old females. However the results suggest that HCC is able to distinguish levels of well-being in healthy older females.


Classifications of subjects with the language PROLOG.
The logical language PROLOG is used for the definition and characterization of groups of subjects. The groups are firstly defined by sets of variables with comparable scales. Secondly, the single members of the groups are characterized by logically structured combinations of variables which do not necessarily have comparable scales. The performance of the characterizations is estimated by determining the rates sensitivity and specificity. The new classification method is applied in a follow-up study including the assessment of the activity of 76 healthy subjects during two controlled experiments. The classification with PROLOG is then compared with the methods of logistic regression and with discriminant analysis. The comparisons demonstrate that, under similar conditions, the results of a classification with PROLOG parallel the results of statistically based classification procedures. In addition, PROLOG permits characterizations of single subjects based on variables from different scientific disciplines.


When to suspect spinal cord lesions in the elderly.
Motor or sensory disturbance in the lower extremities--sometimes with gait disturbance--is the most common symptom of spinal cord disease. History and examination may localize the lesion, but spine x-rays and myelography usually are necessary to determine its cause. The most common causes of cord compression in the elderly are spondylosis and neoplasm. Compressive lesions are usually treated by surgery. Once compression has been excluded and diagnosis established, treatment should be directed toward the underlying disorder.


REACH of Interventions Integrating Primary Care and Behavioral Health.
This study reports REACH (the extent to which an intervention or program was delivered to the identified target population) of interventions integrating primary care and behavioral health implemented by real-world practices. Eleven practices implementing integrated care interventions provided data to calculate REACH as follows: 1) Screening REACH defined as proportion of target patients assessed for integrated care, and 2) Integrated care services REACH-defined as proportion of patients receiving integrated services of those who met specific criteria. Difference in mean REACH between practices was evaluated using t test. Overall, 26.2% of target patients (n = 24,906) were assessed for integrated care and 41% (n = 836) of eligible patients received integration services. Practices that implemented systematic protocols to identify patients needing integrated care had a significantly higher screening REACH (mean, 70%; 95% CI [confidence interval], 46.6-93.4%) compared with practices that used clinicians' discretion (mean, 7.9%; 95% CI, 0.6-15.1; P = .0014). Integrated care services REACH was higher among practices that used clinicians' discretion compared with those that assessed patients systematically (mean, 95.8 vs 53.8%; P = .03). REACH of integrated care interventions differed by practices' method of assessing patients. Measuring REACH is important to evaluate the extent to which integration efforts affect patient care and can help demonstrate the impact of integrated care to payers and policy makers.


Transitory macrophages in the white matter of the developing visual cortex. II. Development and relations with axonal pathways.
Clusters of 'gitter cells' develop in the white matter of the occipital cortex of the cat at the end of the first postnatal week. These clusters, and others already present at birth, disappear by the end of the first postnatal month. The life span of the clusters in the occipital white matter corresponds to the period when transitory callosal axons are eliminated. The clusters have close contact with callosal axons and can be labeled by HRP injected in the contralateral hemisphere and transported through the corpus callosum. One of the clusters clearly forms in a part of the white matter crossed by transitory callosal axons. The 'gitter cells' might be involved in the elimination of these axons. Consistent with this hypothesis, ultrastructural observations show groups of axons completely surrounded by 'gitter cell' cytoplasm as if they were being phagocytosed.


Benzothioate Glycoside from a terrestrial Streptomyces sp. TBRC 11511 from Thailand.
A new benzothioate glycoside metabolite, phitsanoside A, together with its new and known derivatives were isolated from Streptomyces sp. TBRC 11511 collected from sediment of a dry evergreen forest located in Phitsanulok Province, Thailand. The structure elucidation of the new compound was interpreted on the basis of spectroscopic data analysis. The configuration of the sugar moiety was derived based on NOESY nuclear magnetic resonance correlations, a vicinal coupling constant analysis, and the measurement of an optical rotation from the hydrolyzed sugar unit, which was identified as β-D-glucopyranose. Phitsanoside A did not exhibit antibacterial activity against Bacillus cereus, Mycobacterium tuberculosis or Staphylococcus aureus, but phitsanoside B showed activity against all of them with MIC values of 3.13, 25 and 12.5 μg ml-1, respectively.


Large decreases in standardized uptake values after definitive radiation are associated with better survival of patients with locally advanced non-small cell lung cancer.
We evaluated potential associations between maximum standardized uptake value (SUV(max)) on (18)F-FDG PET before and after radiation therapy (RT) and survival outcomes for patients with locally advanced non-small cell lung cancer. Patients with stage III non-small cell lung cancer (n = 49) who had undergone (18)F-FDG PET at the M.D. Anderson Cancer Center both before and up to 3.5 mo after undergoing radiochemotherapy were studied; exclusion criteria were patients with a history of thoracic surgery, RT, or other cancer or those who had received a total radiation dose less than 60 Gy. We assessed associations between overall survival (OS) or disease-free survival (DFS) and post-RT SUV(max) and the extent of decrease in SUV(max) in the primary tumor (PT) and regional lymph nodes (LNs). SUV(max) was assessed as a continuous variable by Cox proportional hazards regression analysis. Univariate and multivariate analyses showed that having a high post-RT SUV(max) (either PT or LNs) was associated with a higher risk of death (univariate analyses: hazard ratio [HR] for PT SUV(max), 1.27, P < 0.0001; HR for LN SUV(max), 1.32, P = 0.004) and disease recurrence (univariate analyses: HR for PT SUV(max), 1.16, P = 0.004; HR for LN SUV(max), 1.32, P = 0.001). Moreover, after definitive RT, the greater the decrease in SUV(max) in the lesion that had the highest SUV(max) at diagnosis, the longer the OS (HR, 0.06; P = 0.002), DFS (HR, 0.03; P = 0.001), local-regional control (HR, 0.04; P = 0.002), and distant metastasis-free survival (HR, 0.07; P = 0.028). The post-RT SUV(max) in both the PT and the LNs was a predictor of survival-specifically, the higher the residual SUV(max) after RT, the poorer the OS and DFS; and the greater the decrease in SUV(max) in the lesion with the highest SUV(max) at diagnosis, the longer the OS and DFS. This information should help to identify patients who are at high risk of recurrence and for whom additional treatments can be designed accordingly.


Study of the gut microbiome in Egyptian patients with type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) is an autoimmune disease. The gut microbiota has been proposed as a key actor in the pathogenesis of T1DM. To identify the gut microbiome that are likely to be related to T1DM. This may have an impact on the future understanding of the pathogenesis of T1DM and possible approaches to prevent and treat it. The study included 40 T1DM patients and a cross-matching control group of 20 healthy subjects of matched age and sex; stool specimens were taken from each group. Quantitative SYBR Green Real-Time PCR technique targeting 16S rRNA was done for the identification and quantitation of Bacteroides, Prevotella, Ruminococcus, Lactobacillus johnsonii, Lactobacillus reuteri, and Veillonella. T1DM patients showed significantly higher Bacteroides (p < 0.001) and Lactobacillus johnsonii (p = 0.003), but lower Veillonella (p = 0.013) than the control group. However, there was no statistical difference between T1DM and control cases as regards Prevotella (p = 0.204), Ruminococcus (p = 0.598), Lactobacilli (p = 0.901), and Lactobacillus reuteri (p = 0.332). Egyptian patients showed dysbiosis of the gut microbiome that can be related to the pathogenesis of T1DM. This hopefully points to the potential therapeutic benefits of manipulating the composition of the gut microbiome in the management of, or even protection from, T1DM.


Radiosensitization of primary human tumor cell cultures by N-methylformamide.
The effects of the differentiation-inducing agent N-methylformamide (NMF) on the radiation response of ten primary human tumor cell cultures were investigated. Cell survival was determined using an adhesive tumor cell culture system. NMF (1%) was added to cultures on Day 1 and was left for 6 days; cultures were irradiated with graded doses of X rays (1.0-6.0 Gy) on Day 4. Using survival at 2.0 Gy as a comparative endpoint, eight of ten cultures tested exhibited enhanced radiosensitivity upon exposure to NMF. In sensitized cultures, the dose-enhancement factors ranged from 1.3 to 2.5. The NMF-mediated radiosensitization did not appear to be dependent on the histologic cell type. The results presented support previous data obtained from established cell lines and suggest that NMF may offer clinical benefits against a variety of tumor types when used in combination with radiotherapy.


Perceptual-Auditory and Acoustical Analysis of the Voices of Transgender Women.
Voice is an important gender marker in the transition process as a transgender individual accepts a new gender identity. The objectives of this study were to describe and relate aspects of a perceptual-auditory analysis and the fundamental frequency (F0) of male-to-female (MtF) transsexual individuals. A case-control study was carried out with individuals aged 19-52 years who attended the Gender Identity Program of the Hospital de Clínicas of Porto Alegre. Vocal recordings from the MtF transgender and cisgender individuals (vowel /a:/ and six phrases of Consensus Auditory Perceptual Evaluation Voice [CAPE-V]) were edited and randomly coded before storage in a Dropbox folder. The voices (vowel /a:/) were analyzed by consensus on the same day by two judge speech therapists who had more than 10 years of experience in the voice area using the GRBASI perceptual-auditory vocal evaluation scale. Acoustic analysis of the voices was performed using the advanced Multi-Dimensional Voice Program software. The resonance focus and the degrees of masculinity and femininity for each voice recording were determined by listening to the CAPE-V phrases, for the same judges. There were significant differences between the groups regarding a greater frequency of subjects with F0 between 80 and 150 Hz (P = 0.003), and a greater frequency of hypernasal resonant focus (P < 0.001) in the MtF cases and greater frequency of subjects with absence of roughness (P = 0.031) in the control group. The MtF group of individuals showed altered vertical resonant focus, more masculine voices, and lower fundamental frequencies. The control group showed a significant absence of roughness.


Compounds identified in an illicit generic Xanax tablet are the result of a failed synthesis of alprazolam.
Unintended compounds produced by inexperienced clandestine chemists may present a challenge in laboratories tasked with their identification. In March 2020, an anonymously submitted tablet purchased as a generic form of Xanax was analyzed by Erowid's DrugsData.org. The gas chromatography-mass spectrometry (GC-MS) results publicly released online indicated several unidentified compounds due to a lack of database references at that time. Elucidation by our group indicated the presence of several structurally related compounds that were linked to a failed synthesis of alprazolam. For this case study, a published procedure for the synthesis of alprazolam starting with the chloroacetylation of 2-amino-5-chlorobenzophenone was identified as a potential source of this failure. The procedure was reproduced to identify pitfalls of the methodology and examine its possible link to the illicit tablet. Reaction outcomes were analyzed via GC-MS and compared to the tablet submission data. The major compound in this submission, N-(2-benzoyl-4-chlorophenyl)-2-chloroacetamide, along with several related byproducts were successfully reproduced indicating that the tablet contents potentially stem from a failure to synthesize alprazolam.


Active Ca2+ transport by vesicles reconstituted from Triton X-100-solubilized pigeon erythrocyte membrane.
Pigeon erythrocyte membrane was solubilized partially, but relatively unselectively by Triton X-100. Vesicles were reconstituted from mixtures of Triton-solubilized membrane and lipid (phosphatidylcholine plus phosphatidyl-ethanolamine plus cholesterol) by addition of bovine high-density lipoprotein. This efficiently removed the Triton X-100. Sodium dodecyl sulfate-polyacrylamide gel electropherograms of reconstituted vesicles showed band patterns resembling those of the original membrane. The reconstituted vesicles showed ATP-dependent active accumulation of 45Ca2+. ATP-dependent 45Ca2+ uptake by the reconstituted vesicles resembled the corresponding activity of the original membrane vesicles; in both preparations the Ca2+ uptake rate depended on the square of the Ca2+ concentration and had similar [Ca2+]1/2 values, 0.16 microM and 0.18 microM, respectively.


Sequential intracorneal ring segment implantation followed by transepithelial phototherapeutic keratectomy and corneal cross-linking.
To evaluate the safety and visual outcomes of intrastromal corneal ring segment (ICRS) implantation followed by transepithelial phototherapeutic keratectomy (te-PTK) and corneal cross-linking (CXL) in patients with mild keratoconus. Patients with mild keratoconus and contact lens intolerance who underwent sequential ICRS implantation followed by phototherapeutic keratectomy and corneal CXL between April 2015 and July 2018 were retrospectively included in the study. Refractive and visual outcomes, satisfaction questionnaire and complications were recorded at the last follow-up (mean 9.5 months postoperatively). Twenty eyes of 17 patients were enrolled, including 5 women and 15 men. The mean time between the two procedures was 16 months. Based on values before the first procedure and 9.5 months after the second procedure, significant improvements were noted in uncorrected distance visual acuity (UDVA) (0.80±0.35 logMAR vs. 0.46±0.38 logMAR), corrected distance visual acuity (CDVA) (0.38±0.23 logMAR vs. 0.13±0.16 logMAR), maximal K (56.11±4 diopters [D] vs. 50.6±3.56 D), mean K (51.87±3.43 D vs. 48.45±2.91 D), cylinder (7.99±3.94 D vs. 4.23±3.49 D), and spherical equivalent (-3.84±3.36 D vs. -0.99±2.15 D) (P<0.01). Among the outcomes, we noted 5 (25%) superficial corneal scarring (haze); 75% of eyes gained>=1 logMAR line of CDVA. In all, 94.5% of patients reported that they were satisfied with their outcomes. Combining ICRS implantation followed by te-PTK and corneal CXL appears to be a safe and effective approach for improving visual outcomes and quality of life in keratoconus patients.


The First Ring Enlargement Induced Large Piezoelectric Response in a Polycrystalline Molecular Ferroelectric.
Inorganic ferroelectrics have long dominated research and applications, taking advantage of high piezoelectric performance in bulk polycrystalline ceramic forms. Molecular ferroelectrics have attracted growing interest because of their environmental friendliness, easy processing, lightweight, and good biocompatibility, while realizing the considerable piezoelectricity in their bulk polycrystalline forms remains a great challenge. Herein, for the first time, through ring enlargement, a molecular ferroelectric 1-azabicyclo[3.2.1]octonium perrhenate ([3.2.1-abco]ReO4 ) with a large piezoelectric coefficient d33 up to 118 pC/N in the polycrystalline pellet form is designed, which is higher than that of the parent 1-azabicyclo[2.2.1]heptanium perrhenate ([2.2.1-abch]ReO4 , 90 pC/N) and those of most molecular ferroelectrics in polycrystalline or even single crystal forms. The ring enlargement reduces the molecular strain for easier molecular deformation, which contributes to the higher piezoelectric response in [3.2.1-abco]ReO4 . This work opens up a new avenue for exploring high piezoelectric polycrystalline molecular ferroelectrics with great potential in piezoelectric applications.


Isoflurane preconditioning inhibited isoflurane-induced neurotoxicity.
The commonly used inhaled anesthetic isoflurane has been shown to be both neuroprotective and neurotoxic in various cell cultures and animal models. We hypothesize that, like cerebral ischemia, isoflurane is inherently neurotoxic. Limited exposure of isoflurane provides neuroprotection via induction of endogenous neuroprotective mechanisms (preconditioning), while prolonged exposure of isoflurane induces neurotoxicity directly by its inherent neurotoxic effects. To test this hypothesis, we treated rat primary cortical neurons at different days in vitro (DIV) and rat pheochromocytoma neurosecretory (PC12) cells with or without Alzheimer's mutated presenilin-1 (PS1) with 2.4% isoflurane for 24 h to induce cell damage determined by both MTT (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) reduction and LDH (lactate dehydrogenase) release assays. For isoflurane preconditioning, we treated the above cells with isoflurane at 0.6%, 1.2% and 2.4% for 60 min, 4 h prior to a prolonged exposure of 2.4% isoflurane for 24 h. One hour of preconditioning with isoflurane dose-dependently inhibited neurotoxicity induced by 2.4% isoflurane for 24 h in both primary cortical neurons and PC12 cells. This neuroprotection was most dramatically observed in matured cortical neurons (DIV 16) and PC12 cells with over expression of Alzheimer's mutated PS1 (L286V). Preconditioning L286V PC12 cells with equivalent two minimal alveolar concentrations (MAC) of halothane (1.5%), but not sevoflurane (4%), also abolished the neurotoxicity induced by 2.4% isoflurane for 24 h. Overall, these results suggest that isoflurane may be both neuroprotective and neurotoxic, depending on the exposure concentrations and duration.


Detection of occult colonic ischemia during aortic procedures: use of an intraoperative photoplethysmographic technique.
A photoplethysmographic technique was used in 30 consecutive patients who had abdominal aortic reconstruction to assess colonic viability intraoperatively. A sterile pulse oximeter probe was used to measure arterial pulsatility and transcolonic oxygen saturation (TCOS) in the proximal, midportion, and distal sigmoid colon before and after the reconstruction. No attempt at inferior mesenteric revascularization was made, irrespective of the photoplethysmographic results. The status of the colon was assessed between the third and sixth postoperative day by a colonoscopist unaware of the intraoperative data. Before the reconstructive procedure photoplethysmography displayed pulsatile flow in all patients with a mean TCOS of 95% +/- 0.4%. After reconstruction, 28 patients (93%) demonstrated unchanged pulsatility with mean TCOS of 94% +/- 0.4%. Despite ligation of a patent inferior mesenteric artery in 10 of these patients, all 28 had normal colonoscopic examinations. By contrast, two patients (6.7%) had a loss of photoplethysmographic pulsatility with unmeasurable TCOS. Both of these patients had ligation of an initially patent inferior mesenteric artery and demonstrated evidence of ischemic mucosal changes at colonoscopy. Intraoperative colonic photoplethysmography represents an easily performed, accurate method for predicting colonic viability. A loss of pulsatility suggests inadequate postreconstructive colonic perfusion and mandates revascularization of the inferior mesenteric artery.


Serotonin 5-HT2 receptor binding on blood platelets--a peripheral marker for depression?
Several methods of platelet membrane preparation and binding conditions were screened in order to optimize the labeling of serotonergic 5-HT2 receptors on previously frozen human platelet membranes with tritiated ketanserin. Under optimal conditions, 5-HT2 receptors in normal subjects (5 males, 7 females, age range 21 to 71) have a Kd of 1.5 +/- 0.2 nM and a Bmax of 33.9 +/- 5.3 fmole/mg protein. In a group of patients with major depressive disorder exactly matched for age and sex with the normal control group, we find a significant increase in receptor density, to 66.8 +/- 11.4 fmole/mg, with no significant change in the affinity (2.3 +/- 0.5 nM). Four weeks of treatment with antidepressant drugs result in a significant decrease of Bmax, down to control levels (29.4 +/- 3.9). Thus, ketanserin can be used to monitor changes in platelet serotonin 5-HT2 receptors which may be a relevant marker for the state of depression.


Tunica layers of the carotid artery of the rat: isolation and macromolecular synthetic abilities.
The tunicas media and adventitia can be isolated, intact, from the rat carotid artery by simple mechanical extrusion. While morphologically normal, when incubated for 24 hr in vitro in appropriate radioactive precursor the isolated layers synthesized DNA, RNA and protein at very low levels which was only a fraction (5-15%) of that synthesized by the intact vessel.


Prevalence and clinical outcomes of cardiac injury in patients with COVID-19: A systematic review and meta-analysis.
Emerging data have linked the presence of cardiac injury with a worse prognosis in novel coronavirus disease 2019 (COVID-19) patients. However, available data cannot clearly characterize the correlation between cardiac injury and COVID-19. Thus, we conducted a meta-analysis of recent studies to 1) explore the prevalence of cardiac injury in different types of COVID-19 patients and 2) evaluate the association between cardiac injury and worse prognosis (severe disease, admission to ICU, and mortality) in patients with COVID-19. Literature search was conducted through PubMed, the Cochrane Library, Embase, and MedRxiv databases. A meta-analysis was performed with Stata 14.0. A fixed-effects model was used if the I2 values ≤ 50%, otherwise the random-effects model was performed. The prevalence of cardiac injury was 19% (95% CI: 0.15-0.22, and p < 0.001) in total COVID-19 patients, 36% (95% CI: 0.25-0.47, and p < 0.001) in severe COVID-19 patients, and 48% (95% CI: 0.30-0.66, and p < 0.001) in non-survivors. Furthermore, cardiac injury was found to be associated with a significant increase in the risk of poor outcomes with a pooled effect size (ES) of 8.46 (95% CI: 3.76-19.06, and p = 0.062), severe disease with an ES of 3.54 (95% CI: 2.25-5.58, and p < 0.001), admission to ICU with an ES of 5.03 (95% CI: 2.69-9.39, and p < 0.001), and mortality with an ES of 4.99 (95% CI: 3.38-7.37, and p < 0.001). The prevalence of cardiac injury was greatly increased in COVID-19 patients, particularly in patients with severe disease and non-survivors. COVID-19 patients with cardiac injury are more likely to be associated with poor outcomes, severity of disease, admission to ICU, and mortality.


Assessing the emulsifying properties of Tenebrio molitor larvae protein preparations: Impact of storage, thermal, and freeze-thaw treatments on o/w emulsion stability.
Insect proteins have gained attention as novel ingredients, which may contribute to the development of high-value-added products. This study evaluates the emulsifying and emulsion-stabilizing properties of Tenebrio molitor larvae protein preparations obtained through different procedures, leading to the following rich-in-protein samples: ASP (∼67 %), AIP (∼75 %), and SSP (∼62 %). The method applied for protein isolation influenced the molecular and structural characteristics of the preparations, thus affecting their adsorption behaviour at oil-water interfaces and ability to stabilize emulsions. O/w emulsions were prepared, and their physicochemical stability was assessed with respect to droplet size, oil droplet flocculation/coalescence, microstructure, and creaming upon storage as well as after thermal and freeze-thaw treatments. The use of ASP and AIP protein preparation as emulsifiers led to higher stability during storage. All emulsions were stable upon heating and able to withstand two freeze-thaw cycles without phase separation, although there was an increase in droplet size. Interestingly, the AIP emulsion remained stable after the 3rd freeze-thaw cycle, indicating remarkable stability under freezing compared to the other two emulsions. These findings are of great importance for the formulation of food-grade emulsions using insect protein preparations and their future exploitation in developing food items subjected to different treatments.


Facile synthesis of antibacterial chitosan/CuO bio-nanocomposite hydrogel beads.
CuO nanoparticles were synthesized in situ during the formation of physically cross-linked chitosan hydrogel beads using sodium tripolyphosphate as the cross-linker. The aim of the study was to investigate whether these nanocomposite beads have the potential to be used in drug delivery applications. The formation of CuO nanoparticles (CuONPs) in the hydrogels was confirmed by X-ray diffraction and scanning electron microscopy studies. SEM micrographs revealed the formation of CuONPs with size range of 10-25 nm within the hydrogel matrix. Furthermore, the antibacterial and swelling properties of the beads were studied. The prepared nanocomposite hydrogels showed a pH sensitive swelling behavior. The CuO nanocomposite hydrogels have rather higher swelling in different aqueous solutions in comparison with neat hydrogel. The nanocomposite hydrogels demonstrated good antibacterial effects against Escherichia coli and Staphylococcus aureus bacteria.


Pulmonary circulation abnormalities in post-acute COVID-19 syndrome: dual-energy CT angiographic findings in 79 patients.
To evaluate the frequency and pattern of pulmonary vascular abnormalities in the year following COVID-19. The study population included 79 patients remaining symptomatic more than 6 months after hospitalization for SARS-CoV-2 pneumonia who had been evaluated with dual-energy CT angiography. Morphologic images showed CT features of (a) acute (2/79; 2.5%) and focal chronic (4/79; 5%) PE; and (b) residual post COVID-19 lung infiltration (67/79; 85%). Lung perfusion was abnormal in 69 patients (87.4%). Perfusion abnormalities included (a) perfusion defects of 3 types: patchy defects (n = 60; 76%); areas of non-systematized hypoperfusion (n = 27; 34.2%); and/or PE-type defects (n = 14; 17.7%) seen with (2/14) and without (12/14) endoluminal filling defects; and (b) areas of increased perfusion in 59 patients (74.9%), superimposed on ground-glass opacities (58/59) and vascular tree-in-bud (5/59). PFTs were available in 10 patients with normal perfusion and in 55 patients with abnormal perfusion. The mean values of functional variables did not differ between the two subgroups with a trend toward lower DLCO in patients with abnormal perfusion (74.8 ± 16.7% vs 85.0 ± 8.1). Delayed follow-up showed CT features of acute and chronic PE but also two types of perfusion abnormalities suggestive of persistent hypercoagulability as well as unresolved/sequelae of microangiopathy. Despite dramatic resolution of lung abnormalities seen during the acute phase of the disease, acute pulmonary embolism and alterations at the level of lung microcirculation can be identified in patients remaining symptomatic in the year following COVID-19. • This study demonstrates newly developed proximal acute PE/thrombosis in the year following SARS-CoV-2 pneumonia. • Dual-energy CT lung perfusion identified perfusion defects and areas of increased iodine uptake abnormalities, suggestive of unresolved damage to lung microcirculation. • This study suggests a complementarity between HRCT and spectral imaging for proper understanding of post COVID-19 lung sequelae.


The bioactivity of flavonoid glucuronides and free aglycones in the context of their absorption, II phase metabolism and deconjugation at the inflammation site.
One of the most spread group of phenolics are flavonoids. Many studies focusing on the digestion and bioavailability of flavonoids have been carried out. Several possible directions of flavonoid metabolism are suspected and described in the literature. The aim of the present study was to evaluate the bioactivity of 8 flavonoid 3-O- and 7-O- glucuronides and 7 free aglycones on inflammatory response of PMNs and HUVECs in the context of their fate in humans after oral intake. The present study for the first time compared the activity of several most popular in plant flavonol and flavone aglycones and their beta-glucuronides. The results showed that in all in vitro experiments only aglycones have anti-inflammatory activity in PMNs and HUVECs models in the concentration range 1-50 μM. The most significant influence on the inflammatory response was observed in the case of HUVECs. Compounds were able to down-regulate levels of adhesion molecules (ICAM, VCAM and E-selectin). The possible deconjugation phenomenon at the inflammation site was evaluated using enzymes produces by stimulated PMNs. This is the first report suggesting the role of β-glucuronidase in the inflammatory process taking place on the inflammation site. Additionally, the anti-inflammatory effect was significantly better for flavones.


Carbon source nutrition of rapamycin biosynthesis in Streptomyces hygroscopicus.
Chemically-defined media were developed for rapamycin production by Streptomyces hygroscopicus. Thirty-five carbon sources were tested for their effect on production. Eight failed to support growth and seven appeared to repress or inhibit rapamycin formation. The best combination of two carbon sources were 2% fructose and 0.5% mannose. Acetate and propionate, which are known to contribute most of the carbon atoms of the lactone ring, were unsatisfactory for growth and/or rapamycin production.


Value of renal biopsy in chronic renal failure.
A total of 120 patients with chronic renal failure secondary to parenchymatous kidney disease were biopsied. Percutaneous approach was tried and open technique was employed when there was contraindication to or failure of the percutaneous technique. In 72 cases the histopathologic lesions were identified, in 30 cases it was not possible to identify them and in 18 cases there was no sufficient kidney tissue. The diagnosis was very critical in at least 10 cases: there were 3 cases of primary oxalosis, one case of haemolytic uraemic syndrome, one case of necrotizing glomerulonephritis, one case of Wagner's granulomatosis, 3 cases of focal segmental glomerulosclerosis and one case of Fabry's disease. All but one of these were not diagnosed clinically. There was no patient mortality, and morbidity was significantly higher after open approach. We concluded that kidney biopsy in patients with chronic renal failure is mandatory especially if they are going to be transplanted and it is relatively safe especially when the percutaneous technique is employed.


Crystal structures and Hirshfeld surface analyses of tetra-kis-(4,5-di-hydro-furan-2-yl)silane and tetra-kis-(4,5-di-hydro-furan-2-yl)germane.
The title compounds Si(C4H5O)4 (1) and Ge(C4H5O)4 (2) are di-hydro-furyl compounds of silicon and germanium and are useful building blocks for the functionalization of these elements. Both structures crystallize in space group P21/n in the monoclinic crystal system with two mol-ecules in the asymmetric unit: the Si and Ge atoms adopt slightly distorted tetra-hedral geometries, while the C4H5O moieties exhibit shallow envelope conformations. Through a Hirshfeld surface analysis of the structures, inter-actions within the crystal packing could be elucidated: compound 1 features a polymeric chain in the (101) plane via C-H⋯O hydrogen bonds whereas in 2 C-H⋯O hydrogen bonds create a polymeric chain in the (010) plane.


The crucial role of exercise and physical activity in weight management and functional improvement for seniors.
Exercise and daily physical activity play a critical role in weight management and are the greatest determinants of weight maintenance following weight loss. Physicians and other qualified health care professionals should provide their patients with an exercise prescription that takes into consideration the individual's previous level of activity, interests, time constraints, and physical impairments. Exercise programs for elderly patients who are obese can incorporate aerobic, flexibility, strengthening, and balance exercises and should be designed to improve function. The incorporation of lifestyle activity to a weight-loss program can be an alternative or adjunct to more structured, continuous forms of exercise. It is essential that health care professionals consistently intervene when dealing with individuals who have overweight to prevent weight progression to the level of obesity.


The effect of Kinesio-tape® on pain and vertical jump performance in active individuals with patellar tendinopathy.
Patellar tendinopathy is a common inflammatory condition in athletes who undergo large volumes of running and jumping. Kinesio-tape® (KT) is proposed to provide pain relief; however, its effect has not been examined on patellar tendinopathy. To examine the effects of KT on pain modulation for active individuals with patellar tendinopathy during functional activities. Thirteen symptomatic knees from seven college-aged females (6 bilateral; 1 unilateral) were included. Participants underwent three data collection sessions with KT, sham, and no tape (NT) in a randomized order. During the session, participants performed a maximum vertical jump, single-leg squats and isometric knee extension. The KT intervention was applied according to the KT manual and the sham utilized the same pattern without tension. Pain level was evaluated using the numeric pain scale before, during and after each activity. Function was assessed as maximum vertical jump height and maximum isometric strength. A separate repeated measures ANOVA was used to compare each dependent variable (pain level, vertical jump height, and isometric strength) among the conditions. Reported pain scores were significantly lower (p = 0.05) during the maximal vertical jump test for KT (3.38 ± 1.26) compared to NT (4.54 ± 2.22). Significantly lower jump heights were found under KT (17.73 ± 3.06in) during the maximum vertical jump test compared to sham (18.65 ± 2.17in, p = 0.000) and NT (18.18 ± 2.93in, p = 0.008). The use of the KT tape with a tendon corrective strip and muscle facilitative strip was effective for decreasing pain associated with patellar tendinopathy during jump landing but led to decreased maximum jump height. NCT04153877.


Robust Genome Editing with Short Single-Stranded and Long, Partially Single-Stranded DNA Donors in Caenorhabditis elegans.
CRISPR-based genome editing using ribonucleoprotein complexes and synthetic single-stranded oligodeoxynucleotide (ssODN) donors can be highly effective. However, reproducibility can vary, and precise, targeted integration of longer constructs-such as green fluorescent protein tags remains challenging in many systems. Here, we describe a streamlined and optimized editing protocol for the nematode Caenorhabditis elegans We demonstrate its efficacy, flexibility, and cost-effectiveness by affinity-tagging 14 Argonaute proteins in C. elegans using ssODN donors. In addition, we describe a novel PCR-based, partially single-stranded, "hybrid" donor design that yields high efficiency editing with large (kilobase-scale) constructs. We use these hybrid donors to introduce fluorescent protein tags into multiple loci, achieving editing efficiencies that approach those previously obtained only with much shorter ssODN donors. The principals and strategies described here are likely to translate to other systems, and should allow researchers to reproducibly and efficiently obtain both long and short precision genome edits.


Type III secretion genes in Aeromonas salmonicida subsp salmonicida are located on a large thermolabile virulence plasmid.
Type III secretion genes in Aeromonas salmonicida subsp. salmonicida are located on a large plasmid of approximately 140 kb. Cultivation of this organism at elevated temperatures such as 25 degrees C can, however, result in loss of this plasmid. This is accompanied by a loss of virulence for cultured fish cells.


Reliability of phase-encode mapping in the presence of spatial non-stationarity of response latency.
Phase-encode mapping has been used as the primary functional magnetic resonance imaging (fMRI) technique to reveal spatial variation of response properties in both visual and auditory cortex (e.g., retinotopy and tonotopy). Spatial variation in the time of response produces a map of cortical sensitivity to a time-varying property of the presented stimulus. Inherently, this technique assumes that response latency is invariant across cortex. However, the latency of the fMRI response has been found to exhibit both temporal and spatial non-stationarity, with variance across cortex increasing with longer stimulus duration--a critical concern given the typically long duration (e.g., 48-64 s) of stimuli presented in phase-encode mapping experiments. This study addresses two issues--assessment of error rates caused by latency variance and reliability of maps identified using phase-encode mapping. Our findings suggest that the latency variance was found to have a greater effect on the type II error (missed detection) rate than on the type I error (false alarm) rate, with the size of the cortical map controlling the type I error rate. Moreover, empirical determination of false alarm rates provides the first approximation of the statistical significance (i.e., P values) of observed maps in both retinotopic and tonotopic studies, with maps as short as three voxels in length achieving the P < 0.05 significance level for a single subject.


Dog demographics and husbandry practices related with rabies in Cameroon.
Dog demographics are considered as one of the main factors in the control of rabies. Having reliable data on dog population and husbandry practices on how they are managed is a key point in the elaboration of any control program to fight against human deaths due to rabies which are mainly due to dogs. However, the lack of data regarding dog population is one of the main hindrances to elaborate effective fighting projects in developing countries, particularly in Africa. In order to contribute for reliable data on dog demographics and husbandry practices related to rabies, this study was carried out in the cities of Ngaoundéré, Garoua and Yaoundé, respectively located in Adamaoua, North and Centre regions of Cameroon from October 2013 to April 2014. A survey was conducted within 2500 households selected randomly to which 45 questions were addressed, while the vaccine status of dogs was checked in the houses by verifying the vaccination booklet and in public and private veterinary clinics. Various aspects of dogs such as dog population, husbandry practices, ownership and age distribution were assessed. Out of these households, 45% of them (1118) had exploitable data. From these, 46% of them owned at least 1 dog for a total of 707 dogs, with a dog per household ratio of 6.3:10 for a dog per human ratio of 1.16:10. The age distribution of these dogs showed that the mean age of male and female was around 2 years with a male per female ratio of 29:10. The estimation of roaming dogs gave a ratio of 2.3:10 per human. Concerning the reasons for having a dog, the main motivation was guarding (76%) and company (17%). Husbandry practices applied to these dogs were a complete restrained (52%), semi-restrained (29%) and a complete roaming (18%). In relation to rabies, only 34% of dog owners were able to prove the effective vaccination of their dogs and no reason was given to explain the non-vaccination by the majority (78%) of the owners. So this study provides for the first time a baseline on dog population for an objective fighting program but also shows that the husbandry practices applied by the owners can be a hindrance to a fighting program against rabies.


Prevalence of chronic kidney disease and its association with cardio-metabolic risk factors in the adult Romanian population: the PREDATORR study.
PREDATORR is the first national study analyzing the prevalence of chronic kidney disease and its prognosis and association with socio-demographic, cardio-metabolic and lifestyle risk factors in the adult Romanian population. Chronic kidney disease was defined according to the KDIGO 2012 criteria as an estimated glomerular filtration rate <60 mL/min/1.73 m(2) and/or urinary albumin-to-creatinine ratio ≥30 mg/g. The socio-demographic, lifestyle and anamnestic data were collected through interviewer-administered questionnaires. Physical examination and biochemical assays were also performed. This cross-sectional study conducted between December 2012 and February 2014 in Romania included 2717 adults. The overall age- and sex-adjusted prevalence of chronic kidney disease was 6.74 % (95 %CI 5.60-7.88 %), of which 3.31 % (2.50-4.13 %) had only reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), 2.98 % (2.21-3.76 %) had only albuminuria, and 0.45 % (0.14-0.74 %) had both. The prevalence of chronic kidney disease increased with age and was similar in women and in men. Age, hyperuricemia, impaired glucose regulation (diabetes/prediabetes), hypertriglyceridemia and a family history of renal disease were independent risk factors for the presence of chronic kidney disease. The PREDATORR study showed a high prevalence of chronic kidney disease in the adult Romanian population providing data on its prognosis and association with several cardio-metabolic risk factors.


Elementary Students' Physical Activity Levels and Behavior When Using Stability Balls.
Physical activity is positively related to improved student behaviors. Stability balls have been used as interventions to affect student behavior. The objective of this study was to determine whether the use of stability balls elicits more physical activity than the use of regular chairs and whether stability balls positively influence behavior. Participants (n = 43 fourth graders) sat on stability balls during class and wore accelerometers. Eight were randomly selected for behavioral observations using momentary time sampling. Significant decreases in accelerometer counts were found. No obvious difference for on-task behaviors was found between students using stability balls and those using chairs. Stability balls do not necessarily elicit more physical activity than do chairs; however, students accumulate light-intensity physical activity when using them. Classroom behavior was not detrimentally affected by stability ball use; thus, stability balls do not appear to detract from the classroom instructional atmosphere.


What are the psychiatric sequelae of burn pain?
Burn injuries and their subsequent treatment cause one of the most excruciating forms of pain imaginable. Practitioners in the field have been concerned about the suboptimal management of acute pain in this population. Recent studies have shown that greater levels of acute pain are associated with negative long-term psychologic effects such as depression, suicidal ideation, and post-traumatic stress disorder for as long as 2 years after the initial burn injury. Research in other non-burn trauma populations has also pointed to the potential for unmanaged acute pain to delay wound healing and lead to other medical complications, such as infection and extended hospitalization period. The concept of allostatic load is presented as a potential explanation for the relationship between acute pain and subsequent psychologic and physiologic outcomes. A biopsychosocial model is also presented as a means of obtaining better inpatient pain management and helping to mediate this relationship.


Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism.
Excessive uptake of fatty acids and glucose by adipose tissue triggers adipocyte dysfunction and infiltration of immune cells. Altered metabolic homeostasis in adipose tissue promotes insulin resistance, type 2 diabetes, hypertension, and cardiovascular disease. Inflammatory and metabolic processes are mediated by certain proteolytic enzymes that share a common cellular target, protease-activated receptor 2 (PAR2). This study showed that human and rat obesity correlated in vivo with increased expression of PAR2 in adipose tissue, primarily in stromal vascular cells (SVCs) including macrophages. PAR2 was expressed more than other PARs on human macrophages and was increased by dietary fatty acids (palmitic, stearic, and myristic). A novel PAR2 antagonist, GB88 (5-isoxazoyl-Cha-Ile-spiroindene-1,4-piperidine), given orally at 10 mg/kg/d (wk 8-16) reduced body weight by ∼10% in obese rats fed a high-carbohydrate high-fat (HCHF) diet for 16 wk, and strongly attenuated adiposity, adipose tissue inflammation, infiltrated macrophages and mast cells, insulin resistance, and cardiac fibrosis and remodeling; while reversing liver and pancreatic dysfunction and normalizing secretion of PAR2-directed glucose-stimulated insulin secretion in MIN6 β cells. In summary, PAR2 is a new biomarker for obesity, and its expression is stimulated by dietary fatty acids; PAR2 is a substantial contributor to inflammatory and metabolic dysfunction; and a PAR2 antagonist inhibits diet-induced obesity and inflammatory, metabolic, and cardiovascular dysfunction.