Prognostic value of nectin-4 in human cancers: A meta-analysis.
Many reports have described that abnormal nectin-4 expression may be used as a prognostic marker in many tumors. However, these studies failed to reach a consensus. Here, we performed a meta-analysis to comprehensively evaluate the prognostic value of nectin-4 in cancers. Relevant studies were identified through a comprehensive search of PubMed, EMBASE and Web of science until August 31, 2022. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate the relationship between nectin-4 expression and overall survival (OS) and disease-free survival/progression-free survival/relapse-free survival (DFS/PFS/RFS). Odds ratios (ORs) with 95% CIs were applied to assess the relationship between nectin-4 expression and clinicopathologic features. Subgroup analysis was performed to explore the sources of heterogeneity. Sensitivity analysis and funnel plot were used to test the reliability of the results. All data analyses were performed using STATA version 12.0 software. Fifteen articles involving 2245 patients were included in the meta-analysis. The pooled analysis showed that high nectin-4 expression was significantly associated with poor OS (HR: 1.75, 95% CI: 1.35-2.28). There was no relationship between high nectin-4 expression and DFS/PFS/RFS (HR: 178, 95% CI: 0.78-4.08).Subgroup analyses revealed that that high nectin-4 expression mainly presented adverse OS in esophageal cancer (EC) (HR: 1.78, 95% CI: 1.30-2.44) and gastric cancer (GC) (HR: 1.92, 95% CI: 1.43-2.58). We also found that high nectin-4 expression was associated with tumor diameter (big vs small) (OR: 1.96, 95% CI: 1.02-3.75), tumor stage (III-IV vs I-II) (OR: 2.04, 95% CI: 1.01-4.12) and invasion depth (T3+T4 vs T2+T1) (OR: 3.95, 95% CI: 2.06-7.57). Nectin-4 can be used as an effective prognostic indicator for specific cancers.


Autophagy Promoted Neural Differentiation of Human Placenta-derived Mesenchymal Stem Cells.
Human placenta-derived mesenchymal stem cells (hPMSCs) are multipotent and possess neurogenicity. Numerous studies have shown that Notch inhibition and DNA demethylation promote neural differentiation. Here, we investigated the modulation of autophagy during neural differentiation of hPMSCs, induced by DAPT and 5-Azacytidine. hPMSCs were treated with DAPT to induce neural differentiation, and the autophagy regulating molecules were used to assess the impact of autophagy on neural differentiation. The hPMSCs presented with typical mesenchymal stem cell phenotypes, in which the majority of cells expressed CD73, CD90 and CD105. hPMSCs were multipotent, capable of differentiating into mesodermal cells. After treatment with DAPT, hPMSCs upregulated the expression of neuronal genes including SOX2, Nestin, and βIII-tubulin, and the autophagy genes LC3I/II and Beclin. These genes were further increased when 5-Azacytidine was co-supplemented in the culture medium. The inhibition of autophagy by chloroquine impeded the neural differentiation of hPMSCs, marked by the downregulation of βIII-tubulin, while the activation of autophagy by valproic acid (VPA) instigated the emergence of βIII-tubulin-positive cells. During the differentiation process, autophagy was modulated, implying that autophagy could play a significant role during the differentiation of these cells. The blockage and stimulation of autophagy could either hinder or induce the formation of neural-like cells, respectively. Therefore, the refinement of autophagic activity at an appropriate level might improve the efficiency of stem cell differentiation.


Active sleep-related depolarization of feline trigemino-thalamic afferent terminals.
Presynaptic depolarization of trigemino-thalamic (TGT) terminals may contribute to modulation of ascending oro-facial somatosensory information during active (or rapid eye movement) sleep. The relative excitability of TGT terminals was inferred from changes in the current required to maintain an antidromic firing probability of 50% (EC50) during quiet wakefulness as compared to active sleep. Depolarization or hyperpolarization of TGT terminals was defined as a decrease or increase, respectively, in the EC50. Overall, the EC50 of 8 TGT terminals was reduced by a mean 8.8+/-3.6 microA during active sleep relative to quiet wakefulness. This result suggests that depolarization of TGT terminals, which may act to suppress the transfer of sensory information from the trigeminal nucleus to the thalamus, occurs during active sleep.


[Philological structure of Dan xi shou jing (Danxi's Hand Mirror)].
Zhu Danxi, one of the four Major Schools of the Jin-Yuan Dynasties, had a lot of works circulated with its authorship in disarray. Part of the works were compiled by his disciples, while others were by his self-taught followers based on prior circulated Danxi's originals, plus some apocryphal so-called Danxi's works circulated posthumously. When sorting out Danxi's Hand Mirror, we found that some of its contents are closely related to Bei ji qian jin yao fang (Essential Prescriptions Worth a Thousand Gold for Emergencies), Qian jin yi fang (Supplements to Qian jin yao fang), Tai ping sheng hui fang (Peaceful Holy Benevolent Prescriptions), Zhu jie shang han lun (Annotated Treatises of Cold Pathogenic Disease), Shang han ming li lun (Elucidation of Cold Pathogenic Disease), Ge zhi yu lun (Treatise of Inquiring the Properties of Things), either by transcription or with an identical origin. By clearing their relationships, it can provide assistance to the research of the philological structure of Danxi's hand Mirror.


Physiological strain during kitchen work in relation to maximal and task-specific peak values.
Six female and three male subjects from a hospital kitchen volunteered for the study. The subjects were working on a conveyor belt collecting and sorting dirty plates, glasses and cutlery for cleaning. In the study, a medical examination, a maximal clinical exercise test with a 12-lead electrocardiogram (ECG) and a maximal arm cranking test were performed in the laboratory. Further, each subject was studied for 30 min during a normal work shift in the kitchen. Oxygen uptake (VO2) and heart rate (HR) were continuously registered. During the work period, a rating of perceived exertion (RPE) was asked at the 5th, 15th and 30th minute. Physiological responses were measured by a portable system (K4) both in the laboratory and in the field. VO2 and HR measured in the field were proportioned to corresponding maximal values during cycling and to peak values during arm-cranking. The mean VO2 for the male and the female subjects during kitchen work was 0.65 +/- 0.16 l min-1. This corresponded to 24% of VO2max and to 41% of VO2peak during arm-cranking. The difference was significant (p < 0.001). Owing to a magnetic field at the conveyor belt, reliable HR values were obtained only from the female subjects. The mean HR during work among the female subjects was 101 beats min-1. It corresponded to 55% of HRmax and 67% of HRpeak during arm-cranking (p < 0.05). The present study shows that the relative work intensity is markedly higher when it is expressed relative to the corresponding muscle group's VO2peak instead of the VO2max. Similar difference was also seen in the HR response. More task-specific testing of physical capacity may provide improved evaluation of physical strain in a job.


Characteristics and prognostic impact of plasma fibrin monomer (soluble fibrin) in patients with coronary artery disease.
We measured fibrin monomer (FM), soluble fibrin, as a marker of thrombin activity in plasma samples obtained in parallel with the first two routine samples for cardiac markers in 165 patients with acute chest pain admitted consecutively to our hospital. A reference limit of FM in a healthy population was set at 3.0 mg/l. Elevated plasma FM was observed in 48.8% of patients with acute coronary syndromes, in 42.3% of patients with specific non-coronary disease, in 31.5% of those with stable angina pectoris and in 18.2% of patients with non-specific chest pain. No significant difference was observed between sample 1 and sample 2 in patients not receiving thrombolytic treatment during the sampling period (P = 0.46). In patients with coronary artery disease, FM was significantly related to the level of cardiac troponin T (P = 0.001), but no correlation was observed between the individual plasma FM and cardiac troponin T values. Outcome analysis during the following 30 months after the index event in patients with acute coronary syndromes revealed higher FM levels in those with coronary re-events or death than in patients without new events (P = 0.001). This observation indicates a prognostic potential of FM in risk evaluation of patients with coronary artery disease.


Comparative analysis of intrathecal antibody synthesis and DNA amplification for the diagnosis of cytomegalovirus infection of the central nervous system in AIDS patients.
We evaluated 49 paired cerebrospinal fluid (CSF) and serum samples of 35 patients infected with the human immunodeficiency virus type 1 (HIV-1) for laboratory evidence of cytomegalovirus (CMV) infection. The patients were grouped according to clinical criteria as probable CMV encephalitis/polyradiculomyelitis, CMV retinitis, cerebral toxoplasmosis, progressive multifocal leukoencephalopathy, HIV-1-related cognitive/motor complex, HIV-1-associated myelopathy, and other neurological diseases. Paired CSF and serum samples were analysed for CMV deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR), quantitative intrathecal synthesis of immunoglobulin G (IgG) antibodies specific for recombinant phosphoprotein 150 (pp150) of CMV and CMV-specific serum IgM. Intrathecal synthesis of pp150-specific IgG was detected in 26% of patients (9/35), serum IgM was found in 23% of patients (8/35), and PCR of CSF was positive in 11% of patients (4/35). Detection of CMV-specific DNA in CSF preceded the intrathecal antibody synthesis in three patients for whom serial samples were available. PCR results of the CSF became negative in one patient with CMV polyradiculomyelitis after successful therapy with 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (DHPG). PCR has a higher diagnostic specificity in the acute phase of CMV infection than intrathecal antibody synthesis. The serum IgM response to CMV cannot be used to monitor a compartmentalized immune response in the central nervous system while an intrathecal immune response seems to be associated with recovery either spontaneously or as a result of treatment.


A collision tumor of solitary fibrous tumor/hemangiopericytoma and meningioma: A case report with literature review.
An intracranial collision tumor is a rare lesion composed of two histologically different neoplasms in the same anatomic location. Even more rare is the collision tumor of a solitary fibrous tumor/hemangiopericytoma (SFT/HPC) and meningioma. The patient was a 46-year-old woman who had a 40 × 35 × 30-mm mass in the vermis of the cerebellum. Histologically, the mass consisted of two different components. One component showed the morphology of meningioma (World Health Organization (WHO) grade I), and the other component exhibited small round cell proliferation with hypercellular density, which was revealed to be SFT/HPC (WHO grade III) based on STAT6 immunohistochemistry. STAT6 showed completely different immunohistochemistry results in these two components (nuclear-negative in meningioma and nuclear-positive in SFT/HPC). Since these two neoplasms are associated with different prognoses, they should be distinguished from each other. When meningioma and an SFT/HPC-like lesion are identified morphologically, it is important to recognize the presence of such a collision tumor composed of meningioma and SFT/HPC, and identify the SFT/HPC component by employing STAT6 immunohistochemistry.


Molecular, epidemiological and infectivity characterisation of a Mycobacterium tuberculosis strain prevalent in Madrid.
The most prevalent strain of Mycobacterium tuberculosis in Madrid, Spain (strain 5) was recovered from 45 cases between 1997 and 2004 and showed a highly homogeneous genetic composition. This strain was not exclusive to Spain, and its spoligotyping signature (ST20) was found in entries from different countries in the SITVIT1 database. Patients infected with strain 5 were more frequently positive for human immunodeficiency virus and autochthonous, and had been in prison more frequently, but strain 5 did not show increased infectivity in an in-vitro model of infection.


SNARE Regulatory Proteins in Synaptic Vesicle Fusion and Recycling.
Membrane fusion is a universal feature of eukaryotic protein trafficking and is mediated by the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) family. SNARE proteins embedded in opposing membranes spontaneously assemble to drive membrane fusion and cargo exchange in vitro. Evolution has generated a diverse complement of SNARE regulatory proteins (SRPs) that ensure membrane fusion occurs at the right time and place in vivo. While a core set of SNAREs and SRPs are common to all eukaryotic cells, a specialized set of SRPs within neurons confer additional regulation to synaptic vesicle (SV) fusion. Neuronal communication is characterized by precise spatial and temporal control of SNARE dynamics within presynaptic subdomains specialized for neurotransmitter release. Action potential-elicited Ca2+ influx at these release sites triggers zippering of SNAREs embedded in the SV and plasma membrane to drive bilayer fusion and release of neurotransmitters that activate downstream targets. Here we discuss current models for how SRPs regulate SNARE dynamics and presynaptic output, emphasizing invertebrate genetic findings that advanced our understanding of SRP regulation of SV cycling.


Evaluation of a Novel Visual Field Analyzer Application for Automated Classification of Glaucoma Severity.
To describe the Glaucoma Staging Application (GSA), a new application for automated classification of visual field (VF) severity that can be used in any Humphrey perimeters. We also tested and validated its performance in staging glaucomatous VFs defects and assessed its reproducibility. The GSA is based upon the modified University of São Paulo Glaucoma Visual Field Staging System, and consists of 3 sections: severity based on the visual field index; defect location based on eccentricity; and extent of topographic damage by hemifields. We analyzed 612 VFs of 32 patients. VFs were analyzed by a glaucoma expert and then compared with the output of the GSA. To evaluate the repeatability, the same search criteria were repeated 1 week later using the same GSA. The classification given by the software was considered correct if it completely agreed in all variables (severity, location, and extent of topographic damage) with the classification performed manually by the glaucoma expert. One hundred seventy-eight eyes were classified as early VF damage, 148 moderate, and 156 severe. One hundred thirty-one VFs were classified as normal. When repeated, 1 week later, the GSA showed excellent repeatability. The automated classification agreed with the expert's grading in 100% of cases. The GSA allows an automated, fast, reproducible, and objective classification system for multiple 24-2 VFs of Humphrey perimetry. This study is a proof-of-concept that could translate into a useful tool to analyze and stage VFs more objectively and thus help detecting progression of different types of VFs defects.


Surfactant concentration and type affects the removal of Escherichia coli from pig skin during a simulated hand wash.
The effect of surfactant type and concentration on a bland soap formulation's ability to remove bacteria from hands remains largely unstudied. Several combinations of surfactants and water were combined to test bacterial removal efficacy using a hand-washing device (two pieces of pig skin and a mechanical motor) to simulate a hand wash. A nalidixic acid-resistant, nonpathogenic strain of Escherichia coli (ATCC 11229) was used. Two anionic surfactants, sodium lauryl sulphate and sodium stearoyl lactylate, and two nonionic surfactants, poloxamer 407 and sorbitan monostearate, each in concentrations of 2, 5 and 10% were studied. A slight positive (r2 = 0·17) but significant (P = 0·03) correlation was observed between hydrophile-lipophile balance value and mean log reduction. No correlation was observed between pH of the treatment solution and the mean log reduction (r2 = 0·05, P = 0·25). A 10% sodium lauryl sulphate mixture showed the highest log reduction (x¯ = 1·1 log CFU reduction, SD = 0·54), and was the only treatment significantly different from washing with water (P = 0·0005). There was a correlation between increasing surfactant concentrations above the critical micelle concentration, and mean microbial reduction (r2 = 0·62, P = 0·001). This study characterizes the role of surfactants in removing microbes during a hand wash. Numerous studies address how surfactants support antimicrobial effect in soap, or cause irritation of skin, but no published studies show which surfactants are best for removing microbes. We used pig skin as a model for human skin and a lathering device to simulate a hand wash. A 10% sodium lauryl sulphate mixture was the only treatment significantly different from a water wash. There was a strong correlation between increasing surfactant concentrations above the critical micelle concentration and mean microbial reduction.


Functioning and Gene Expression of Adenosine A1 Receptor During Zebrafish (Danio rerio) Development.
The A1 adenosine receptor is the most widely expressed P1 receptor in vertebrates, performing inhibitory tone of the nervous system. Increased levels of adenosine are crucial to promote tissue protection in threatening situations, such as convulsion and hypoxia. Zebrafish is an established model organism for studies on health and disease. In this study, we evaluated the functionality of A1 adenosine receptor through development of zebrafish (6-7-day-, 3-, 8-, and 24-month-old), assessing: (I) the effects of the agonist N6-cyclopenthyladenosine (CPA) over locomotor parameters, (II) the anticonvulsant properties of CPA and adenosine per se in the pentylenetetrazol-induced seizure, and (III) the gene expression of adora1b through development. CPA promoted decreased distance traveled in the highest concentrations/doses tested (larvae: 75 to 500 μM; adults: 20 mg.kg-1), altered mean velocity (larvae: 50-500 μM; adults: 20 mg.kg-1) and time in the bottom zone of apparatus (adults: decrease in 20 mg.kg-1). Adenosine increased the latency of the larvae to reach stage II at 5 and 10 μM. CPA anticonvulsant effect against convulsive stage II was reached at 75 μM, although it decreased basal locomotor activity in larvae. For adults, CPA 10 mg.kg-1 was effective as anticonvulsant without locomotory effects. Adenosine had minor anticonvulsant effects in the concentration tested (larvae: 5 and 10 μM). The level of gene expression of adora1b was stable in brain from adult animals (8- and 24-month-old animals). These results suggest that zebrafish has similar responses to CPA as mammals. To avoid confounding factors, such as locomotor effects, during any brain function investigation using A1 adenosine receptor as a target, the concentration below 75 μM or below the dose of 20 mg.kg-1 of CPA is ideal for zebrafish at larval and adult stages, respectively.


Exploring oxygen in graphene chemical vapor deposition synthesis.
Graphene's practical applications require its reproducible production with controlled means. In particular, graphene synthesis by chemical vapor deposition on metals has been shown to be a promising way to produce large-size and high-quality graphene film at low cost. Understanding the reaction mechanisms during the synthesis process is vital for process and product controllability. There have been a great deal of studies regarding the mutual interplays between the metal, graphene, and hydrogen in graphene production, leading to significant advances in controllable graphene synthesis. Recently, oxygen has been found to play a key role in each step of graphene synthesis, especially on Cu. Taking oxygen into consideration, one can explain the divergent experimental results under similar conditions reported before and can grasp it as another powerful tool that can help to regulate the synthesis processes. The primary discoveries of the function of oxygen in graphene synthesis are summarized and discussed herein, divided into four aspects, corresponding to the elementary steps in graphene synthesis. Oxygen may also further promote graphene synthesis toward the final goal of developing wafer-scale single crystals with definite layer numbers and defects.


Study of hemodynamic changes with oxygen inhalation in VSD associated with pulmonary hypertension.
Pre- and postoperative pulmonary hemodynamic changes were studied in 28 cases with ventricular septal defect, in whom pulmonary-systemic blood pressure ratio was more than 70%. Pp/Ps decreased and Qp/Qs increased in majority of cases and Rp/Rs decreased in all cases after 100% oxygen inhalation. In survivors, Rp/Rs decreased to under 0.5 and Qp/Qs increased to more than 2.0 after oxygen inhalation or radical operation. In nonsurvivors, Rp/Rs decreased but stayed over 0.5, and Qp/Qs increased but stayed under 2.0. It is emphasized that when Rp/Rs falls down to under 0.5 after oxygen inhalation, it will be an enough indication for operation even pulmonary hypertension is so advanced in the ventricular septal defect.


LIM-only protein, CRP2, switched on smooth muscle gene activity in adult cardiac myocytes.
Smooth muscle alpha-actin gene activity appears in promyocardial cells well before cardiac myocyte differentiation and is down-regulated during the onset of rhythmic contractility and cardiac morphogenesis. The levels of LIM-only CRP2 correlated well with smooth muscle gene activity. Cardiomyocyte-specific expression of CRP2 in transgenic mice showed robust expression of smooth muscle cell-specific transcripts and protein filaments in the adult heart. Protein transduction of a recombinant CRP2 protein, fused to the protein transduction domain of HIV, into neonatal heart cells induced de novo synthesis of smooth muscle cell-specific transcripts and proteins. The LIM zinc fingers in CRP2 were found to collaborate with Brg1 of the SNF/SWI complexes, recruited serum response factor, and remodeled smooth muscle target gene chromatin through histone acetylation. CRP2 may have a cytoskeletal role, but as a nuclear protein, CRP2 acted as a potent transcription coadaptor that remodeled silent cardiac myocyte chromatin and directed serum response factor-dependent smooth muscle gene activity.


Circular RNA circRHOT1 contributes to pathogenesis of non-small cell lung cancer by epigenetically enhancing C-MYC expression through recruiting KAT5.
Non-small cell lung cancer (NSCLC) one of the most prevalent and severe malignancies globally and the molecular mechanisms of NSCLC are poor understood, limiting the development of diagnostic biomarkers and targeted therapies. Circular RNAs (circRNAs) have been identified as a sort of critical regulator in cancer progression. In this study, we identities the epigenetic regulation function of circular RNA circRHOT1 in promoting NSCLC cell proliferation. We found that circRHOT1 were elevated in the clinical tumor tissues relative to that in the peritumor tissues from NSCLC patients. circRHOT1 was up-regulated in human lung cancer cell lines compared with normal human lung epithelial cell line. MTT assays revealed that the silencing of circRHOT1 by siRNA suppressed cell viabilities of NSCLC cells. Colony formation and Edu assays confirmed that circRHOT1 knockdown attenuated NSCLC cell proliferation in vitro. Meanwhile, the depletion of circRHOT1 induced NSCLC cell apoptosis and cell cycle arrest in vitro. Mechanically, the depletion of circRHOT1 remarkably reduced c-MYC mRNA and protein expression in NSCLC cells. Inhibition of circRHOT1 reduced the enrichment of transcription active marker histone H3 lysine 27 acetylation (H3K27ac) and RNA polymerase II on the promoter of c-MYC. RNA pull down analysis showed that circRHOT1 was able to directly interact with acetyltransferase KAT5 in NSCLC cells. In summary, we concluded that circRHOT1 contributed to pathogenesis of NSCLC by epigenetically enhancing c-MYC expression through recruiting KAT5. CircRHOT1 and KAT5 may be used as the potential targets for NSCLC therapy.


Anencephalic infants as sources of organs. Issues and implications for nurses.
This article discusses anencephalic infants as potential sources of organs for infants and young children. Ethical issues relating to screening pregnant women, parental consent for organ donation, and the postnatal care of anencephalic infants are addressed. Professional responsibilities are identified to enable nurses to act ethically when confronted by these issues in caring for mothers and their infants.


In situ Expression of CD40 and CD40 ligand in psoriasis.
The interaction between CD40 and CD40 ligand (CD40L) provides a signal that contributes to the initiation of cellular immune responses. However, little information on the in vivo expression of CD40 and CD40L in cutaneous inflammation has been reported. To investigate the potential role of CD40-mediated signals in the pathogenesis of psoriasis. In situ CD40 and CD40L expression was examined immunohistochemically in different stages of psoriatic lesions: fully developed and initial pinpoint. In normal skin, faintly positive immunoreactivity for CD40 was seen in the basal keratinocytes and dermal endothelial cells. These showed almost the same intensity as that seen in psoriatic lesional skin. In the dermal infiltrates of psoriatic lesions, CD40 was intensely expressed and some of these positive cells appeared to be dendritic in shape. Whereas CD40 expression was observed almost in all specimens of psoriatic lesions, the expression of CD40L was predominantly detected in the initial pinpoint lesions of psoriasis. These seemed to be distributed close to CD40-positive cells. These results suggested that CD40L-triggered signals could be involved in the early stage of psoriatic lesion formation.


Suppression of damping in a diamagnetically levitated dielectric sphere via eddy currents and static charge reduction.
Diamagnetically levitated micro-nano oscillators play a crucial role in fundamental physics research and the advancement of high-precision sensors. Achieving high sensitivity in acceleration or force sensing is a fundamental requirement within these research domains. The primary limitation in achieving such sensitivity is thermal noise, which is directly proportional to the motion damping of the oscillator. Theoretical modeling suggests the presence of significant damping mechanisms induced by eddy currents. In this study, we validated the theoretical model by optimizing the structure of the magnet trap, confirming the impact of eddy currents on the damping of the oscillators. Additionally, we observed another type of damping caused by static charge in moving levitated dielectrics. Subsequently, we proposed an innovative theoretical model to explain this phenomenon and verified its validity during the charge neutralization process. Through these efforts, we successfully reduced the total damping from 1.6 mHz to 0.15 mHz, resulting in an order of magnitude improvement in performance. Our sensing system achieved the highest sensitivity of acceleration sensing in diamagnetically levitated submillimeter-scale dielectric to date, measuring 7.6±0.8)×10-10g/Hz. The exploration conducted in this study regarding the analysis and suppression of electromagnetic damping, along with associated thermal noise, holds significant promise for frontier research involving sensing with levitating dielectrics.


Pain Catastrophizing: Controversies, Misconceptions and Future Directions.
Recent reports have pointed to problems with the term 'pain catastrophizing'. Critiques of the term pain catastrophizing have come from several sources including individuals with chronic pain, advocates for individuals with chronic pain, and pain scholars. Reports indicate that the term has been used to dismiss the medical basis of pain complaints, to question the authenticity of pain complaints, and to blame individuals with pain for their pain condition. In this paper, we advance the position that the problems prompting calls to rename the construct of pain catastrophizing have little to do with the term, and as such, changing the term will do little to solve these problems. We argue that continued calls for changing or deleting the term pain catastrophizing will only divert attention away from some fundamental flaws in how individuals with pain conditions are assessed and treated. Some of these fundamental flaws include the inadequate training of health and allied health professionals in 1) evidence-based models of pain, 2) in the use of psychological assessment and intervention tools for the clinical management of pain, and 3) in gender equity and anti-racism. Critiques that pain scholars have leveled against the defining, operational and conceptual bases of pain catastrophizing are also addressed. Arguments for reconceptualizing pain catastrophizing as a worry-related construct are discussed. Recommendations are made for remediation of the problems that have contributed to calls to rename the term pain catastrophizing. PERSPECTIVE: The issues prompting calls to rename the construct of pain catastrophizing have their roots in fundamental flaws in how individuals with pain are assessed and treated. Efforts to address these problems will require more than a simple change in terminology.


Application of a single-colony coculture technique to the isolation of hitherto unculturable gut bacteria.
Molecular studies have led to postulation of a relationship between gut microbiota and certain diseases. However, because studies of hitherto uncultured species in vivo are essential for characterizing the biology and pathogenic properties of gut bacteria, techniques for culturing and isolating such bacteria must be developed. Here, a technique is described that partially overcomes the obstacles that prevent detection of interbacterial communication in vitro and are thus responsible for the failure to culture certain bacterial species. For this purpose, a ring with a membrane filter at the bottom was designed and a relatively simple nutrient medium was used instead of conventional media. Gut bacteria were cocultivated in soft agar separated by the membrane filter to simulate interbacterial communication in vitro. Use of this soft agar coculture technique led to the successful isolation of hitherto uncultured bacteria and the demonstration of multistage interbacterial communication among gut bacteria in vitro. Cultivation and isolation of single colonies of bacteria that require other bacteria for growth will enhance efforts to better understand the physiological and pathogenic roles of gut microbiota.


Local fasciocutaneous flap skin coverage for the dorsal foot and ankle.
Recalcitrant wounds of the distal leg and foot are notorious for requiring complex solutions even when deceptively small or benign in appearance. The simplicity of local flap options is always preferable, but is limited about the dorsal foot and ankle region. Inclusion of the well-defined deep fascia with the overlying integument in this area permits creation of local fasciocutaneous flaps that may be an important viable alternative. Over the past 6 years, 13 patients have had 15 such fasciocutaneous flaps for ankle or dorsal foot soft tissue reconstruction, with vascular ischemia being the most common etiology. Although four major complications occurred (27%), no limb amputation was a sequela as local wound care was satisfactory for eventual healing. Seven of these patients (54%) either declined or technically were not candidates for a complicated microvascular tissue transfer, which usually would have been preferable, but nevertheless all results proved satisfactory.


The Peroxisome-Mitochondria Connection: How and Why?
Over the past decades, peroxisomes have emerged as key regulators in overall cellular lipid and reactive oxygen species metabolism. In mammals, these organelles have also been recognized as important hubs in redox-, lipid-, inflammatory-, and innate immune-signaling networks. To exert these activities, peroxisomes must interact both functionally and physically with other cell organelles. This review provides a comprehensive look of what is currently known about the interconnectivity between peroxisomes and mitochondria within mammalian cells. We first outline how peroxisomal and mitochondrial abundance are controlled by common sets of cis- and trans-acting factors. Next, we discuss how peroxisomes and mitochondria may communicate with each other at the molecular level. In addition, we reflect on how these organelles cooperate in various metabolic and signaling pathways. Finally, we address why peroxisomes and mitochondria have to maintain a healthy relationship and why defects in one organelle may cause dysfunction in the other. Gaining a better insight into these issues is pivotal to understanding how these organelles function in their environment, both in health and disease.


Evaluation of a Sample-to-Result POCKIT Central SARS-CoV-2 PCR System.
The emergence of COVID-19 has caused unprecedented impacts on global public health and many other aspects. Meanwhile, many types of methods have been developed to detect the causative agent, SARS-CoV-2; this has greatly advanced the technologies in the diagnostic field. Here, we describe the development and validation of a sample-in-result-out POCKIT Central SARS-CoV-2 PCR system for detecting SARS-CoV-2 in comparison with a commercial reference real-time RT-PCR assay (TaqPath COVID-19 Combo Kit). Both assays were specific and did not cross-react with non-SARS-CoV-2 agents. Both assays were able to detect various SARS-CoV-2 strains including some variants. Based on testing serial dilutions of SARS-CoV-2 USA-WA1/2020 isolate, the limit of detection was 0.8 TCID50/mL (1.87 × 103 genomic copies/mL) for POCKIT Central SARS-CoV-2 PCR and 0.16 TCID50/mL (3.75 × 102 genomic copies/mL) for the reference PCR. Subsequently, 183 clinical samples were tested by both assays and the diagnostic sensitivity, specificity, and agreement of the POCKIT Central SARS-CoV-2 PCR were 91.7%, 100%, and 94.0%, respectively, when compared to the reference PCR. The compact sample-to-result POCKIT Central SARS-CoV-2 PCR system is a simplified and efficient point-of-care tool for SARS-CoV-2 detection. In addition, this platform can be readily adapted to detect other human and animal viruses.


Evaluation of haplotype-aware long-read error correction with hifieval.
The PacBio High-Fidelity (HiFi) sequencing technology produces long reads of >99% in accuracy. It has enabled the development of a new generation of de novo sequence assemblers, which all have sequencing error correction (EC) as the first step. As HiFi is a new data type, this critical step has not been evaluated before. Here, we introduced hifieval, a new command-line tool for measuring over- and under-corrections produced by EC algorithms. We assessed the accuracy of the EC components of existing HiFi assemblers on the CHM13 and the HG002 datasets and further investigated the performance of EC methods in challenging regions such as homopolymer regions, centromeric regions, and segmental duplications. Hifieval will help HiFi assemblers to improve EC and assembly quality in the long run. The source code is available at https://github.com/magspho/hifieval.


A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects.
Subsequent nights with partial sleep restriction result in impaired glucose tolerance, but the effects on insulin sensitivity have not been characterized. The aim of this study was to evaluate the effect of a single night of partial sleep restriction on parameters of insulin sensitivity. Nine healthy subjects (five men, four women) were studied once after a night of normal sleep duration (sleep allowed from 2300 to 0730 h), and once after a night of 4 h of sleep (sleep allowed from 0100 to 0500 h). Sleep characteristics were assessed by polysomnography. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies (from 1130 to 1430 h) with infusion of [6,6-(2)H(2)]glucose. Sleep duration was shorter in the night with sleep restriction than in the unrestricted night (226 +/- 11 vs. 454 +/- 9 min; P< 0.0001). Sleep restriction did not affect basal levels of glucose, nonesterified fatty acids, insulin, or endogenous glucose production. Sleep restriction resulted in increased endogenous glucose production during the hyperinsulinemic clamp study compared to the unrestricted night (4.4 +/- 0.3 vs. 3.6 +/- 0.2 micromol x kg lean body mass(-1) x min(-1); P = 0.017), indicating hepatic insulin resistance. In addition, sleep restriction decreased the glucose disposal rate during the clamp (32.5 +/- 3.6 vs. 40.7 +/- 5.1 micromol x kg lean body mass(-1) x min(-1); P = 0009), reflecting decreased peripheral insulin sensitivity. Accordingly, sleep restriction decreased the rate of glucose infusion by approximately 25% (P = 0.001). Sleep restriction increased plasma nonesterified fatty acid levels during the clamp study (68 +/- 5 vs. 57 +/- 4 micromol/liter; P = 0.005). Partial sleep deprivation during only a single night induces insulin resistance in multiple metabolic pathways in healthy subjects. This physiological observation may be of relevance for variations in glucoregulation in patients with type 1 and type 2 diabetes.


Inverse compton effect: some consequences for quasars.
The inverse Compton effect can transform enough energy of relativistic electrons into radiation so that an upper limit to the mean energy of the electrons is set. In quasars, the limit is too small to allow the production of any appreciable amount of synchrotron or inverse Compton radiation, unless either the distances are not cosmological or the lifetimes of the relativistic electrons are extremely short, of the order of hours.


Proactive treatment with calcipotriol reduces recurrence of plaque psoriasis.
Topical calcipotriol is a widely used treatment for plaque-type psoriasis worldwide, and has been shown to improve psoriatic plaques as well as very potent corticosteroids. However, there remains the practical question of whether calcipotriol application should continue on healed pigmentation/depigmentation associated with psoriatic plaques. Therefore, we conducted a pilot clinical study to answer this question. Plaque-type psoriatic patients not receiving systemic treatment were enrolled and treated with calcipotriol for 8 weeks (stage I) to achieve maximum effect. The patients were then divided into two groups: group A continued to apply calcipotriol to the entirety of the previous lesion (including pigmentation/depigmentation) regardless of whether skin was healed or not, while group B applied calcipotriol to the remaining lesion only. Patients were followed for 12 weeks (stage II) and dates of plaque recurrence were recorded. A total of 29 patients (13 men, 16 women) were enrolled. During stage I, reductions in scores for redness, induration and scale occurred in 40%, 47% and 55% of patients, respectively. After stage II was completed, group A (n = 19) showed a significantly better Kaplan-Meier curve of non-recurrence than group B (n = 8, P < 0.01). The mean non-recurrence duration was 76.8 ± 11.8 in group A and 35.0 ± 12.0 in group B. Our study showed that applying topical calcipotriol on seemingly healed psoriatic plaque lesions suppresses recurrence better than applying it only on remaining plaques. This finding may be important for instructing psoriatic patients on topical calcipotriol treatment.


Deep learning for diagnosis of head and neck cancers through radiographic data: a systematic review and meta-analysis.
This study aims to review deep learning applications for detecting head and neck cancer (HNC) using magnetic resonance imaging (MRI) and radiographic data. Through January 2023, a PubMed, Scopus, Embase, Google Scholar, IEEE, and arXiv search were carried out. The inclusion criteria were implementing head and neck medical images (computed tomography (CT), positron emission tomography (PET), MRI, Planar scans, and panoramic X-ray) of human subjects with segmentation, object detection, and classification deep learning models for head and neck cancers. The risk of bias was rated with the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. For the meta-analysis diagnostic odds ratio (DOR) was calculated. Deeks' funnel plot was used to assess publication bias. MIDAS and Metandi packages were used to analyze diagnostic test accuracy in STATA. From 1967 studies, 32 were found eligible after the search and screening procedures. According to the QUADAS-2 tool, 7 included studies had a low risk of bias for all domains. According to the results of all included studies, the accuracy varied from 82.6 to 100%. Additionally, specificity ranged from 66.6 to 90.1%, sensitivity from 74 to 99.68%. Fourteen studies that provided sufficient data were included for meta-analysis. The pooled sensitivity was 90% (95% CI 0.820.94), and the pooled specificity was 92% (CI 95% 0.87-0.96). The DORs were 103 (27-251). Publication bias was not detected based on the p-value of 0.75 in the meta-analysis. With a head and neck screening deep learning model, detectable screening processes can be enhanced with high specificity and sensitivity.


[Brain abscess in children].
Brain abscess is a rare infection in infants. Morbidity and mortality are high but have decreased due to advances in neuroimaging studies and the use of new antibiotics. We describe six cases of brain abscess diagnosed at the Gregorio Marañón Children's Hospital between January 1996 and September 2003. We performed a retrospective chart review of patients with brain abscess. The variables analyzed were age, sex, clinical symptoms and signs, radiological studies, etiology, therapy, and clinical outcome. Age ranged from 8 to 15 years (mean age: 11 years). There were three girls and three boys. The most frequent symptoms were neurological with associated sinusitis in four patients, congenital cyanogenic cardiopathy in one patient and meningitis in one patient. Diagnosis was established through computed tomography (CT) of the brain in five patients and through magnetic resonance imaging (MRI) in one patient. In five patients the abscess was located in the frontal lobe. All patients received broad-spectrum antibiotics and five underwent surgical drainage. Two patients had neurological sequelae. Although rare, brain abscess should be considered in patients with neurological manifestations associated with otorhinolaryngological infections or congenital cyanotic cardiopathy. When suspected, a CT or MRI must be performed to rule out this diagnosis and, if confirmed, prompt therapy with broad-spectrum antibiotics should be started. Surgical drainage may be needed.


Supporting pediatric cancer survivors with neurocognitive late effects: a model of care.
Educational difficulties are common for childhood survivors of central nervous system (CNS) cancers. Children who have been treated for brain tumors and those who have received treatments involving the CNS are at increased risk of developing neurocognitive late effects including difficulties with attention, executive functioning, speed of processing, and academic functioning. These children are also at risk for difficulties with social functioning and social isolation. This hospital's School Liaison Program (SLP) provides ongoing psychoeducation, advocacy, and consultation services for parents, schools, and medical staff to address the educational needs associated with the late effects of treatment for pediatric CNS-involved patients. This article provides an overview of the SLP model of care and discusses parent-perceived quality and program effectiveness. In general, parents attributed SLP involvement to improved academic performance, home-school communication, and school-level understanding of unique student cognitive profiles and learning needs.


Optimal treatment regimes for survival endpoints using a locally-efficient doubly-robust estimator from a classification perspective.
A treatment regime at a single decision point is a rule that assigns a treatment, among the available options, to a patient based on the patient's baseline characteristics. The value of a treatment regime is the average outcome of a population of patients if they were all treated in accordance to the treatment regime, where large values are desirable. The optimal treatment regime is a regime which results in the greatest value. Typically, the optimal treatment regime is estimated by positing a regression relationship for the outcome of interest as a function of treatment and baseline characteristics. However, this can lead to suboptimal treatment regimes when the regression model is misspecified. We instead consider value search estimators for the optimal treatment regime where we directly estimate the value for any treatment regime and then maximize this estimator over a class of regimes. For many studies the primary outcome of interest is survival time which is often censored. We derive a locally efficient, doubly robust, augmented inverse probability weighted complete case estimator for the value function with censored survival data and study the large sample properties of this estimator. The optimization is realized from a weighted classification perspective that allows us to use available off the shelf software. In some studies one treatment may have greater toxicity or side effects, thus we also consider estimating a quality adjusted optimal treatment regime that allows a patient to trade some additional risk of death in order to avoid the more invasive treatment.


Removal of ferritin-bound iron by DL-dihydrolipoate and DL-dihydrolipoamide.
The naturally occurring dithiols DL-dihydrolipoate and DL-dihydrolipoamide were tested for their ability in the removal of ferritin-bound iron. Both compounds remove the iron stored inside the protein by complexing it in the ferric form. The iron can be reduced to the ferrous form by excess dithiol, but this is not necessary for complete removal. Reaction is complete in few hours and, at molar ratios of chelator to metal higher than 10, more than 60% of the ferritin-bound iron was removed. The amount of iron stored in the ferritin molecule does not affect the rate and the yield of the removal reaction. The iron-removing ability of DL-dihydrolipoate was found to be identical to that of an equimolar solution of sodium dithionite, and to be pH-dependent. Results are discussed in terms of the molecular architecture of ferritin and of the chelators, and their possible physiological relevance is pointed out.


Generation of an Enhancer-Trapping Vector for Insertional Mutagenesis in Zebrafish.
Enhancer trapping (ET) is a powerful approach to establish tissue- or cell-specific reporters and identify expression patterns of uncharacterized genes. Although a number of enhancer-trapping vectors have been developed and a large library of fish lines with distinct tissue- or cell-specific expression of reporter genes have been generated, the specificity and efficiency of trapping vectors need to be improved because of the bias interaction of minimal promoters with genomic enhancers. Accordingly, we generated an enhancer-trapping vector pTME that contains a minimal mouse metallothionein gene (mMTI) promoter upstream of EGFP reporter. In the first round of screening, twelve zebrafish lines that carry a single copy of ET cassettes were characterized to have tissue- or cell-specific EGFP expression. One of the highly conserved noncoding elements near an insertion site of trapping cassettes was characterized as an enhancer that can specifically regulate the expression of EGFP in cells of the central nervous system. In addition, the pTME vector contains a mutation-cassette that is able to effectively block the transcription of an endogenous gene in an ET line with ubiquitous EGFP expression. Thus, the pTME vector can be used as an alternative tool for both enhancer trapping and mutagenesis across a target genome.


Sexual professional boundaries perceived by undergraduate and graduate physiotherapists: a cross sectional survey.
To compare self-reported experiences of and attitudes towards sexual professional boundaries (SPB) in a cohort of undergraduate and graduate physiotherapists domiciled in the UK and Australia. A cross sectional survey design was utilised to capture data from two UK cohorts. Data was collected from a University in the Midlands region of England. Fifty one final year undergraduate students and 17 graduate students took part in this study. This was compared to published data from Australian undergraduates (n=67) and Australian graduates (n=939). A questionnaire consisting of 3 distinct sections was distributed. Section 1 established demographic information, section 2 considered personal experience of the SPB, and section 3 considered attitudes to 6 vignettes describing a variety of scenarios examining the SPB. Graduate students in both cohorts demonstrated a greater awareness of professionals crossing the SPB. Self reported sexual attraction towards a patient was significantly higher in graduate students (50%) compared to undergraduates (9%). Six percent and 4% of UK and Australian graduates reporting they had dated a patient. However, a much higher percentage (53% and 17% respectively) reported knowing a colleague who had dated a patient. A significant difference between graduates and undergraduate in their attitudes towards selected vignettes describing SPB crossings was also identified. The current results provide evidence of inappropriate sexual behaviour occurring within the UK. Both graduates and undergraduates require training pertinent to the topic of SPB. Further research is required to enhance our understanding of this topic area.


Practical tips on coding for diabetes care.
This article is designed to assist with the challenging effort to obtain reimbursement for health-care services to patients with diabetes. The basics of coding diagnoses and services are presented, including background information and specific examples of the use of codes that are particularly pertinent to the clinical endocrinologist's care of the patient with diabetes. The coding of diagnoses with use of the current International Classification of Diseases, 9th revision, clinical modification (ICD-9-CM) classification system and the coding of outpatient and inpatient services by using current procedural terminology (CPT) codes and modifiers are outlined, including the use of the relatively new prolonged physician services codes. A discussion of reimbursement for diabetes education and pertinent revenue codes for hospital services is included, and resource references for further study are provided.


Jerome A. Berson (1924-2017).
Jerome A. Berson, Sterling Professor Emeritus at Yale University, passed away on January 13, 2017. Berson was a major figure in physical organic chemistry and the study of organic reaction mechanisms, and he published two outstanding books on the history of chemistry.


Increasing Access to Auricular Acupuncture for Postoperative Nausea and Vomiting.
Postoperative nausea and vomiting (PONV) affects more than 30% of surgical patients. Auricular acupuncture (AA) has been shown to decrease the incidence of PONV in select populations. An evidence-based quality improvement project made AA available to all adult surgical patients, and the results were recorded in a database. A retrospective between-groups analysis of 210 database entries was conducted, of those 25 receiving AA. More risk factors for PONV were present in the AA group (P < .001). Both groups experienced a less-than-expected rate of PONV. Similar rates were shown between groups for PONV, postanesthesia care unit length of stay, and opioid consumption. Patient satisfaction was 96% with AA. The AA group was treated with less antiemetic medication (P < .001), yet PONV rates remained similar. A multimodal approach treating patients at risk for PONV is recommended. Administration of multiple antiemetics may result in unnecessary cost or unfavorable side effects when effective and less costly alternatives exist. AA is a viable treatment for PONV, considering cost and patient satisfaction.


Illuminating lncRNA Function Through Target Prediction.
Most of the transcribed human genome codes for noncoding RNAs (ncRNAs), and long noncoding RNAs (lncRNAs) make for the lion's share of the human ncRNA space. Despite growing interest in lncRNAs, because there are so many of them, and because of their tissue specialization and, often, lower abundance, their catalog remains incomplete and there are multiple ongoing efforts to improve it. Consequently, the number of human lncRNA genes may be lower than 10,000 or higher than 200,000. A key open challenge for lncRNA research, now that so many lncRNA species have been identified, is the characterization of lncRNA function and the interpretation of the roles of genetic and epigenetic alterations at their loci. After all, the most important human genes to catalog and study are those that contribute to important cellular functions-that affect development or cell differentiation and whose dysregulation may play a role in the genesis and progression of human diseases. Multiple efforts have used screens based on RNA-mediated interference (RNAi), antisense oligonucleotide (ASO), and CRISPR screens to identify the consequences of lncRNA dysregulation and predict lncRNA function in select contexts, but these approaches have unresolved scalability and accuracy challenges. Instead-as was the case for better-studied ncRNAs in the past-researchers often focus on characterizing lncRNA interactions and investigating their effects on genes and pathways with known functions. Here, we focus most of our review on computational methods to identify lncRNA interactions and to predict the effects of their alterations and dysregulation on human disease pathways.


Studies on the Mechanism of the Volatile Oils from Caoguo-4 Decoction in Regulating Spleen Deficiency Diarrhea by Adjusting Intestinal Microbiota.
The Caoguo-4 decoction, a classical Mongolian medicine formula, is widely used to treat spleen deficiency diarrhea (SDD) in Mongolian for decades. Previously, the Caoguo-4 decoction volatile oil has been confirmed to be effective in ameliorating symptoms of spleen deficiency diarrhea in an animal model. However, the underlying mechanism of the Caoguo-4 decoction volatile oil is yet to be established. The aim of the current study was to investigate the antidiarrheal effects and mechanism of the Caoguo-4 decoction volatile oil. Wistar rats were randomly divided into 5 groups of 10 animals including control, model, positive, Caoguo-4 decoction, and Caoguo-4 decoction volatile oil groups (10 rats in each group). All the rats, besides those in the control group, were induced to develop SDD by a bitter-cold purgation method with Xiaochengqi decoction. The antidiarrheal effect of Caoguo-4 decoction volatile oil was evaluated by pathological section, serum D-xylose and AMS content, plasma MTL content, and gut microbiota analysis via 16S rRNA sequencing. The results showed that the developed SDD rat model (model group) had decreased food intake, increased weight loss, soft stool, and bad hair color. When compared with the control group, serum was significantly reduced serum D-xylose and AML but increased MTL levels in the model group (p < 0.05). However, after treatment with either the Caoguo-4 decoction (the decoction group) or Smecta (the positive group) or volatile oil from the Caoguo-4 decoction (the volatile oil group), a significant increase in the serum D-xylose levels was observed. Additionally, AML levels significantly increased in the positive and volatile oil groups, and MTL levels significantly decreased in the decoction and volatile oil groups, when compared with the model group (p < 0.05). The pathological changes of the intestinal mucosa showed that the structure of the epithelium in the villi of the small intestine was affected, deformed, and incomplete in the model group when compared with the control group. However, either the decoction group or the volatile oil group recovered the villous morphology. The results of OTU analysis and alpha diversity analysis of intestinal bacteria showed that the intestinal microbiota of the SDD model rats showed an obvious decrease in richness and diversity of intestinal microbiota. But the intervention treatment of decoction and volatile oil could significantly recover the richness and diversity of intestinal microbiota. The intestinal microbiota destroyed in SDD modelling could be significantly improved by the Caoguo-4 decoction volatile oils, which provides reference for clinical medication.


Chimeric antigen receptor-engineered T cells for liver cancers, progress and obstacles.
Chimeric antigen receptor-engineered T cells therapy has become the hottest topic of immunotherapy, as its great successes achieved in treating refractory hematological malignancies. These successes also paved the road to novel strategies of treating various solid tumors including liver cancer. Many specific proteins can be expressed aberrantly in liver cancers; therefore, a series of experimental and clinical researches exploring chimeric antigen receptor-engineered T cells and liver cancer are in progress, acquiring obvious antitumor effect and revealing its feasibility in treating liver cancer. However, lots of challenges and obstacles are emerging simultaneously, such as low infiltration, side effects, safety of chimeric antigen receptor-engineered T cells, and limited data of studies or clinical trials. Researchers have been working out many innovative ways to directly stroke these obstacles, theoretically or practically. This review focuses more on the progress and obstacles from chimeric antigen receptor-engineered T cells therapy to treat liver cancer, summarizing new breakthroughs in shooting those obstacles, meanwhile, hoping to provide enlightenment to this promising immunotherapeutic method.


Effect of low intensity pulsed ultrasound stimulation on sinus augmentation in rabbits.
The objective of the present study was to evaluate the efficacy of low intensity pulsed ultrasound stimulation (LIPUS) and to determine the optimal frequency for enhancing bone regeneration in sinus augmentation using a rabbit model. Thirty male rabbits underwent sinus augmentation. Two rectangular nasal bone windows were outlined bilaterally. LIPUS was applied at two different frequencies (1 MHz and 3 MHz) on experimental sites daily for 2, 4 and 8 weeks. Each histological area of the experimental and control sites was divided into upper and lower parts from the parietal region to a depth of 5 mm. Each area of new bone was measured. At 2, 4 and 8 weeks, the experimental sites in the 1 MHz group exhibited significantly more new bone growth than the control sites in both the upper and lower parts. When the upper and lower parts of each area were measured in combination there was a statistical difference between the test and control sites in the 1 MHz group at 2, 4 and 8 weeks; however, there were no statistical differences between the test and control sites in the 3 MHz group. The results suggest that clinical application of LIPUS for sinus augmentation may promote new bone formation, and that the effect of LIPUS for sinus augmentation at a frequency of 1 MHz was greater than at 3 MHz until 8 weeks after sinus augmentation.


Adapting crop production to climate change and air pollution at different scales.
Air pollution and climate change are tightly interconnected and jointly affect field crop production and agroecosystem health. Although our understanding of the individual and combined impacts of air pollution and climate change factors is improving, the adaptation of crop production to concurrent air pollution and climate change remains challenging to resolve. Here we evaluate recent advances in the adaptation of crop production to climate change and air pollution at the plant, field and ecosystem scales. The main approaches at the plant level include the integration of genetic variation, molecular breeding and phenotyping. Field-level techniques include optimizing cultivation practices, promoting mixed cropping and diversification, and applying technologies such as antiozonants, nanotechnology and robot-assisted farming. Plant- and field-level techniques would be further facilitated by enhancing soil resilience, incorporating precision agriculture and modifying the hydrology and microclimate of agricultural landscapes at the ecosystem level. Strategies and opportunities for crop production under climate change and air pollution are discussed.


Regulation of expression of mammalian gonadotrophin-releasing hormone receptor genes.
Gonadotrophin-releasing hormone (GnRH), acting via its cognate GnRH receptor (GnRHR), is the primary regulator of mammalian reproductive function, and hence GnRH analogues are extensively used in the treatment of hormone-dependent diseases, as well as for assisted reproductive techniques. In addition to its established endocrine role in gonadotrophin regulation in the pituitary, evidence is rapidly accumulating to support the expression and functional roles for two forms of GnRHR (GnRHR I and GnRHR II) in multiple and diverse extra-pituitary mammalian tissues and cells. These findings, together with findings indicating that mutations of the GnRHR are linked to the disease hypogonadotrophic hypogonadism and that GnRHRs play a direct role in neuronal migration and reproductive cancers, have presented new therapeutic targets and intensified research into the structure, function and mechanisms of regulation of expression of GnRHR genes. The present review focuses on the current knowledge on tissue-specific and hormonal regulation of transcription of mammalian GnRH receptor genes. Emerging insights, such as the discovery of diverse regulatory mechanisms in pituitary and extra-pituitary cell types, nonclassical mechanisms of steroid regulation, the use of composite elements for cell-specific expression, the increasing profile of hormones involved in regulation, the complexity of kinase pathways that target the GnRHR I gene, as well as species-differences, are highlighted. Although further research is necessary to understand the mechanisms of regulation of expression of GnRHR I and GnRHR II genes, the GnRHR is emerging as a potential target gene for facilitating cross-talk between neuroendocrine, immune and stress-response systems in multiple tissues via autocrine, paracrine and endocrine signalling.


The relationship between blood serum lipids and periodontal condition.
the study analyzed he relationship between blood serum lipids and periodontal condition, as well as the relationship between the left ventricular mass index and the condition of periodontium. The study included 261 subjects--140 women and 121 men. Mean age of the subjects was 38 years. The condition of periodontal tissues during the study was evaluated with the help of the CPITN index (Community Periodontal Index of Treatment Needs). The study was performed at Kaunas University of Medicine (KMU) Clinic of Dental and Oral Diseases. Laboratory blood lipid studies were performed at the laboratory of the Hospital of Kaunas University of Medicine (HKUM). The studies included the determination of the total blood cholesterol level, triglyceride level, HDL cholesterol level, and LDL cholesterol level (mmol/l). Patients with hypertension (102 patients) underwent ultrasound examination of the heart at KMU Clinic of Cardiology. On the basis of the findings of the ultrasound study, left ventricular mass index (g/m(2)) was calculated. The findings of our study showed that there was no difference in the blood serum concentration of total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol between people with healthy periodontium and those with gingivitis or periodontitis. Mean rank of the left ventricular mass index in subjects with healthy periodontium or gingivitis (CPITN codes 0, 1, 2) was 48.3, and in subjects with periodontitis (CPITN codes 3, 4) - 61.36 (p<0.05).


[Progressive sensorineural hearing loss: metabolic, hormonal and vascular etiology].
Metabolic, hormonal and vascular disorders are considered to cause hearing dysfunction such as progressive sensorineural hearing loss (PSNHL). The diseases most commonly associated with PSNHL are diabetes mellitus, congenital and acquired hypothyroidism, chronic renal failure, chronic labyrinthine ischemia determined by non-hematologic factors (tissue perfusion pressure, blood vessel diameter) or by hematologic factors (blood viscosity and/or rigidity of the red blood cells). In this study a review of data on the relationship between these clinical disorders and the presence and deterioration of the hearing function was carried out. PSNHL seems to be significantly associated with diabetes mellitus, in particular the mitochondrial type: a progressive deterioration of the hearing function is reported in 60% of the patients suffering from this type of disease with mitochondrial mutations. Regarding hypothyroid disorders, the data do not support a pathogenetic link between PSNHL and acquired hypothyroidism, whereas in subjects with congenital hypothyroidism both clinical and experimental results indicate a progressive damage of hearing function if the thyroid disorder is not treated early in life. Also, in patients with chronic renal failure the hearing thresholds seem to be significantly worse than in control subjects, particularly in patients undergoing dialysis, whereas the effect of kidney transplantation on auditory function is still not understood. Finally a relationship between PSNHL and chronic labyrinthine ischemia due to alterations of hematologic factors (increase of blood viscosity and/or increase of rigidity of the red blood cells) has been reported by several authors. However, data on high blood pressure and hyperlipoproteinemia as causes of deterioration of hearing acuity are controversial, and it is often difficult to understand whether the progressive hearing deficit is due only to these factors or also to the elderly age of patients.


Degradation of neural representations in higher visual cortex by sleep deprivation.
A night of total sleep deprivation (TSD) impairs selective attention and is accompanied by attenuated activation within ventral visual cortex (VVC). However, finer details of how TSD compromises selectivity of visual processing remain unclear. Drawing from prior work in cognitive aging, we predicted that TSD would result in dedifferentiation of neural responses for faces and houses within the VVC. Instead, we found preservation of category selectivity. This was observed both in voxels highly selective for each category, and also across multiple voxels evaluated using MVPA. Based on prior findings of impaired attentional modulation following TSD, we also predicted reduced biasing of neural representations towards the attended category when participants viewed ambiguous face/house images. When participants were well rested, attention to houses (or faces) caused activation patterns to more closely resemble those elicited by isolated house (face) images than face (house) images. During TSD, attention to faces enhanced neural similarity to both target (face) and distractor (house) representations, signifying reduced suppression of irrelevant information. Degraded sensory processing reflected in reduced VVC activation following TSD, thus appears to be a result of impaired top-down modulation of sensory representations instead of degraded selectivity of maximally category sensitive voxels, or the dedifferentiation of neural activation patterns.


Functional recovery from neuroinvasive West Nile Virus: A tale of two courses.
In 2012, the highest numbers of West Nile Virus (WNV) cases were reported by the Center for Disease Control since 2003. This outbreak included over half of the identified patients being classified with one of the more debilitating neuroinvasive subtypes of WNV. Despite improvements in diagnosis and treatment options in symptom management, longitudinal research on WNV neurocognitive and functional outcomes is limited by sample size, retrospective review, and/or reliance on self-report measures for cognitive status and level of independence. This study describes the cases of 2 patients diagnosed with WNV as they complete rehabilitation across the continuum of care. Review of two cases that experience different rehabilitation outcomes 4-18 months post diagnosis. The cases presented here demonstrate the potentially differential courses of recovery and outcomes for physical (e.g., balance, ambulation, upper extremity function), cognitive (e.g., attention, executive functions, memory, language, visuospatial), and emotional functioning, as assessed via measures administered by the patient's physical therapists and neuropsychologists. These patients were evaluated as part of the standard clinical practice to monitor changes, track recovery, and provide recommendations across the continuum of care from admission to discharge from acute inpatient rehabilitation, during outpatient day neurorehabilitation, and while receiving outpatient neuropsychology services. These cases highlight the variability in rehabilitative course for individuals diagnosed with WNV. Consistent follow-up with patients is recommended to ensure management of remitting and chronic symptoms.


Autoimmune antibodies in first-episode psychosis with red flags: A hospital-based case-control study protocol.
Research is increasingly identifying an overlap between psychosis and immunological dysregulation. Certain autoantibodies are being identified in a small but probably relevant subgroup of patients with psychosis. The term "autoimmune psychosis" (AIP) and its corresponding red-flag signs present the opportunity for a new field in psychiatry to promote diagnostic workup and immunomodulating therapy in individual cases. The present protocol aims to determine the seroprevalence of autoantibodies in first-episode psychosis (FEPs) using AIP red flag signs, and to explore the frequency of autoantibody subtypes and potential mediating confounders. This is a hospital-based case-control study. All participants will be consecutively selected from the main tertiary psychiatric hospital in Shenzhen City, China. Individuals admitted to the psychiatric ward and diagnosed with FEPs will be enrolled. Based on recent consensus, participants with red flags of AIPs will be defined as cases, while the remainder will be matched as controls. Seropositive antibodies will be detected and verified in cerebrospinal fluid (CSF) samples based on the fixed cell-based assay (CBA) method. The propensity score-adjusted odds ratios will be determined to investigate the key mediating confounders regarding autoantibody subtypes and red flag subsets. The results of this study will facilitate the early identification of AIPs in FEP patients using the red flag sign and help identify key mediators that improve the accuracy of diagnostic algorithms. It will have clinical significance to focus on serum antibodies that have been verified in CSF samples, due to its consistency with clinical practices in current psychiatry.


Hapten-specific T-cell unresponsiveness induced bybenzylpenicilloyl autologous gamma globulin conjugates in human lymphocyes in vitro.
The aim of these studies was to determine whether unresponsiveness to the main determinant of penicillin, benzylpenicilloyl, can be induced in human peripheral lymphocytes in vitro by conjugates of benzylpenicilloyl (BPO) autologous gamma globulin (HGG). Initially it was shown that conjugates of BPO-keyhole limpet hemocyanin (KLH) elicited lymphocyte proliferation in the peripheral blood lymphocytes of six out of nine adult individuals in vitro. In contrast, conjugates of dinitrophenylated KLH and of BPO-HGG and the carriers HGG and KLH alone failed to do so. Similarly, release of the non-specific helper factor, lymphocyte mitogenic factor (LMF) occurred only after BPO-KLH stimulation. LMF activity was measured by B-cell proliferation and incorporation of radioactive amino acids into secreted immunoglobulin. Treatment with BPO-HGG for 24 h in vitro inhibited BPO-KLH-induced lymphocyte proliferation and LMF release. Treatment with either HGG, dinitrophenylated HGG, BPO-KLH, or BPO-human serum albumin failed to abrogate T-cell lymphocyte proliferation of human lymphocytes in vitro. The antigen specificity of the reduced immunologic responsiveness was further demonstrated by the observation that lymphocytes treated with BPO-HGG for 24 h in vitro responded normally to tetanus toxoid antigen.The data suggest that conjugates of BPO-HGG induce hapten-specific helper T-cell unresponsiveness in vitro.


Cost-effectiveness analysis, extended dominance, and ethics: a quantitative assessment.
The principle of extended dominance is applied in incremental cost-effectiveness analysis to eliminate from consideration strategies whose costs and benefits are improved by a mixed strategy of two other alternatives. Ethical considerations arise, however, in that equal care is not provided to all of the population. To explore these concerns, the authors establish a theoretical health care example with three diagnostic strategies. They demonstrate, both algebraically and geometrically, how to calculate the set of all possible mixed strategies that dominate the strategy eliminated by extended dominance. With the consideration of budget constraints, they define the "coefficient of inequity" as the minimum proportion of the population that would receive an inferior health care strategy if a mixed strategy were to be used instead of the dominated strategy. The implications of cost-effectiveness analysis are made explicit, revealing classic economic concerns about the tradeoff of equity and efficiency.


Presumed late recurrence of Acanthamoeba keratitis exacerbated by exposure to topical corticosteroids.
A 28-year-old female with a history of contact lens wear presented with a 1 week history of pain and photophobia in her left eye. In vivo confocal microscopy (IVCM) and corneal scrape confirmed the diagnosis of Acanthamoeba keratitis (AK) which was treated with intensive topical propamidine isethionate (0.1%) and chlorhexidine (0.02%) with tapering dosage over 11 months. Five years after complete resolution of AK and cessation of all contact lens wear, the subject presented to her optometrist with a history of ocular discomfort and mild photophobia. Without further investigation she was prescribed topical corticosteroids. Three weeks later she presented with pain and reduced vision in the left eye. Slit-lamp examination revealed focal, inferior corneal stromal edema. IVCM confirmed widespread Acanthamoeba cysts. Treatment with topical polyhexamethylene biguanide (PHMB) 0.02% and propamidine isethionate 0.1% resulted in resolution of the AK. Despite an initially mild AK, this subject presumably retained viable Acanthamoeba cysts in her cornea 5 years after the initial episode. This report highlights the importance of caution when using corticosteroids in patients with a previous history of AK, even in the relatively distant past. Patients with AK should be warned regarding the risks of recurrence following presumed resolution.


Dictyostelium transcriptional responses to Pseudomonas aeruginosa: common and specific effects from PAO1 and PA14 strains.
Pseudomonas aeruginosa is one of the most relevant human opportunistic bacterial pathogens. Two strains (PAO1 and PA14) have been mainly used as models for studying virulence of P. aeruginosa. The strain PA14 is more virulent than PAO1 in a wide range of hosts including insects, nematodes and plants. Whereas some of the differences might be attributable to concerted action of determinants encoded in pathogenicity islands present in the genome of PA14, a global analysis of the differential host responses to these P. aeruginosa strains has not been addressed. Little is known about the host response to infection with P. aeruginosa and whether or not the global host transcription is being affected as a defense mechanism or altered in the benefit of the pathogen. Since the social amoeba Dictyostelium discoideum is a suitable host to study virulence of P. aeruginosa and other pathogens, we used available genomic tools in this model system to study the transcriptional host response to P. aeruginosa infection. We have compared the virulence of the P. aeruginosa PAO1 and PA14 using D. discoideum and studied the transcriptional response of the amoeba upon infection. Our results showed that PA14 is more virulent in Dictyostelium than PA01using different plating assays. For studying the differential response of the host to infection by these model strains, D. discoideum cells were exposed to either P. aeruginosa PAO1 or P. aeruginosa PA14 (mixed with an excess of the non-pathogenic bacterium Klebsiella aerogenes as food supply) and after 4 hours, cellular RNA extracted. A three-way comparison was made using whole-genome D. discoideum microarrays between RNA samples from cells treated with the two different strains and control cells exposed only to K. aerogenes. The transcriptomic analyses have shown the existence of common and specific responses to infection. The expression of 364 genes changed in a similar way upon infection with one or another strain, whereas 169 genes were differentially regulated depending on whether the infecting strain was either P. aeruginosa PAO1 or PA14. Effects on metabolism, signalling, stress response and cell cycle can be inferred from the genes affected. Our results show that pathogenic Pseudomonas strains invoke both a common transcriptional response from Dictyostelium and a strain specific one, indicating that the infective process of bacterial pathogens can be strain-specific and is more complex than previously thought.


Vogt-Koyanagi-Harada syndrome in a 10-year-old child.
A 10-year-old female child attended outpatients department of Regional Institute of ophthalmology, Kolkata with the complaints of gradual dimness of vision of both eyes, recurrent pain, redness and photophobia. On examination, she was found to have bilateral anterior uveitis, poliosis and vitiligo. Laboratory tests were performed to rule out other causes of granulomatous uveitis. She was treated with topical and systemic steroids and topical cycloplegic. Then pars plana vitrectomy with lensectomy was carried out. The vision still remained poor.


CSF serotonin metabolite (5-HIAA) studies in depression, impulsivity, and violence.
A neuroanatomical central nervous system (CNS) mechanism for the expression of emotions and behaviors in animals has now been proposed for over 50 years. More specifically, alterations in CNS serotonin associated with aggressive behavior in certain animal models have been among the most frequent, reliable, and replicable findings. Because alterations in CNS monoamines, i.e., catechols and indols, have been related to hypotheses for affective disorders and associated with both suicidal and aggressive behaviors, human clinical implications have emerged. The original studies, which reported an association between low cerebrospinal fluid 5-hydroxyindole-acetic acid concentration and impulsive, destructive behaviors, particularly where aggression and violence are involved, have now been replicated rather consistently in a number of countries and cultures.


An HDAC inhibitor, trichostatin A, induces a delay at G2/M transition, slippage of spindle checkpoint, and cell death in a transcription-dependent manner.
Histone deacetylases (HDACs), a promising target for cancer therapy, play a role in regulating cell-cycle progression. The mechanisms for HDAC inhibition-induced regulation of G(2)/M transition and mitotic progression remain to be elucidated. Herein, we report that trichostatin A (TSA), an HDAC inhibitor, induces a delay at the G(2)/M transition, chromosome missegregation and multi-nucleation, and thereby leads to cell death by promoting exit from aberrant mitosis without spindle checkpoint. These results are associated with a transcriptional modulation of key regulator genes of the cell cycle, including CyclinB1, Plk1, Survivin, and p21(WAF1/Cip1). Actinomycin D, a transcriptional inhibitor, abrogated the TSA-induced delay of G(2)/M transition and transcriptional modulation of cell-cycle regulator genes, indicating that the impact of TSA in this manner is transcription dependent. Overall, our findings indicate that TSA provides a barrier to cell-cycle progression for antiproliferation and promotes escape from mitotic catastrophe and cell death, by inhibiting an HDAC-mediated transcriptional action.


A clade of New World primates with distinctive alphoid satellite DNAs.
Centromerically located alphoid satellite DNAs are present in all primates. They typically consist of arrays of a 340-bp monomeric unit that is composed of related, but diverged, 170-bp subunits. A unique monomeric unit has recently been described: the alphoid satellite monomers of the neotropical primate Chiropotes satanas (bearded saki) are typically 539 bp in length. In addition, a number of smaller satellite sequences are present in this species. Analysis of two primates closely related to Chiropotes, Pithecia irrorata (saki) and Cacajao melanocephalus (uakari), show that they also contain unique alphoid satellites that are different from those of Chiropotes and different from one another. Southern blot and sequence analyses suggest that an alphoid satellite rearrangement(s) occurred early in the history of the tribe Pitheciini (Chiropotes, Pithecia, Cacajao) and that rearrangements are continuing to occur in this group of primates.


[Etoposide effect on cell cycle kinetics of a human lung cancer cell line].
The lethal and kinetic effects of Etoposide on a cell line of human small cell carcinoma of the lung (PC-6) were analyzed in vitro using flow cytometric measurement of DNA content. The drug effect is dependent on concentration and exposure time. When PC-6 cells were exposed to Etoposide for 1 hour then washed, a increase of cells in G2 phase was observed followed by prompt recovery. Continuous treatment with Etoposide for 24 hours caused a retardation of S phase transit, and high concentrations (greater than 10 micrograms/ml) resulted in stoppage of the whole cell cycle. This drug may be useful in combination chemotherapy regimens.


[If the level of cystatin C in children and adolescents with type 1 diabetes an early marker for diabetic nephropathy?].
The most important complication in the course of diabetes mellitus type I is diabetic nephropathy. Nowadays, apart from assessing the increased amount of albumins in urine, we are not able to identify early enough these patients whose health might be endangered by nephropathy. Looking for other biochemical indicators which could mark the early symptoms of kidney damage/renal malfunction seems to be justified. 1. What is the concentration of cystatin C among children and teenagers suffering from diabetes mellitus type 1 and whether its level depends on the age of patient, the age in which the patient was affected with the disease, the length of the disease, metabolic compensation, diabetes control and the presence of microangiopathy? 2. Is there any interdependence between cystatin C and microalbuminuria and the renal efficiency rates? Study group. A group of 130 patients (60 girls and 70 boys aged from 7 and 20,8) who have been suffering from juvenile diabetes from 1 to 17 years was examined. The control group were healthy youngsters, matched for age and sex, without any /burdening/ medical history. All the patients were examined in the following way: anthropometric measurements were taken, BMI in kg/m2 was defined, metabolic compensation based on HbA1c (%) was estimated. Ophthalmological examination and a circadian monitoring of arterial blood pressure were carried out. Microalbuminuria in a 24-hour urine collection was determined. In both groups glomerular filtration rate with the help of endogenous creatinine clearance and the concentration of cystatin C were evaluated. The results were subject to statistical analysis. The average age of the whole examined group was 15+/-3,0 the average disease length 6,85+/-3,36 years. The concentration of cystatin C among diabetic patients was higher in comparison with the control group (0.75+/-0.13 vs. 0.68+/-0.12 mg/l). It was also discovered that the concentration of cystatin C was increasing along with the length of the disease reaching the highest level in the group of patients suffering from this disease longer than 10 years (0.52+/-0.11 vs. 0.67+/-0.13 vs. 0.93+/-0.13 mg/l), which is again statistically significant. Moreover the concentration of cystatin C is higher among patients with insufficient diabetes control (0.765+/-0.12 mg/l vs. 0.71+/-0.12 pg/ml, p<0.05). These patients who additionally developed vascular complications (retinopathy, nephropathy, arterial hypertension) had significantly higher condensation of cystatin C (0.75+/-0.13 vs. 0.69+/-0.11 mg/l, p<0.05). Having considered the initial results, the following conclusion can be reached: only further, long-term research can supply us with the reliable data whether assessing the level of cystatin C concentration in children's and teenagers' serum in diabetic patients could become the earlier marker of renal malfunction than microalbuminuria.


Ultrafast predissociation dynamics of water molecules excited to the electronic C and D states.
Two-photon excitation with femtosecond laser pulses in the spectral range 240-250 nm was used to prepare vapor phase H(2)O and D(2)O in the C (1)B(1) and D (1)A(1) states. Both states are predissociated via the B (1)A(1) state, forming excited OH/OD(A (2)Sigma(+)) as well as ground state OH/OD(X (2)Pi). We used ultrashort infrared probe pulses (1.65-2.42 microm) to control the ratio between these excited and ground state fragments originating from the dissociation process. Time resolved detection of the OH/OD(A (2)Sigma(+)) --> OH/OD(X (2)Pi) fluorescence allows us to monitor the dynamics of the predissociation. For the heterogeneous predissociation out of the C(1)B(1) state life times of (0.5 +/- 0.1) ps and (1.2 +/- 0.1) ps were found for H(2)O and D(2)O, respectively. The purely homogeneous character of the predissociation out of the D (1)A(1) state was monitored.


Comparative usefulness of MEDLINE searches performed by a drug information pharmacist and by medical librarians.
The usefulness of MEDLINE searches conducted by a drug information pharmacist who had received online training was compared with the usefulness of searches conducted by medical librarians. Searches for literature pertinent to select drug information requests received at a university drug consultation service during a three-month period were conducted independently by the pharmacist and one of three reference librarians. The three librarians had received extensive online search training and were experienced in conducting MEDLINE searches; the pharmacist was trained by a fourth experienced librarian-searcher using National Library of Medicine (NLM) training materials. For each drug information request, the pharmacist and the librarian searched two MEDLINE files on the NLM service. The printouts generated by the two searchers were evaluated by two drug information pharmacists in terms of how useful each list of citations would be in enabling the drug information pharmacists to answer the related question. The majority of printouts in 48 sets of searches were judged to be useful. Of the 96 possible "best search" votes (two votes for each of the 48 sets of printouts), the pharmacist's searches received 34 votes, the librarians' searches received 28 votes, and there were 34 tie votes. The numbers of useful primary and alternate citations were found to be the best predictors of whether a given printout would receive the "best search" rating. MEDLINE searches performed by a drug information pharmacist with online training, in response to drug information requests, were judged by drug information pharmacists to be as useful as searches performed by librarians.


Thermal Losses of Tertiary Butylhydroquinone (TBHQ) and Its Effect on the Qualities of Palm Oil.
The rules and patterns of thermal losses of tertiary butylhydroquinone (TBHQ) in palm oil (PO) and its effect on the qualities of PO were investigated by oven heating method. Volatilization and transformation products of TBHQ in PO were also studied in detail under heating treatment. Results showed that at low temperature (< 135°C), TBHQ had better antioxidative properties, while its antioxidative potency to PO was significantly weakened at high temperature (≥ 135°C). In addition, as heating temperatures increased and heating time prolonged, losses of TBHQ significantly increased in PO. Volatilization was the major pathway for losses of TBHQ in PO under heating treatment. Meanwhile, a small portion of TBHQ was transformed and the major transformation product was 2-tertbutyl-1,4- benzoquinone (TQ). Moreover, TQ and several decomposition products of PO were also observed in the volatilization products of TBHQ.


Integration of proliferation and differentiation phenomena during rodent kidney ontogeny.
In order to integrate proliferation and differentiation patterns during kidney development, precise ontogenic profiles of several morphometric and biochemical parameters were determined in the mouse. During early nephron formation (before the age of 15 days postnatal), rates of kidney growth and cell proliferation proceed in an independent fashion. DNA synthesis, as measured by 3H-thymidine incorporation, falls rapidly during early metanephrogenesis and is characterized by 3 transitional phases or plateaus. On the other hand, brush border enzyme activities, namely alkaline phosphatase and gamma-glutamyltransferase, increase progressively during this period, although both ontogenic profiles also reveal 3 distinct transitory phases. The plateaus occur synchronously: all are initiated at 16 days of gestation, at birth and at 6 days postnatally. During the final phase of metanephrogenesis (from 15 days onward), kidney and body weights now increase proportionally. In fact, kidney/body (K/B) weight ratios remain remarkably uniform, as defined by the function: K = 12.1 x B.84. Considered together, these results demonstrate that global metanephric development can be separated into early and final stages. The early stage is characterized by complex organo-genetic processes in which proliferation and differentiation profiles seem to be reciprocally related. The late phase, on the other hand, is associated with the interruption of nephronic induction and a constant relationship between organ weight and body weight. Establishing precise developmental profiles of nephronic proliferation and differentiation should provide for a better understanding of metanephrogenesis regulation.


Sulfhydryl groups in relation to the metabolism and motility of human spermatozoa.
1. The motility and metabolism of human spermatozoa are inhibited by substances which have an affinity for sulfhydryl groups. 2. These inhibitions can be prevented, and in part, reversed, by the addition to the cell + inhibitor system of sulfhydryl compounds such as cysteine or glutathione. 3. Cysteine and glutathione, under aerobic conditions or in a system in which these substances can be oxidized, show widely different effects on the motility of the spermatozoa. Cysteine destroys the motility of the spermatozoa, whereas glutathione has no effect upon it. 4. Possible mechanisms of these effects are discussed.


Unchanged survival rates of Shadoo knockout mice after infection with mouse-adapted scrapie.
Previous studies have demonstrated that Shadoo (Sho), a GPI-linked glycoprotein encoded by the Sprn gene with a membrane localization similar to PrP(C), is reduced in the brains of rodents with terminal prion disease. To determine the functional significance of Sho in prion disease pathogenesis, Sho-deficient mice were generated by gene targeting. Sho knockout and control wild-type (WT) mice were infected with themouse-adapted scrapie strains 22L or RML. No significant differences in survival, the incubation period of prion disease or other disease features were observed between Sho mutant and WT mice. In this model of prion disease, Sho removal had no effect on disease pathogenesis.


Phosphodiesterase type 5 inhibitors and risk of melanoma: A meta-analysis.
The association between phosphodiesterase type 5 (PDE5) inhibitors and melanoma risk is controversial. We quantify the association between use of PDE5 inhibitors and melanoma. We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for studies that were conducted up to July 13, 2016, and evaluated the association between PDE5 inhibitors and skin cancer. Random effects meta-analyses were used to calculate the adjusted odds ratio (OR) with the 95% confidence interval (CI). Five observational studies were included. Compared with PDE5 inhibitor nonuse, PDE5 inhibitor use was slightly but significantly associated with an increased risk for development of melanoma (OR, 1.12; 95% CI, 1.03-1.21) and basal cell carcinoma (OR, 1.14; 95% CI, 1.09-1.19) but not squamous cell carcinoma. For melanoma risk, none of the prespecified factors (dose of PDE5 inhibitor, study design, and study region) significantly affected the results (P > .05). Our sensitivity analysis confirmed the stability of the results. We included only observational studies, which had some heterogeneities and inconsistent controlling for potential confounders. Use of PDE5 inhibitors may be associated with a slightly increased risk for development of melanoma and basal cell carcinoma but not squamous cell carcinoma. However, further large well-conducted prospective studies with adequate adjustment for potential confounders are required for confirmation.


Influence of long-term airflow deprivation on the dimensions of the nasal cavity: a study of laryngectomy patients using acoustic rhinometry.
We conducted a prospective study to investigate the long-term effect of nasal airflow deprivation on nasal dimensions after total laryngectomy. We evaluated 48 patients who had an initial diagnosis of laryngeal cancer; 6 were disqualified during follow-up, leaving us with data on 42 patients for our final analysis. Acoustic rhinometry was used to measure the minimum cross-sectional area (MCSA) and the volume of the nasal cavity on both the left and right sides before and after laryngectomy. In addition, patients underwent endoscopic nasal examinations and answered questionnaires pre- and postoperatively. At both the 1- and 2-year follow-ups, the mean MCSAs and the mean nasal volumes of both the left and right nostrils were significantly smaller than the preoperative values (p < 0.001). The endoscopic examinations revealed only a mild deterioration in the appearance of the nasal mucosa over the long term. Questionnaire responses obtained at the 2-year follow-up visit revealed that all 42 evaluable patients were experiencing a moderate degree of nasal obstruction while inhaling through the nose. Our data indicate that the dimensions of the nasal cavity appear to be substantially and permanently reduced after total laryngectomy. Our study had two important advantages over other similar studies. First, because ours was a prospective study, we were able to obtain preoperative data and use it to make postoperative comparisons of the same patients rather than using healthy controls as comparators. Second, we used acoustic rhinometry, while most other studies relied on anterior rhinoscopy or rhinomanometry, which are inferior methods ofmaking the evaluations in question. We believe that our findings represent a substantial contribution to our knowledge of the physiologic and functional alterations of the nasal cavity that occur as a result of a complete cessation of nasal airflow.