Comparative efficacy and safety of antihyperglycemic drug classes for patients with type 2 diabetes following failure with metformin monotherapy: A systematic review and network meta-analysis of randomized controlled trials.
To compare the efficacy and safety of antihyperglycemic agents, taken in combination with metformin, for the treatment of type 2 diabetes mellitus (T2DM). A previous 2016 comprehensive search of Ovid MEDLINE, PubMed, and Cochrane CENTRAL was updated to October 2018, and a systematic review and network meta-analysis (NMA) was conducted. Randomized controlled trials (RCTs) of patients with T2DM taking an antihyperglycemic agent in combination with metformin were included. Bayesian NMA was performed to assess the relative efficacy and safety of the antihyperglycemic classes. In total, 204 RCTs were included, which assessed the efficacy and safety of eight antihyperglycemic drug classes (i.e., sulfonylureas, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, basal and biphasic insulin, dipeptidyl peptidase 4 inhibitors, glucagon-like-peptide-1 receptor agonists and sodium-glucose cotransport-2 inhibitors). All drug classes significantly reduced haemoglobin A1c (HbA1c) compared to metformin monotherapy (mean reduction from 0.50 to 0.92). The drug classes varied in their relative effects on hypoglycemia, body weight, body mass index, systolic and diastolic blood pressure, total cholesterol, high and low density lipoprotein cholesterol, and the classes had differing safety profiles on total adverse events, urogenital adverse events, heart failure, serious adverse events, and withdraw due to adverse events. All eight antihyperglycemic drug classes, taken in combination with metformin, reduced HbA1c levels; however, the effects of the agents on other outcomes varied among the classes.


Proteosome-hydrophobic 'foot' malaria peptide vaccines for Plasmodium falciparum and P. vivax.
The immunogenicity of synthetic peptides representing the repeating portions of circumsporozoite proteins of Plasmodium sporozoites was greatly increased by complexing them to proteosomes via hydrophobic moieties added to their amino termini. Proteosomes have been used safely in people in the development of meningococcal vaccines and therefore proteosome-peptide vaccines are prime candidates for use against malaria.


Alanyl-glutamine preserves hepatic glutathione stores after 5-FU treatment.
Glutathione (GSH) is a major antioxidant that protects tissues from free radical injury. 5-fluorouracil (5-FU) considered the most active antineoplastic agent in the treatment of advanced gastrointestinal malignancies, causes hepatic GSH depletion. Glutamine (GLN) augments host defenses and may be important in GSH synthesis. We hypothesized that alanyl-glutamine (ALA-GLN) may protect liver cells from oxidant injury, like GLN, by increasing hepatic GSH stores. Two rat groups received standard parenteral nutrition (STD) supplemented with or without ALA-GLN for 7 days. After the antineoplastic agent 5-FU was injected, the concentration measurements were significantly different in ALA-GLN group compared with STD animals for serum GLN (687.3 +/- 49.8 vs. 504.9 +/- 38.6 uMol/L, P < 0.05), serum GSH (14.37 +/- 5.16 vs. 7.08 +/- 3.16 uMol/L, P < 0.01) and in liver GSH content (6.86 +/-2.46 vs. 4.38 +/-1.63 uMol/g liver tissue, P < 0.05). Rats in ALA-GLN group had lower elevations in hepatic enzymes induced by 5-FU. The experiment demonstrated that the supplemented nutrition ALA-GLN, like glutamine, protected the liver function and improved survival during 5-FU treatment by increasing GSH biosynthesis and by preserving the GSH stores of hepatic tissue.


Effects of microplastics alone or with sorbed oil compounds from the water accommodated fraction of a North Sea crude oil on marine mussels (Mytilus galloprovincialis).
Microplastics (MPs) can adsorb persistent organic pollutants such as oil hydrocarbons and may facilitate their transfer to organisms (Trojan horse effect). The aim of this study was to examine the effects of a 21 day dietary exposure to polystyrene MPs of 4.5 μm at 1000 particles/mL, alone and with sorbed oil compounds from the water accommodated fraction (WAF) of a naphthenic North Sea crude oil at two dilutions (25 % and 100 %), on marine mussels. An additional group of mussels was exposed to 25 % WAF for comparison. PAHs were accumulated in mussels exposed to WAF but not in those exposed to MPs with sorbed oil compounds from WAF (MPs-WAF), partly due to the low concentration of PAHs in the studied crude oil. Exposure to MPs or to WAF alone altered the activity of enzymes involved in aerobic (isocitrate dehydrogenase) and biotransformation metabolism (glutathione S-transferase). Prevalence of oocyte atresia and volume density of basophilic cells were higher and absorption efficiency lower in mussels exposed to MPs and to WAF than in controls. After 21 days MPs caused DNA damage (Comet assay) in mussel hemocytes. In conclusion, a Trojan horse effect was not observed but both MPs and oil WAF caused an array of deleterious effects on marine mussels at different levels of biological organization.


Hydrolysis of microcrystalline cellulose using functionalized Bronsted acidic ionic liquids - A comparative study.
Cellulose conversion to platform chemicals is required to meet the demands of increasing population and modernization of the world. Hydrolysis of microcrystalline cellulose was studied with SO3H, COOH and OH functionalized imidazole based ionic liquid using 1-butyl-3-methylimidazolium chloride [BMIM]Cl as a solvent. The influence of temperature, time, acidity of ionic liquids and catalyst loading was studied on hydrolysis reaction. The maximum %TRS yield 85%, was obtained at 100°C and 90min with 0.2g of SO3H functionalized ionic liquid. UV-vis spectroscopy using 4-nitro aniline as an indicator was performed to find out the Hammett function of ionic liquid and acidity trends are as follows: SO3H>COOH>OH. Density functional theory (DFT) calculations were performed to optimize the ionic liquid and their conjugate bases at B3LYP 6-311G++ (d, p) level using Gaussian 09 program. Theoretical findings are in agreement with the experimental results.


Additional Plasmodium species from Anolis lizards of Hispaniola and Panama.
Saurian malaria parasites in the Caribbean were previously represented by only two species, Plasmodium azurophilum and P. floridense. An additional three species of Plasmodium occur on Hispaniola which appear, because of morphometric and qualitative similarities, to be related to South and Middle American species: a subspecies of Plasmodium tropiduri in Anolis cybotes; a population of Plasmodium minasense anolisi in A. cybotes and A. distichus; and another parasite in A. distichus which is designated as a subspecies of a previously undescribed Plasmodium species in Anolis limifrons. Taxonomic descriptions based upon morphology of mature schizonts and gametocytes are given, the previously unknown parasites are described as new species/subspecies, and comparison is made with P. floridense which also occurs in their respective host species. A Fallisia species was also present but is not described. The increased diversity of Plasmodium parasites in Hispaniolan anoles is attributed to colonization of the island by four separate evolutionary lines of Anolis lizards, in comparison to fewer invasions of Jamaica and Puerto Rico, where only P. floridense and P. azurophilum are found.


Diagnostic criteria currently proposed for "ictal epileptic headache": Perspectives on strengths, weaknesses and pitfalls.
When we published the diagnostic criteria for "ictal epileptic headache" in 2012, we deliberately and consciously chose to adopt restrictive criteria that probably underestimate the phenomenon, rather than spread panic among patients and physicians who are reluctant to accept this entity. Here we discuss four intriguing clinical cases to highlight why we believe, to this day, that it is necessary to follow these restrictive diagnostic criteria. EEG is not recommended as a routine examination for children diagnosed with headache, but it is mandatory and must be carried out promptly in cases of prolonged headache that does not respond to antimigraine drugs, if epilepsy is suspected or has been diagnosed previously. This is not a marginal or irrelevant question because possible isolated, non-motor, ictal manifestations should be taken into account before declaring that an epileptic patient is "seizure free" so as to ensure that any decision taken to suspend anticonvulsant therapy is safe.


Custom Pediatric Oncology Next-Generation Sequencing Panel Identifies Somatic Mosaicism in Archival Tissue and Enhances Targeted Clinical Care.
Disorders in the PIK3CA-related overgrowth spectrum because of somatic mosaicism are associated with segmental overgrowth of the body in conjunction with vascular, skeletal, and brain malformations such as hemimegalencephaly. A pathogenic variant may only be detectable in affected tissue and not in peripheral blood or saliva samples; therefore archival tissue may be the only relevant available specimen for testing. Although this is a common approach for cancer testing, it is not typically used for constitutional genetic disorders. PIK3CA mosaicism was assessed with a custom pediatric oncology next-generation sequencing panel (OncoKids) designed to capture somatic mutations in pediatric malignancies. The panel covers a wide range of targets including PIK3CA and AKT1 hotspots. We used OncoKids on archival formalin-fixed, paraffin-embedded or frozen samples from seven patients with facial hemihypertrophy and lipomas, hemimegalencephaly, or hemihypertrophy with a lymphovascular malformation. The age of the archival tissue examined by next-generation sequencing ranged from two to 13 years (median 5 years). Every patient had clinical manifestations within the PIK3CA-related overgrowth spectrum and had a sample of an affected tissue available for testing from a prior surgical intervention. PIK3CA mosaicism was detected in all seven patients and the mutant allele fraction was lower in the lymphovascular malformation tissues (8% to 11%) than in brain (20% to 32%) and lipomatous (16% to 23%) tissues. Our study highlights the clinical utility of using a robust, oncology-focused next-generation sequencing assay to identify PIK3CA mosaicism in noncancer cases. It is feasible to use archival samples that are more than a decade old to obtain a molecular diagnosis, which can then be used to improve health care management.


Safety assessment of organic micropollutants in reclaimed water: Chemical analyses, ecological risk assessments, and in vivo endocrine-disrupting studies.
Reclaimed water from municipal wastewater has great potential in mitigating the water resource crisis, while the inevitable residue of organic micropollutants (OMPs) challenges the safety of reclaimed water reuse. Limited information was available regarding the overall adverse effects of mixed OMPs in reclaimed water, especially the endocrine-disrupting effects on living organisms. Herein, chemical monitoring in two municipal wastewater treatment plants showed that 31 of 32 candidate OMPs including polycyclic aromatic hydrocarbons (PAHs), phenols, pharmaceuticals and personal care products (PPCPs) were detected in reclaimed water, with a concentration ranging from ng/L to μg/L. Then, based on the risk quotient value, phenol, bisphenol A, tetracycline, and carbamazepine were ranked as high ecological risks. Most PAHs and PPCPs were quantified as medium and low risks, respectively. More importantly, using aquatic vertebrate zebrafish as an in vivo model, the endocrine-disrupting potentials of OMP mixtures were comprehensively characterized. We found that a realistic exposure to reclaimed water induced estrogen-like endocrine disruption and hyperthyroidism in zebrafish, abnormal expression of genes along the hypothalamus-pituitary-thyroid (-gonad) axes, reproductive impairment, and transgenerational toxicity. Based on the chemical analyses, risk quotient calculations, and biotoxicity characterization, this study contributed to understanding the ecological risks of reclaimed water and developing the control standards for OMPs. In addition, application of the zebrafish model in this study also highlighted the significance of in vivo biotoxicity test in water quality evaluation.


Primary intraosseous carcinoma arising in dentigerous cyst: Case report.
Carcinomas arising in odontogenic cysts are uncommon. Malignant transformation of a dentigerous cyst is a rare observation. A primary intraosseous carcinoma from a dentigerous cyst in a 69 years old female is presented in this case report. The patient initially consulted for pain in the mandibular left molar region. Primary investigations firstly showed a probably benign lesion but immunochemistry analysis finally revealed a squamous cell carcinoma arising in a dentigerous cyst. An extension assessment was performed and no evidence of lymph node extension or distant metastasis were found. A non-interrupting mandibular bone resection without neck dissection was realized. The patient made a good recovery after surgery without postoperative complication. No clinical symptoms or sign of local recurrence or metastasis was detected after 17 months follow-up. PIOC arising in a dentigerous cyst is a rare observation. PIOC from odontogenic cysts have an incident rate of 0,3 to 2% and only 16%-51% of them are PIOC from dentigerous cyst. There are no clinical or radiological pathognomonic characteristics. They often look like benign lesion and the diagnosis is often made fortuitously. A surgical excision with clear margin is the cornerstone of treatment. Clinical and radiological follow-up of the patient is recommended. This case underlines the importance of a systematic and careful microscopic analysis of any lesion, even benign at first sight. Surgeons and pathologists should be aware of the malignant potential of odontogenic cysts. This can modify the surgical management and the follow-up of the patient.


CSF 5HIAA and personal and family history of suicide in affectively ill patients: a negative study.
Personal and family histories of suicidality were gathered in 45 patients who met Research Diagnostic Criteria for major affective disorder (n = 32, bipolar; n = 13, unipolar) and compared to CSF values of 5HIAA obtained by two different assays (n = 20, fluorometric; n = 25, high performance liquid chromatography). In separate analyses of the two assay groups, patients who had made a suicide attempt were not significantly different from those who had not in terms of 5HIAA value or family history of suicidality. Furthermore, in suicide attempters, 5HIAA was unrelated to the severity of the attempt.


Present and future outlooks on environmental DNA-based methods for antibiotic discovery.
Novel antibiotics are in constant demand to combat a global increase in antibiotic-resistant infections. Bacterial natural products have been a long-standing source of antibiotic compounds, and metagenomic mining of environmental DNA (eDNA) has increasingly provided new antibiotic leads. The metagenomic small-molecule discovery pipeline can be divided into three main steps: surveying eDNA, retrieving a sequence of interest, and accessing the encoded natural product. Improvements in sequencing technology, bioinformatic algorithms, and methods for converting biosynthetic gene clusters into small molecules are steadily increasing our ability to discover metagenomically encoded antibiotics. We predict that, over the next decade, ongoing technological improvements will dramatically increase the rate at which antibiotics are discovered from metagenomes.


Background species effect on aqueous arsenic removal by nano zero-valent iron using fractional factorial design.
This study describes the removal of arsenic species in groundwater by nano zero-valent iron process, including As(III) and As(V). Since the background species may inhibit or promote arsenic removal. The influence of several common ions such as phosphate (PO4(3-)), bicarbonate (HCO3-)), sulfate (SO4(2-)), calcium (Ca2+), chloride (Cl-), and humic acid (HA) were selected to evaluate their effects on arsenic removal. In particular, a 2(6-2) fractional factorial design (FFD) was employed to identify major or interacting factors, which affect arsenic removal in a significant way. As a result of FFD evaluation, PO4(3-) and HA play the role of inhibiting arsenic removal, while Ca2+ was observed to play the promoting one. As for HCO3- and Cl-, the former one inhibits As(III) removal, whereas the later one enhances its removal; on the other hand, As(V) removal was affected only slightly in the presence of HCO3- or Cl-. Hence, it was suggested that the arsenic removal by the nanoiron process can be improved through pretreatment of PO4(3-) and HA. In addition, for the groundwater with high hardness, the nanoiron process can be an advantageous option because of enhancing characteristics of Ca2+.


Ultrasound-Guided vs. Landmark Method for Subclavian Vein Catheterization in an Academic Emergency Department.
Ultrasound guidance has been shown to decrease complication rates and improve success for internal jugular and femoral vein catheterization in the emergency department (ED). However, the current data on the efficacy and safety of ultrasound-guided subclavian vein catheterization has failed to provide support for similar conclusions. To determine if ultrasound-guided subclavian vein catheterization is safer and more efficacious than the traditional landmark method in an ED setting. A prospective randomized trial was conducted from April 2004 through June 2009 in an urban tertiary care academic ED with an annual census of >50,000 patients. Four primary data endpoints were calculated: 1) overall success for both resident and attending physicians; 2) number of attempts by each group of providers; 3) complication rate with each method; and 4) time to which the subclavian line was obtained. Eighty-five patients were enrolled in the study. The ultrasound method was more successful in obtaining subclavian catheter placement when compared with the landmark method. When comparing successful cannulation attempts in both groups, the ultrasound group showed a statistically significant longer time to success when compared with the landmark group. There was no difference in the success or complication rates between residents and attending physicians. There was no significant difference in complications rates between ultrasound-guided and landmark methods. Ultrasound-guided subclavian vein catheterization was found to be associated with a higher overall success rate compared with the landmark method with no significant difference with respect to complication rate in an ED setting. © 2022 Elsevier Inc.


Anodic stripping voltammetry at in situ bismuth-plated carbon and gold microdisc electrodes in variable electrolyte content unstirred solutions.
Carbon and gold microdisc electrodes (30 and 10 microm, respectively) have been tested as substrates for in situ bismuth film plating from unstirred solutions of variable acetate buffer content and were subsequently used in the anodic stripping voltammetry determination of Pb(II) and Cd(II) ions. The effects of Bi(III) concentration, analyte accumulation time, stirring as well as supporting electrolyte content have been studied. Under optimal conditions good voltammetric responses were obtained by means of square wave anodic stripping voltammetry in unstirred analyte solutions of 5 x 10(-8) to 10(-6)M, even in the absence of added buffer. In an indicative application, Pb(II) ion levels were determined in tap water using bismuth-plated carbon microdisc electrodes.


Medicaid Expansion Under the Affordable Care Act and Association With Cardiac Care: A Systematic Review.
The goal of the Affordable Care Act was to improve health outcomes through expanding insurance, including through Medicaid expansion. We systematically reviewed the available literature on the association of Affordable Care Act Medicaid expansion with cardiac outcomes. Consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we performed systematic searches in PubMed, the Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature using the keywords such as Medicaid expansion and cardiac, cardiovascular, or heart to identify titles published from 1/2014 to 7/2022 that evaluated the association between Medicaid expansion and cardiac outcomes. A total of 30 studies met inclusion and exclusion criteria. Of these, 14 studies (47%) used a difference-in-difference study design and 10 (33%) used a multiple time series design. The median number of postexpansion years evaluated was 2 (range, 0.5-6) and the median number of expansion states included was 23 (range, 1-33). Commonly assessed outcomes included insurance coverage of and utilization of cardiac treatments (25.0%), morbidity/mortality (19.6%), disparities in care (14.3%), and preventive care (41.1%). Medicaid expansion was generally associated with increased insurance coverage, reduction in overall cardiac morbidity/mortality outside of acute care settings, and some increase in screening for and treatment of cardiac comorbidities. Current literature demonstrates that Medicaid expansion was generally associated with increased insurance coverage of cardiac treatments, improvement in cardiac outcomes outside of acute care settings, and some improvements in cardiac-focused prevention and screening. Conclusions are limited because quasi-experimental comparisons of expansion and nonexpansion states cannot account for unmeasured state-level confounders.


Vascular access for daunorubicin during childhood acute lymphoblastic leukaemia induction treatment: a UKCCSG supportive care group and MRC childhood leukaemia working party survey.
Daunorubicin was reintroduced into induction chemotherapy in UK protocols for intermediate- and high-risk childhood acute lymphoblastic leukaemia in 1999. Concern about the risk of central venous catheter-associated venous thromboembolism led to a recommendation that induction treatment should be given by peripheral venous access wherever possible, whilst recognising anxieties concerning the risk of daunorubicin extravasation. A survey performed to determine how these conflicting concerns influenced practice in the administration of daunorubicin revealed considerable variation. The results highlight that recommendations were not being followed and that local practice and guidance were being utilised in this area of practice. However, there is a need to identify patients at higher risk of venous thromboembolism during induction treatment and better strategies to prevent this complication.


Effect of muscle creatine content manipulation on contractile properties in mouse muscles.
The effects of muscle creatine manipulation on contractile properties in oxidative and glycolytic muscles were evaluated. Whereas control mice (NMRi; n = 12) received normal chow (5 g daily), three experimental groups were created by adding creatine monohydrate (CR group; 5%, 1 week; n = 13); beta-guanidinoproprionic acid, an inhibitor of cellular creatine uptake (beta-GPA group; 1%, 2 weeks; n = 12); or CR following beta-GPA (beta-GPA+CR group; n = 11). Total creatine (TCr) and the contractile properties of incubated soleus and extensor digitorum longus (EDL) muscles were determined. For the soleus, compared with control, TCr increased in the CR group (+25%), decreased in beta-GPA group (-50%), and remained stable in the beta-GPA+CR group, whereas, for the EDL, TCr was similar in the CR, and lower in the beta-GPA (-40%) and beta-GPA+CR (-15%) groups. None of the experimental groups (CR, beta-GPA, or beta-GPA+CR) showed changes in peak tension (P(peak)), time to peak tension, or relaxation in soleus or EDL during twitch or tetanic stimulation. For the soleus, fatigue reduced P(peak) to approximately 60% of initial P(peak); 5 min of recovery restored P(peak) to values approximately 15% higher in CR than in controls. P(peak) recovery was not affected by beta-GPA or beta-GPA+CR in the soleus or any treatment in the EDL. Thus, peak tension recovery is enhanced by creatine intake in oxidative but not glycolytic muscles. This may be implicated in the beneficial action of creatine loading.


Genes for human U3 small nucleolar RNA contain highly conserved flanking sequences.
Six human genomic clones containing sequences homologous to the U3 small nuclear RNA (snRNA) were isolated and characterized. Four of these clones were real U3 snRNA genes because they were transcribed in frog oocytes and the DNA sequences corresponding to the U3 snRNA were identical to the U3 snRNA of HeLa cells. The nucleotide sequences of four true U3 snRNA genes, 537 nucleotides on the 5'-flanking region and 340 nucleotides on the 3'-flanking region, were found to be identical. In addition, the restriction patterns, upto 2 kb on the 5' side and 2.2 kb on the 3' side, appeared to be same. All the isolated U3 clones, containing 15-20 kb of genomic DNA, contained only one U3 snRNA gene, indicating that the human U3 snRNA genes are several kilobases apart. One of the U3 clones contained a full-length U3 pseudogene. Southern blot analysis of genomic DNA with cloned U3 DNA as probe indicated that human DNA contains two families of U3 genes which differ in their flanking sequences. In the 5' flanking region of human U3 snRNA genes, homology to U-gene promoter element, an octamer motif, the 'U3 box', SP1 binding sites and a consensus 3' box in the 3' flanking region, were observed. These data show that the genomic organization and the sequence motifs that control transcription of human nucleolar U3 snRNA genes are similar to those of human U1 and U2 snRNA genes and suggest common mechanism(s) in the evolution of snRNA genes.


Functional analysis of a homologue of the FLORICAULA/LEAFY gene in litchi (Litchi chinensis Sonn.) revealing its significance in early flowering process.
Litchi (Litchi chinensis Sonn.) is an important subtropical fruit crop with high commercial value due to its high nutritional values and favorable tastes. However, irregular bearing attributed to unstable flowering is a major ongoing problem for litchi producers. Previous studies indicate that low-temperature is a key factor in litchi floral induction. In order to reveal the genetic and molecular mechanisms underlying the reproductive process in litchi, we had analyzed the transcriptome of buds before and after low-temperature induction using RNA-seq technology. A key flower bud differentiation associated gene, a homologue of FLORICAULA/LEAFY, was identified and named LcLFY (GenBank Accession No. KF008435). The cDNA sequence of LcLFY encodes a putative protein of 388 amino acids. To gain insight into the role of LcLFY, the temporal expression level of this gene was measured by real-time RT-PCR. LcLFY was highly expressed in flower buds and its expression correlated with the floral developmental stage. Heterologous expression of LcLFY in transgenic tobacco plants induced precocious flowering. Meantime, we investigated the sub-cellular localization of LcLFY. The LcLFY-Green fluorescent protein (GFP) fusion protein was found in the nucleus. The results suggest that LcLFY plays a pivotal role as a transcription factor in controlling the transition to flowering and in the development of floral organs in litchi.


New prenylchalcones from the hops of Humulus lupulus.
Two new prenylchalcones, xanthohumol C and D, together with two known prenylchalcone derivatives, xanthohumol (1) and 5''-(2''-hydroxyisopropyl)-dihydrofurano-[2'',3''-b]-4,4'-dihydroxy-6'-methoxy-chalcone (4) were isolated and identified from the hops of Humulus lupulus L. The structures of xanhohumol C and D were elucidated as 5''-hydroxy-6'',6''-dimethyl-dihydropyrano-[2'',3''-b]-4,4'-dihydroxy-6'-methoxy-chalcone (2) and 5''-hydroxy-6'',6''-dimethyl-dihydropyrano-[2'',3''-b]-4',6'-dimethoxy-4-hydroxy-chalcone (3) on the basis of HRFAB-MS, 1D and 2D NMR (HMQC, HMBC) spectroscopic data. Among the new prenylchalcones, compound 2 showed marginal cytotoxic activity against human stomach carcinoma BGC-823 and human hepatic carcinoma HepG2 cells.


[Postoperative self-training after surgery of the hand (author's transl)].
By means of a training box the patient is enabled to train his hand by himself. The training materials can individually adapted to the programme.


Does psychological characteristic influence physicians' communication styles? Impact of physicians' locus of control on interviews with a cancer patient and a relative.
Physicians' psychological characteristics may influence their communication styles and may thus interfere with patient-centred communication. Our aim was to test the hypothesis that, in interviews with a cancer patient and a relative, physicians with an "external" locus of control (LOC; who believe that life outcomes are controlled by external forces such as luck, fate or others) have a communication style different from that of physicians with an "internal" LOC (who believe that life outcomes are controlled by their own characteristics or actions). Eighty-one voluntary physicians practising in the field of oncology were recorded while performing an actual and a simulated interview with a cancer patient and a relative. Physicians' communication skills were assessed using the Cancer Research Campaign Workshop Evaluation Manual. Physicians' LOC was assessed using the Rotter I-E scale. The communication skills of the upper and lower quartiles of physicians in respect of their scores on this scale were compared using Student's t test. In actual interviews, physicians with an "external" LOC talked more to the relative (P=0.017) and used more utterances with an assessment function (P=0.010) than physicians with an "internal" LOC. In simulated interviews, physicians with an "external" LOC used less utterances that give premature information (P=0.031) and used more utterances with a supportive function, such as empathy and reassurance (P=0.029), than physicians with an "internal" LOC. These results provide evidence that physicians' LOC can influence their communication styles. Physicians' awareness of this influence constitutes a step towards a tailoring of their communication skills to every patient's and relative's concerns and needs and thus towards a patient-centred communication.


Remarkable benefits of intravenous immunoglobulin (IVIG) in a patient with polymyositis-associated acute interstitial lung disease.
Polymyositis (PM) and dermatomyositis (DM) are subtypes of autoimmune inflammatory myopathies. Interstitial lung disease (ILD) involvement is common in PM/DM. There is no evidence base for immunosuppression in DM/PM-ILD and current evidence is based on case stories and expert opinions. We present a 63-year-old male with severe respiratory failure due to PM-ILD who was treated successfully with intravenous immunoglobulin, recovered the acute phase and survived more than 4 years.


Randomized study of stability and change in patients' advance directives.
Little is known about ethnic differences in understanding or using advance directives (ADs). Although health practitioners may presume AD intentions are durable over time, there is no supporting evidence. This randomized study intended to (a) examine differences between hospitalized Hispanic and non-Hispanic patients' AD preferences, (b) assess AD stability, and (c) discover if the Life Support Preferences Questionnaire (LSPQ) influences AD preferences. Hispanics and non-Hispanics showed no difference in AD preferences. However, non-Hispanics were more likely to change AD preferences. The LSPQ itself prompted change in AD preferences, delivering an educational effect with no specific educational intent. Change seen in patients' ADs, even over a brief interval, suggests revisiting AD preferences with patients and their families after hospitalization.


Re-irradiation of mouse skin: similarity of dose reductions for healing and macrocolony endpoints.
The amount of residual injury in mouse tail skin, assessed by the decrease in re-irradiation dose for equal effect, was similar whether assessed using healing or colony endpoints (17-21% after single priming doses). There were tendencies towards an increased sensitivity of the colony-forming cells by a factor of about 2, and less residual injury after multifractionated priming doses. These observations are compatible with a lower alpha/beta ratio characterising the response to dose fractionation for residual injury than for the acute healing response.


Challenges of Raman spectra to estimate carbonyl index of microplastics: A case study with environmental samples from sea surface.
This study investigates the feasibility of using the carbonyl index (CI) derived from Raman spectra as an indicator of plastic degradation and its relationship with the CI calculated from Fourier transform infrared (FTIR) spectra, using microplastic samples of polyethylene (PE) from surface seawater. Multiple methods were used to calculate the CI values of FTIR spectra, while proposed methods were used to calculate the corresponding CI values of Raman spectra. Some significant relations between FTIR CI and Raman CI were observed. However, small R2 values suggest weak functional relationships, which can be attributed to the low signal-to-noise ratio (SNR) of Raman spectra. These results highlight the challenges of establishing a functional relationship between FTIR CI and Raman CI, including challenges such as the uniformity of Raman spectra, determining optimal Raman measurement parameters, selecting appropriate peaks for Raman CI calculation, deciding on spectral processing methods, and addressing the interdependence of these issues.


Designing of graphene oxide-induced p-NiO/n-MoO3 heterostructures for improved photocatalytic activity through plasmon-enhanced S-scheme mechanism and its biological and electrochemical performance.
An environmentally benign, economically advantageous microwave hydrothermal approach is used in synthesis of desirably tailored graphene oxide-induced p-NiO/n-MoO3 (GNM) heterostructures. Various analytical techniques such XPS, XRD, UPS, EIS, and Mott-Schottky were conducted to comprehend complete morphology and functioning of the novel ternary heterostructure photocatalysts. Also, SEM and HR-TEM images were presented for better interpretation. The strategic plasmonic step scheme (S-scheme) charge migration approach was used to describe the effective charge recombination process. Hydroxyl and oxide active species were corollaries of the reactive radical-scavenging experiments and electron spin resonance. The work function has been confirmed using ultraviolet photoelectron spectroscopy (UPS), which assessed an electron transfer between NiO and MoO3, yielding work function values of 6.32 eV and 5.26 eV, respectively. The cell apoptosis of the HeLa cell line approves the material's biocompatibility. Cyclic voltammetry and electrochemical impedance spectroscopy reveal electrochemical performance of GNM heterostructures. We anticipate our results would pave the way for current and future applications. In order to ensure eco-restoration such photocatalyst which are eco and cost friendly are synthesized. Assessment of pollutant risks presents the impact of them on human and terrestrial and aquatic animals. Sustainability of material is acknowledge as they use solar light for photocatalysis and dye degradation, and hence can be green material. One such material for the treatment of wastewater, dye-infused waters, and industrial water has been tailored, which is capable of dye degradation, heavy metal, and other pollutant removal. Very importantly, the synthesized material is a biocompatible one.


Cytochemical and molecular biological aspects of the pituitary and pituitary adenomas--cell differentiation and transcription factors.
The anterior pituitary is composed of several cell types, each responsible for the production of specific hormones. Each hormone secreting cells is defined by the activation of its respective hormone genes in a temporally and spatially regulated manner. Recent development in cytochemistry and molecular biology have provided various aspects of human pituitary adenomas, i.e., functional differentiation and classification. The molecular factors that determine hormone production have now been identified as transcription factors. Many novel transcription factors that play a role in anterior pituitary development are implicated. In this review, we focus on the transcriptional factors roles on functional differentiation of the pituitary cells and adenomas and the contribution of cytochemistry and recent development in molecular biological techniques.


[IV: Small group workshop for developing future measures and projects. Evidence-based therapy in rheumatology with special reference to applications of new drugs--formulation of possible goals and possibilities for meeting them. Osteoporosis in rheumatic diseases].
Secondary osteoporosis is a common, late complication of inflammatory rheumatic diseases. Despite its great socio-economic implications for the individual, there is still a lack of appreciation of this problem. This may result in an inadequate or insufficient prophylaxis and therapy. The participants of this discussion group, therefore, approve of further investigations in this field to gather new relevant data, e.g., for our core documentation on rheumatic diseases. Of special importance is the registration of long-term patients obtaining documented, individual long-term therapy (e.g., cortisone). As well as epidemiologic and clinical research projects, it is imperative to do basic research into the pathogenesis of secondary osteoporosis and find new therapeutic approaches for curing rheumatic disease.


Recurrent hearing loss after myelography treated with epidural blood patch.
Transient hearing impairment is a known sequel after various procedures that result in loss of cerebrospinal fluid, such as lumbar puncture, spinal anesthesia and myelography. But persistent or recurrent hearing loss after dural puncture is a rare entity. We present a case with recurrent low-frequency sensorineural hearing loss after myelography. The patient was treated successfully by means of an epidural blood patch, although the conservative treatment was ineffective.


Identification of a drought tolerant introgression line derived from Dongxiang common wild rice (O. rufipogon Griff.).
Construction of introgression lines using cultivated rice as recipient and wild rice is a novel approach to explore primitive and broad genetic resources in rice breeding. We recently generated a set of 159 introgression lines via a backcrossing program using an elite Indica cultivar rice Guichao 2 (O. sativa L. ssp. indica) as recipient and a common wild rice Dongxiang accession (O. rufipogon Griff.) as donor. In this study, we have evaluated the previously constructed 159 introgression lines for drought-tolerance. A total of 12 quantitative trait loci (QTLs) related to drought tolerance were mapped. Furthermore, a drought tolerant introgression line, IL23, was identified and characterized. Genotype analysis of IL23 demonstrated that IL23 contained two QTLs associated with drought tolerance, qSDT2-1 and qSDT12-2, which were located on chromosome 2 and 12 within the two introgressed segments derived from the common wild rice, respectively. Physiological characterization, including measurement of water loss, osmotic potential, electrolytical leakage, MDA content, soluble sugars content and the leaf temperature, revealed that IL23 showed the characteristics associated with drought tolerance. Identification and characterization of IL23 would provide a useful basis for isolation of novel genes associated with drought tolerance and for molecular breeding of drought tolerant rice. Furthermore, the results in this study indicated that construction of introgression lines from common wild rice should be an appropriate approach to obtain favorable genetic materials.


Graphene Oxide Foam Supported Titanium(IV): Recoverable Heterogeneous Catalyst for Efficient, Selective Oxidation of Arylalkyl Sulfides to Sulfoxides Under Mild Conditions.
An efficient and environmentally friendly method was designed for the oxidation of sulfides to sulfoxides with a recyclable, carbon-skeleton-based heterogeneous catalyst developed by titanium sulfate [Ti(SO4)2] mineralization on the surface of graphene oxide foam [Ti(SO4)2@GOF] by using 30 wt% H2O2 as oxidant. Several different substituted sulfides were examined to explore the scope of substrates of the selective oxidation. The excellent reusability and durability of Ti(SO4)2@GOF was demonstrated by recycling experiments and the catalyst was further applied in the preparation of pantoprazole sodium in a one-pot process.


Immunohistochemical analysis of the distribution of cathepsin D throughout human nervous system with reference to developmental aspects.
The aspartic endopeptidase cathepsin D was demonstrated in post mortem human brain by means of the peroxidase-antiperoxidase technique. The enzyme protein was found to be present in multiple neurons as well as in some glial cells. In embryonic nervous tissue cathepsin D was detected as early as at the 12th gestational week. During neuroontogenesis there was a continuous increase in cathepsin D immunoreactivity.


Penetration of foliar-applied Zn and its impact on apple plant nutrition status: in vivo evaluation by synchrotron-based X-ray fluorescence microscopy.
The absorption of foliar fertilizer is a complex process and is poorly understood. The ability to visualize and quantify the pathway that elements take following their application to leaf surfaces is critical for understanding the science and for practical applications of foliar fertilizers. By the use of synchrotron-based X-ray fluorescence to analyze the in vivo localization of elements, our study aimed to investigate the penetration of foliar-applied Zn absorbed by apple (Malus domestica Borkh.) leaves with different physiological surface properties, as well as the possible interactions between foliar Zn level and the mineral nutrient status of treated leaves. The results indicate that the absorption of foliar-applied Zn was largely dependent on plant leaf surface characteristics. High-resolution elemental maps revealed that the high binding capacity of the cell wall for Zn contributed to the observed limitation of Zn penetration across epidermal cells. Trichome density and stomatal aperture had opposite effects on Zn fertilizer penetration: a relatively high density of trichomes increased the hydrophobicity of leaves, whereas the presence of stomata facilitated foliar Zn penetration. Low levels of Zn promoted the accumulation of other mineral elements in treated leaves, and the complexation of Zn with phytic acid potentially occurred owing to exposure to high-Zn conditions. The present study provides direct visual evidence for the Zn penetration process across the leaf surface, which is important for the development of strategies for Zn biofortification in crop species.


Air quality prediction model based on mRMR-RF feature selection and ISSA-LSTM.
Severe air pollution poses a significant threat to public safety and human health. Predicting future air quality conditions is crucial for implementing pollution control measures and guiding residents' activity choices. However, traditional single-module machine learning models suffer from long training times and low prediction accuracy. To improve the accuracy of air quality forecasting, this paper proposes a ISSA-LSTM model-based approach for predicting the air quality index (AQI). The model consists of three main components: random forest (RF) and mRMR, improved sparrow search algorithm (ISSA), and long short-term memory network (LSTM). Firstly, RF-mRMR is used to select the influential variables affecting AQI, thereby enhancing the model's performance. Next, ISSA algorithm is employed to optimize the hyperparameters of LSTM, further improving the model's performance. Finally, LSTM model is utilized to predict AQI concentrations. Through comparative experiments, it is demonstrated that the ISSA-LSTM model outperforms other models in terms of RMSE and R2, exhibiting higher prediction accuracy. The model's predictive performance is validated across different time steps, demonstrating minimal prediction errors. Therefore, the ISSA-LSTM model is a viable and effective approach for accurately predicting AQI.


Manual delineation approaches for direct imaging of the subcortex.
The growing interest in the human subcortex is accompanied by an increasing number of parcellation procedures to identify deep brain structures in magnetic resonance imaging (MRI) contrasts. Manual procedures continue to form the gold standard for parcellating brain structures and is used for the validation of automated approaches. Performing manual parcellations is a tedious process which requires a systematic and reproducible approach. For this purpose, we created a series of protocols for the anatomical delineation of 21 individual subcortical structures. The intelligibility of the protocols was assessed by calculating Dice similarity coefficients for ten healthy volunteers. In addition, dilated Dice coefficients showed that manual parcellations created using these protocols can provide high-quality training data for automated algorithms. Here, we share the protocols, together with three example MRI datasets and the created manual delineations. The protocols can be applied to create high-quality training data for automated parcellation procedures, as well as for further validation of existing procedures and are shared without restrictions with the research community.


Diversity, host, and habitat specificity of oomycete communities in declining reed stands (Phragmites australis) of a large freshwater lake.
We studied the diversity of oomycetes in a declining reed belt (Phragmites australis) of Lake Constance, Germany, using conventional baiting with specific reed and standard oak baits, accompanied by molecular techniques. Apart from an Aphanomyces sp. and a Phytophthora sp., baiting from reed rhizosphere samples from flooded, as well as drier, littoral sites revealed only Pythium spp. A total of 67 oomycete isolates was classified according to PCR-RFLP banding patterns and ITS sequencing, and 18 different sequence types could be separated. The majority of these seemed previously unknown species, as indicated by the degree of similarity to those deposited in nucleotide databases. Species communities in both flooded and drier habitats or both reed and oak baits clearly differed from one another, and only few species occurred in both dry and flooded sites, or in both oak and reed baits. A frequently occurring group of related Pythium species appeared to be specifically associated with reed, and these were the only species that proved pathogenic towards this host in vitro. Our study proved that unexplored natural ecosystems harbour diverse communities of oomycete species with specific habitat and host preferences within close-by, but ecologically contrasting, sites. Among the species isolated, those associated with the predominating plant might accumulate and thus may be reed pathogens of considerable importance.


Sarcocystis cernae: A parasite increasing the risk of predation of its intermediate host, Microtus arvalis.
1)The transmission dynamics of the protozoan parasite Sarcocystis carnae (Černá and Loučková 1976) (Apicomplexa, Eimeroidea, Sarcocystidae) in natural populations were studied in the Lauwersmeerpolder in the northern Netherlands. This parasite needs two hosts to complete its life cycle; the common vole (Microtus arvalis) as its intermediate host and the kestrel (Falco tinnunculus) which preys on the vole, as its final host. 2) Seasonal variation in prevalence of infection in snap-trapped common voles was determined in two years, 1984 and 1985. It was found to be lowest in November (6% of the voles infected) and it increased gradually to a peak in May (33%). 3) Data collected in three successive kestrel breeding seasons (1983-85) revealed that voles in the kestrel summer diet are infected twice as frequently as those in snap-trap samples, 21% and 9% respectively. This difference (P<0.05, X2-test) suggests that the parasite influences its intermediate host behaviour in such a way that it enhances the probability of parasite transmission to the final host.


Effect of selective cyclooxygenase-2 inhibitor meloxicam on liver fibrosis in rats with ligated common bile ducts.
Cholestasis triggers fibrogenesis in the liver. Hepatic cyclooxygenase-2 (COX-2) expression increases in various chronic liver diseases caused either by viruses or toxins. We hypothesized that selective COX-2 inhibitor meloxicam could suppress inflammation and fibrogenesis in a rat model of cholestasis induced by bile duct ligation (BDL). Forty-three Sprague-Dawley rats were assigned to one of four treatment groups (sham-operation, BDL, daily meloxicam injections following BDL, and daily meloxicam injection without BDL). Liver histopathology was analyzed with hematoxylin-eosin and Masson's trichrome staining. The expression of alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta1 (TGF-beta1), and COX-2 were measured with immunohistochemical staining. The levels of COX-2, TGF-beta1, and matrix metalloproteinase-9 (MMP-9) production were measured with the Western blot method and an enzyme immunoassay. Meloxicam treatment attenuated the expression of alpha-SMA, TGF-beta1, and COX-2 in rats that were treated with BDL for 3 weeks. This was associated with a marked reduction in collagen accumulation and histological improvement. In addition, meloxicam treatment was found to downregulate the levels of hepatic COX-2, TGF-beta1, and MMP-9 production. Cholestasis in BDL rats induces hepatic COX-2 expression. Selective COX-2 inhibitor meloxicam reduces BDL-induced hepatic fibrosis, and this is associated with reduced hepatic TGF-beta1 expression as well as decreased cyclooxygenase activity in the liver.


Health literacy, cognitive abilities, and mortality among elderly persons.
Low health literacy and low cognitive abilities both predict mortality, but no study has jointly examined these relationships. We conducted a prospective cohort study of 3,260 community-dwelling adults age 65 and older. Participants were interviewed in 1997 and administered the Short Test of Functional Health Literacy in Adults and the Mini Mental Status Examination. Mortality was determined using the National Death Index through 2003. In multivariate models with only literacy (not cognition), the adjusted hazard ratio was 1.50 (95% confidence of interval [CI] 1.24-1.81) for inadequate versus adequate literacy. In multivariate models without literacy, delayed recall of 3 items and the ability to serial subtract numbers were associated with higher mortality (e.g., adjusted hazard ratios [AHR] 1.74 [95% CI 1.30-2.34] for recall of zero versus 3 items, and 1.32 [95% CI 1.09-1.60] for 0-2 vs 5 correct subtractions). In multivariate analysis with both literacy and cognition, the AHRs for the cognition items were similar, but the AHR for inadequate literacy decreased to 1.27 (95% CI 1.03 - 1.57). Both health literacy and cognitive abilities independently predict mortality. Interventions to improve patient knowledge and self-management skills should consider both the reading level and cognitive demands of the materials.


Cardiovascular complications and its impact on outcomes in COVID-19.
Coronavirus disease 2019 (COVID-19) has led to a widespread morbidity and mortality. Limited data exists regarding the involvement of cardiovascular system in COVID-19 patients. We sought to evaluate the cardiovascular (CV) complications and its impact on outcomes in symptomatic COVID-19 patients. This was a single center observational study among symptomatic COVID-19 patients. Data regarding clinical profile, laboratory investigations, CV complications, treatment and outcomes were collected. Cardiac biomarkers and 12 lead electrocardiograms were done in all while echocardiography was done in those with clinical indications for the same. Corrected QT-interval (QTc) at baseline and maximum value during hospitalization were computed. Of the 108 patients, majority of them were males with a mean age of 51.2 ± 17.7 years. Hypertension (38%) and diabetes (32.4%) were most prevalent co-morbidities. ECG findings included sinus tachycardia in 18 (16.9%), first degree AV block in 5 (4.6%), VT/VF in 2 (1.8%) and sinus bradycardia in one (0.9%). QTc prolongation was observed in 17.6% subjects. CV complications included acute cardiac injury in 25.9%, heart failure, cardiogenic shock and acute coronary syndrome in 3.7% each, "probable" myocarditis in 2.8% patients. Patients with acute cardiac injury had higher mortality than those without (16/28 [57.1%] vs 14/78 [17.5%]; P < 0.0001). Multivariate logistic regression analysis showed that acute cardiac injury (OR: 11.3), lymphopenia (OR: 4.91), use of inotropic agents (OR: 2.46) and neutrophil-lymphocyte ratio (OR:1.1) were independent predictors of mortality. CV complications such as acute cardiac injury is common in COVID-19 patients and is associated with worse prognosis.


The specificity of synovial mononuclear cell responses to microbiological antigens in Reiter's syndrome.
Statistical assessment has been made of synovial mononuclear cell responses to ureaplasma, chlamydial, enterobacteriaceae and mumps antigens in 16 cases of sexually transmitted Reiter's syndrome, 8 cases of enteric Reiter's syndrome and 12 cases of rheumatoid arthritis. These 3 groups of patients can be differentiated by synovial mononuclear cell responses to these microbial antigens and the microbiological origin of the arthritis in Reiter's syndrome can probably be suggested by this investigative approach.


[Lapidus procedure in patients with rheumatoid arthritis--short-term results].
Hallux valgus combined with flat foot is one of the most common foot deformities affecting patients with rheumatoid arthritis. The Lapidus procedure is indicated when the hallux valgus angle is more than 15 degrees or the first tarsometatarsal joint is hypermobile. We aimed to evaluate the results of the Lapidus procedure in patients with rheumatoid arthritis. We performed the Lapidus procedure in 31 patients between 2002 and 2005. In ten patients we performed a bilateral procedure and in ten patients we performed a single Lapidus procedure. In 27 cases we combined the procedure with a resection of the second-fifth metatarsal heads (Hoffmann procedure), in four cases with a Weil osteotomy of the second-fifth metatarsal necks. We performed an excision of the articular surface of the first metatarsal head (Mayo) in 10 patients, a Keller resection procedure in 9 patients, an arthrodesis of the first metatarsophalangeal joint in 3 patients, and an Akin wedge osteotomy of the proximal phalanx of the thumb in 3 patients. Arthrodesis was fixed by two K-wires in 5 cases, by 2 compression screws in 7 cases, and in thirty-four cases we used memory staples. We evaluated the outcomes of forty-one procedures in thirty-one patients (24 female, 7 male). The averge age at surgery was 54.3 years. Thirty-two feet were without pain after the procedures, in five cases the patients felt moderate pain in the dorsal part of the foot and in four cases the patients felt pain in the transverse arch of foot. Complications included delayed primary wound closure in five cases, in one case we performed a revision procedure for a deep infection. Delayed hallux valgus developed in 5 cases. The mean first intermetatarsal angle before surgery was 19.5 degrees (range 12 - 27 degrees) and improved to 8 degrees after surgery. In 3 cases we found an unsatisfactory intermetatarsal angle correction with partial renewal of the hallux valgus. A correctly performed Lapidus procedure enables correction of the varus position of 1st metatarsus and hallux valgus.


Sonohysterography of the uterine cavity: preliminary investigations.
To compare sonohysterography (SH), in the exploration of the uterine cavity, with classical transvaginal sonography (TVS), hysterography (HSG), and hysteroscopy. 104 consecutive patients evaluated for uterine disorders underwent both TVS and SH. SH was obtained by distension of the uterine cavity with the instillation of an isotonic saline solution; 36 patients also underwent HSG; 82 women underwent surgery. Histologic findings were considered as gold standard. The criteria used to compare these methods were sensitivity, specificity, and negative and positive predictive values (NPV, PPV) for identifying pathology. 3 instillation failures occurred. SH was found to be more effective (sensitivity 94%, specificity 98%) than HSG (sensitivity 67%, specificity 94%). The difference between TVS and SH was less marked, SH showing some superiority (sensitivity 88%, specificity 98%) to TVS (sensitivity 77%, specificity 93%). SH represents an improvement over conventional TVS and is fully capable of replacing HSG for the study of the uterine cavity.


A test of the Booth energy flow model (Mark 3) on feeding patterns of mice.
Booth's dynamic model is a particular realization of a general hypothesis ascribing the start and stop of rat meals to fluctuations in the value of the net energy flow entering into the lean body mass. The Mark 3 version of this model has been adapted to the mouse Mus musculus C3H. Recordings for 11.5 consecutive hours of diurnal and nocturnal sequences of feeding behaviour in six mice have made it possible to compare not only the simulated and observed ingested amounts, but also the corresponding time patterns. The results show the consistency of the energy flow hypothesis with the feeding pattern in mice. The results also show that satiety conditioning does not improve simulated patterns and indicate which modification of the model parameters allow the simulation of the observed differences between day and night patterns. Finally, detailed discrepancies between observed and simulated results suggest that the model would be improved by taking into account other behaviours liable to interact with feeding behaviour.


Surveillance of foodborne outbreaks of infectious intestinal disease in England and Wales 1992-1999: contributing to evidence-based food policy?
Between 1992 and 1999, a total of 1426 general outbreaks of infectious intestinal disease reported to the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC) were described as foodborne. Where the evidence base to support the conclusions drawn was provided (66.3% of outbreaks) a combination of microbiological and analytical evidence was reported in 4% of outbreaks (60/1426); microbiological evidence alone in 10% of outbreaks (149/1426); analytical evidence alone in 23% of outbreaks (322/1426); microbiological evidence in combination with descriptive epidemiology in 3% of outbreaks (46/1426) and descriptive epidemiology alone in 26% of outbreaks (365/1426). Information supplied to CDSC by local investigators appears to be of varying quality and depth and may be influenced by the individual characteristics of outbreaks such as size and duration, outbreak setting, causative organism, vehicles of infection and time of year. These findings have implications for the use of these surveillance data in developing evidence-based food policy.


Sex differences and chronic stress effects on the neural circuitry underlying fear conditioning and extinction.
There are sex differences in the rates of many stress-sensitive psychological disorders such as posttraumatic stress disorder (PTSD). As medial prefrontal cortex and amygdala are implicated in many of these disorders, understanding differential stress effects in these regions may shed light on the mechanisms underlying sex-dependent expression of disorders like depression and anxiety. Prefrontal cortex and amygdala are key regions in the neural circuitry underlying fear conditioning and extinction, which thus has emerged as a useful model of stress influences on the neural circuitry underlying regulation of emotional behavior. This review outlines the current literature on sex differences and stress effects on dendritic morphology within medial prefrontal cortex and basolateral amygdala. Such structural differences and/or alterations can have important effects on fear conditioning and extinction, behaviors that are mediated by the basolateral amygdala and prefrontal cortex, respectively. Given the importance of extinction-based exposure therapy as a treatment for anxiety disorders such as PTSD, understanding the neural mechanisms by which stress differentially influences fear learning and extinction in males and females is an important goal for developing sex-appropriate interventions for stress-related disorders.


Recent advances in the physiology of whole body immersion.
Recent investigations have furnished a complete analysis of the hemodynamic events accompanying whole-body immersion. About 700 ml of blood are translocated into the intrathoracic circulation, and heart volume increases by 180 +/- 62 ml. These changes are followed by an increase in stroke volume and cardiac output of over 30%. At the same time a reflex reduction of total peripheral resistance and venous tone occurs. Renin and aldosterone activity are reduced while the 17-hydroxycorticosteroid is not affected. Treatment of the subject with DOCA attenuates but does not extinguish the excess sodium excretion of immersion. This finding strengthens the arguments in favor of an unknown factor enhancing sodium excretion. Finally, the relative activation of the three factors that serve volume control, the excretory function of the kidney, capillary filtration pressure, and the thirst mechanism, is discussed.


Development of microRNA-based therapeutics for central nervous system diseases.
MicroRNA (miRNA)-mediated gene silencing is a method of RNA interference in which a miRNA binds to messenger RNA sequences and regulates target gene expression. MiRNA-based therapeutics have shown promise in treating a variety of central nervous system diseases, as verified by results from diverse preclinical model organisms. Over the last decade, several miRNA-based therapeutics have entered clinical trials for various kinds of diseases, such as tumors, infections, and inherited diseases. However, such clinical trials for central nervous system diseases are scarce, and many central nervous system diseases, including hemorrhagic stroke, ischemic stroke, traumatic brain injury, intractable epilepsy, and Alzheimer's disease, lack effective treatment. Considering its effectiveness for central nervous system diseases in preclinical experiments, microRNA-based intervention may serve as a promising treatment for these kinds of diseases. This paper reviews basic principles and recent progress of miRNA-based therapeutics and summarizes general procedures to develop such therapeutics for treating central nervous system diseases. Then, the current obstacles in drug development are discussed. This review also provides a new perspective on possible solutions to these obstacles in the future.


Novel Targets, Novel Treatments: The Changing Landscape of Non-Small Cell Lung Cancer.
Treatment of non-small cell lung cancer (NSCLC) has undergone a paradigm shift. Once a disease with limited potential therapies, treatment options for patients have exploded with the availability of molecular testing to direct management and targeted therapies to treat tumors with specific driver mutations. New in vitro diagnostics allow for the early and non-invasive detection of disease, and emerging in vivo imaging techniques allow for better detection and monitoring. The development of checkpoint inhibitor immunotherapy has arguably been the biggest advance in lung cancer treatment, given that the vast majority of NSCLC tumors can be treated with these therapies. Specific targeted therapies, including those against KRAS, EGFR, RTK, and others have also improved the outcomes for those individuals bearing an actionable mutation. New and emerging therapies, such as bispecific antibodies, CAR T cell therapy, and molecular targeted radiotherapy, offer promise to patients for whom none of the existing therapies have proved effective. In this review, we provide the most up-to-date survey to our knowledge regarding emerging diagnostic and therapeutic strategies for lung cancer to provide clinicians with a comprehensive reference of the options for treatment available now and those which are soon to come.


The disconnection in anomic aphasia between semantic and phonological lexicons.
PB, a right handed woman aged 26, has developed anomic language disturbances following right frontal and left temporal brain damage due to a road traffic accident. Her anomia shows exceptional features: it occurs in naming tasks in test conditions but not in continuous speech; it involves comprehension deficits but very few semantic errors in expression; it improves with phonemic, but not with semantic cues. These features, it is argued, indicate the disconnection between two intact lexicons: the semantic and the phonological.


Late gestational lung hypoplasia in a mouse model of the Smith-Lemli-Opitz syndrome.
Normal post-squalene cholesterol biosynthesis is important for mammalian embryonic development. Neonatal mice lacking functional dehydrocholesterol Delta7-reductase (Dhcr7), a model for the human disease of Smith-Lemli-Opitz syndrome, die within 24 hours of birth. Although they have a number of biochemical and structural abnormalities, one cause of death is from apparent respiratory failure due to developmental pulmonary abnormalities. In this study, we characterized further the role of cholesterol deficiency in lung development of these mice. Significant growth retardation, beginning at E14.5 through E16.5, was observed in Dhcr7-/- embryos. Normal lobation but smaller lungs with a significant decrease in lung-to-body weight ratio was noted in Dhcr7-/- embryos, compared to controls. Lung branching morphogenesis was comparable between Dhcr7-/- and controls at early stages, but delayed saccular development was visible in all Dhcr7-/- embryos from E17.5 onwards. Impaired pre-alveolar development of varying severity, inhibited cell proliferation, delayed differentiation of type I alveolar epithelial cells (AECs) and delayed vascular development were all evident in knockout lungs. Differentiation of type II AECs was apparently normal as judged by surfactant protein (SP) mRNAs and SP-C immunostaining. A significant amount of cholesterol was detectable in knockout lungs, implicating some maternal transfer of cholesterol. No significant differences of the spatial-temporal localization of sonic hedgehog (Shh) or its downstream targets by immunohistochemistry were detected between knockout and wild-type lungs and Shh autoprocessing occurred normally in tissues from Dhcr7-/- embryos. Our data indicated that cholesterol deficiency caused by Dhcr7 null was associated with a distinct lung saccular hypoplasia, characterized by failure to terminally differentiate alveolar sacs, a delayed differentiation of type I AECs and an immature vascular network at late gestational stages. The molecular mechanism of impaired lung development associated with sterol deficiency by Dhcr7 loss is still unknown, but these results do not support the involvement of dysregulated Shh-Patched-Gli pathway in causing this defect.


New data on the mobility of Pt emitted from catalytic converters.
The mobility and speciation of Pt was investigated in dust deposited in highway tunnels and in gully sediments. For this, a sequential extraction technique was used in combination with a microwave digestion procedure, followed by detection of Pt with high resolution ICP-MS. A digestion procedure using HNO(3)/HCl/H(2)O(2) was developed and its efficiency tested for environmental materials. Total Pt contents ranged from approximately 100 to 300 microg/kg. The high share of chemically mobile Pt in the tunnel dust (up to about 40%) indicates that Pt is predominantly emitted in a mobile form from the converter. The absence of a mobile fraction in the gully sediment is explained by the elution of Pt by run-off. Except for the mobile and easily mobilised fractions none of the other fractions of the sequential extraction contains Pt, neither in the dust samples nor in the gully sediment.


Development of a Three-Dimensional Electrochemical System Using a Blue TiO2/SnO2-Sb2O3 Anode for Treating Low-Ionic-Strength Wastewater.
Reducing energy use is crucial to commercialize electrochemical oxidation technologies. We developed a three-dimensional (3-D) electrochemical system that can significantly reduce the applied voltage and effectively degrade organic contaminants in low-ionic-strength wastewaters. The 3-D system consisted of a composite wire mesh anode (composed of blue TiO2 nanotubes covered with SnO2-Sb2O3), a proton exchange membrane, and a stainless-steel wire mesh cathode, which were compressed firmly together. For the 3-D system, we placed the anode of a 3-D electrode toward the wastewater that flowed past the anode. Both the two-dimensional (2-D) and 3-D systems had the same anode and cathode. We found that the 3-D system could reduce the applied voltage by 75.7% and reduce the electrical efficiency per log order reduction (EE/O) by 73% for 0.001 M Na2SO4. For Na2SO4 concentrations greater than 0.05 M, the 2-D system had a slightly lower EE/O. We also compared the EE/O of electrochemical advanced oxidation processes (EAOPs) with that of other advanced oxidation processes (UV/H2O2, UV/persulfate, O3/H2O2, UV/ TiO2, and UV/chlorine). We found that EAOPs have a much higher EE/O for low BA concentrations (20 mg/L) and a much lower EE/O for high BA concentrations (2000 mg/L).


Acupuncture-movement therapy for acute lumbar sprain: a randomized controlled clinical trial.
Several studies have reported that acupuncture is effective for treatment of acute lumbar sprain, but they neglected to consider that acupuncture cannot remarkably improve lumbar activity. We performed a randomized controlled trial to evaluate the effect of acupuncture-movement therapy versus conventional acupuncture in the treatment of acute lumbar sprain. Sixty patients were randomized into four groups: the acupuncture-movement (AM) group, sham acupuncture-movement (SAM) group, conventional acupuncture (CA) group, and physical therapy (PT) group. Patients in the AM group were treated with acupuncture at Yintang (EX-HN 3) and exercise of the lumbar region during acupuncture. Patients in the SAM group were treated with sham acupuncture at Yintang (EX-HN 3) and exercise of the lumbar region during sham acupuncture. Conventional acupuncture was performed in the CA group, and physical therapy was applied in the PT group. Each treatment lasted for 20 min. Patients were assessed before and after treatment using a visual analogue scale (VAS) and the Roland Morris Questionnaire (RMQ). The VAS and RMQ scores in the AM group were significantly lower after than before treatment (P < 0.01). The AM group reported lower RMQ scores in after-treatment and 24 h after treatment and lower VAS score in 24 h after treatment in comparison with those of the CA, SAM, and PT groups (P < 0.05). Acupuncture-movement therapy is effective for treating acute lumbar sprain with a persistent pain-relief and remarkable improvement of lumbar activity. Movement, that is, lumbar exercise during acupuncture, enhances the effect of acupuncture.


Treatment outcomes of elderly salivary gland cancer patients undergoing radiotherapy - Results from a large multicenter analysis.
To evaluate oncological outcomes and treatment-related toxicities of elderly salivary gland cancer patients undergoing (chemo)radiotherapy. Local/locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) of elderly patients ≥ 65 years with primary salivary gland cancers undergoing (chemo)radiotherapy between 2005 and 2020 at three tertiary cancer centers were calculated. The impact of clinicopathological and treatment parameters on outcomes were analyzed, and acute and chronic toxicities were quantified. 288 elderly salivary gland cancer patients were included in this multicenter analysis, and their median LRC, PFS and OS amounted to 113, 39 and 75 months, respectively. Age, performance status, comorbidities, definitive vs. adjuvant (chemo)radiotherapy as well as locally/locoregionally advanced cancers and distant metastases correlated with reduced outcomes in elderly salivary gland patients. Patients receiving dose-escalated radiotherapy (total doses > 70 GyEQD2) with carbon ion boost radiation resulted in improved LRC, but no improvements in PFS or OS. Concomitant chemoradiotherapy did not improve treatment outcomes in elderly salivary gland carcinoma patients. Radiotherapy of elderly salivary gland cancer patients resulted in moderate higher-grade toxicities despite dose escalation with 70 (24.3%) and 48 patients (16.7%) experiencing acute and chronic grade 3 toxicities, respectively. No grade 4/5 toxicities were observed in this patient cohort. Data from the largest multicenter analysis of elderly salivary gland cancer patients undergoing (chemo)radiotherapy demonstrate favorable LRC and tolerable toxicity rates. Decision-making for these vulnerable patients should be based on patient performance rather than chronological patient age.


Social determinants associated with loss of an eye in the United States using the All of Us nationwide database.
To identify common factors associated with the loss of an eye using the NIH All of Us database. In this case-controlled study, we extracted electronic health record and socio-demographic data for 231 cases of eye loss from All of Us enrollment sites. Controls (N = 924) matched the demographic characteristics of the 2020 United States Census. Bivariate analyses and multivariable logistic regression identified variables significantly associated with increased odds of eye loss. Medical and social determinants associated with increased odds of losing an eye. Among cases, the average age (standard deviation) was 60.1 (14.4) years. The majority (125, 54.1%) were male. 87 (37.7%) identified as African American, and 49 (21.2%) identified as Hispanic or Latino. Loss of eye was more likely in those with ocular tumor (odds ratio [OR] 421.73, 25 95% confidence interval [CI] 129.81-1959.80, p < .001), trauma (OR 13.38, 95% CI 6.64-27.43, p < .001), infection (OR 11.46, 95% CI 4.11-32.26, p = .001) or glaucoma (OR 8.33, 95% CI 4.43- 15.81, p < .001). African American (OR 2.39, 95% CI 1.39-4.09, p = .002) and Hispanic or Latino (OR 1.80, 95% CI 1.01-3.15, p = .04) participants were disproportionately affected. Racial and ethnic disparities exist among those with loss of an eye from underlying conditions. Addressing health inequities may mitigate the risk of this morbid outcome.


Validation of a coronary prognostic index for the Chinese--a tale of three cities.
In order to confirm the efficacy of a new coronary prognostic index for the prediction of mortality of acute myocardial infarction in the Chinese in general, this index was applied to 886 patients from six general hospitals in Hong Kong (435 patients), Guangzhou (212 patients) and Shanghai (239 patients), respectively. They could be successfully stratified into seven clinical subsets with stepwise increasing mortality. The overall mortality tallied with that predicted by the original coronary prognostic index. The efficacy of this prognostic index for the prediction of mortality from acute myocardial infarction among the Chinese is verified and its application in the objective assessment of patients with acute myocardial infarction is recommended.


An implanted neuromuscular stimulator for fecal continence following previously implanted gracilis muscle. Report of a case.
A young woman had been treated previously with a gracilis muscle transposition because of anal atresia thus enabling her to maintain continence by active muscle contraction, which, however, she could sustain for only a few minutes. Implantation of a neuromuscular stimulator resulted in perfectly controllable sphincter function.


Skin Microbiome as Years Go By.
The skin microbial communities, i.e., the microbiota, play a major role in skin barrier function so must remain dynamic to adapt to the changes in the niche environment that occur across the different body sites throughout the human lifespan. This review provides an overview of the major alterations occurring in the skin microbiome (microbial and genomic components) during the various stages of life, beginning with its establishment in the first weeks of life through to what is known about the microbiome in older populations. Studies that have helped identify the factors that most influence skin microbiome function, structure, and composition during the various life stages are highlighted, and how alterations affecting the delicate balance of the microbiota communities may contribute to variations in normal physiology and lead to skin disease is discussed. This review underlines the importance of improving our understanding of the skin microbiome in populations of all ages to gain insights into the pathophysiology of skin diseases and to allow better monitoring and targeted treatment of more vulnerable populations.


Estimation of minimal clinically important change of the Japanese version of EQ-5D in patients with chronic noncancer pain: a retrospective research using real-world data.
Quality of life (QoL) is routinely assessed and evaluated in medical research. However, in Japan, there is a lack of solid cutoff criteria for evaluating QoL improvement in chronic noncancer pain management. The present study was conducted to identify the minimal clinically important change (MCIC) of the Japanese version of EuroQol-5D 3L(EQ-5D) utility score and numeric rating scale (NRS) with an emphasis on chronic noncancer pain. The data source for this post hoc research was the post-marketing surveillance (PMS) data for a tramadol/acetaminophen combination tablet, which was previously conducted in real-world settings. The parameters extracted from the PMS data were sociodemographic characteristics, NRS, EQ-5D, and dichotomous physician's global impression of treatment effectiveness (PGI). The optimal cutoff points of MCIC for EQ-5D utility and NRS scores were evaluated using receiver operating characteristics (ROC) analysis. An anchor-based approach using PGI was applied. Data of 710 patients with chronic noncancer pain were extracted from the PMS database. The NRS score decreased by 2.7 (standard deviation, 2.3) points, whereas the EQ-5D score increased by 0.16 (0.20) points at 4 weeks from baseline. The changes from baseline in NRS and EQ-5D were significantly correlated (r = 0.53, p < 0.001). The estimated optimal cutoff points of MCIC for EQ-5D and NRS were 0.10 and -2.0 points, respectively. The area under the curve of ROC was > 0.80 in both analyses. These results demonstrated novel cutoff criteria for the Japanese version of EQ-5D, focusing on patients with chronic noncancer pain. The obtained criteria were fairly consistent and can be confidently utilized as an evaluation tool in medical research on chronic noncancer pain in Japan, with additional functionality and usability for QoL assessment in pain management practice. The data source of this post hoc research was a PMS study with the identifier number UMIN000015901 at umin.ac.jp, UMIN clinical trial registry (UMIN-CTR).


Cardiac pacing in patients with dilated cardiomyopathy.
Studies of both the acute and chronic effects of permanent cardiac pacing in patients with dilated cardiomyopathy have produced contradictory results. Similarly, theoretically promising novel pacing techniques such as multisite, His bundle, and right ventricular outflow tract pacing have also yielded mixed results in preliminary studies. In general, at the present time, pacing therapy should be considered investigational for patients with dilated cardiomyopathy who do not have traditional bradycardia indications; nevertheless, pacing therapy may be useful in a small population of patients with dilated cardiomyopathy who have inappropriate timing of left ventricular and left atrial contraction. The beneficial effects of cardiac pacing in some patients with DCM cannot be dismissed out of hand; they must be explained. What is needed is clarification of the best methods to measure any benefits of this therapy: among the options are echocardiographically determined parameters of forward flow and AV valve function, exercise test parameters such as duration and O2 consumption, global and regional ejection fraction, functional classification, quality of life questionnaires, neurohumoral parameters such as plasma atrial natriuretic peptide and catecholamines, and, finally, disease progression and survival.


Engaging, Supporting, and Sustaining the Invisible Partners in Care: Young Caregivers of Veterans From the Post-9/11 Era.
Few studies have explored the health effects of caregiving for post-9/11 veterans who have been traumatically injured, have traumatic brain injuries, or have post-traumatic stress disorder. Post-9/11 veterans and their caregivers tend to be younger than veterans who served exclusively prior to 9/11. In response to the needs of caregivers, Public Law 111-163, the Caregivers and Veterans Omnibus Health Services Act of 2010, was passed, providing unprecedented support for informal caregivers of veterans. This support includes a monthly stipend and health insurance for caregivers who meet eligibility criteria. The uptake in these support services, and the resulting cost of services, has far surpassed expectations. As the Department of Veterans Affairs continues to provide caregiver support services, it is essential to determine the value and direct impact of the services provided to caregivers and veterans.


Elderly woman with sharp shoulder pain.
The patient denied recent trauma or any heavy lifting, but she'd lost 10 pounds over the previous month. What was causing her shoulder pain?


Abrogation of greater graft failure risk of female-to-male liver transplantation with donors older than 40 years or graft macrosteatosis greater than 5.
Greater graft-failure-risk of female-to-male liver transplantation (LT) is thought to be due to acute decrease in hepatic-estrogen-signaling. Our previous research found evidence that female hepatic-estrogen-signaling decreases after 40 years or with macrosteatosis. Thus, we hypothesized that inferiority of female-to-male LT changes according to donor-age and macrosteatosis. We stratified 780 recipients of grafts from living-donors into four subgroups by donor-age and macrosteatosis and compared graft-failure-risk between female-to-male LT and other LTs within each subgroup using Cox model. In recipients with ≤ 40 years non-macrosteatotic donors, graft-failure-risk was significantly greater in female-to-male LT than others (HR 2.03 [1.18-3.49], P = 0.011). Within the subgroup of recipients without hepatocellular carcinoma, the inferiority of female-to-male LT became greater (HR 4.75 [2.02-11.21], P < 0.001). Despite good graft quality, 1y-graft-failure-probability was 37.9% (23.1%-57.9%) in female-to-male LT within this subgroup while such exceptionally high probability was not shown in any other subgroups even with worse graft quality. When donor was > 40 years or macrosteatotic, graft-failure-risk was not significantly different between female-to-male LT and others (P > 0.60). These results were in agreement with the estrogen receptor immunohistochemistry evaluation of donor liver. In conclusion, we found that the inferiority of female-to-male LT was only found when donor was ≤ 40 years and non-macrosteatotic. Abrogation of the inferiority when donor was > 40 years or macrosteatotic suggests the presence of dominant contributors for post-transplant graft-failure other than graft quality/quantity and supports the role of hepatic-estrogen-signaling mismatch on graft-failure after female-to-male LT.


Pyelonephritis following pediatric renal transplant: increased incidence with vesicoureteral reflux.
The association between pyelonephritis and vesicoureteral reflux (VUR) following pediatric renal transplantation is unclear. To understand the relationship of vesicoureteral reflux with urinary tract infection (UTI) and pyelonephritis, 67 patients were evaluated for reflux and pyelonephritis. Sixty-seven pediatric patients, aged 2 to 18 (39 males and 28 females) underwent renal transplantation. Beginning in 1982, all patients underwent voiding cystourethrography or radionuclide voiding studies 1 to 3 months postoperatively to assess the incidence of VUR. Techniques of ureteroneocystostomy (UNC) included the Leadbetter-Politano (L-p) in 39 cases, and two different modifications of the LICH (herein called LICH-1 and LICH-2) in 30 cases. Urinary cultures were performed routinely. Pyelonephritis was considered present in any patient with UTI and increased serum creatinine or fever greater than 38.5. VUR occurred in 36% of patients; highest in LICH-1 (79%), intermediate in L-P (22%), and lowest in LICH-2 (9%). VUR was not statistically significantly higher in females (43%) v males (31%). UTI occurred in 37% of patients. The difference in incidence between females (54%) and males (26%) was significant (P less than .05). The frequency of UTI in patients with VUR was 46% v 33% in patients without reflux (NS). However, pyelonephritis that occurred in 16% of cases overall was present in 82% of UTIs in patients with reflux v 14% of UTIs in patient without reflux (P less than .01). Pyelonephritis is significantly increased in pediatric renal transplant patients with UTI was have VUR. A nonrefluxing UNC is advocated in all patients. All renal transplant patients should have routine monitoring of urinary cultures and should be evaluated of VUR posttransplant.


Interaction between the blood fluke, Sanguinicola inermis and humoral components of the immune response of carp, Cyprinus carpio.
The effect of Sanguinicola inermis on serum antibody and complement activity in Cyprinus carpio was assessed using an ELISA and haemolytic assays. Possible immune evasion strategies were assessed using immunodetection of host proteins on the surface of the parasite. Carp acclimatized to 20 or 25 degrees C were infected by exposure to 500 cercariae or injected intraperitoneally with 150 cercariae, and serum monitored over a 63-day period. In cercariae-injected carp, irrespective of time and temperature, a significant increase occurred in complement activity being greatest at 25 degrees C. In addition, fish exposed to the cercariae of S. inermis and maintained at 20 degrees C the level of complement activity was significantly higher after 5 weeks compared to controls. At 20 degrees C intraperitoneal injections of parasites increased serum antibody levels which peaked after 7 days. In contrast, at 25 degrees C, antibody levels were maintained over 63 days. Exposure of fish to infection did not appear to stimulate antibody production. Immunofluorescence studies revealed 'host-like' molecules on the surface of the cercarial body exposed to carp serum and adult flukes obtained directly from the fish or cultured for 24 h in L15 medium. The possible role of 'host-like' molecules in immune evasion is discussed and the response at different temperatures is related to infection dynamics.


Age-at-onset-dependent effects of sulfur amino acid restriction on markers of growth and stress in male F344 rats.
Trade-offs in life-history traits are clinically and mechanistically important. Sulfur amino acid restriction (SAAR) extends lifespan. But whether this benefit comes at the cost of other traits including stress resistance and growth is unclear. We investigated the effects of SAAR on growth markers (body weight, IGF1, and IGFBP3) and physiological stresses. Male-F344 rats were fed control (0.86% Met) and SAAR (0.17% Met) diets starting at 2, 10, and 20 months. Rats were injected with keyhole-limpet-hemocyanin (KLH) to measure immune responses (anti-KLH-IgM, anti-KLH-IgG, and delayed-type-hypersensitivity [DTH]). Markers of ER stress (FGF21 and adiponectin), detoxification capacity (glutathione [GSH] concentrations, GSH-S-transferase [GST], and cytochrome-P450 -reductase [CPR] activities), and low-grade inflammation (C-reactive protein [CRP]) were also determined. SAAR decreased body weight, liver weight, food intake, plasma IGF1, and IGFBP3; the effect size diminished with increasing age-at-onset. SAAR increased FGF21 and adiponectin, but stress damage markers GRP78 and Xbp1s/us were unchanged, suggesting that ER stress is hormetic. SAAR increased hepatic GST activity despite lower GSH, but CPR activity was unchanged, indicative of enhanced detoxification capacity. Other stress markers were either uncompromised (CRP, anti-KLH-IgM, and DTH) or slightly lower (anti-KLH-IgG). Increases in stress markers were similar across all ages-at-onset, except for adiponectin, which peaked at 2 months. Overall, SAAR did not compromise stress responses and resulted in maximal benefits with young-onset. In survival studies, median lifespan extension with initiation at 52 weeks was 7 weeks (p = .05); less than the 33.5-week extension observed in our previous study with 7-week initiation. Findings support SAAR translational studies and the need to optimize Met dose based on age-at-onset.


Atomic force microscopy for imaging human metaphase chromosomes.
The present study introduces the principle of atomic force microscopy (AFM) and reviews our results of human metaphase chromosomes obtained by AFM. AFM imaging of the chromosomes revealed that the chromatid arm was not uniform in structure but had ridges and grooves along its length, which was most prominent in the late metaphase. The arrangement of these ridges and grooves was roughly symmetrical with the counterpart of the paired sister chromatids. AFM imaging of banded chromosomes also showed that the ridges and grooves were related to the G/Q-positive and G/Q-negative bands, respectively. At high magnification, the chromatid was seen to be produced by the compaction of highly twisted chromatin fiber loops, and its compaction tended to be stronger in the ridged regions of the chromosomes than in the grooved regions. Our AFM studies also showed the presence of catenation of chromatin fibers between the ridged portions of the chromatid in the late metaphase. Thus, AFM is useful for obtaining the three-dimensional surface topography not only in ambient conditions but also in physiological liquid conditions, and is expected to be an attractive tool for investigating the structure of chromosomes.


Ultrasensitive immunoassay for CA125 detection using acid site compound as signal and enhancer.
A novel sensitive electrochemical immunosensor was proposed for detection of CA125 based on ferrocenecarboxylic acid (FA), HCl-doped polyaniline (H-PANI) and chitosan hydrochloride (CS-HCl), which were used as substrate materials to generate signal and to enlarge specific surface area. The composite of these three materials (acid center compound, FA@H-PANI@CS-HCl) can be connected by hydrogen (H) in each molecule. Ag@Co3O4 nanosheets were used in the immunosensor to amplify the antibody capacity and to enhance the sensitivity of the immunoassay. This kind of sensor was novel, concise and it is the first time to be used in the detection of CA125. The biosensor exhibited low detection limit (0.25 pg/mL) and wide linear range (0.001-25 ng/mL). The stability, selectivity and reproducibility were acceptable. Serum sample analysis proved that the proposed sensor owned well precision and it might be used in potential clinic testing application in the future.


Noncatalytic protein component of elastase from horse leucocytes. A protein with regulatory function.
1. Noncatalytic protein component (NPC), a strongly acidic protein (pH = 4.5) was separated from native horse leucocyte elastase 1. 2. This protein reduces elastinolytic properties of elastases: 1 and 2A probably by decreasing their isoelectric points. 3. A possible regulatory role of this protein may be inferred from a higher affinity of elastase 1 to NPC rather than to elastin.


A population-based study of human papillomavirus deoxyribonucleic acid testing for predicting cervical intraepithelial neoplasia.
Our purpose was to determine the predictive values of primary or secondary screening for cervical human papillomavirus infection for cytologic detection of cervical intraepithelial neoplasia. Most of the 254 women referred for colposcopy in Västerbotten County in Sweden during October 1993 through December 1995 and 320 age-matched women from the general population were screened for human papillomavirus deoxyribonucleic acid by nested general-primer polymerase chain reaction. Ninety-six percent of women with high-grade cervical intraepithelial neoplasia had human papillomavirus, compared with 4% of women with normal findings (odds ratio 606; 95% confidence interval 137 to 5607). Thirty-seven percent of referred women and 48% of referred women >39 years old had mostly minor cytologic abnormalities with no human papillomavirus. The human papillomavirus-associated positive predictive value for cervical intraepithelial neoplasia was 76% in the colposcopy group and 11% in the general population, whereas the negative predictive value was >97% in both populations. Testing for human papillomavirus deoxyribonucleic acid seems diagnostically useful among women referred for colposcopy.


Interaction between negative inotropic effects of halothane and nifedipine in the isolated rat heart.
Isobolographic analysis was used to assess quantitatively the combined direct negative inotropic effect of halothane and nifedipine as well as to define the type of interaction between these two agents. Experiments were performed on an isolated rat heart preparation. Developed left ventricular pressure and dP/dtmax were used as indices of inotropic action. It was found that the combination of halothane and nifedipine gives mostly additive direct negative inotropic effect. However, with a small level of myocardial depression (ED25), there was some deviation from the additive interaction toward an infra-additive effect (p less than 0.01), and with a high level of depression (ED75), some deviation toward a supra-additive effect (p less than 0.05).


[The modified performance of the goniotrepanation with scleral flap after J. Fronimopoulos (author's transl)].
In a small group of patients goinotrepanation was performed with the scleral flap shaped to include a scleral tag. This operation method has no disadvantages when compared to the classical methods. In addition, in some cases the diameter of the trepanation can be reduced by the use of a scleral tag because of the favourable flowing relationships for the filter fluid.


Amplified met gene linked to double minutes in human glioblastoma.
The met proto-oncogene was found to be amplified in a human glioblastoma cell line (T3095) established from a glioblastoma multiform WHO grade IV. Amplification of epidermal growth factor receptor, transforming growth factor alpha and N-myc which have been described previously in glioblastoma were not observed in T3095. There was, however, an 8-fold met amplification. Giemsa-stained metaphases of T3095 cells revealed multiple (> 5) double minutes (dmins) in the majority of cells. Following xenografting in nude mice there was a significant increase in the number and frequency of dmins. The increase in dmins correlates with the level of met amplification (50-fold), suggesting localisation of the amplified met on dmins. Here we report the first case of met amplification in glioblastoma. Correlation between met amplification and extrachromosomal elements (dmins) has not been reported previously.


TORC2 signaling antagonizes SKN-1 to induce C. elegans mesendodermal embryonic development.
The evolutionarily conserved target of rapamycin (TOR) kinase controls fundamental metabolic processes to support cell and tissue growth. TOR functions within the context of two distinct complexes, TORC1 and TORC2. TORC2, with its specific component Rictor, has been recently implicated in aging and regulation of growth and metabolism. Here, we identify rict-1/Rictor as a regulator of embryonic development in C. elegans. The transcription factor skn-1 establishes development of the mesendoderm in embryos, and is required for cellular homeostasis and longevity in adults. Loss of maternal skn-1 function leads to mis-specification of the mesendodermal precursor and failure to form intestine and pharynx. We found that genetic inactivation of rict-1 suppressed skn-1-associated lethality by restoring mesendodermal specification in skn-1 deficient embryos. Inactivation of other TORC2 but not TORC1 components also partially rescued skn-1 embryonic lethality. The SGK-1 kinase mediated these functions downstream of rict-1/TORC2, as a sgk-1 gain-of-function mutant suppressed the rict-1 mutant phenotype. These data indicate that TORC2 and SGK-1 antagonize SKN-1 during embryonic development.