A guide to architecture for the public health workforce.
Public health and environmental challenges facing the world in the 21st century, including the ageing population, increasing urbanisation, rise of non-communicable diseases and climate instability, require an interdisciplinary response. A significant proportion of the population's time is spent indoors, be it at home, school, work or in leisure time; the work of an architect can cover all of these sectors, but their role in health and well-being remains an under explored area. This article examines the architecture profession's potential to contribute to improved health and well-being of the population through healthier buildings and places. This short communication adopts a descriptive approach. First, it maps the remit, skills and influence of the architecture profession and applies this to a well-accepted public health model, the prevention pyramid. Second, it uses themes identified by the Royal Society for Public Health to discuss ways to improve engagement with the architecture profession as part of the wider public health workforce. This article finds that the remit, skills and potential influence of architects places them in a key position to improve the health and well-being of the population. Despite this, there has been relatively little engagement between public health and this profession. Much more attention to date has been on integrating the planning sector with public health. Opportunities for improved engagement exist through partnership working, incorporating health into both undergraduate and postgraduate education and continuing professional development training, building the evidence base and developing architecture and health-related policy and legislation.


10-year follow-up of chronic non-malignant pain patients: opioid use, health related quality of life and health care utilization.
In Denmark, opioids have been used liberally for many years in the treatment of non-malignant pain, but long-term consequences as tolerance and influence on health related quality of life remain unknown. Adherence to medical treatment, opioid dose escalation, health related quality of life, anxiety, depression, coping strategies and health care utilization were evaluated in chronic pain patients 10 years after treatment in a multidisciplinary pain centre. Information was gathered from medical records, postal questionnaires and a central hospital register. Opioid dose escalation occurred in only a few patients. Increase and decrease in opioid dose were almost equally frequent. Sixty percent of those discharged on long acting opioids were still on that treatment at follow-up. Twenty-eight percent of the patients initiated opioid treatment after discharge from the pain centre. Occupational status was identified as a determining factor for future opioid use. Opioid users had a lower health related quality of life, higher occurrence of depression and more frequent use of coping strategies like 'Catastrophizing' and 'Hoping and Praying'. Adjuvant analgesics were highly discontinued. Multidisciplinary pain treatment reduced the number of hospital admissions and in-hospital days. We recommend that future research on opioid treatment does not only focus on biological issues. The effect of opioids needs to be viewed in a much more complex context where consequences like health related quality of life, depression and the role of various coping strategies are included.


Cholesterol and mood states at 3 days after delivery.
The aim of this study was to investigate the relationship between cholesterol and mood states in the initial puerperal period. The Profile of Mood States (POMS) was administered to 72 women on the third day after normal pregnancy, uncomplicated vaginal delivery and healthy baby. Plasma cholesterol concentration was measured the same day. Our study indicates that reduced plasma cholesterol concentration is associated with major feelings of fatigue and depressed mood. The implications of these results are discussed.


Temporal bone histopathological and quantitative analysis of mitochondrial DNA in MELAS.
Although hearing loss is common in MELAS (syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes), the histopathology of the temporal bone has not been reported. The majority of cases of MELAS are linked to a mitochondrial DNA (mtDNA) mutation at nucleotide 3243. In MELAS, normal mtDNA and mutant mtDNA coexist in a heteroplasmic manner. The purpose of the study was to report the otopathological findings from two patients with MELAS and quantitative mtDNA analysis in the inner ear of one of these patients. Basic scientific histopathological examination and quantitative mtDNA analysis of the temporal bone. Temporal bones were embedded in celloidin and sectioned for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht. For quantitative mtDNA analysis, total DNA from the membranous part of the inner ear was collected, amplified by polymerase chain reaction, and digested with the restriction enzyme. The percentage of mutant/total mtDNA was measured by the ratio of fluorescence intensity. Histopathological examination revealed severe degeneration of the stria vascularis and degenerative change of spiral ganglion cells in both patients. The quantitative DNA studies showed that the proportion of mutant to wild-type mtDNA was similar in both histologically affected and histologically unaffected tissues within the inner ear. Dysfunction of the stria vascularis and spiral ganglion cells causes sensorineural hearing loss in MELAS.


Placental development and function in trisomy 21 and mouse models of Down syndrome: Clues for studying mechanisms underlying atypical development.
Down syndrome (DS) is the most common genetic disorder leading to developmental disability. The phenotypes associated with DS are complex and vary between affected individuals. Placental abnormalities in DS include differences in cytotrophoblast fusion that affect subsequent conversion to syncytiotrophoblast, atypical oxidative stress/antioxidant balance, and increased expression of genes that are also upregulated in the brains of individuals with Alzheimer's disease. Placentas in DS are prematurely senescent, showing atypical evidence of mineralization. Fetuses with DS are especially susceptible to adverse obstetric outcomes, including early in utero demise, stillbirth and growth restriction, all of which are related to placental function. The placenta, therefore, may provide key insights towards understanding the phenotypic variability observed in individuals with DS and aid in identifying biomarkers that can be used to evaluate phenotypic severity and prenatal treatments in real time. To address these issues, many different mouse models of DS have been generated to identify the mechanisms underlying developmental changes in many organ systems. Little is known, however, regarding placental development in the currently available mouse models of DS. Based upon the relative paucity of data on placental development in preclinical mouse models of DS, we recommend that future evaluation of new and existing models routinely include histologic and functional assessments of the placenta. In this paper we summarize studies performed in the placentas of both humans and mouse models with DS, highlighting gaps in knowledge and suggesting directions for future research.


Focal orchitis presenting as bilateral testicular masses.
A 14-year-old male presented with bilateral scrotal pain. Ultrasound with Doppler revealed multiple bilateral testicular masses that were hypoechoic and hypervascular. Tumor markers and endocrinologic work-up were normal. Bilateral inguinal exploration of the testicles was done and biopsy revealed inflammation with no evidence of malignancy. The patient's pain resolved a few weeks postoperatively. Follow-up ultrasound revealed resolution of the masses. Multiple pathologic testicular entities can present as hypoechoic areas on sonography. Thorough work-up should be performed prior to advocating orchiectomy based only on ultrasound findings.


The sorting platform in the type III secretion pathway: From assembly to function.
The type III secretion system (T3SS) is a specialized nanomachine that enables bacteria to secrete proteins in a specific order and directly deliver a specific set of them, collectively known as effectors, into eukaryotic organisms. The core structure of the T3SS is a syringe-like apparatus composed of multiple building blocks, including both membrane-associated and soluble proteins. The cytosolic components organize together in a chamber-like structure known as the sorting platform (SP), responsible for recruiting, sorting, and initiating the substrates destined to engage this secretion pathway. In this article, we provide an overview of recent findings on the SP's structure and function, with a particular focus on its assembly pathway. Furthermore, we discuss the molecular mechanisms behind the recruitment and hierarchical sorting of substrates by this cytosolic complex. Overall, the T3SS is a highly specialized and complex system that requires precise coordination to function properly. A deeper understanding of how the SP orchestrates T3S could enhance our comprehension of this complex nanomachine, which is central to the host-pathogen interface, and could aid in the development of novel strategies to fight bacterial infections.


Switch-function of amino sugar on elsamicin A, a DNA binding antitumor antibiotic.
There are a considerable number of DNA binding natural products equipped with amino sugar residues. The amino sugar of elsamicin A significantly takes part in DNA binding and antitumor activity. In addition, we found that an acetylation of the amino group on elsamicin A sugar portion plays an important switch-function for the activity of elsamicin A. The biological implication of this switch has been discussed.


[Frequency of genes corresponding to adenosine deaminase, 6-phosphogluconate dehydrogenase and esterase D polymorphism in the Parisian population].
The frequencies of the genes expressing the variation of erythrocytic enzymes ADA, 6PGD and esterase D have been estimated in Paris population. These results are as follows: (formula see text). These are compared to those of other european populations. Although ADA shows the lowest frequency in the french population, the distribution is not significantly different from the whole european distribution. No difference is noticeable for 6PGD and esterase D.


Studies in knockout mice reveal that anti-chlamydial protection requires TH1 cells producing IFN-gamma: is this true for humans?
Chlamydia trachomatis is one of the major causes of infertility and preventable blindness in the world. The organism is of particular interest from an immunological point of view because it is one of the few obligate intracellular bacterial pathogens. There is some evidence that repeated infections in humans stimulate protective immunity. However, until recently, it was unclear which components of the adaptive immune system give rise to protection. Studies in gene knockout mice reported here and elsewhere now give a coherent and cogent picture of the importance of the Th1 response, in particular IFN-gamma, for the localization and eradication of C. trachomatis genital tract infection. The key questions still to be addressed are the identity of the IFN-gamma responsive cells and whether the mouse is truly representative of host protection against chlamydiae in humans.


Ionization quenching in LSC.
Ionization quench function Q(E) introduces an important correction in the CIEMAT/NIST tracing method. In this paper we present a detailed analysis of the equations used to compute the counting efficiency of 55Fe. The counting efficiency of this radionuclide is very sensitive to the shape and values of Q(E) for this method. We demonstrate that the Birks equation and stopping power are not adequate to obtain low discrepancies between the experimental and computed efficiencies. An empirical procedure to compute accurate Q(E) functions is also given.


Maintenance of normothermia during burn surgery with an intravascular temperature control system: a non-randomised controlled trial.
Hypothermia remains one of the major factors limiting surgery in extensively burned patients. We evaluated the effectiveness of an intravascular rewarming technique using CoolGard 3000™ system and Icy™ catheter to maintain normothermia during surgeries of severe burned patients and compared these findings to a historical control group. This was a controlled non-randomised trial conducted between March 2008 and August 2009. Patients with burns greater than or equal to 40% of the total body surface area were included. Before the first burn excision, the Icy™ catheter was placed in the inferior vena cava via the femoral vein. Warming was then initiated and maintained until the bladder temperature reached over 37.5°C. The bladder temperature was recorded every 30min during surgery and for the first hour post-operatively and compared to a historical control group. We enrolled 4 patients and 11 surgeries in the CoolGard™ group and compared them to 3 patients and 10 surgeries in the historical cohort. All intraoperative bladder temperatures from T=30 were statistically different in the two groups. In the CoolGard™ group, no patient became hypothermic and no surgery was aborted because the patient's temperature had rapidly fallen below the threshold temperature (35.5°C). No device-related complication was reported. The use of an intravenous warming catheter is a novel approach to maintain normothermia during surgery in burn victims and may be more effective than traditional methods.


Cardiomyocyte-specific disruption of soluble epoxide hydrolase limits inflammation to preserve cardiac function.
Endotoxemia elicits a multiorgan inflammatory response that results in cardiac dysfunction and often leads to death. Inflammation-induced metabolism of endogenous N-3 and N-6 polyunsaturated fatty acids generates numerous lipid mediators, such as epoxy fatty acids (EpFAs), which protect the heart. However, EpFAs are hydrolyzed by soluble epoxide hydrolase (sEH), which attenuates their cardioprotective actions. Global genetic disruption of sEH preserves EpFA levels and attenuates cardiac dysfunction in mice following acute lipopolysaccharide (LPS)-induced inflammatory injury. In leukocytes, EpFAs modulate the innate immune system through the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. However, the mechanisms by which both EpFAs and sEH inhibition exert their protective effects in the cardiomyocyte are still elusive. This study investigated whether cardiomyocyte-specific sEH disruption attenuates inflammation and cardiac dysfunction in acute LPS inflammatory injury via modulation of the NLRP3 inflammasome. We use tamoxifen-inducible CreER recombinase technology to target sEH genetic disruption to the cardiomyocyte. Primary cardiomyocyte studies provide mechanistic insight into inflammasome signaling. For the first time, we demonstrate that cardiomyocyte-specific sEH disruption preserves cardiac function and attenuates inflammatory responses by limiting local cardiac inflammation and activation of the systemic immune response. Mechanistically, inhibition of cardiomyocyte-specific sEH activity or exogenous EpFA treatment do not prevent upregulation of NLRP3 inflammasome machinery in neonatal rat cardiomyocytes. Rather, they limit downstream activation of the pathway leading to release of fewer chemoattractant factors and recruitment of immune cells to the heart. These data emphasize that cardiomyocyte sEH is vital for mediating detrimental systemic inflammation.NEW & NOTEWORTHY The cardioprotective effects of genetic disruption and pharmacological inhibition of sEH have been demonstrated in a variety of cardiac disease models, including acute LPS inflammatory injury. For the first time, it has been demonstrated that sEH genetic disruption limited to the cardiomyocyte profoundly preserves cardiac function and limits local and systemic inflammation following acute LPS exposure. Hence, cardiomyocytes serve a critical role in the innate immune response that can be modulated to protect the heart.


Effect of modulating the allosteric sites of N-methyl-D-aspartate receptors in ischemia-reperfusion induced acute kidney injury.
Acute kidney injury (AKI) is one of the major health problems in developed as well as developing countries. The literature regarding the role of N-methyl-D-aspartate receptors (NMDAR) and the impact of the modulation of its allosteric sites on renal function is inadequate. The present study investigated the effect of modulating allosteric sites of NMDAR in ischemia-reperfusion-induced AKI. We subjected rats to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. We measured blood urea nitrogen, serum creatinine, uric acid, and lactate dehydrogenase to assess kidney injury. We assayed the thiobarbituric acid-reactive substances, reduced glutathione level, and myeloperoxidase and catalase activity to assess oxidative stress in renal tissue, and used hematoxylin-eosin staining to observe histopathologic changes. Ischemia-reperfusion induced AKI, as demonstrated by an increase in serum parameters, oxidative stress and histopathologic changes in renal tissue. The NMDA agonist glutamic acid and polyamine binding site agonist spermidine significantly aggravated oxidative stress and ischemia-reperfusion-induced AKI. Various NMDA receptor antagonists, including glycine binding site inhibitor kynurenic acid, polyamine binding site inhibitor ketamine, and channel blocking agent magnesium sulfate, attenuated ischemia-reperfusion-induced AKI and significantly reduced oxidative stress, which suggests a role for NMDA receptors and the importance of regulating its allosteric sites in AKI. Acute kidney injury is associated with the activation of NMDA receptors, as well as significant oxidative stress. The antagonism of various allosteric sites of NMDA receptors affords significant benefit against ischemia-reperfusion-induced AKI.


Acceptance and effectiveness for learning of a simulation manikin for suprapubic aspiration in toddlers constructed with simple means.
Skills trainings are increasing in popularity in undergraduate medical education enhancing clinical competencies and motivation for clinical practice. A suprapubic aspiration (SPA) is the gold standard to obtain urine from toddlers and young infants with fever and unclear focus to prove an urinary tract infection. In a blended-learning scenario with virtual patients and skills lab training students were trained for a SPA. Currently, no toddler simulation manikin for SPA is available on the market so we constructed one with simple means. Students' acceptance and their view on relevant aspects of the manikin for learning effectiveness were assessed. With an expenditure regarding work of 3½ h and material costs of 188.12 Euro we were able to construct a paediatric manikin for suprapubic bladder punction using a cheap basic life support manikin. N = 56 students rated their learning success with the manikin as high (77.2 ± 21.6; mean and standard deviation; visual analogue scales from 100 = totally agree to 0 = don't agree at all). The model was rated as useful for training (84.2 ± 17.2) and realistic (62.1 ± 23.5). Important factors for students' learning success were (in descending order) that "urine" could be aspirated (81.4 ± 19.5), the feel of the needle inserted in the manikin (71.5 ± 23.2), and--notably less important--the outer appearance in general (40.3 ± 24.6). We present a construction of a paediatric manikin for suprapubic aspiration with simple means for a realistic learning scenario with high learning success.


A recombinant Modified Vaccinia virus Ankara expressing prME of tick-borne encephalitis virus affords mice full protection against TBEV infection.
Tick-borne encephalitis virus (TBEV) is an important human pathogen that can cause a serious disease involving the central nervous system (tick-borne encephalitis, TBE). Although approved inactivated vaccines are available, the number of TBE cases is rising, and breakthrough infections in fully vaccinated subjects have been reported in recent years. In the present study, we generated and characterized a recombinant Modified Vaccinia virus Ankara (MVA) for the delivery of the pre-membrane (prM) and envelope (E) proteins of TBEV (MVA-prME). MVA-prME was tested in mice in comparison with a licensed vaccine FSME-IMMUN® and proved to be highly immunogenic and afforded full protection against challenge infection with TBEV. Our data indicate that MVA-prME holds promise as an improved next-generation vaccine for the prevention of TBE.


Effect of bilateral lesions of the suprachiasmatic nucleus on hyperglycemia caused by 2-deoxy-D-glucose and vasoactive intestinal peptide in rats.
In mammals, the brain usually uses glucose as a sole energy source. Thus, under a central glucopenic condition after intracranial injection of 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, it has been shown that rats elevate their blood glucose level through excitation of the sympathetic nerves. Experiments were conducted with rats to examine the role of the hypothalamic suprachiasmatic nucleus (SCN) in the hyperglycemic response to intracerebroventricular injection of either 2DG or vasoactive intestinal peptide (VIP). It was observed that, (1) intracerebroventricular injection of a VIP-antagonist inhibited the hyperglycemic and hyperglucagonemic responses to the intracranial injection of 2DG; (2) bilateral electrolytic lesioning of the SCN suppressed the hyperglycemic and hyperglucagonemic responses to intracranial injection of 2DG, and intracerebroventricular injection of VIP restored these responses to 2DG; and (3) bilateral electrolytic lesioning of the SCN also suppressed the hyperglycemic and hyperglucagonemic responses to the VIP injection, and additional intracerebroventricular injection of 2DG caused hyperglycemia. These findings indicate that in rats with bilateral lesions of the SCN intracranial injection of 2DG is able to elicit hyperglycemia when VIP was administered intracranially, and suggest that neurons containing VIP-like immunoreactive substance (VIP-neurons) in the SCN have an important role in the mechanism of hyperglycemia elicitation following intracranial injection of 2DG. Moreover, these findings show that 2DG and VIP are able to realize their functions through acting on the brain sites outside the SCN.


Antidepressants for the virtually eviscerated patient: options instead of oral dosing.
Alternate ways of administering antidepressants when oral intake is impossible are discussed. Reviews of 1) the medical circumstances that preclude oral medication administration and 2) novel administration strategies for antidepressants were conducted. Consultation psychiatrists not infrequently encounter depressed patients who lack a functioning gastrointestinal tract and who thus cannot absorb oral antidepressant medication. Under these circumstances, antidepressants can be administered intravenously, by rectal suppository, or topically. There are options for administration of antidepressant medication when oral intake is impossible.


Fisetin attenuates arsenic and fluoride subacute co-exposure induced neurotoxicity via regulating TNF-α mediated activation of NLRP3 inflammasome.
Groundwater is considered safe, however, the occurrence of contaminants like arsenic and fluoride has raised a major healthcare concern. Clinical studies suggested that arsenic and fluoride co-exposure induced neurotoxicity, however efforts to explore safe and effective management of such neurotoxicity are limited. Therefore, we investigated the ameliorative effect of Fisetin against arsenic and fluoride subacute co-exposure-induced neurotoxicity, and associated biochemical and molecular changes. Male BALB/c mice were exposed to Arsenic (NaAsO2: 50 mg/L) and fluoride (NaF: 50 mg/L) through drinking water and fisetin (5, 10, and 20 mg/kg/day) was administered orally for 28 days. The neurobehavioral changes were recorded in the open field, rotarod, grip strength, tail suspension, forced swim, and novel object recognition test. The co-exposure resulted in anxiety-like behaviour, loss of motor coordination, depression-like behaviour, and loss of novelty-based memory, along with enhanced prooxidant, inflammatory markers and loss of cortical and hippocampal neurons. The treatment with fisetin reversed the co-exposure-induced neurobehavioral deficit along with restoration of redox & inflammatory milieu, and cortical and hippocampal neuronal density. Apart from antioxidants, inhibition of TNF-α/ NLRP3 expression has been suggested as one of the plausible neuroprotective mechanisms of Fisetin in this study.


P3 peptide, a truncated form of A beta devoid of synaptotoxic effect, does not assemble into soluble oligomers.
In previously proposed models of A beta soluble oligomers, the N-terminal domain A beta(1-16), which is missing in p3 peptides, protects the hydrophobic core of the oligomers from the solvent. Without this N-terminal part, oligomers of p3 peptides would likely expose hydrophobic residues to water and would consequently be less stable. We thus suggest, based on theoretical and experimental results, that p3 peptides would have a low propensity to assemble into stable oligomers, evolving then directly to fibrillar aggregates. These properties may explain why p3 would be devoid of any impact on synaptic function and moreover, strengthen the hypothesis that A beta oligomers are the principal synaptotoxic forms of A beta peptides in Alzheimer disease.


A new distinguishing attack on reduced round ChaCha permutation.
This work concentrates on differential-linear distinguishing attacks on the prominent ARX-based permutation ChaCha. Here, we significantly improve the 7-round differential-linear distinguisher for ChaCha permutation by introducing a new path of linear approximation. We first introduce a new single-bit differential distinguisher for the 3.5th round of the permutation that assists us in inventing a new path for the differential-linear distinguisher. We show that one can distinguish a 7-round ChaCha permutation with time complexity of [Formula: see text]. This improves the recent work of Coutinho et al. (in: Advances in Cryptology-ASIACRYPT 2022-28nd International Conference on the Theory and Application of Cryptology and Information Security, Taipei, Taiwan, December 5-9, 2012, Springer, 2022), which achieved time complexity [Formula: see text]. We also propose a distinguisher for the 7.25-round of ChaCha permutation and this is the first distinguishing attack for more than 7-round of ChaCha permutation. We provide theoretical proofs and the corresponding experimental results for the linear approximations that we use for differential-linear distinguisher. We point out that the existing multibit distinguishing attacks on the cipher ChaCha are invalid. These attacks are worked only for the ChaCha permutation.


Characterization of polyphenol oxidase from Cape gooseberry (Physalis peruviana L.) fruit.
Cape gooseberry (Physalis peruviana) is an exotic fruit highly valued, however it is a very rich source of polyphenol oxidase (PPO). In this study, Cape gooseberry PPO was isolated and biochemically characterized. The enzyme was extracted and purified using acetone and aqueous two-phase systems. The data indicated that PPO had the highest substrate affinity for chlorogenic acid, 4-methylcatechol and catechol. Chlorogenic acid was the most suitable substrate (Km=0.56±0.07 mM and Vmax=53.15±2.03 UPPO mL(-1) min(-1)). The optimal pH values were 5.5 for catechol and 4-methylcatechol and 5.0 for chlorogenic acid. Optimal temperatures were 40°C for catechol, 25°C for 4-methylcatechol and 20°C for chlorogenic acid. In inhibition tests, the most potent inhibitor was found to be ascorbic acid followed by L-cysteine and quercetin. This study shows possible treatments that can be implemented during the processing of Cape gooseberry fruits to prevent browning.


Analysis of Glucose Levels in Patients Hospitalized With COVID-19 During the First Phase of This Pandemic in West Texas.
Patients with hyperglycemia during hospitalization, especially during ICU hospitalizations, often have worse outcomes, even if they do not have a premorbid diagnosis of diabetes. High glucose levels can provide insight into the underlying pathogenesis of a disease and can contribute to tissue injury. Some patients with COVID-19 have hyperglycemia during hospitalizations. The Infectious Disease and Control office at University Medical Center in Lubbock, Texas, provided a list of patients with a COVID-19 infection hospitalized between March 1 and May 15, 2020. The medical records were reviewed to collect information on age, gender, history of diabetes, and glucose levels on admission and through the first 7 days of hospitalization. This study included 63 patients with a mean age of 62.1 ± 14.1 years. Thirty-five patients (55.6%) were males. The in-hospital mortality rate was 30.2%. The mean admission glucose level was 129.4 ± 57.1 mg/dL in patients who survived (N = 47) and 189.6 ± 112.2 mg/dL in patients who died during hospitalization (N = 16, P = .007). An admission glucose greater than 180 mg/dL predicted mortality in a model adjusted for a diabetes, age, and male gender. The mean differences between the maximum and minimum glucose levels calculated over the first 7 days of hospitalization were 112.93 ± 115.4 (N = 47) in patients who survived and were 240.5 ± 97.7 (N = 15) in patients who died during hospitalization (P = .0003). A difference between the maximum and minimum glucose level greater than 105 mg/dL was associated with increased mortality. Patients who died during hospitalization for COVID-19 had higher admission glucose levels than patients who survived. Larger differences between maximum and minimum glucose levels during the first 7 days of hospitalization were associated with increased mortality. These results suggest that high glucose levels identify patients at increased risk for mortality and warrant more study.


Aorto-left renal artery bypass as an adjunct to suprarenal abdominal aortic aneurysm repair.
Renal ischemia remains a vexing issue in the repair of suprarenal abdominal aortic aneurysms (SR-AAAs). Multiple reconstruction methods have been described, including fish-mouth anastomoses, renal artery reimplantation, and aortorenal interposition grafts. We present an alternative method of SR-AAA repair that minimizes renal ischemia time. We describe our approach in two patients with SR-AAAs. Both patients had normal preoperative renal function. Maximal aneurysm diameters were 6.0 and 7.4 cm. In each case, the abdominal aorta was exposed via the retroperitoneal approach and the supraceliac aorta was dissected from the surrounding tissue. A partially occluding side-biting aortic clamp was placed at this level to facilitate placement of a synthetic 6 mm interposition graft that was sewn in an end-to-side fashion to the suprarenal aorta first. These grafts were then sewn end-to-end to the left renal artery, completing the aorto-left renal bypass. Left renal ischemia times were 12 and 14 min. The aneurysm was then repaired with a beveled proximal anastomosis, accommodating the right renal artery orifice. Both patients had minimal postoperative renal dysfunction, with peak creatinine levels of 1.9 and 1.4 mg/dl. At discharge, both patients had a creatinine level of 1.1 mg/dl. Urinary output remained normal throughout the hospital stays, and neither patient required dialysis. Retroperitoneal aortic exposure with preliminary aorto-left renal artery bypass is an effective method of treating SR-AAAs. Proximal anastomosis can be done with less urgency and minimal right renal ischemia, by revascularizing the left kidney first.


Knockdown of CEACAM19 suppresses human gastric cancer through inhibition of PI3K/Akt and NF-κB.
Gastric cancer directly affects the quality of human life worldwide. Some members, which belong to carcinoembryonic antigen-related cell adhesion molecule (CEACAM) subfamily, are deregulated in tumors. Of the subfamily, CEACAM19, a new member was the research object. Our study sought to explore the potential role of CEACAM19 in gastric cancer. According to the immunohistochemistry (IHC), RT-PCR and Western blot, CEACAM19 was over-expressed in gastric cancer tissues and cells. Moreover, the Western blot analysis showed that the expression of MMP2 and MMP9 was inhibited in CEACAM19 knockdown gastric cancer cells. Meanwhile, in SGC-7901 and MGC-803 cells, the knockdown of CEACAM19 reduced proliferation, migration and invasion. Additionally, the Western blot assay revealed that the phosphorylation levels of Akt and p65 were declined by the knockdown of CEACAM19. Furthermore, the influence of CEACAM19 knockdown was confirmed by the studies in vivo. Collectively, our results revealed that the CEACAM19 knockdown prevented the gastric cancer progression likely related to inactivating the PI3K/Akt and NF-κB signaling pathways. Our findings provided insights into a promising biomarker of gastric cancer and the potential molecule clues for the prevention of gastric cancer.


The effects of noninvasive brain stimulation on cognitive function in patients with mild cognitive impairment and Alzheimer's disease using resting-state functional magnetic resonance imaging: A systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to evaluate the efficacy of noninvasive brain stimulation (NIBS) on cognition using functional magnetic resonance imaging (fMRI) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), thus providing the neuroimaging mechanism of cognitive intervention. English articles published up to April 30, 2023 were searched in the PubMed, Web of Science, Embase, and Cochrane Library databases. We included randomized controlled trials where resting-state fMRI was used to observe the effect of NIBS in patients with MCI or AD. RevMan software was used to analyze the continuous variables, and SDM-PSI software was used to perform an fMRI data analysis. A total of 17 studies comprising 258 patients in the treatment group and 256 in the control group were included. After NIBS, MCI patients in the treatment group showed hyperactivation in the right precuneus and decreased activity in the left cuneus and right supplementary motor area. In contrast, patients in the control group showed decreased activity in the right middle frontal gyrus and no hyperactivation. The clinical cognitive scores in MCI patients were significantly improved by NIBS, while not in AD. Some evidence regarding the modulation of NIBS in resting-state brain activity and functional brain networks in patients with AD was found. NIBS could improve cognitive function in patients with MCI and AD. fMRI evaluations could be added to evaluate the contribution of specific NIBS treatment therapeutic effectiveness.


Glycyrrhizin alleviates experimental allergic asthma in mice.
Asthma is a chronic respiratory disease, the incidence of which is increasing globally. The existing therapy is inadequate and has many adverse effects. It needs a better therapeutic molecule preferably of natural origin, which has negligible or no adverse effects. In view of this, we evaluated Glycyrrhizin (GRZ), a major constituent of a plant Glycyrrhiza glabra, for its efficacy on asthmatic features in a mouse model of asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to develop the asthmatic features such as airway hyperresponsiveness: allergen induced airway constriction and airway hyperreactivity (AHR) to methacholine (MCh), and pulmonary inflammation. The mice were orally treated with GRZ (2.5, 5, 10 and 20 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect, respectively on the above asthmatic features. The status of airway hyperresponsiveness was measured by monitoring specific airway conductance (SGaw) using a non-invasive method and the pulmonary inflammation was assessed by haematoxylin and eosin staining of lung sections. Several other parameters associated with asthma such as interleukin (IL)-4, IL-5 interferon-gamma (IFN-gamma), OVA-specific IgE, total IgG(2a) and cortisol were measured by ELISA. GRZ (5 mg/kg) markedly inhibited OVA-induced immediate airway constriction, AHR to MCh (p<0.01), lung inflammation, and infiltration of eosinophils in the peribronchial and perivascular areas. It prevented the reduction of IFN-gamma (p<0.02), and decreased IL-4 (p<0.05), IL-5 (p<0.05) and eosinophils (p<0.0002) in the BAL fluid. Also, it reduced OVA-specific IgE levels (p<0.01) and prevented the reduction of total IgG(2a) (p<0.01) in serum. We have also showed that it has no effect on serum cortisol levels. Our results demonstrate that GRZ alleviates asthmatic features in mice and it could be useful towards developing a better therapeutic molecule in the future.


Impact of Fungicides Chlorothalonil and Propiconazole on Microbial Activities in Groundnut (Arachis hypogaea L.) Soils.
Introduction of agrochemicals (fungicides) into soil may have lasting effects on soil microbial activities and thus affect soil health. In order to determine the changes in microbial activity in a black clay and red sandy loam soils of groundnut (Arachis hypogaea L.) cultivated fields, a case study was conducted with propiconazole and chlorothalonil to evaluate its effects on soil enzymes (cellulase and invertase) throughout 40 days of incubation under laboratory conditions with different concentrations (1.0, 2.5, 5.0, 7.5, and 10.0 kg ha(-1)). Individual application of the two fungicides at 1.0, 2.5, and 5.0 kg ha(-1) to the soil distinctly enhanced the activities of cellulase and invertase but at higher concentrations of 7.5 and 10 kg ha(-1) was toxic or innocuous to both cellulase and invertase activities. In soil samples receiving 2.5-5.0 kg ha(-1) of the fungicides, the accumulation of reducing sugar was pronounced more at 20 days, and the activity of the cellulase and invertase was drastically decreased with increasing period of incubation up to 30 and 40 days.


Cell-free transmission in adult Swiss mice of a disease having the character of a leukemia.
A disease with the characteristics of a leukemia has been found to be serially transmissible in adult Swiss mice by means of cell-free filtrates. Thus far, the disease has been transmitted through twenty-six serial passages with filtrates as well as cell suspensions. The agent readily passes through Selas 03, Berkefeld N, and gradocol membrane filters-these last having an average pore size of 220 mmicro. Filtrates remain stable when stored for long periods at -70 degrees C. or when lyophilized. Splenic tissue containing the agent, which was subjected to massive doses of x-ray (50,000 r),-far more than sufficient to kill the cells,-show undiminished infectivity. The agent is inactivated by heating to 56 degrees C. for 30 minutes and by exposure to ether or formalin. The disease can be transmitted to adult Swiss mice or DBA/2 mice, but not to adult PRI, C(3)H, A, C(57)B1/6, or F(1)(C(58) x BALB) mice. Intraperitoneal, subcutaneous, intracerebral, and intramuscular injections are all effective.


Self-described impact of noncompliance among users of a combined hormonal contraceptive method.
A number of factors related to the user and the method affect contraceptive compliance. This cross-sectional multicenter study was designed to assess self-described impact of noncompliant behavior among 26,250 typical users of a combined hormonal contraceptive method who consulted their physicians for control visits. A self-administered questionnaire was completed. Sixty-five percent of women used the pill, 23% the vaginal ring and 12% the transdermal patch. Noncompliant behavior (missing/delays in taking/application, insertion or removal of the pill/skin patch/vaginal ring) was recorded in 71% of pill users, 32% of patch users and 21.6% of vaginal ring users (p<.0001). Emergency contraception was requested by 14% of pill users, 11% of patch users and 6.3% of ring users. About 40% of women in all groups called or visited a physician. Seventy percent of women continued to have active sex life, and 60% used an additional contraceptive method. Noncompliant behavior negatively affected work activities and/or couple relationships in 10-20% of cases. More than 50% of women reported they were worried and about 20% were scared due to inconsistent use of the contraceptive method. After filling out the questionnaire, 64.7% of pill users continued to prefer the pill, 61.7% of patch users preferred the patch and 96.6% of women using the vaginal ring preferred the ring. Noncompliant behavior had noticeable effects on emotional well-being, prompted request for physicians' advice, and use of emergency contraception. Despite recognition of problems associated with inconsistent use, women tended to prefer the currently used contraceptive method.


Early appearance of aging phenomenon in the interdigital nerves of the foot.
To test the hypothesis that the interdigital nerves of the foot are the first to be affected by aging, we studied sensory nerve conduction in the nerves of normal subjects between the ages of 10 and 79, using the near-nerve needle technique. In normal individuals up to the seventh decade we could get sensory CNAPs without any difficulty by 256 averagings. In 10% of the 70-79-year-old group we could not obtain those potentials in some digital or interdigital nerves. Between the 10-49-year-old and 50-79-year-old groups, there was a significant slowing in the sensory NCVs, a significant decline in the amplitude of the sensory CNAPs, and a significant prolongation of the duration of sensory CNAPs for the various interdigital nerves. Thus, our study documented the earlier presence of aging phenomenon in the sensory nerve conduction of the interdigital nerves of the foot compared with the previously reported sensory nerve conduction change with age in the other nerves. We conclude that the "degeneration" of various interdigital nerves of the foot is accelerated from the early 50s on, possibly resulting from the normal aging process.


Two novel HLA-C alleles, HLA-C*15:228 and -C*04:434, detected in inhabitants from the island of Crete.
Characterization of the novel HLA-C*15:228 and HLA-C*04:434 alleles in two Greek individuals of Cretan origin.


Leucothoe eltoni sp. n., a new species of commensal leucothoid amphipod from coral reefs in Raja Ampat, Indonesia (Crustacea, Amphipoda).
A new species of leucothoid amphipod, Leucothoe eltoni sp. n., is described from coral reefs in Raja Ampat, Indonesia where it inhabits the branchial chambers of solitary tunicates. With an inflated first gnathopod superficially resembling the genus Paraleucothoe, this new species has a two-articulate maxilla 1 palp characteristic of the genus Leucothoe. While described from coral reef environments in tropical Indonesia and the Philippines, it is an established invasive species in the Hawaiian Islands. The most likely mode of introduction was a US Navy dry dock transported to Pearl Harbor in 1992 from Subic Bay, Philippines.


The regulation of acyl-CoA dehydrogenases in adipose tissue by rosiglitazone.
The acyl-CoA dehydrogenases (ACADs), which catalyze the rate-limiting step in the mitochondrial beta-oxidation spiral, were investigated in white adipose tissue (WAT) of C57Bl/6 mice treated with 10 mg/kg/day rosiglitazone. Rosiglitazone was also administered to PPAR-alpha knockout mice. ACAD abundance and activity were determined using western blotting and an ACAD enzyme activity assay. Rosiglitazone increased ACAD activity in both epididymal and inguinal WAT but not in brown adipose tissue, liver, or muscle. Given the known function of PPAR-alpha in regulating the expression of ACAD genes in liver, it was hypothesized that PPAR-alpha may be involved in upregulating the ACADs during rosiglitazone-mediated adipose tissue remodeling. However, the effect of rosiglitazone on adipose tissue ACAD activity was the same in wild-type and PPAR-alpha knockout mice. In conclusion, rosiglitazone increases expression and activity of ACAD enzymes in WAT independently of PPAR-alpha.


Ribosome Profiling in Maize.
Ribosome profiling (also known as Ribo-seq) provides a genome-wide, high-resolution, and quantitative accounting of mRNA segments that are occupied by ribosomes in vivo. The method has been used to address numerous questions in bacteria, yeast, and metazoa, but its application to questions in plant biology is just beginning. This chapter provides a detailed protocol for profiling ribosomes in plant leaf tissue. The method was developed and optimized with maize, but it has been used successfully with Arabidopsis and tobacco as well. The method captures ribosome footprints from the chloroplast and cytosol in the same preparation, but it is not optimal for detecting the footprints of mitochondrial ribosomes. The protocol is robust and simpler than many of the methods reported previously for ribosome profiling in plants.


Formation of multilayer rosettes in phytohemagglutinin-stimulated lymphocytes: correlation with chromatin condensation conformation in premature chromosome condensation.
We found that the formation of multilayer rosettes by transformed human blood lymphocytes after phytohemagglutinin (PHA) stimulation is correlated with conformational changes of the chromatin as seen by premature chromosome condensation (PCC). The frequency distribution of grades of PCC and multilayer rosette formation suggests that changes in chromatin are a prerequisite for rosette formation. Rosette formation was most pronounced for 24-h and 48-h cultures. Chromatin decondensation and rosette formation showed identical patterns. The possibility that multilayer rosette formation is directly dependent on conformational changes of chromatin is discussed.


The eQTL-missense polymorphisms of APOBEC3H are associated with lung cancer risk in a Han Chinese population.
APOBEC (Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) enzymes may involve in mutagenic processes in multiple cancer types, including lung cancer. APOBEC family of cytidine deaminases induces base substitutions with a stringent TCW motif, which is widespread in multiple human cancers. We hypothesized that common missense variants in coding regions of APOBEC genes might damage the structure of proteins and modify lung cancer risk. To test this hypothesis, we systematically screened predicted deleterious polymorphisms in the exon regions of 10 APOBEC core genes (APOBEC1, APOBEC2, APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3D, APOBEC3F, APOBEC3G, APOBEC3H, and APOBEC4) and evaluated them with a case-control study including 1200 cases and 1253 controls. We found that the T allele of rs139293 in exon 2 of APOBEC3H was significantly associated with decreased risk of lung cancer (odds ratio = 0.76, 95% confidence interval: 0.63-0.91). Similar inverse association of this variant was observed in subgroups. Further study showed that the T allele of rs139293 was associated with the altered expression of APOBEC3H and APOBEC3C and that the two genes were co-expressed in both tumor and adjacent normal tissues. These results indicate that genetic variants in APOBEC3H may contribute to lung cancer susceptibility in Chinese population.


Study of an antigenic site of human serum albumin with monoclonal antibodies.
Two monoclonal anti-HSA antibodies, HA1 and HA2, have been shown to be specific for a univalent fragment of 6000 mol. wt, F1, located near the C-terminus of HSA (Doven, Pesce & Lapresle, Immunology Letters 3, 365-370, 1981). Both monoclonal antibodies have been shown to react with the same site, which includes the following components: the last small loop of HSA (558-567) the disulfide bridge 514-559 and the residue 570. This site is as available on HSA and F1, but partially masked on the 'Inhibitor' fragment from which F1 derives. Polyclonal anti-F1 antibodies, purified from rabbit sera or mouse ascites by affinity chromatography, react with the same site as HA1 and HA2. However, polyclonal antibodies are heterogenous, most probably because they consist of anti-F1 specific antibodies and of antibodies specific against other parts of the albumin molecule which cross-react with F1. In addition, monoclonal antibodies can recognize the mutation of a single amino acid residue in the albumin molecule.


The cationization of synthetic polymers in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: Investigations of the salt-to-analyte ratio.
Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization technique that when used to analyze synthetic polymer analytes often requires the addition of a metal cationization agent (herein termed the "salt"). The choice of both the matrix and the cationization agent needs to be taken into account when considering the polymer under study; different polymers have shown different affinities toward different cationization agents, and their selectivity can change as the matrix changes. Salt-to-analyte ratio (S/A) plots are used in this work to investigate the effect of the quantity of cationization agent employed in the analysis of a poly (methylmethacrylate) (PMMA) analyte with different MALDI matrices. The point at which analyte signal stops increasing with the added cationization agent is termed the "cation saturation point," and it was found to occur around a S/A of 1. When the analyte signal after this point remains constant, it is termed an "ideal case." The "non-ideal case" occurs when the analyte signal decreases after the cation saturation point. The amount of matrix present (measured as the matrix-to-analyte molar ratio, M/A) and the use of different counterions for the salt are also found to affect the intensity of the analyte signal. In non-ideal cases, changes in the counterion or an increase in the M/A are found to increase the analyte signal, often converting an initially observed non-ideal case into an ideal case. Several experiments attempting to uncover the reason for observation of the non-ideal S/A behavior are also described.


Cardiac size and function during adrenocorticotropic hormone-induced systolic systemic hypertension in infants.
The effects of adrenocorticotropic hormone (ACTH) on systolic blood pressure, and echocardiographic indexes of heart size and function were investigated in 14 infants. After 25 days (range 13 to 46) of treatment with ACTH, systolic blood pressure increased from 93 +/- 9 to 118 +/- 20 mm Hg (p < 0.001; mean +/- 1 SD). Systolic hypertension (systolic blood pressure greater than the 95th percentile for age) developed in 10 of 14 infants and was associated with an increase in left ventricular (LV) shortening fraction from 41 +/- 5% to 52 +/- 8% (p < 0.001). Myocardial hypertrophy and an increase in echocardiographic indexes of myocardial contractility were observed also. To assess the temporal relation between the onset of systolic hypertension and these cardiac changes, data from 8 infants with serial echocardiograms and blood pressure determinations were examined. After a mean 14 days (range 8 to 18) of ACTH, LV shortening fraction increased from 39 +/- 6% to 53 +/- 8% (p < 0.01), whereas systolic blood pressure remained normal in 7 of 8 infants. In addition, a decrease in LV end-systolic dimension was observed during this early phase. This report documents myocardial changes in individual patients, which occur before and during the development of systolic hypertension.


Activity of ventrolateral thalamic neurons in relation to a simple reaction time task in the cat.
Unrestrained cats performed ballistic forelimb flexion movements triggered by an auditory stimulus (CS) on a simple reaction time (RT) paradigm. During the variable foreperiod the subject was required to hold down a lever and to release it on presentation of the CS. The RTs ranged from 200 to 300 ms. The activity of single neurons of the ventrolateral nucleus of the thalamus (VL) was recorded bilaterally. More than 40% of the 166 units recorded in the VL contralateral to the performing limb presented, after the CS, changes of activity with a latency less than 100 ms and were classified into three types: (1) Twenty-five units had a short latency transient increase of activity 10 to 30 ms after the CS, followed by a longer increase or decrease in activity. Short latency increase as well as subsequent increase of the firing rate were not correlated to the RTs. (2) Twenty-nine units showed a 40-60 ms latency increase of activity which lasted long enough to continue during the forelimb movement. These units displayed a correlation between the RTs and the mean firing rate measured in the 40-100 ms period after the CS. The more the cells were activated, the shorter the RTs. (3) Fifteen units presented a reciprocal pattern of discharge with respect to the type (2) units. The firing rate decreased with latencies ranging from 20 to 90 ms after the CS. Only 14,5% of the 96 units recorded in the VL ipsilateral to the performing limb presented changes of activity starting in the 100 ms period following the CS. Background firing levels as well as phasic activity were rather low compared to those observed contralaterally. Sixteen units showed burst activity while the cat was performing but burst pattern was not time-related to the task. In an unconditioned animal, a very low level of activity and an absence of modulations were observed in both VLs.


Cytogenetic response of normal human and ataxia telangiectasia G2 cells exposed to X-rays and ara C.
The kinetics of rejoining of chromatid deletions and the formation of exchanges has been studied in X-irradiated normal and ataxia telangiectasia (AT) fibroblasts treated in the presence or absence of the nucleoside analogue 1-beta-D-arabinofuranosylcytosine (ara C). Ara C is a powerful inhibitor of DNA synthesis as well as an inhibitor of DNA double-strand break repair. Treatment with ara C was found to increase the frequency of X-ray-induced chromatid deletions in both lines with increasing incubation time while deletions were found to rejoin with first-order kinetics and a t1/2 of 2.4-3.1 h in both cell lines. The increase in deletions in the presence of ara C is thought to be due to an interaction of ara C-induced lesions (as yet unidentified) with lesions induced by X-rays, leading to additional chromatid breaks. These results are in contrast to those previously obtained with the same lines treated with X-rays and 9-beta-D-arabinofuranosyladenine (ara A). In this case the frequency of deletions in X-irradiated cells remained constant in both lines in the presence of ara A. We therefore propose that there is a major difference in the mode of action of ara C and ara A on X-ray-induced DNA damage in G2 cells. Exchanges were formed in X-irradiated cells in the presence and absence of ara C in both lines and the frequency increased with post-irradiation incubation time. A higher frequency was formed in ara C-treated cells than in cells given X-rays alone, but the enhancement by ara C was less than that previously found in cells treated with ara A.


A simple and rapid HPLC method for the determination of atorvastatin in human plasma with UV detection and its application to pharmacokinetic studies.
A rapid and sensitive high-performance liquid chromatographic method for the determination of atorvastatin (CAS 134523-00-5) in plasma was developed in this study. Atorvastatin was isolated from plasma using protein precipitation by acetonitrile. Diltiazem (CAS 33286-22-5) was used as internal standard. The chromatographic conditions were as follows: analytical 125 x 4 mm (i.d.) Nucleosil C8 column (5 microm particle size), mobile phase consisting of sodium dihydrogen phosphate buffer-acetonitrile (60:40, v/v) adjusted to pH 5.5 at a flow rate of 1.5 ml/min, UV detection at 245 nm. The detection limit for atorvastatin in plasma was 1 ng ml(-1). The calibration curve was linear over the concentration range 20-800 ng ml(-1). The recovery was complete. The inter-day and intra-day assay coefficients of variation were found to be less than 7%. The present validated method was successfully used for pharmacokinetic studies of atorvastatin in human subjects.


Uterus didelphys with unilateral imperforate vagina: a rare cause of acute urinary retention.
The first case is reported of acute urinary retention caused by hematocolpos owing to uterus didelphys with a unilateral imperforate vagina. A brief description of this rare anomaly and its usual presenting signs and symptoms is presented. Finally, a synopsis of the embryologic defects responsible for the development of the anomaly and the recommended management of the disorder are outlined.


Comparison of multiparameter flow cytometry with cluster analysis and immunohistochemistry for the detection of CD10 in diffuse large B-Cell lymphomas.
CD10 is a critical antigen for the distinction of follicle-center lymphoma from other B-cell lymphomas composed of small cells in fine-needle aspiration specimens, tissue core biopsies, and bone marrow. In addition, CD10 is expressed in a subset of diffuse large B-cell lymphomas (DLBCLs), where it may be an adverse prognostic indicator. We have previously demonstrated that CD10 expression detected by multiparameter flow cytometry (FC) with cluster analysis is highly sensitive and specific for follicle-center lymphoma in the differential diagnosis of small B-cell lymphomas. In this study, we assessed the utility of paraffin section immunohistochemistry (IHC) for CD10 compared with FC in a cohort of 50 DLBCLs. IHC for CD10 was technically successful in 47 of the 50 (94%) DLBCLs; 3 failed based on lack of internal CD10 reactivity. CD10 was expressed by FC in 20 of 47 DLBCLs (43%); CD10 was positive by IHC in 15 of these (75%). All 27 cases that were CD10(-) by FC were negative by IHC. The level of CD10 expression by FC in the 5 FC(+)/IHC(-) cases ranged from relatively dim to bright. Our results indicate 75% sensitivity and 100% specificity of CD10 expression by IHC compared with multiparameter FC with cluster analysis and a 6% technical failure rate.


The prospective relation between eating behaviors and BMI from middle childhood to adolescence: A 5-wave community study.
Some eating behaviors are associated with increased risk of childhood obesity and are thus potential targets for obesity prevention. However, longitudinal research, especially on older children and adolescents, is needed to substantiate such a claim. Using data from a representative birth cohort of Norwegian children followed up biennially from age 6 to age 14 (analysis sample: n = 802), we tested if change in eating behaviors predicts increased body mass index (BMI) throughout childhood and adolescence, or if it is the other way around; higher BMI predicting more obesogenic eating. Eating behaviors were measured using the Children's Eating Behaviour Questionnaire (CEBQ) and BMI was measured objectively using digital scales. To separate within-person- and between-person effects and control for all time-invariant confounders (i.e., variables that do not change over the study period), we applied an autoregressive latent trajectory model with structured residuals (ALT-SR). Results showed that increases in obesogenic eating behaviors did not predict higher BMI at any age. It was the other way around: Increased BMI predicted increases in food responsiveness and emotional overeating at all time points, and enjoyment of food from 8 to 10 years and from 10 to 12 years. Furthermore, increased BMI predicted decreases in satiety responsiveness at all time points except from age 12 to age 14, as well as diminished emotional undereating from 12 to 14 years. One implication of our findings, if replicated, is that targeting obesogenic eating behaviors to change weight outcomes may be less effective in children older than age 6.


Proteomics in living cells.
The study of protein dynamics in vivo is central to understanding the chemical machinery that makes up the process of life: in determining how, when, where and under what conditions proteins are created, form complexes, are modified and disintegrate. Until recently, facile methods to study these processes in intact living cells did not exist. This review describes promising experimental strategies that have been devised to visualize the dynamic nature of proteins and protein complex formation occurring in living cells. The approaches described are based largely on genetically encoded fusions to proteins of interest combined with labelling strategies. The feasibility of employing such strategies in genome-wide biochemical pathway mapping efforts is discussed.


What Constitutes an "Adequate" Trial in Migraine Prevention?
Comprehensively assessing the quality of prior preventive treatment attempts often reveals modifiable variables that may account for treatment failure. Similarly, a comprehensive and systematic approach when planning a preventive medication trial is critical for optimizing the chances of treatment success. In this review, we summarize the key elements to be included when assessing the adequacy of a preventive treatment trial. We have developed and included checklists that can be used by providers to improve their assessments of prior preventive treatment trials and to assist with planning a high-quality treatment trial with a new migraine preventive medication.


Dietary Bacillus subtilis FPTB13 and chitin, single or combined, modulate systemic and cutaneous mucosal immunity and resistance of catla, Catla catla (Hamilton) against edwardsiellosis.
Effects of dietary administration of Bacillus subtilis FPTB13 and chitin, single or combined, on the systemic immunity, mucosal immunity and resistance of catla (Catla catla) against Edwardsiella tarda infection were investigated. The probiotic attributes of B. subtilis was tested by conducting antagonism study, safety in catla, in vitro immunomodulation and dietary immunomodulation. Results of these studies indicated the probiotic potential of the strain. From the preliminary dietary immunomodulation study, a dose of 10(9) B. subtilis cells g(-1) was selected for inclusion into diets for subsequent experiments. Experimental diets were prepared by adding B. subtilis (10(9) cells g(-1)), chitin (2%) and their combination to the basal diet. Different systemic and mucosal immunological parameters viz. oxygen radical production, myeloperoxidase content, lysozyme activity, total protein content and alkaline phosphatase activity showed significant enhancement (p<0.05) after 2 weeks of feeding with the combined diet. B. subtilis and chitin alone also significantly elevated most of the immune responses. All the diets significantly increased the resistance of catla against E. tarda challenge. The highest post-challenge survival was observed in combined group (i.e. 63.33%). In conclusion, B. subtilis and chitin, alone or combined, had a health ameliorating effect in catla. The results also collectively suggest the usefulness of applying a combined probiotic and immunostimulant supplemented diet to achieve greater benefits.


Effects of misoprostol on cell migration and transit in the dog stomach.
Prostaglandins of the E series increase stomach mucosal mass by inducing hyperplasia, which could be the result either of increased cell production or of decreased cell loss. This report describes an investigation of the effect of the prostaglandin E1 analogue, misoprostol, on cell migration and transit. 3H-thymidine was used to label those cells synthesizing deoxyribonucleic acid in dogs that had been given an oral dose of 300 micrograms/kg per day misoprostol for 11 weeks. The animals were killed at timed intervals, and tissue from the gastric fundus was prepared for autoradiography. The distribution of labeled cells at various times after labeling was used to follow the movement of the wave of label and to calculate median cell migration rates and transit times. The migration rate of cells toward the gastric lumen was significantly increased from 1.4 +/- 0.3 to 3.6 +/- 0.6 cell positions per day in the misoprostol-treated group (p less than 0.001); however, the gland length (from the most basal mucous neck cell to the luminal surface) was also increased (from 52.1 +/- 1.1 to 74.0 +/- 1.6; p less than 0.001), thus there was no significant difference in the (transit) time taken for cells to reach the top of the gland (control, 17.5 +/- 9.8 days; test, 12.2 +/- 7.1 days).


OECD Case Studies of Integrated Regional and Strategic Impact Assessment: What Does 'Integration' Look Like in Practice?
Increasingly, protocols for assessing the impacts of land-uses and major resource development projects focus not only on environmental impacts, but also social and human health impacts. Regional and Strategic Environmental Assessment (RSEAs) are one innovation that hold promise at better integrating these diverse land-use values into planning, assessment, and decision-making. In this contribution, a realist review methodology is utilized to identify case studies of "integrated RSEA"-those which are strategic, have a regional assessment approach, and seek to integrate environmental, community and health impacts into a singular assessment architecture. The results of a systematic literature review are described and six RSEA-like case studies are identified: Kimberly Browse LNG SEA; HS2 Appraisal of Sustainability; Lisbon International Airport SEA; Beaufort Regional Environmental Assessment; Nordstream 2 Transboundary EIA; and the Portland Harbour Sustainability Project. The case studies are examined according to their unique contexts, mechanisms and outcomes of their assessment protocols to determine the degree to which they consider more than environmental valued components, and the means by which they were included. Findings suggest that RSEA has a contentious relationship with the integration of more than environmental values, but that there are significant lessons to be learned to support project planning, especially for assessment contexts characterized by large, transboundary projects.


Relationship between premenstrual symptoms and dysmenorrhea in Japanese high school students.
To determine the relationship between premenstrual symptoms and dysmenorrhea among Japanese adolescent girls, a total of 1,431 high school students were assessed. Of them, 11.3% were classified with "moderate to severe premenstrual syndrome (PMS)" and 3.2% with "premenstrual dysphoric disorder (PMDD)." Eighty-five percent of the girls had dysmenorrhea. The rates of prevalence of PMDD and moderate to severe PMS were increased according to the severity of dysmenorrhea (rs = 0.479), showing a correlation between the severity of PMS/PMDD and dysmenorrhea in adolescents.


Lack of inhibition of ACTH-induced aldosterone stimulation by des-asp1-,ileu8-angiotensin II in man.
In 5 normal men an intravenous injection of 0.5 mg of synthetic 1-24 ACTH caused a significant increase in plasma aldosterone and a simultaneous intravenous infusion of 600 ng/kg/min of des-asp1-, ileu8-angiotensin II (AIIIA) did not inhibit this increase. Since this dose of AIIIA is known to inhibit an angiotensin II-induced increase in plasma aldosterone in normal men, the present results suggest that the ACTH-induced aldosterone stimulation is mediated by an adrenocortical receptor which is different from angiotensin II receptors.


Oxidative stress in Adamantiades-Behçet's disease.
Adamantiades-Behçet's disease is a chronic systemic disorder associating oral and genital ulcerative lesions with ocular and cutaneous manifestations. Previous publications report increased superoxide production by neutrophils and macrophages, increases in cytokines and malondialdehyde (MDA), as well as low levels of enzymatic antioxidant defenses. We looked for another marker of oxidative stress in Adamantiades-Behçet's disease: the presence of clastogenic factors (CF) in patients' plasma. In addition, we determined plasma endproducts of lipid peroxidation (MDA). We studied 20 patients and 20 controls. The clastogenic activity was evaluated by means of cytogenetic methods. This test (CF test) detects circulating prooxidants, due to their clastogenic effects after exposure of lymphocyte cultures of healthy persons to plasma ultrafiltrates from patients. The clastogenic prooxidants are lipid peroxidation products and cytokines, in particular TNF-alpha. Lipid peroxidation was evaluated by the Yagi method. The CF test was positive in 18 out of 20 patients, while it was negative in all 20 control persons. The mean increase in chromosomal breaks was 10.6 +/- 3.8 in cultures exposed to patients' plasma and 1.3 +/- 2.4 for cultures receiving control plasma (p <0.001). The clastogenic effect of patients' plasma ultrafiltrates was significantly inhibited by superoxide dismutase (EC 184.108.40.206), suggesting an important role of the superoxide radical in the clastogenic pathway. Thiobarbituric-acid-reactive substances (expressed as nanomoles MDA per milliliter) were also significantly increased in these patients: 10.6 +/- 3.2 for patients and 6.6 +/- 1.4 for controls (p <0.001). The presence of CF in the plasma of patients, indicating the presence of circulating prooxidants with chromosome-damaging effects, confirms an oxidative stress in Adamantiades-Behçet's disease. The anticlastogenic effect of superoxide dismutase in vitro suggests the implication of the superoxide radical. MDA levels were also significantly increased in patients.


Sulawesifulvius thailandicus - a new species of the genus Sulawesifulvius Gorczyca, Chérot & Štys from Thailand (Hemiptera, Heteroptera, Miridae, Cylapinae).
A new species of the genus Sulawesifulvius, Sulawesifulvius thailandicus Wolski, Yasunaga & Gorczyca, sp. n., is described from Thailand. The present finding also represents the first distribution record in Indochina for the genus. Color adult habitus images for Sulawesifulvius thailandicus and Sulawesifulvius schuhi (type species of the genus), male genital drawings of Sulawesifulvius thailandicus, and scanning electron micrographs of selected structures of Sulawesifulvius schuhi and Sulawesifulvius thailandicus are provided.


Characteristics of alpha-adrenoceptors in two human colorectal cancer cell lines.
The DiFi and HT-29 human colorectal cancer cell lines were characterized and compared with respect to binding properties of alpha adrenoceptors present on the cell surface. Both cell lines possessed alpha-1 and alpha-2 adrenoceptors of high affinity; however, DiFi cells were rich in alpha-1 adrenoceptors, whereas HT-29 cells were rich in alpha-2 adrenoceptors. In each cell line, specificity of radioligand binding to alpha-1 or alpha-2 adrenoceptors was proved via competition studies using non-tritiated drugs. We believe this to be the first characterization of alpha-1 adrenoceptors in cell line HT-29 and of alpha-1 and alpha-2 adrenoceptors in DiFi cells. Differences between these cell lines in alpha adrenoceptor expression are discussed in relation to colon carcinogenesis. The high level of alpha-1 adrenoceptors seen in DiFi cells should make this cell line useful in studies of the function and regulation of this adrenoceptor subtype.


Quantitative proteomics in medication-related osteonecrosis of the jaw: A proof-of-concept study.
Medication-related osteonecrosis of the jaw (MRONJ) is a paradoxical effect associated with bone-modifying agents (BMAs) and other drugs. Currently, no valuable diagnostic or prognosis biomarkers exist. The goal of this research was to study MRONJ-related salivary proteome. This case-control aimed to study salivary proteome in MRONJ versus control groups (i) formed from BMAs consumers and (ii) healthy individuals to unravel biomarkers. Thirty-eight samples of unstimulated whole saliva (18 MRONJ patients, 10 BMA consumers, and 10 healthy controls) were collected. Proteomic analysis by SWATH-MS coupled with bioinformatics analysis was executed. A total of 586 proteins were identified, 175 proteins showed significant differences among MRONJ versus controls. SWATH-MS revealed differentially expressed proteins among three groups, which have never been isolated. These proteins had distinct roles including cell envelope organization, positive regulation of vesicle fusion, positive regulation of receptor binding, or regulation of low-density lipoprotein particle clearance. Integrative analysis prioritized 3 proteins (MMP9, AACT, and HBD). Under receiver-operating characteristic analysis, this panel discriminated MRONJ with a sensitivity of 90% and a specificity of 78.9%. These findings may inform a novel biomarker panel for MRONJ prediction or diagnosis. Nonetheless, further research is needed to validate this panel.


Juvenile localised scleroderma: a retrospective review of response to systemic treatment.
Juvenile localised scleroderma (JLS) is a rare connective tissue disorder in childhood. Most lesions are benign and self-limiting, but some progress to cause functional disabilities and cosmetic disfigurement. These lesions require systemic treatment, the mainstay of which is corticosteroids and methotrexate. To report the experience of the use of systemic treatment in children with JLS in our department. We performed a retrospective chart review looking at the patients who received systemic treatment over 14 years and recorded their outcomes. Ten children with aggressive JLS were treated with systemic immunosuppressive therapy. There was an 80% response to treatment. Three of the responders relapsed off treatment, but responded to a further course of therapy. Mean disease duration at diagnosis was 8 months. Treatment was generally well tolerated with few side effects. Early recognition of aggressive localised scleroderma and appropriate referral is imperative for a good outcome.


Discovery of segmented Fermi surface induced by Cooper pair momentum.
A sufficiently large supercurrent can close the energy gap in a superconductor and create gapless quasiparticles through the Doppler shift of quasiparticle energy caused by finite Cooper pair momentum. In this gapless superconducting state, zero-energy quasiparticles reside on a segment of the normal-state Fermi surface, whereas the remaining Fermi surface is still gapped. We use quasiparticle interference to image the field-controlled Fermi surface of bismuth telluride (Bi2Te3) thin films under proximity effect from the superconductor niobium diselenide (NbSe2). A small applied in-plane magnetic field induces a screening supercurrent, which leads to finite-momentum pairing on the topological surface states of Bi2Te3. We identify distinct interference patterns that indicate a gapless superconducting state with a segmented Fermi surface. Our results reveal the strong impact of finite Cooper pair momentum on the quasiparticle spectrum.


Dual selectivity: electrophile and nucleophile selective cross-coupling reactions on a single aromatic substrate.
The development of a high yielding, both nucleophile and electrophile selective cross-coupling reaction with aromatic rings is presented. The reaction is general with respect to functional groups. Furthermore, the products still contain a boronic ester and a bromide. These two functional groups allow them to be easy-to-prepare, highly complex starting materials for further reactions, avoiding protecting group transformations.


Serum aminotransferase ratio is independently correlated with hepatosteatosis in patients with HCV: a cross-sectional observational study.
The incidence of non-alcoholic fatty liver disease (NAFLD) is significant in hepatitis C virus (HCV) carriers due to multiple mechanisms, and this worsens the progression of chronic liver diseases, such as cirrhosis and hepatocellular carcinoma, and death. The purpose of this study was to examine whether the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio correlates with the status of hepatosteatosis. A cross-sectional observational study. Community-based annual examination in northern Taiwan. A total of 1354 participants (age 20 years or over) were enrolled after excluding participants with HCV seronegative, laboratory or questionnaires loss, moderate alcohol consumption, liver cirrhosis, tumours and postlobectomy. Fatty liver was diagnosed according to echogenic findings. NAFLD included grades 1-3 fatty liver and high-degree NAFLD defined grades 2-3 fatty liver. 580 males and 774 females with a mean age of 47.2 (SD=16.1) years were cross-sectionally studied. The participants with NAFLD have significantly higher levels of ALT/AST ratio, fasting glucose, triglyceride and systolic/diastolic blood pressure than non-NAFLD participants. The association between NAFLD and ALT/AST was significant even when adjusting for the metabolic syndrome (aOR 1.90; 95% CI 1.37 to 2.65; p<0.001). In patients with a high degree of NAFLD, the ALT/AST ratio was still a significant predictor for hepatosteatosis (aOR 2.44; 95% CI 1.58 to 3.77; p<0.001). The ALT/AST ratio could be a strong risk of hepatosteatosis in patients with chronic HCV infection.


Association between Diet and Xerostomia: Is Xerostomia a Barrier to a Healthy Eating Pattern?
Xerostomia is a subjective feeling of dry mouth and is commonly observed in patients with autoimmune diseases. Our study examines the association between xerostomia and diet. The cross-sectional study includes 1405 adults from 15 Lithuanian geographical areas (52% response rate). A self-reported questionnaire inquired about xerostomia, sex, age, education, residence, and consumption of selected 23 diet items. For the multivariable analysis, 23 diet items were categorized into eight major diet groups. The data were analyzed by bivariate and multivariable analyses. When comparing participants with and without xerostomia, there were significant differences in consumption frequencies concerning cold-pressed oil (p = 0.013), bread (p = 0.029), processed meat products (p = 0.016), fat and lean fish (p = 0.009), and probiotic supplements (p = 0.002). In the multivariable binary logistic regression model, when controlled for other determinants, the higher consumption of carbohydrates (OR 0.39, 95% CI 0.23-0.65), proteins (OR 0.56, 95% CI 0.32-0.99), and oils (OR 0.58, 95% CI 0.34-1.00) was associated with a lower likelihood of xerostomia. The association between xerostomia and the consumption of the six diet items-cold-pressed oils, lean and fat fish, bread, processed meat, and probiotic supplements- and the three major diet groups-carbohydrates, proteins, and oils-was observed. Longitudinal studies are needed to validate the observed associations.


Chemical reaction network approaches to Biochemical Systems Theory.
This paper provides a framework to represent a Biochemical Systems Theory (BST) model (in either GMA or S-system form) as a chemical reaction network with power law kinetics. Using this representation, some basic properties and the application of recent results of Chemical Reaction Network Theory regarding steady states of such systems are shown. In particular, Injectivity Theory, including network concordance [36] and the Jacobian Determinant Criterion [43], a "Lifting Theorem" for steady states [26] and the comprehensive results of Müller and Regensburger [31] on complex balanced equilibria are discussed. A partial extension of a recent Emulation Theorem of Cardelli for mass action systems [3] is derived for a subclass of power law kinetic systems. However, it is also shown that the GMA and S-system models of human purine metabolism [10] do not display the reactant-determined kinetics assumed by Müller and Regensburger and hence only a subset of BST models can be handled with their approach. Moreover, since the reaction networks underlying many BST models are not weakly reversible, results for non-complex balanced equilibria are also needed.


Inhibition of protein phosphatases blocks myogenesis by first altering MyoD binding activity.
To examine the role of protein phosphatases in skeletal muscle differentiation, C2C12 myoblasts were treated with okadaic acid, a potent in vitro inhibitor of protein phosphatases 1 and 2A which regulate various cellular events in intact cells. We now show that okadaic acid treatment of the mouse myoblast C2C12 cell line reversibly altered the morphology of the cells and blocked differentiation. At a molecular level, it extinguished expression of the myogenic determination genes, MyoD1 and myogenin, but induced the expression of an inhibitor of differentiation, Id. Analysis of the MyoD1 promoter showed that inhibition of MyoD1 expression by okadaic acid occurs at the transcriptional level. These changes occur 10-20 h after okadaic acid treatment. However, within 1 h of treatment the ability of muscle extracts to support a specific MyoD-dependent gel mobility shift using a MyoD DNA binding site is lost. These data suggest that protein phosphatases play an important role during myogenic differentiation.


Cognition and motor function: The gait and cognition pooled index.
There is a need for outcome measures with improved responsiveness to changes in pre-dementia populations. Both cognitive and motor function play important roles in neurodegeneration; motor function decline is detectable at early stages of cognitive decline. This proof of principle study used a Pooled Index approach to evaluate improved responsiveness of the predominant outcome measure (ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale) when assessment of motor function is added. Candidate Pooled Index variables were selected based on theoretical importance and pairwise correlation coefficients. Kruskal-Wallis and Mann-Whitney U tests assessed baseline discrimination. Standardized response means assessed responsiveness to longitudinal change. Final selected variables for the Pooled Index include gait velocity, dual-task cost of gait velocity, and an ADAS-Cog-Proxy (statistical approximation of the ADAS-Cog using similar cognitive tests). The Pooled Index and ADAS-Cog-Proxy scores had similar ability to discriminate between pre-dementia syndromes. The Pooled Index demonstrated trends of similar or greater responsiveness to longitudinal decline than ADAS-Cog-Proxy scores. Adding motor function assessments to the ADAS-Cog may improve responsiveness in pre-dementia populations.


Subsidizing high-quality remanufactured products for sustainability.
This study aims to analyze the impact of government subsidy policies on the development of remanufacturing enterprises and product quality in the context of carbon peaking and carbon neutrality, to promote the sustainable development of the remanufacturing industry. It establishes a comparative game model for two cases of remanufacturing enterprises respectively producing low-quality and high-quality remanufactured products. In the context of government subsidies for only high-quality remanufactured products, we investigate the effects of government subsidies on remanufactured products' forms, prices, profits, and consumer preferences. The results show that government subsidies for high-quality remanufactured products help not only reduce the quality cost of remanufactured products and lower the wholesale and retail prices but also increase consumer preference for high-quality remanufactured products, enhance the market demand for remanufactured products, and promote scale expansion of the remanufacturing industry. This study provides decision support for governments to formulate subsidy coefficients for remanufacturing enterprises, offers theoretical and methodological support for the decarbonization and scale-up of remanufacturing and reduction of environmental pollution, and has significant practical value for achieving carbon peak and carbon neutralization goals.


Streptomyces monashensis sp. nov., a novel mangrove soil actinobacterium from East Malaysia with antioxidative potential.
A new Streptomyces species discovered from Sarawak mangrove soil is described, with the proposed name - Streptomyces monashensis sp. nov. (strain MUSC 1JT). Taxonomy status of MUSC 1JT was determined via polyphasic approach. Phylogenetic and chemotaxonomic properties of strain MUSC 1JT were in accordance with those known for genus Streptomyces. Based on phylogenetic analyses, the strains closely related to MUSC 1JT were Streptomyces corchorusii DSM 40340T (98.7%), Streptomyces olivaceoviridis NBRC 13066T (98.7%), Streptomyces canarius NBRC 13431T (98.6%) and Streptomyces coacervatus AS-0823T (98.4%). Outcomes of DNA-DNA relatedness between strain MUSC 1JT and its closely related type strains covered from 19.7 ± 2.8% to 49.1 ± 4.3%. Strain MUSC 1JT has genome size of 10,254,857 bp with DNA G + C content of 71 mol%. MUSC 1JT extract exhibited strong antioxidative activity up to 83.80 ± 4.80% in the SOD assay, with significant cytotoxic effect against colon cancer cell lines HCT-116 and SW480. Streptomyces monashensis MUSC 1JT (=DSM 103626T = MCCC 1K03221T) could potentially be a producer of novel bioactive metabolites; hence discovery of this new species may be highly significant to the biopharmaceutical industry as it could lead to development of new and useful chemo-preventive drugs.


Temporal Effects of Perpetrating or Receiving Intimate Partner Aggression on Alcohol Consumption: A Daily Diary Study of Community Couples.
Survey studies provide evidence that experiencing intimate partner aggression (IPA) contributes to subsequent alcohol use. However, it is unknown whether the increase in alcohol use over time reflects a temporal effect of IPA. We examined verbal and physical IPA as predictors of alcohol use and heavy drinking within the next few hours. We also investigated whether both victims and perpetrators drank following IPA, and if it mattered which partner reported the aggression. The data reported here were derived from a 56-day diary study examining the association between alcohol use and partner aggression in 118 heterosexual couples. We examined whether alcohol use in a given hour could be predicted by IPA in the previous 3 hours, taking into account victim/perpetrator status, source of the report (self, other), and gender. Victims were twice as likely to use alcohol in a given hour when they reported having received verbal IPA in the previous 3 hours, independent of the perpetrator's report. Similarly, perpetrators were more than twice as likely to use alcohol in a given hour when they reported having perpetrated verbal IPA in the previous 3 hours, independent of the victim's report. Results were similar when reports of mutual IPA were considered. Verbal IPA increased the likelihood of drinking but not the likelihood of heavy drinking. Results for physical IPA were not significant. Verbal IPA is a proximal predictor of alcohol use for both victims and perpetrators. However, effects emerge only when individuals report aggression, and not when their partner provides the sole report, emphasizing the importance of the individual's perception of IPA.


Expression of PCOS candidate genes in bovine fetal and adult ovarian somatic cells.
Polycystic ovary syndrome (PCOS) is an endocrine metabolic disorder that appears to have a genetic predisposition and a fetal origin. The fetal ovary has two major somatic cell types shown previously to be of different cellular origins, different morphologies and to differentially express 15 genes. We isolated the somatic gonadal ridge epithelial-like (GREL) cells (n = 7) and ovarian fetal fibroblasts (n = 6) by clonal expansion. Using qRT-PCR, we compared the gene expression levels of PCOS candidate genes with previous data on the expression levels in whole fetal ovaries across gestation. We also compared these levels with those in bovine adult ovarian cells including fibroblasts (n = 4), granulosa cells (n = 5) and surface epithelial cells (n = 5). Adult cell types exhibited clear differences in the expression of most genes. In fetal ovarian cells, DENND1A and ERBB3 had significantly higher expression in GREL cells. HMGA2 and TGFB1I1 tended to have higher expression in fetal fibroblasts than GREL cells. Another 19 genes did not exhibit differences between GREL cells and fetal fibroblasts and FBN3, FSHB, LHCGR, FSHR and ZBTB16 were very lowly expressed in GREL cells and fibroblasts. The culture of fetal fibroblasts in EGF-containing medium resulted in lower expression of NEIL2, but higher expression of MAPRE1 compared to culture in the absence of EGF. Thus, the two fetal ovarian somatic cell types mostly lacked differential expression of PCOS candidate genes.


Achiral guest-induced chiroptical changes of a planar-chiral pillar[5]arene containing one π-conjugated unit.
A planar-chiral pillar[5]arene derivative containing one π-conjugated unit was prepared. Chiroptical changes were observed upon addition of the achiral guest 1,4-dicyanobutane.


Evaluation of cytotoxic, genotoxic and inflammatory responses of nanoparticles from photocopiers in three human cell lines.
Photocopiers emit nanoparticles with complex chemical composition. Short-term exposures to modest nanoparticle concentrations triggered upper airway inflammation and oxidative stress in healthy human volunteers in a recent study. To further understand the toxicological properties of copier-emitted nanoparticles, we studied in-vitro their ability to induce cytotoxicity, pro-inflammatory cytokine release, DNA damage, and apoptosis in relevant human cell lines. Three cell types were used: THP-1, primary human nasal- and small airway epithelial cells. Following collection in a large volume photocopy center, nanoparticles were extracted, dispersed and characterized in the cell culture medium. Cells were doped at 30, 100 and 300 μg/mL administered doses for up to 24 hrs. Estimated dose delivered to cells, was ~10% and 22% of the administered dose at 6 and 24 hrs, respectively. Gene expression analysis of key biomarkers was performed using real time quantitative PCR (RT-qPCR) in THP-1 cells at 5 μg nanoparticles/mL for 6-hr exposure for confirmation purposes. Multiple cytokines, GM-CSF, IL-1β, IL-6, IL-8, IFNγ, MCP-1, TNF-α and VEGF, were significantly elevated in THP-1 cells in a dose-dependent manner. Gene expression analysis confirmed up-regulation of the TNF-α gene in THP-1 cells, consistent with cytokine findings. In both primary epithelial cells, cytokines IL-8, VEGF, EGF, IL-1α, TNF-α, IL-6 and GM-CSF were significantly elevated. Apoptosis was induced in all cell lines in a dose-dependent manner, consistent with the significant up-regulation of key apoptosis-regulating genes P53 and Casp8 in THP-1 cells. No significant DNA damage was found at any concentration with the comet assay. Up-regulation of key DNA damage and repair genes, Ku70 and Rad51, were also observed in THP-1 cells, albeit not statistically significant. Significant up-regulation of the key gene HO1 for oxidative stress, implicates oxidative stress induced by nanoparticles. Copier-emitted nanoparticles induced the release of pro-inflammatory cytokines, apoptosis and modest cytotoxicity but no DNA damage in all three-human cell lines. Taken together with gene expression data in THP-1 cells, we conclude that these nanoparticles are directly responsible for inflammation observed in human volunteers. Further toxicological evaluations of these nanoparticles, including across different toner formulations, are warranted.


Issues in Melanoma Detection: Semisupervised Deep Learning Algorithm Development via a Combination of Human and Artificial Intelligence.
Automatic skin lesion recognition has shown to be effective in increasing access to reliable dermatology evaluation; however, most existing algorithms rely solely on images. Many diagnostic rules, including the 3-point checklist, are not considered by artificial intelligence algorithms, which comprise human knowledge and reflect the diagnosis process of human experts. In this paper, we aimed to develop a semisupervised model that can not only integrate the dermoscopic features and scoring rule from the 3-point checklist but also automate the feature-annotation process. We first trained the semisupervised model on a small, annotated data set with disease and dermoscopic feature labels and tried to improve the classification accuracy by integrating the 3-point checklist using ranking loss function. We then used a large, unlabeled data set with only disease label to learn from the trained algorithm to automatically classify skin lesions and features. After adding the 3-point checklist to our model, its performance for melanoma classification improved from a mean of 0.8867 (SD 0.0191) to 0.8943 (SD 0.0115) under 5-fold cross-validation. The trained semisupervised model can automatically detect 3 dermoscopic features from the 3-point checklist, with best performances of 0.80 (area under the curve [AUC] 0.8380), 0.89 (AUC 0.9036), and 0.76 (AUC 0.8444), in some cases outperforming human annotators. Our proposed semisupervised learning framework can help with the automatic diagnosis of skin disease based on its ability to detect dermoscopic features and automate the label-annotation process. The framework can also help combine semantic knowledge with a computer algorithm to arrive at a more accurate and more interpretable diagnostic result, which can be applied to broader use cases.


Genetic effects of anorganic bovine bone (Bio-Oss) on osteoblast-like MG63 cells.
Bio-Oss (Geistlich, Wolhusen, Switzerland) is composed by anorganic bovine bone and is widely used in several bone regeneration procedures in oral surgery. How this biomaterial alters osteoblast gene expression to promote bone formation is poorly understood. We therefore attempted to address this question by using microarray techniques to identify genes that are differentially regulated in osteoblasts exposed to Bio-Oss. By using DNA microarrays containing 20,000 genes, we identified in osteoblast-like cells line (MG-63) cultured with Bio-Oss several genes which expression was significantly up- and down-regulated. The differentially expressed genes cover a broad range of functional activities: (a) signaling transduction, (b) transcription, (c) cell cycle regulation, (d) vesicular transport, (e) apoptosis, and (f) immunity. These results could explain the reported bioaffinity of Bio-Oss to host animals, its biological affinity to osteogenic cells and its capability to stimulate osteoblastic differentiation. The data reported are, to our knowledge, the first genetic portrait of Bio-Oss effects. They can be relevant to our improved understanding of the molecular mechanism underlying bone regenerative procedures and as a model for comparing other materials with similar clinical effects.


Altered metabolic incorporation of fucose and leucine into PNS myelin of 25-week-old diabetic (C57BL/Ks [db/db]) mice: effects of untreated diabetes on nerve metabolism.
Sciatic nerves of 25-week-old genetically diabetic (C57BL/Ks [db/db]) mice and their litter-mate controls were removed, and their metabolic incorporation of [3H]fucose and [14C]leucine into myelin was studied in vitro. Untreated diabetic animals showed significant increases (p less than 0.05) in the fucose/leucine incorporation into myelin when compared to values found for their litter-mates. These results correlated well with previous experiments performed on alloxan or streptozotocin-diabetic rats and thus show the in vitro incubation procedure to be a good indicator of altered metabolic conditions in peripheral nerves due to diabetes mellitus. The resulting ratio increases seen in diabetic animals is at variance with the decrease in ratios found in animals undergoing typical Wallerian degeneration. These results suggest that different metabolic processes operate in untreated diabetics than in normals or in those undergoing other degenerative nerve processes.


Microvasculature dropout detected by the optical coherence tomography angiography in nonarteritic anterior ischemic optic neuropathy.
To investigate microcirculation characteristics of peripapillary superficial retina and optic disc in eyes with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography angiography (OCTA). Forty-one eyes of 30 NAION patients and 30 eyes of 30 normal subjects were evaluated with OCTA (AngioVue, Optovue). The whole vessel density, inside disc vessel density, peripapillary vessel density, and vessel densities based on the sectorial division in the nerve head mode peripapillary superficial retina and RPC mode optic disc were measured respectively. In the NAION group, vessel densities in both the peripapillary superficial retina and optic disc were significant reduced (P < 0.01), as compared with the control group. The whole vessel density of the optic disc in chronic NAION group were significantly lower than that in acute NAION group (P < 0.01). The whole and temporal vessel density of the peripapillary superficial retina was significantly correlated with log MAR VA (r = -0.381 and r = -0.337, both P < 0.05). Vessel densities in both the peripapillary superficial retina and optic disc were reduced (P < 0.05) in unilateral involved eyes, as compared to the unaffected fellow eyes, except for the inside disc (P = 0.270) and SN (P = 0.054) vessel density in the optic disc, while there was no difference in the fellow eyes compared to the normal eyes. In NAION patients, a dropout of microvasculature in peripapillary superficial retina and optic disc could be detected by OCTA directly. OCTA might become a useful tool for detection and monitoring of NAION. Lasers Surg. Med. 50:194-201, 2018. © 2017 Wiley Periodicals, Inc.