Artificial-Intelligence-Based Imaging Analysis of Stem Cells: A Systematic Scoping Review.
This systematic scoping review aims to map and identify the available artificial-intelligence-based techniques for imaging analysis, the characterization of stem cell differentiation, and trans-differentiation pathways. On the ninth of March 2022, data were collected from five electronic databases (PubMed, Medline, Web of Science, Cochrane, and Scopus) and manual citation searching; all data were gathered in Zotero 5.0. A total of 4422 articles were collected after deduplication; only twenty-seven studies were included in this systematic scoping review after a two-phase screening against inclusion criteria by two independent reviewers. The amount of research in this field is significantly increasing over the years. While the current state of artificial intelligence (AI) can tackle a multitude of medical problems, the consensus amongst researchers remains that AI still falls short in multiple ways that investigators should examine, ranging from the quality of images used in training sets and appropriate sample size, as well as the unexpected events that may occur which the algorithm cannot predict.


Emergency surgery after coronary disruption complicating PTCA. Report of four cases.
Four out of 150 patients having a PTCA at our institution sustained a coronary artery disruption and underwent emergency surgery. All of them presented a severe stenosis of the LAD, in 2 of them there was also a stenosis at the origin of a diagonal branch. In each case the injured vessel was a diagonal branch. Three patients had a rupture of subepicardial arteries and developed cardiac tamponade. In another patient the rupture was located intramyocardially. Severe hemodynamic derangement occurred in all 4 cases, one resulting in cardiac arrest. The latter was the only patient who died postoperatively, due to neurological damage. Two of the surviving patients sustained a non-transmural myocardial infarction in the area of the injured vessel. However, all 3 survivors recovered easily and are doing well 6 months after surgery.


Influence of Co-amorphization on the Physical Stability and Dissolution Performance of an Anthelmintic Drug Flubendazole.
In this work, the co-amorphization approach was applied to flubendazole (FluBZ), resulting in the formation of two novel solid forms of FluBZ with l-phenylalanine (Phe) and l-tryptophan (Trp). A variety of physicochemical techniques have been used to describe new systems, including powder X-ray diffraction, thermal methods, infrared spectroscopy, and scanning electron microscopy. Co-amorphization has been shown to suppress crystallization tendency and considerably increase the shelf-life storage of amorphous flubendazole solid across a wide range of relative humidities. The dissolution behavior of the amorphous forms in biorelevant media at pH = 1.6, pH = 6.5, and 37 °C has been studied in terms of Cmax (maximum FluBZ concentration), Tmax (time to attain peak drug concentration), and AUC (concentration area under the curve during dissolution). At pH = 6.5, a continuous supersaturation and the highest AUC value of all examined systems were observed for the FluBZ-Phe (1:1) system. The phase solubility diagrams revealed that the reason for the better dissolution performance of FluBZ-Phe (1:1) at pH = 6.5 is a complexation between the components in a solution. This work highlights the applicability of co-amorphous systems in improving the physical stability and dissolution performance of drug compounds with poor biopharmaceutical characteristics.


Split-pool method for synthesis of solid-state material combinatorial libraries.
The synthesis and analysis of inorganic material combinatorial libraries by the split-pool bead method were demonstrated at the proof-of-concept level. Millimeter-size spherical beads of porous gamma-alumina, a commonly used support material for heterogeneous catalysts, were modified with Al(13)O(4)(OH)(24)(H(2)O)(12)(7+) cations in order to promote irreversible adsorption of the anionic fluorescent dyes Cascade Blue, Lucifer Yellow, and Sulforhodamine 101. The compositions of individual beads were easily determined through three split-pool cycles using a conventional fluorescence plate reader. Small split-pool material libraries were made by adsorbing noble metal salts (H(2)PtCl(6), H(2)IrCl(6), and RhCl(3)) into the beads. Analysis of these beads by micro-X-ray fluorescence showed that quantitative adsorption of metal salts without cross-contamination of beads could be achieved at levels (0.3 wt % metal loading) relevant to heterogeneous catalysis. The method offers the potential for synthesis of rather large libraries of inorganic materials through relatively simple benchtop split-pool chemistry.


Oximetry based on diffuse photon density wave differentials.
The quantification of tissue optical properties for calculating blood saturation and hemoglobin concentration using measurements of diffuse photon density waves at some distance away from an intensity-modulated light source, generally requires the determination of the amplitude and phase of this light source. This determination may become a severe impediment for measurements performed in the clinical environment. In this work we extend a self-calibrating methodology developed for constant wave and modulation depth-phase measurements, to include amplitude and phase measurements of diffuse photon density waves. The method uses amplitude and phase changes of intensity modulated light, under the assumption of known index of refraction and invariant reduced scattering coefficient mu's, to quantify the absorption coefficient mu(a) without requiring initial amplitude and phase knowledge. Quantification of the mu(a) at selected time points during a measurement can then be employed to calibrate numerical solutions of the diffusion equation and compute the mu(a) for the remaining time points of the experiment. It is shown that the method is quite insensitive to the knowledge of the exact mu's value so that an assumption on the average mu's value for the tissue measured may be employed. The sensitivity of calculating blood saturation and hemoglobin concentration, as a function of the deviation of the mu's used in the calculation versus the real mu's value is investigated using simulated data. It is also demonstrated that the saturation calculation is especially insensitive to the mu's guess. The performance of the method to quantify blood oxygen saturation and the concentrations of oxy- and deoxy-hemoglobin is examined with experimental measurements at two wavelengths on specially constructed blood model phantoms. To validate the method the measurements are monitored by a time-resolved spectrometer. The method is shown to be accurate to within +/-5% in calculating blood saturation and to within +/-10% in calculating hemoglobin concentration compared to the results obtained with the time-resolved spectrometer and the expected theoretical values.


Pallister-Killian syndrome: report of one case.
Pallister-Killian Syndrome (PKS) is a rare sporadic congenital anomaly disorder, characterized by multiple congenital anomalies, especially craniofacial dysmorphism. It is also associated with mental retardation, seizure, skin pigmentation, and visceral malformations such as congenital diaphragmatic hernia, congenital heart defect, anorectal anomalies, and genital malformation. This syndrome usually presents with tissue-limited mosaicism of supernumerary 12p isochromosome i (12p). Moreover, diagnosis of Pallister-Killian Syndrome (PKS) is difficult because the ratio of abnormal to normal karyotyping is much lower in peripheral lymphocytes than in skin fibroblasts. We report the first case in Taiwan, who has tetrasomy 12p mosaic in peripheral lymphocytes.


Immune Responses to Muscle-Directed Adeno-Associated Viral Gene Transfer in Clinical Studies.
Muscle-directed gene therapy with adeno-associated viral (AAV) vectors is undergoing clinical development for treating neuromuscular disorders and for systemic delivery of therapeutic proteins. Although these approaches show considerable therapeutic benefits, they are also prone to induce potent immune responses against vector or transgene products owing to the immunogenic nature of the intramuscular delivery route, or the high doses required for systemic delivery to muscle. Major immunological concerns include antibody formation against viral capsid, complement activation, and cytotoxic T cell responses against capsid or transgene products. They can negate therapy and even lead to life-threatening immunotoxicities. Herein we review clinical observations and provide an outlook for how the field addresses these problems through a combination of vector engineering and immune modulation.


High-altitude pulmonary edema: potential protection by red wine.
High-altitude pulmonary edema (HAPE) is the predominant cause of death due to high-altitude illness. At first sight, the observation that mountaineers regularly consume red wine in order to "feel better" seems to be paradoxical because, especially at higher altitudes, alcohol consumption could be detrimental. In this article, we review the potential mechanisms by which the components of red wine may beneficially affect the development of HAPE. The underlying cause of HAPE is the altitude-related reduction in barometric pressure, which leads to a decrease in partial pressure of oxygen in the alveolae and subsequently in the pulmonary capillaries and arterial system. Two cellular mechanisms have been described, both of which increase pulmonary vascular tone: enhanced endothelin 1 production and the increased generation of reactive oxygen species. Recent evidence has indicated that some of the compounds of red wine suppress endothelin 1 gene expression, and the anti-oxidative properties of red wine have been previously reported. This article briefly summarises the pathophysiological cellular events leading to HAPE and describes the potential mechanisms by which the ingredients of red wine may have a beneficial effect.


Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats.
Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats. Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining. The rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-α levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P < 0.05). Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.


Successful treatment of a diffuse type tenosynovial giant cell tumor in the thoracic spine mimicking spinal metastasis by frozen recapping laminoplasty in a patient with thyroid cancer.
Tenosynovial giant cell tumor of the diffuse type (TGCT-D) involving the spine is rare. Its differential diagnosis includes metastatic disease; however, there have been few reports of spinal TGCT-D mimicking spinal metastasis in patients with a history of malignancy. We report on a 35-year-old woman with a history of papillary thyroid cancer who was diagnosed with TGCT-D of the thoracic spine mimicking spinal metastasis. Preoperative computed tomography (CT) revealed a 1.0 × 1.0-cm lytic bone lesion involving the left T7 vertebral lamina, pedicle, and the T6-7 facet joint; the thoracic spine lesion was markedly fluorodeoxyglucose-avid on positron-emission tomography/computed tomography (PET/CT). Spinal metastasis was initially suspected given the patient's history of papillary thyroid cancer. Total excision was performed with recapping laminoplasty. The resected lamina was frozen in liquid nitrogen and used as a frozen autograft (frozen recapping laminoplasty) for spinal reconstruction with posterior instrumentation. Histological findings supported a diagnosis of TGCT-D. The patient had no evidence of local recurrence 2 years post-surgery. Bone union was achieved 3 years post-surgery. TGCT-D can mimic metastasis in PET/CT and should be included in the differential diagnosis if a lytic lesion affecting the posterior elements of the vertebrae involves the facet joints. CT-guided biopsy is recommended for accurate diagnosis when an occult tumor, such as TGCT, is incidentally detected on PET-CT, even in patients with a history of malignant neoplasm. Frozen recapping laminoplasty is useful for complete resection of a spinal tumor, preventing local recurrence, and preservation of the posterior spinal elements.


Biochemical reconstitution of steroid receptor•Hsp90 protein complexes and reactivation of ligand binding.
Hsp90 is an essential and highly abundant molecular chaperone protein that has been found to regulate more than 150 eukaryotic signaling proteins, including transcription factors (e.g. nuclear receptors, p53) and protein kinases (e.g. Src, Raf, Akt kinase) involved in cell cycling, tumorigenesis, apoptosis, and multiple eukaryotic signaling pathways (1,2). Of these many 'client' proteins for hsp90, the assembly of steroid receptor•hsp90 complexes is the best defined (Figure 1). We present here an adaptable glucocorticoid receptor (GR) immunoprecipitation assay and in vitro GR•hsp90 reconstitution method that may be readily used to probe eukaryotic hsp90 functional activity, hsp90-mediated steroid receptor ligand binding, and molecular chaperone cofactor requirements. For example, this assay can be used to test hsp90 cofactor requirements and the effects of adding exogenous compounds to the reconstitution process. The GR has been a particularly useful system for studying hsp90 because the receptor must be bound to hsp90 to have an open ligand binding cleft that is accessible to steroid (3). Endogenous, unliganded GR is present in the cytoplasm of mammalian cells noncovalently bound to hsp90. As found in the endogenous GR•hsp90 heterocomplex, the GR ligand binding cleft is open and capable of binding steroid. If hsp90 dissociates from the GR or if its function is inhibited, the receptor is unable to bind steroid and requires reconstitution of the GR•hsp90 heterocomplex before steroid binding activity is restored (4) . GR can be immunoprecipitated from cell cytosol using a monoclonal antibody, and proteins such as hsp90 complexed to the GR can be assayed by western blot. Steroid binding activity of the immunoprecipitated GR can be determined by incubating the immunopellet with [(3)H]steroid. Previous experiments have shown hsp90-mediated opening of the GR ligand binding cleft requires hsp70, a second molecular chaperone also essential for eukaryotic cell viability. Biochemical activity of hsp90 and hsp70 are catalyzed by co-chaperone proteins Hop, hsp40, and p23 (5). A multiprotein chaperone machinery containing hsp90, hsp70, Hop, and hsp40 are endogenously present in eukaryotic cell cytoplasm, and reticulocyte lysate provides a chaperone-rich protein source (6). In the method presented, GR is immunoadsorbed from cell cytosol and stripped of the endogenous hsp90/hsp70 chaperone machinery using mild salt conditions. The salt-stripped GR is then incubated with reticulocyte lysate, ATP, and K(+), which results in the reconstitution of the GR•hsp90 heterocomplex and reactivation of steroid binding activity (7). This method can be utilized to test the effects of various chaperone cofactors, novel proteins, and experimental hsp90 or GR inhibitors in order to determine their functional significance on hsp90-mediated steroid binding (8-11).


Current risk of transfusion-associated human immunodeficiency virus infection.
The procedures designed to minimize the risk of human immunodeficiency virus (HIV) transmission through transfusion include donor self-exclusion, health history questions, confidential unit exclusion, donor call back to withdraw donation, and HIV antibody testing. Each step is important for reducing the number of units collected from donors who are at risk for HIV infection. Although HIV antibody test kit sensitivity exceeds 99%, recently infected persons who are in the "window" between infection and seroconversion are not detected. "Worst scenario" estimates indicate that 1 of 36,000 to 1 of 300,000 components may be collected from donors who have false-negative test results. Since some risk of infection transmission remains, physicians must prescribe transfusion therapy only when the benefit outweighs the potential risk.


The 9p21 locus as a potential therapeutic target and prognostic marker in colorectal cancer.
Colorectal cancer (CRC) is a major cause of cancer-related-death worldwide. Despite extensive efforts to identify valid biomarkers for the risk stratification of CRC patients, there are few of proven clinical utility. It is recognized that genetic factors play a major role in determining susceptibility to CRC. Recent genome-wide association studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CRC. Several genetic polymorphisms have been identified in this region that are associated with CRC. Three genes are located at this locus; CDKN2B(encoding-p15ink4b), CDKN2A (encoding-p16ink4a/p14ARF) and 3' end of CDKN2BAS (termed-antisense-noncoding-RNA in the INK4-locus [ANRIL]). ANRIL has a post-transcriptional modulatory activity, which has been shown to perturb the expression of nearby genes. It also plays an important role in coordinating tissue remodeling through regulation of cell proliferation, apoptosis, aging, extra-cellular matrix remodeling and inflammatory response. However, the role of ANRIL is not well understood in CRC. Hypermethylation of the p14ARF and p16INK4a genes is often found in some tumors, including CRC. However, further studies are necessary to explore the clinical utility of these putative markers in risk stratification, and in the assessment of prognosis. In this review, we have summarized the prognostic and therapeutic potential of the p14ARF and p16INK4a genes in patients with colorectal cancer.


JNK and ERK mitogen-activated protein kinases mediate THDA-induced apoptosis in K562 cells.
2-(6-(2-thieanisyl)-3(Z)-hexen-1, 5-diynyl) aniline (THDA), an enediyne compound, was identified in our laboratory as a novel antineoplastic agent against human leukemia K562 cells. THDA-induced apoptosis was associated with the upregulation of Bax, downregulation of X-linked inhibitor of apoptosis (XIAP), as well as the activation of caspase-3 and caspase-9. In addition, the mitogen-activated protein family kinases, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) kinases, and the transcription factor c-Jun were all activated by phosphorylation after 6 h exposure to THDA. Phosphorylation (activation) of JNK and ERK kinases by THDA was blocked by an ERK inhibitor, PD98059, or a JNK inhibitor, JNK-1, respectively, suggesting that THDA-induced apoptosis in K562 cells is ERK and JNK dependent. Moreover, the blockade of ERK and JNK also attenuated the modulation of Bax and XIAP, as well as the activation of caspase-3 and caspase-9 induced by THDA. These findings suggest that the activation of JNK and ERK is involved in the THDA-induced apoptosis of K562 cells. Therefore, this investigation, for the first time, uncovered the biological properties of this novel antitumor enediyne.


Meeting report of the STAR-Sensitization in Transplantation Assessment of Risk: Naïve Abdominal Transplant Organ subgroup focus on kidney transplantation.
The development of de novo donor-specific HLA antibody (dnDSA) is a critical feature contributing to late allograft failure. The complexity of the issue is further complicated by organ-specific differences, detection techniques, reliance of tissue histopathology and changing diagnostic criteria, ineffective therapies, and lack of consensus. To tackle these issues, the Sensitization in Transplantation Assessment of Risk (STAR) 2017 was initiated as a collaboration of the American Society of Transplantation and American Society of Histocompatibility and Immunogenetics consisting of 8 working groups with the goal to provide guidelines on how to assess risk and risk stratify patients based on their potential alloimmune and DSA status. Herein is a summary of discussions by the Naïve Abdominal Working Group, highlighting currently available data and identifying gaps in our knowledge on the development and impact of dnDSA following kidney transplantation.


The impact of delaying colonoscopies during the COVID-19 pandemic on colorectal cancer detection and prevention.
The COVID-19 pandemic resulted in a partial to total shutdown of endoscopy in many healthcare centers. This study aims to quantify the impact of the reduction in colonoscopies on colorectal cancer (CRC) detection and screening. After institutional ethics board approval, the endoscopy database at an academic tertiary-care center in Montreal, Canada, was searched for all colonoscopies performed from during the first wave locally (March-June 2020), and during the ramp up period where endoscopy service resumed (July to August 2020). We compared these periods to the same periods in 2019, the pre-pandemic periods. The indications, CRC and adenoma detection rates, as well as the prioritization of urgent procedures were compared. In the first wave, only 462 colonoscopies were performed, compared to 2515 in the same period in 2019, an 82% reduction. The ramp up period saw 843 colonoscopies performed compared to 1328 in 2019, a 35% reduction. Urgent and inpatient colonoscopies numbers increased (324 (24.8%) vs. 220 (5.7%)) while surveillance and high-risk screening colonoscopies fell (376 (28.8%) vs 1869 (48.6%)). Emergency access to colonoscopy was preserved with a median time to endoscopy of < 1 day (IQR 0,1) in both pandemic periods. During the pandemic periods, there was an absolute reduction in CRC diagnosis of 28, despite the CRC detection per colonoscopy rate increasing slightly in the first wave from 1.7% (44) to 3.9% (18), and in the ramp up period from 2.5% (33) to 3.6% (31). The rate of adenoma detection per colonoscopy did not increase significantly between the pre- and pandemic periods, resulting in reduction in adenoma removal in 723 patients. The restriction of access to colonoscopy resulted in a significant reduction in screening and surveillance of high-risk patients, adenomas removed, and CRCs diagnosed. Clinicians and patients will face the oncologic ramifications this the coming years.


Surveillance in ulcerative colitis: is chromoendoscopy-guided endomicroscopy always better than conventional colonoscopy? A randomized trial.
Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer. Chromoendoscopy showed superiority to conventional colonoscopy (CC) in surveillance studies including high-risk patients. We aimed to compare chromoendoscopy-guided endomicroscopy (CGE) with CC for intraepithelial neoplasia (IN) detection in patients with longstanding UC without primary sclerosing cholangitis and/or history of IN. One hundred sixty-two patients with longstanding (≥ 8 yr) distal/extensive UC and without primary sclerosing cholangitis and/or history of IN were prospectively randomized to undergo CGE (group A) or CC (group B). Seventeen patients were excluded. In group A (n = 72), circumscribed lesions highlighted by pan-chromoendoscopy were evaluated by endomicroscopy, and targeted biopsy/polypectomy was performed. In group B (n = 73), 4 random biopsies every 10 cm and targeted biopsy/polypectomy of detected lesions were performed. Thirteen IN, all low grade, were detected: 7 IN in group A and 6 in group B (P > 0.05), distributed, respectively, by 6 and 4 patients (P > 0.05). Significantly, more biopsies were performed in group B (4.7 ± 4.9 versus 36.0 ± 6.2, P < 0.001), and the per-biopsy yield of IN was higher in group A (1/48 versus 1/438, P < 0.001). Examination time was 61.5 ± 15.6 minutes in group A and 40.7 ± 8.7 minutes in group B (P < 0.001). The IN detection by endomicroscopy revealed: sensitivity = 85.7%, specificity = 97.9%, positive predictive value = 75.0%, and negative predictive value = 98.9%. CGE does not improve the detection of IN in the endoscopic screening of patients with longstanding UC without primary sclerosing cholangitis and/or history of IN. CGE takes longer than CC, but it decreases the number of biopsies performed and significantly increases the per-biopsy yield of IN. Endomicroscopy is an accurate tool for IN detection.


Results of living donor liver transplantation in five children with congenital cardiac malformations requiring cardiac surgery.
In the pediatric population, the concomitant presentation of end-stage liver disease and congenital cardiac malformation occurs rarely. Determining the surgical priority in these cases is a challenge due to the presence of hemodynamic alterations that increase surgical risks. We examined five cases that received living-donor liver transplantation. In four patients that had congenital heart disease with a left to right shunt, two had cardiac surgery first, one had both heart and liver surgery simultaneously, and one underwent liver transplantation first. Both of the patients that received heart surgery before liver transplantation needed emergency liver transplantation because of post-operative liver failure. All five patients had a good outcome. Meticulous surgery, close monitoring, and adequate volume management, in addition to tailoring management decisions to the patient's specific condition, make it possible to correct both the liver and the heart abnormalities with satisfactory results.


Cost of childbirth in Upper West Region of Ghana: a cross-sectional study.
Out-of-pocket payment (OOPP) is reported to be a major barrier to seeking maternal health care especially among the poor and can expose households to a risk of catastrophic expenditure and impoverishment.This study examined the OOPPs women made during childbirth in the Upper West region of Ghana. We carried out a cross-sectional study and interviewed women who gave birth between January 2013 and December 2017. Data on socio-demographic characteristics, place of childbirth, as well as direct cost (medical and non-medical) were collected from respondents. The costs of childbirth were estimated from the patient perspective. Logistics regression was used to assess the factors associated with catastrophic payments cost. All analyses were done using STATA 16.0. Out of the 574 women interviewed, about 71% (406/574) reported OOPPs on their childbirth. The overall average direct medical and non-medical expenditure women made on childbirth was USD 7.5. Cost of drugs (USD 8.0) and informal payments (UDD 5.7) were the main cost drivers for medical and non-medical costs respectively. Women who were enrolled into the National Health Insurance Scheme (NHIS) spent a little less (USD 7.5) than the uninsured women (USD 7.9). Also, household childbirth expenditure increased from primary health facilities level (community-based health planning and services compound = USD7.2; health centre = USD 6.0) to secondary health facilities level (hospital = USD11.0); while home childbirth was USD 4.8. Overall, at a 10% threshold, 21% of the respondents incurred catastrophic health expenditure. Regression analysis showed that place of childbirth and household wealth were statistically significant factors associated with catastrophic payment. The costs of childbirth were considerably high with a fifth of households spending more than one-tenth of their monthly income on childbirth and therefore faced the risk of catastrophic payments and impoverishment. Given the positive effect of NHIS on cost of childbirth, there is a need to intensify efforts to improve enrolment to reduce direct medical costs as well as sensitization and monitoring to reduce informal payment. Also, the identified factors that influence cost of childbirth should be considered in strategies to reduce cost of childbirth.


[Blood lactate levels during fast-track cardiac anesthesia].
Lactate is a very sensitive marker of outcomes in critically ill patients. The aim of this study was to investigate the significance of blood lactate measurement during fast-track cardiac anesthesia. We examined arterial blood lactate levels of 12 patients following coronary artery bypass graft surgery under intermittent aortic cross clamping with fast-track cardiac anesthesia. Anesthesia was induced with propofol and fentanyl, and maintained with propofol, fentanyl (total 400-1000 micrograms) and isoflurane. Blood samples were collected from a radical artery catheter. At the termination of the extracorporeal circulation, the blood lactate was 10.3 +/- 2.0 (7.4-12.5) mmol.l-1. This value decreased slowly to 1.5 +/- 0.4 mmol.l-1 on the second postoperative day. All patients were extubated within 4 hours after surgery. Vital signs were stable, and no cardiac events occurred perioperatively. A continuous decline in blood lactate levels was related to a favorable postoperative course. Further research might be required to prevent transient hyperlactecemia at the end of cardiopulmonary bypass.


The molecular dynamics of osteoclast adhesions.
Podosomes are specialized adhesive structures that play a central role in bone resorption. In this article we address the molecular diversity and dynamics of podosomes at different states of organization, ranging from scattered distribution over the entire ventral membrane of non-polarized cells, via formation of podosome clusters and developing rings to the assembly of a peripheral belt, resembling the sealing zone of polarized, bone-resorbing osteoclasts. Based on published data and on our own results, we describe here the spatial relationships between key podosome-associated proteins. Using quantitative microscopy, we show here a dramatic increase in the local levels of F-actin, vinculin, paxillin, and alpha-actinin, which occurs upon the transformation of clustered podosomes into rings and sealing zone-like structures. This change is accompanied by a marked decrease in phosphotyrosine levels in the same region. Therefore, our data suggest that a major change in the molecular composition of podosomes is taking place during osteoclast polarization, a change that may be related to adhesion "reinforcement", associated with the assembly of the bone-resorbing apparatus. Studying the nature of the proteins that undergo de-phosphorylation is critical for the understanding of the mechanisms regulating the processes described above.


Superior gallstone dissolubility and safety of tert-amyl ethyl ether over methyl-tertiary butyl ether.
The use of methyl-tertiary butyl ether (MTBE) to dissolve gallstones has been limited due to concerns over its toxicity and the widespread recognition of the safety of laparoscopic cholecystectomy. The adverse effects of MTBE are largely attributed to its low boiling point, resulting in a tendency to evaporate. Therefore, if there is a material with a higher boiling point and similar or higher dissolubility than MTBE, it is expected to be an attractive alternative to MTBE. To determine whether tert-amyl ethyl ether (TAEE), an MTBE analogue with a relatively higher boiling point (102 °C), could be used as an alternative to MTBE in terms of gallstone dissolubility and toxicity. The in vitro dissolubility of MTBE and TAEE was determined by measuring the dry weights of human gallstones at predetermined time intervals after placing them in glass containers with either of the two solvents. The in vivo dissolubility was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after the direct infusion of each solvent into the gallbladder in both hamster models with cholesterol and pigmented gallstones. The in vitro results demonstrated a 24 h TAEE-dissolubility of 76.7%, 56.5% and 38.75% for cholesterol, mixed, and pigmented gallstones, respectively, which represented a 1.2-, 1.4-, and 1.3-fold increase in dissolubility compared to that of MTBE. In the in vitro experiment, the 24 h-dissolubility of TAEE was 71.7% and 63.0% for cholesterol and pigmented gallstones, respectively, which represented a 1.4- and 1.9-fold increase in dissolubility compared to that of MTBE. In addition, the results of the cell viability assay and western blot analysis indicated that TAEE had a lower toxicity towards gallbladder epithelial cells than MTBE. We demonstrated that TAEE has higher gallstone dissolubility properties and safety than those of MTBE. As such, TAEE could present an attractive alternative to MTBE if our findings regarding its efficacy and safety can be consistently reproduced in further subclinical and clinical studies.


Prevalence of Salmonella isolates and antimicrobial resistance in poultry meat from South Korea.
Contamination of Salmonella was assessed in duck and chicken meat collected from supermarkets, traditional markets, internet shopping malls, and wholesale markets in Jeonlado, South Korea, in 2013. Salmonella contamination was found in 51.3% of duck meat samples and 3.7% of chicken meat samples. Salmonella contamination of duck meat samples differed by meat type, i.e., 69.8% of samples of whole ducks and 33.9% of samples of duck pieces. Six serotypes were identified from 64 Salmonella isolates in duck meat: Salmonella Typhimurium (37.5%), Salmonella Enteritidis (21.8%), Salmonella Stanley (3.1%), Salmonella Regent (1.6%), Salmonella Winterthur (3.1%), and Salmonella Westhampton (1.6%). All isolates were resistant to one or more antibiotics. Resistance to sulfisoxazole was most common (93.8% of isolates), followed by resistance to nalidixic acid (59.4%), ceftazidime (26.6%), and ampicillin (26.6%). To our knowledge, this study is the first to report Salmonella contamination in duck meat from Korea. Duck meat should be considered an important source of foodborne pathogens.


Concentrative uptake of cyclic ADP-ribose generated by BST-1+ stroma stimulates proliferation of human hematopoietic progenitors.
Cyclic ADP-ribose (cADPR) is an intracellular calcium mobilizer generated from NAD(+) by the ADP-ribosyl cyclases CD38 and BST-1. cADPR, both exogenously added and paracrinally produced by a CD38(+) feeder layer, has recently been demonstrated to stimulate the in vitro proliferation of human hemopoietic progenitors (HP) and also the in vivo expansion of hemopoietic stem cells. The low density of BST-1 expression on bone marrow (BM) stromal cells and the low specific activity of the enzyme made it unclear whether cADPR generation by a BST-1(+) stroma could stimulate HP proliferation in the BM microenvironment. We developed and characterized two BST-1(+) stromal cell lines, expressing an ectocellular cyclase activity similar to that of BST-1(+) human mesenchymal stem cells, the precursors of BM stromal cells. Long term co-culture of cord blood-derived HP over these BST-1(+) feeders determined their expansion. Influx of paracrinally generated cADPR into clonogenic HP was mediated by a concentrative, nitrobenzylthioinosine- and dipyridamole-inhibitable nucleoside transporter, this providing a possible explanation to the effectiveness of the hormone-like concentrations of the cyclic nucleotide measured in the medium conditioned by BST-1(+) feeders. These results suggest that the BST-1-catalyzed generation of extracellular cADPR, followed by the concentrative uptake of the cyclic nucleotide by HP, may be physiologically relevant in normal hemopoiesis.


Novel technique for placement of laryngeal mask airway in difficult pediatric airways.
The main responsibility of an anesthesiologist is to safely maintain an open airway and preserve sufficient gas exchange in the lungs. This role becomes more significant when managing children especially those with difficult airways (DA). In such cases, a quick appropriate action can decrease the related mortality and morbidity. Laryngeal mask airway (LMA) is a device used in cases with difficult airways. Its placement is much more difficult in children especially those with DA. There is a greater risk of malpositioning and its insertion with routine techniques is sometimes impossible. In this article, we introduce a new method for replacement of LMA in difficult pediatric airways (DPA). In this before and after, pre and post design clinical trial, we evaluated 30 children with congenital anomalies and difficult airways who were candidates for elective eye surgery (short term). A written consent was obtained from the parents or the legal guardians of those who met the inclusion criteria. Inhalation anesthesia was induced by sevoflurane. The patients had assisted spontaneous respiration. No muscle relaxant was administered. LMA was inserted using the classic method in the anesthesia depth of BIS = 35-40. After 2 unsuccessful attempts according to the criteria for adequate function of LMA, we tried placing the LMA using our innovated method after meeting the primary requirements and reaching the anesthesia depth of 35-40. In this method, the index finger of the left hand was placed on the tongue pushing it downwards (towards the floor of the mouth) when inserting the LMA. This way, we assisted LMA passing down the pharynx resulting in its adequate positioning. Criteria for adequate function of LMA in both classic and innovated insertion methods included monitoring of easy ventilation, no resistance during exhalation, adequate chest movement, no air leakage, optimal airway pressure, optimal lung compliance, level of oxygenation of arterial blood and level of CO2 at the end of exhalation. In case of presence of air leakage with bag pressure below 15 cm of water, lack of chest movement during inhalation, upper airway pressure over 20 cm of water, SPO2 lower than 90% and low compliance of the lung, LMA placement would be considered a failure. In such cases, LMA would be immediately extracted and the required depth of anesthesia would be reached using an oxygen mask and required inhalations. Complications occurring during the procedure and after LMA extraction would be recorded. Our understudy population included 30 children in the age range of 1.5 months to 10 yrs (11 girls and 19 boys) who had clear DA criteria due to syndromes and severe congenital anomalies and were candidates for elective eye surgery. Duration of the operation was 30 to 60 minutes. In all 30 cases, LMA placement with the classic method was not successful after 2 attempts by an expert. LMA was successfully inserted for all cases by the same person using the innovated method after meeting the required criteria (BIS = 35-40). All ventilation indices were met and the operation was performed successfully with no complication. There is always a risk of unsuccessful LMA placement in difficult pediatric airways using the classic method of insertion. The innovated method recommends pushing down the tongue by the index finger of the left hand. Considering the hypersensitivity of children to hypoxia and risk of unsuccessful LMA placement by the classic method, the innovated placement method is advised in children suffering from anomalies associated with macroglossia.


Primary structure of human J chain: alignment of peptides from chemical and enzymatic hydrolyses.
The primary structure of the J chain from a human Waldenströms IgM protein has been determined using a combination of automated and conventional Edman degradative procedures. Eighty-five percent of the sequence was established with peptides isolated from tryptic digests of carboxyamidomethylated and citraconylated J chain, many of which were sequenced completely. Alignment of the tryptic fragments was achieved with peptides generated by chymotrypsin and limited acid hydrolyses. The j chain consits of 129 amino acids and a single oligosaccharide structure linked to asparagine at positon 43 of the sequence. The molecular weight, including 7.5% carbohydrate by weight, is 16 422. The location and arrangement of three half-cystines could be deduced from previous studies, whereas the pairing of the remaining five disulfide bonds still needs to be clarified.


Stabilizing Zr and Ti cations by interaction with a ferrocenyl fragment.
Reaction of the cation Cp(2)ZrMe(mu-MeB(C(6)F(5))(3)) or Cp(tBu(3)PN)TiMe(mu-MeB(C(6)F(5))(3)) with (RC(5)H(4))(2)Fe (R = H, Me) yields remarkably stable, yet reactive cations. The early metal centers are stabilized by dative donation from Fe and an agostic interaction with a CH bond of an Fe-bound cyclopentadienyl ligand.


The role of 5-hydroxytryptamine and 5-hydroxytryptaminergic mechanisms in hypertension.
1. The possible role of 5-hydroxytryptamine (5-HT) and 5-HT-receptors in hypertension, already suggested by Page in 1954, has been subject to a renaissance of interest owing to the development of antihypertensive drugs which interact with 5-HT-receptors. These drugs, like ketanserin, urapidil and flesinoxan are used as tools to study the role of 5-HT and its receptors in hypertension. 2. The following arguments would plead in favour of a certain role of 5-HT and 5-HT-receptors in the pathogenesis and maintenance of hypertension: hyperresponsiveness of blood vessels from hypertensive patients and animals to 5-HT-induced constriction; the antihypertensive/vasodilator activity of the 5-HT2-receptor antagonist ketanserin; enhanced sensitivity of platelets from hypertensives to 5-HT. 3. However, at least as many arguments would deny a role of peripheral 5-HT in hypertension, like for instance: the fact that 5-HT is not a generally accepted pressor agent, whereas its concentration in the circulating blood is subthreshold; the hyperresponsiveness of vessels from hypertensives is not specific for 5-HT; the elevated local concentration of 5-HT released by platelets is mainly limited to the microcirculation; the 5-HT2-receptor antagonist ketanserin is the only agent of this type which lowers blood pressure, other 5-HT2-receptor blockers like ritanserin and LY 53587 being inactive. 4. The various data and arguments available do not unequivocally support a relevant role of peripheral 5-HT and its receptors in hypertensive disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Setup and Use of HepaRG Cells in Cholestasis Research.
Since HepaRG cells can differentiate into well-polarized mature hepatocyte-like cells that synthesize, conjugate, and secrete bile acids, they represent an appropriate surrogate to primary human hepatocytes for investigations on drug-induced cholestasis mechanisms. In this chapter, culture conditions for obtaining HepaRG hepatocytes and the main methods used to detect cholestatic potential of drugs are described. Assays for evaluation of bile canaliculi dynamics and morphology are mainly based on time-lapse and phase-contrast microscopy analysis. Bile acid uptake, trafficking, and efflux are investigated using fluorescent probes. Individual bile acids are quantified in both culture media and cell layers by high-pressure liquid chromatography/tandem mass spectrometry. Preferential cellular accumulation of toxic hydrophobic bile acids is easily evidenced when exogenous primary and secondary bile acids are added to the culture medium.


Differential Effects of Beta-Hydroxybutyrate Enantiomers on Induced Pluripotent Stem Derived Cardiac Myocyte Electrophysiology.
Beta-hydroxybutyrate (βOHB), along with acetoacetate and acetone, are liver-produced ketone bodies that are increased after fasting or prolonged exercise as an alternative fuel source to glucose. βOHB, as the main circulating ketone body, is not only a G-protein coupled receptor ligand but also a histone deacetylases inhibitor, prompting the reexamination of its role in health and disease. In this study, we compared the effects of two commercial βOHB formulations an enantiomer R βOHB and a racemic mixture ±βOHB on induced pluripotent stem cell cardiac myocytes (iPS-CMs) electrophysiology. Cardiac myocytes were cultured in R βOHB or ±βOHB for at least ten days after lactate selection. Flouvolt or Fluo-4 was used to assay iPS-CMs electrophysiology. We found that while both formulations increased the optical potential amplitude, R βOHB prolonged the action potential duration but ±βOHB shortened the action potential duration. Moreover, ±βOHB increased the peak calcium transient but R βOHB reduced the peak calcium transient. Co-culturing with glucose or fatty acids did not ameliorate the effects, suggesting that βOHB was more than a fuel source. The effect of βOHB on iPS-CMs electrophysiology is most likely stereoselective, and care must be taken to evaluate the role of exogenous βOHB in health and disease.


Pathogenicity testing of Macaca arctoides subgingival plaque following chlorhexidine treatment.
POTENTIAL INFECTIVITY of subgingival plaque of Macaca arctoides in guinea pig leg muscle was examined before, during, and after chlorhexidine treatment. The regime of chlorhexidine administration did not appear to alter the monkey subgingival microflora markedly and had no demonstrable effects on the pathogenicity of the subgingival plaque. These data confirm previous suggestions that chlorhexidine essentially does not penetrate into the deeper part of periodontal pockets following a supragingival mode of administration.


CEACAM1 Is a Prognostic Biomarker and Correlated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma.
CEACAM1 has been shown to be aberrantly expressed in a variety of tumors, and modulation of CEACAM1-related signaling pathways has been suggested as a novel approach for cancer immunotherapy in recent years. However, its role in clear cell renal cell carcinoma (ccRCC) is unclear. The relationship between CEACAM1 and ccRCC was demonstrated based on data from TCGA, GEO, and HPA databases. And the relationship between clinicopathological features and CEACAM1 expression was also assessed. Survival curve analysis was performed to analyze the prognostic relationship between CEACAM1 expression and ccRCC. Protein interaction network analysis was used to analyze the relationship between CEACAM1 and microenvironment-related proteins. In addition, the immunomodulatory role of CEACAM1 in ccRCC was assessed by analyzing CEACAM1 and immune cell infiltration. The expression of CEACAM1 was lower in ccRCC tissues than in adjacent normal tissues, and its expression level was negatively correlated with tumor size status (P < 0.001), metastasis status (P = 0.009), pathological stage (P = 0.002), gender (P < 0.001), histological grade (P < 0.001), and primary therapy outcome (P = 0.045) of ccRCC. Survival curve analysis showed that ccRCC patients with lower CEACAM1 expression exhibited shorter overall survival (P < 0.001), and CEACAM1 interacted with microenvironmental molecules such as fibronectin and integrins. Furthermore, immune infiltration analysis showed that CEACAM1 expression correlated with CD8+ and CD4+ T cells, macrophage, neutrophil, and dendritic cell infiltration in ccRCC. CEACAM1 expression correlates with progression, prognosis, and immune cell infiltration in ccRCC patients, and it may be a promising prognostic biomarker and therapeutic target for ccRCC.


Corrigendum.
Liu J, Fei L, Huang G-Q, Shang X-K, Liu M, Pei Z-J, Zhang Y-X. Right ventricle performances with echocardiography and 99mTc myocardial perfusion imaging in pulmonary arterial hypertension patients. Exp Biol Med 2018;243(9):754-761. In this article, the first author's affiliation was incorrect in the OnlineFirst and print versions. It should have appeared as 'Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China'. This has been corrected in the online article.


[Donation of bodies to science].
Teaching and research in anatomy is mainly based on cadaveric dissection. Unclaimed bodies is no more the origin of cadavers, but body donation programs. The dissection is an important part in the anatomical curses of medical students and for anatomical research and special courses devoted to the surgeons. A body donation center was created in Paris in 1953 with the purpose of obtaining bodies for dissection. Donation is a clear will made by people free and informed. Donation is most often by altruism, conferrins life on another. Body donation is regulated by various act or reglementar text according to each country. One of the problem with the body gift is biological hazard, specially in research and clinical courses, but the rule is to consider unembalmed material as contaminated and to use all precautions with barrier for blood and bodily fluid. Body donation is one of the modern expression of solidarity.


Patterns of iodine intake and urinary iodine concentrations during pregnancy and blood thyroid-stimulating hormone concentrations in the newborn progeny.
Appropriate maternal intake of iodine during pregnancy is essential for maternal thyroxine production and thyroid status of the fetus. It should be possible to enhance iodine intake during pregnancy by using iodine fortified salt or taking iodine supplements. In the present report we determined the status of iodine nutrition in pregnant women who were stratified on the basis of their history of taking or not taking iodized salt or iodine supplements. The study was performed in Toledo (Spain), a region in which prior studies have noted borderline iodine sufficiency. Iodine nutrition was assessed by measuring urinary iodine concentration (UIC) and neonatal thyrotropin (TSH). UIC was measured in 525 pregnant women. They were grouped according to their history of iodine intake. Diet Group 1 patients (n = 69) did not take iodized salt or iodine supplements during pregnancy. Diet Group 2 patients (n = 75) took iodized salt but not iodine supplements during pregnancy. Diet Group 3 patients (n = 381) took iodine supplements during pregnancy. Plasma determinations included TSH, free thyroxine, thyroid peroxidase antibody, and thyroglobulin antibody. UIC was measured in a single urine sample from all the pregnant women. Neonatal TSH was measured in capillary spot blood from all the neonates as part of a screening for congenital metabolic abnormalities. The median UIC in all subjects was 164 μg/L (interquartile range [IR]: 116-245). The median UICs in Diet Groups 1, 2, and 3 were 134.5 (IR: 90-196), 146 (IR: 103-205), and 183 (IR: 124-261) μg/L, respectively (p = not significant [NS] for Diet Group 1 vs. 2; p < 0.01 for Diet Group 2 vs. 3; all other comparisons NS). The median (IR) TSH of the neonates in all Diet Groups was 1.0 (IR: 0.7-1.6) μU/mL. Only 2 neonates had blood TSH concentrations >5 mU/L. Neonatal blood TSH concentrations were similar in all Diet Groups. In a region with a history of borderline iodine deficiency the UICs were below 150 μg/L in a substantial percentage of pregnant women who did not take iodine supplements, regardless of whether or not they took iodized salt. Our results support the use of iodine supplements from the start of the pregnancy, or even before pregnancy in women who live in regions with a history of even small degrees of iodine deficiency. In addition, neonate TSH screening is not the best tool to assess whether the iodine status in populations is ideal.


Streamlined Fabrication of Hybrid Lipid Bilayer Membranes on Titanium Oxide Surfaces: A Comparison of One- and Two-Tail SAM Molecules.
There is broad interest in fabricating cell-membrane-mimicking, hybrid lipid bilayer (HLB) coatings on titanium oxide surfaces for medical implant and drug delivery applications. However, existing fabrication strategies are complex, and there is an outstanding need to develop a streamlined method that can be performed quickly at room temperature. Towards this goal, herein, we characterized the room-temperature deposition kinetics and adlayer properties of one- and two-tail phosphonic acid-functionalized molecules on titanium oxide surfaces in various solvent systems and identified optimal conditions to prepare self-assembled monolayers (SAMs), upon which HLBs could be formed in select cases. Among the molecular candidates, we identified a two-tail molecule that formed a rigidly attached SAM to enable HLB fabrication via vesicle fusion for membrane-based biosensing applications. By contrast, vesicles adsorbed but did not rupture on SAMs composed of one-tail molecules. Our findings support that two-tail phosphonic acid SAMs offer superior capabilities for rapid HLB coating fabrication at room temperature, and these streamlined capabilities could be useful to prepare durable lipid bilayer coatings on titanium-based materials.


Asymptomatic ventricular tachycardia: diagnostic pitfalls of Andersen-Tawil syndrome-a case report.
Andersen-Tawil syndrome (ATS) is a rare arrhythmia disorder caused by a mutation in the KCNJ2 gene. Typical presentation includes a triad of cardiac arrhythmia, dysmorphia, and periodic paralysis. However, KCNJ2 mutations can mimic other disorders such as catecholaminergic polymorphic ventricular tachycardia (CPVT) making treatment challenging. A 9-year-old asymptomatic female patient presented with an irregular heart rate noted at a well-child visit. Physical examination revealed short stature and facial dysmorphism. An initial rhythm strip showed intermittent runs of non-sustained bidirectional ventricular tachycardia with a prolonged QT interval of 485 ms at rest. Exercise testing showed no significant increase in ectopy from baseline at higher heart rates. Cardiac imaging was normal, and the burden of ventricular ectopy was significantly reduced on a beta-blocker and Class IC antiarrhythmic combination. Genetic testing marked a D71N mutation in the KCNJ2 gene. Clinical distinction between ATS and CPVT is a challenge. Genetic testing in the above patient attributed a likely pathogenic variant for both ATS and CPVT to a single D71N mutation in the KCNJ2 gene. Further evaluation revealed no clinical CPVT, emphasizing the need for cautious interpretation of genetic results in inherited arrhythmia disorders.


Efficacy of fetal left ventricular modified myocardial performance index in predicting adverse perinatal outcomes in intrahepatic cholestasis of pregnancy.
This study aimed to evaluate the effectiveness of fetal left ventricular modified myocardial performance index in predicting adverse perinatal outcomes for intrahepatic cholestasis of pregnancy. A cross-sectional study was conducted, including 51 women with intrahepatic cholestasis of pregnancy and 80 healthy controls. Using Doppler ultrasonography, E-wave, A-wave, isovolumetric contraction time, isovolumetric relaxation time, and ejection time were recorded and the left ventricular modified myocardial performance index was measured. Findings showed that the mean left ventricular modified myocardial performance index, isovolumetric contraction time, and isovolumetric relaxation time values were statistically significantly higher while the ejection time and E/A ratios were statistically significantly lower in the intrahepatic cholestasis of pregnancy group than the control group. In the intrahepatic cholestasis of pregnancy group, a statistically significant positive correlation was found between left ventricular modified myocardial performance index and adverse perinatal outcomes in the intrahepatic cholestasis of pregnancy group (r=0.478, p<0.001), while a statistically significant negative correlation was found between the E/A ratio and adverse perinatal outcomes (r=-0.701, p<0.001). For intrahepatic cholestasis of pregnancy cases, high fetal left ventricular modified myocardial performance index values were an indicator of ventricular dysfunction, and this correlated with negative perinatal outcomes.


Plasma exchange in Goodpasture's syndrome.
The clinical course and levels of anti-glomerular basement membrane (GBM) antibody were compared in 20 patients with Goodpasture's syndrome treated with plasma exchange and immunosuppression (8 patients), immunosuppression alone (4 patients) or no specific therapy (8 patients). There was a more rapid fall in the level of anti-GBM antibody and pulmonary hemorrhage was less protracted in the 8 patients treated with plasma exchange and immunosuppression. In this group, 1 patient who presented with severe renal failure showed a marked improvement of renal function and there was no progression of disease in the 4 with milder renal involvement. 2 of the 4 patients treated with immunosuppression alone, and only 2 of the 8 patients who received no specific therapy, maintained normal renal function. In the group which received no specific therapy, 1 of the 6 patients who progressed to renal failure had mild renal involvement initially. There was a significant correlation between the level of anti-GBM antibody and the severity of the morphological changes seen at renal biopsy but not between the level of anti-GBM antibody and the severity of lung hemorrhage. The course and outcome of the disease in those patients not treated, or treated with immunosuppression alone, was better than that described in early reports of this disease, while those patients with plasma exchange and immunosuppression fared even better. An adequately stratified controlled trial of immunosuppression and plasma exchange versus immunosuppression alone is in order.


Comparison of gadobenate dimeglumine-enhanced dynamic MRI and 16-MDCT for the detection of hepatocellular carcinoma.
The objective of our study was to compare the diagnostic performance of gadobenate dimeglumine-enhanced MRI with that of 16-MDCT for the detection of hepatocellular carcinoma using receiver operating characteristic (ROC) curve analysis. Thirty-one patients with 53 hepatocellular carcinomas underwent gadobenate dimeglumine-enhanced dynamic MRI and multiphasic CT using 16-MDCT within a mean interval of 5 days (range, 3-9 days). The dynamic MRI examination was performed using 3D fat-saturated volumetric interpolated imaging and sensitivity encoding on a 1.5-T unit. Both dynamic MRI and multiphasic MDCT included dual arterial phase images. Three observers independently interpreted the CT and MR images in random order, separately, and without patient identifiers. The diagnostic accuracy of each technique was evaluated using the alternative-free response ROC method. The sensitivity and positive predictive values were also calculated. The sensitivities of gadobenate dimeglumine-enhanced MRI for all observers were significantly higher than those of MDCT for all the lesions and for lesions 1.0 cm or smaller (p < 0.05); however, for lesions larger than 1.0 cm, the sensitivities of the two imaging techniques were similar. The mean area under the ROC curve (A(z)) of gadobenate dimeglumine-enhanced MRI (0.87 +/- 0.03 [SD]) was higher than that of MDCT (0.83 +/- 0.04), but no significant difference was found between them (p = 0.31). The number of false-positive findings on dynamic MRI was slightly higher than on MDCT, but no significant difference in the positive predictive value between the two imaging techniques was detected (observer 1, p = 0.06; observer 2, p = 0.13; observer 3, p = 1.00). Gadobenate dimeglumine-enhanced MRI has a higher sensitivity for small hepatocellular carcinomas (</= 1 cm) but a higher false-positive rate due to nonspecific enhancement of benign lesions, such as arterioportal shunt, leading to no significant difference of overall accuracy when compared with MDCT.


The Association Between the Albumin and Viral Negative Conversion Rate in Patients Infected with Novel Coronavirus Disease 2019 (COVID-19).
The novel coronavirus disease 2019 (COVID-19) epidemic is the severe global pandemic with large numbers of infected cases and deaths in recent decades. The previous studies were all about the influence of albumin (ALB) for the severity and mortality of in-patients infected with COVID-19. But few studies exist about the influence factors to achieve viral negative conversion. Therefore, this study conducted an exploratory study to investigate the effect of albumin on negative conversion rate. Among the 190 hospitalized patients with moderate COVID-19 who had a course of disease longer than 30 days, 102 achieved viral negative conversion in 30-45 days and 88 not after 45 days. Taking other variables as concomitant variable, Cox proportional hazard regression model was applied to explore the influence of albumin to negative conversion rate under various factors. By comparing patients who could and could not achieve the finally viral negative conversion, a possible nonlinear relationship between the continuous variables and clinical outcomes was examined by a restricted cubic spline regression model. An association was found between albumin levels and hazard ratio of viral negative conversion rate (P = 0.027). The increase of albumin was accompanied with decreases of hazard ratio of viral negative conversion rate (the value of albumin <38 g/L). But when the value of albumin was higher than 38 g/L, the hazard ratio of viral negative conversion rate approached 1, it means that albumin is not a risk factor for the viral negative conversion rate of COVID-19 disease. For patients with COVID-19, albumin is a common and observed laboratory parameter. It is associated with final viral negative conversion rate although its underlying mechanism and relationship with the viral negative conversion rate still need to be clarified.


Environmental fate model for ultra-low-volume insecticide applications used for adult mosquito management.
One of the more effective ways of managing high densities of adult mosquitoes that vector human and animal pathogens is ultra-low-volume (ULV) aerosol applications of insecticides. The U.S. Environmental Protection Agency uses models that are not validated for ULV insecticide applications and exposure assumptions to perform their human and ecological risk assessments. Currently, there is no validated model that can accurately predict deposition of insecticides applied using ULV technology for adult mosquito management. In addition, little is known about the deposition and drift of small droplets like those used under conditions encountered during ULV applications. The objective of this study was to perform field studies to measure environmental concentrations of insecticides and to develop a validated model to predict the deposition of ULV insecticides. The final regression model was selected by minimizing the Bayesian Information Criterion and its prediction performance was evaluated using k-fold cross validation. Density of the formulation and the density and CMD interaction coefficients were the largest in the model. The results showed that as density of the formulation decreases, deposition increases. The interaction of density and CMD showed that higher density formulations and larger droplets resulted in greater deposition. These results are supported by the aerosol physics literature. A k-fold cross validation demonstrated that the mean square error of the selected regression model is not biased, and the mean square error and mean square prediction error indicated good predictive ability.


A high-performance fluorescent hybrid material for fluorometric detection and removal of toxic Pb(ii) ions from aqueous media: performance and challenges.
Lead(ii) is an extremely toxic heavy metal ion that causes various health problems that are difficult to recover from in many developing countries of the world. Fluorescence-based nanosensors have amazing characteristics such as high sensitivity/selectivity, portability, low detection limit, rapid on-site usability, low cost and capability for removal of heavy metal ions. In this paper, a new fluorescent hybrid material based on silica gel (Bodipy-Si) was developed via a click reaction between alkyne-terminal silica gel and azido-terminal Bodipy. The solid support surface was characterized by various techniques such as SEM, FT-IR, etc. The adsorption and fluorometric properties of the fluorescent nanoparticles were also examined using atomic absorption and fluorescence spectroscopies, and in the presence of metal ions, respectively. The results indicated that the prepared hybrid-fluorescent nanoparticles can be used in the removal and detection of toxic Pb(ii) ions. The limit of detection (LOD) was determined from the fluorescence data as 1.55 × 10-7 M and the maximum adsorption capacity was examined by AAS. The complexometric interactions between Pb(ii) and Bodipy-Si affect the adsorptions of the Pb(ii) metal ion at various concentrations.


Investigating the inflammatory status in the patients candidate for second angiography after coronary stent implantation.
Inflammation has been shown to be an important feature of atherosclerosis. We aimed to assess a profile of inflammatory cytokines and growth factors in patients with established coronary artery disease (CAD), 12 months after stent implantation. A total of 193 patients with CAD, who were candidates for angiography, 12 months after stent implantation (cases), were compared with 107 patients with CAD, who were candidates for their first angiography (controls). Fasting blood glucose (FBG), triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and high-sensitive C-reactive protein (hs-CRP) were measured using routine methods. The serum concentrations of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, MCP-1, EGF and VEGF were determined using competitive chemiluminescence immunoassays. Serum levels of FBG (p = .002), TG (p = .029) and hs-CRP (p = .005) were significantly lower in cases than controls. The cytokines and growth factor profiles in cases were significantly different from controls. After multivariate analysis, serum levels of IL-2 (p < .001), IL-4 (p = .028) were significantly lower in cases compared with the controls while serum levels of IL-8, TNF-α, MCP-1, EGF and VEGF were significantly higher in the cases (p < .001). In patients with CAD and higher consumption of drug used (statins, aspirin and glucose lowering agents) to mitigate the risk of a secondary event, the level of hs-CRP one year after stent implantation decreased despite of significant higher serum levels of pro- and anti-inflammatory cytokines and growth factors.


Phosphatidylglyceroylalkylamine, a novel phosphoglycolipid precursor in Deinococcus radiodurans.
We report here the structure of a previously uncharacterized phospholipid in the radiation-resistant bacterium Deinococcus radiodurans. This phospholipid, designated lipid 4, was shown by chemical analysis, HF hydrolysis, and nuclear magnetic resonance spectroscopy to be phosphatidylglyceroylalkylamine. Lipid 4 thus contains the unusual lipid constituents glyceric acid and alkylamines, which have previously been identified in two complex phosphoglycolipids from this organism. By [32P]phosphate pulse-chase labeling techniques, lipid 4 was shown to be the precursor of the complex phosphoglycolipids alpha-galactosyl- and alpha-N-acetylglucosaminylphosphatidylglyceroylalkylamine. While phosphatidylglyceroylalkylamine is rapidly biosynthesized from Pi, its subsequent glycosylation occurs much more slowly. Therefore, we conclude that the final glycosylation step is the rate-limiting event in the biosynthesis of the complex phosphoglycolipids alpha-galactosyl- and alpha-N-acetylglucosaminyl-phosphatidylglyceroylalkylamine.


New strategies to overcome limitations of reversible EGFR tyrosine kinase inhibitor therapy in non-small cell lung cancer.
The epidermal growth factor receptor (EGFR), a member of the HER family of receptors, has become a well-established target for the treatment of patients with non-small cell lung cancer (NSCLC). Several EGFR-targeted agents produce objective responses in a minority of unselected patients, but a majority of those with EGFR-activating mutations; however, all responders eventually develop resistance. The modest activity of agents that target only EGFR may be due, in part, to the complexity and interdependency of HER family signaling. The interdependent signaling that occurs between EGFR and HER2 provides a rationale for the simultaneous inhibition of these receptors with reversible and irreversible inhibitors. Several agents with activity against both EGFR and HER2 are currently under development. Irreversible EGFR/HER2 tyrosine kinase inhibitors (TKIs) (e.g., BIBW 2992, HKI-272) and pan-HER TKIs (e.g., PF00299804) comprise a novel class of agents in clinical development that may prevent and overcome inherent and acquired resistance to first-generation reversible EGFR TKIs. Other agents in development include the monoclonal antibody pertuzumab, and XL-647, which inhibits EGFR and HER2, as well as multiple vascular endothelial growth factor receptor family members. Here we briefly review the currently available EGFR-targeted agents, discuss the rationale for extending inhibition to other HER family members, weigh the merits of irreversible HER family inhibition, and summarize preclinical and clinical data with EGFR/HER2 and pan-HER inhibitors under clinical development.


Prenatal diagnosis of sacrococcygeal teratoma with constitutional partial monosomy 7q/trisomy 2p.
We report the prenatal diagnosis of a fetus with sacrococcygeal teratoma and facial dysmorphism attributed to a constitutional terminal deletion of chromosome 7q and partial trisomy of chromosome 2p likely resulting from a de novo balanced translocation. The cytogenetic abnormality was diagnosed prenatally after sonographic detection of teratoma and confirmed on peripheral blood cells at birth. The newborn died of post-operative complications at seven days of age. FISH analysis demonstrated haploinsufficiency of HLXB9, a gene identified in the triad of a presacral mass (teratoma or anterior meningocele), sacral agenesis, and anorectal malformation, which constitutes the Currarino syndrome. Despite the absence of other features of the triad, the teratoma observed in the fetus we describe might represent a partial form of Currarino syndrome.


Long-Term Plasticity in Reflex Excitability Induced by Five Weeks of Arm and Leg Cycling Training after Stroke.
Neural connections remain partially viable after stroke, and access to these residual connections provides a substrate for training-induced plasticity. The objective of this project was to test if reflex excitability could be modified with arm and leg (A & L) cycling training. Nineteen individuals with chronic stroke (more than six months postlesion) performed 30 min of A & L cycling training three times a week for five weeks. Changes in reflex excitability were inferred from modulation of cutaneous and stretch reflexes. A multiple baseline (three pretests) within-subject control design was used. Plasticity in reflex excitability was determined as an increase in the conditioning effect of arm cycling on soleus stretch reflex amplitude on the more affected side, by the index of modulation, and by the modulation ratio between sides for cutaneous reflexes. In general, A & L cycling training induces plasticity and modifies reflex excitability after stroke.


A potent serotonin-modulating compound AP-267 attenuates morphine withdrawal-induced blood-brain barrier dysfunction in rats.
The possibility that a serotonin 5-HT2c receptor-modulating compound, AP-267, will influence spontaneous morphine withdrawal symptoms and the alterations in the brain fluid microenvironment was examined in a rat model. Daily administration of morphine (10 mg/kg, i.p.) for 10 days resulted in dependence of rats as seen by loss of analgesic response. On the 11th day, no morphine administration was given. This resulted in profound withdrawal symptoms 24 h after morphine withdrawal. The magnitude and severity of these symptoms were increased further 48 h after withdrawal. Measurement of the blood-brain barrier (BBB) permeability, a measure of perturbed brain fluid microenvironment showed leakage of Evans blue and radioiodine tracers in several parts of the brain in rats showing withdrawal symptoms. Whereas, rats treated with AP-267 either on the 1st day or 2nd day morphine withdrawal showed much less symptoms and leakage of the BBB. Taken together, these observations suggest that (a) stress associated with the withdrawal symptoms are sufficient enough to induce breakdown of the BBB function, and (b) modulation of serotonin 5-HT2c receptors may have some protective influence on the stress symptoms and the BBB disruption.


Systematic Review on Crimean-Congo Hemorrhagic Fever Enzootic Cycle and Factors Favoring Virus Transmission: Special Focus on France, an Apparently Free-Disease Area in Europe.
Crimean-Congo hemorrhagic fever (CCHF) is a viral zoonotic disease resulting in hemorrhagic syndrome in humans. Its causative agent is naturally transmitted by ticks to non-human vertebrate hosts within an enzootic sylvatic cycle. Ticks are considered biological vectors, as well as reservoirs for CCHF virus (CCHFV), as they are able to maintain the virus for several months or even years and to transmit CCHFV to other ticks. Although animals are not symptomatic, some of them can sufficiently replicate the virus, becoming a source of infection for ticks as well as humans through direct contact with contaminated body fluids. The recent emergence of CCHF in Spain indicates that tick-human interaction rates promoting virus transmission are changing and lead to the emergence of CCHF. In other European countries such as France, the presence of one of its main tick vectors and the detection of antibodies targeting CCHFV in animals, at least in Corsica and in the absence of human cases, suggest that CCHFV could be spreading silently. In this review, we study the CCHFV epidemiological cycle as hypothesized in the French local context and select the most likely parameters that may influence virus transmission among tick vectors and non-human vertebrate hosts. For this, a total of 1,035 articles dating from 1957 to 2021 were selected for data extraction. This study made it possible to identify the tick species that seem to be the best candidate vectors of CCHFV in France, but also to highlight the importance of the abundance and composition of local host communities on vectors' infection prevalence. Regarding the presumed transmission cycle involving Hyalomma marginatum, as it might exist in France, at least in Corsica, it is assumed that tick vectors are still weakly infected and the probability of disease emergence in humans remains low. The likelihood of factors that may modify this equilibrium is discussed.


Unrelated umbilical cord blood transplantation for children with hereditary leukodystrophy: A retrospective study.
To analyze the efficiency of unrelated umbilical cord blood transplantation (UCBT) in the treatment of hereditary leukodystrophy following busulfan- and cyclophosphamide-based myeloablative chemotherapy. A retrospective study was performed in patients with hereditary leukodystrophy who underwent UCBT after myeloablative chemotherapy between April 2015 and March 2020. The study cohort included 12 pediatric patients (ten males), nine with cerebral adrenoleukodystrophy (ALD) and three with juvenile globoid cell leukodystrophy (GLD). All received HLA-matched or partially mismatched unrelated UCBT. There were no cases of graft rejection. Median neutrophil engraftment time was 20 days [12-33 days] and median platelet engraftment time was 29 days [14-65 days]. Median follow-up was 36 months [1-86 months], and the overall survival rate for patients with cerebral ALD and juvenile GLD after UCBT was 77.8% (7/9) and 100% (3/3), respectively. In patients with ALD, although lipid profiles (serum very-long-chain fatty acid) were improved post-UCBT, six patients demonstrated worse neurologic function score and performance status post-UCBT, and six patients had higher Loes scores at last follow-up compared with baseline. In patients with juvenile GLD, all patients showed stable neurologic function score and performance status despite the Loes score of one patient increased slightly after transplantation. In patients with cerebral ALD, patients with no or mild neurological symptoms can benefit from UCBT, while UCBT cannot reverse advanced disease. In patients with juvenile GLD, UCBT is safe and contributes to stabilize neurological function.


The specificity of anti-cardiolipin antibodies from syphilis patients and from patients with systemic lupus erythematosus.
In order to elucidate the fine specificity of anti-cardiolipin antibodies (ACA) in patients with SLE compared to patients with syphilis (SY) various inhibition experiments were performed. Seven SLE sera and eight SY sera positive for ACA were diluted and preincubated with either cardiolipin VDRL-antigen, mitochondial particles, dsDNA, ssDNA or dilution buffer. The sera were subsequently assayed for residual ACA activity of IgG or IgM class using a sensitive ELISA technique. Significant inhibition of IgM ACA activity in SLE sera was found with cardiolipin, VDRL-antigen and mitochondrial particles. Cardiolipin inhibited binding to a significantly higher extent than the other antigens. In SY sera significant inhibition of the IgM ACA activity was found with all antigens used. The strongest inhibition was seen using VDRL-antigen. Inhibition of IgG ACA activity could only be clearly estimated in SY sera where VDRL-antigen was found to be a much stronger inhibitor than the rest, purified cardiolipin being the weakest. Only two out of seven SLE sera were IgG ACA positive which made a clear conclusion impossible but a strong inhibitory capability of pure cardiolipin and a weaker inhibition with VDRL-antigen was found. This study disclosed a difference between SLE and SY sera showing strong reactivity of ACA in SLE sera with purified cardiolipin, contrasting to ACA in SY sera which predominantly reacted with cardiolipin in the liposome environment, as found in the VDRL-antigen and in mitochondrial particles.


Genetic parameters for testes traits in swine.
Data were collected from 1,245 Duroc boars and 527 Yorkshire boars. This represents 128 Duroc and 57 Yorkshire sires. Body weights, testis length and combined testes width at 140 and 168 d were obtained. Of these boars, 432 were castrated at a later age to evaluate relationships between in situ measures and excised testis traits. Heritabilities for testis length, width and volume at 140 d ranged from .16 to .25 in both Duroc and Yorkshire data. Heritabilities for testis measurements at 168 d ranged from .16 to .36 in both data sets. Favorable negative genetic relationships were found between in situ testis measures and age to 104 kg and backfat adjusted to 104 kg. Correlations among in situ measurements were high and positive. All excised testicular traits were highly heritable except for right epididymis weight and excised testis width. Correlation estimates among excised testis traits were generally positive. Phenotypic and genetic correlation estimates between live (in situ testis and growth performance traits) measurements and excised testis traits were generally favorable. This study suggests that in situ testis measurements should be good predictors of sperm production. It also suggests that selection for testis size should not be antagonistic to selection for growth performance traits.


Blighted ovum and tubal pregnancy: a rare form of heterotopic pregnancy: case report.
Heterotopic pregnancies are rare in spontaneous conceptions. Nonetheless, when it does occur, the intrauterine pregnancy is usually viable. We herein present a true rarity of the coexistence of a blighted ovum and an ectopic pregnancy. A 25 year old G2P1001 married seamstress of African ethnicity at 8 weeks of amenorrhoea presented to our health facility with a 4 day history of lower abdominal pains and vaginal bleeding for which physical examination revealed a closed cervix. Trans-abdominal ultrasound scan confirmed a diagnosis of a blighted ovum and an ectopic pregnancy. Patient was managed with surgical therapy. Evolution thereafter was uneventful. The case presented confirms that HP can occur in the absence of predisposing factors, and that the detection of a blighted ovum should not preclude the possibility of a simultaneous ectopic pregnancy. A high index of suspicion could lead to early diagnosis, prompt management and a favourable prognosis even in a low-income setting.


Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a retinoic acid-metabolizing enzyme in rat liver.
Several cytochrome P450 (CYP) enzymes catalyze the C4-hydroxylation of retinoic acid (RA), a potent inducer of cell differentiation and an agent in the treatment of several diseases. Here, we have characterized CYP2C22, a member of the rat CYP2C family with homology to human CYP2C8 and CYP2C9. CYP2C22 was expressed nearly exclusively in hepatocytes, where it was one of the more abundant mRNAs transcripts. In H-4-II-E rat hepatoma cells, CYP2C22 mRNA was upregulated by all-trans (at)-RA, and Am580, a nonmetabolizable analog of at-RA. In comparison, in primary human hepatocytes, at-RA increased CYP2C9 but not CYP2C8 mRNA. Analysis of the CYP2C22 promoter region revealed a RA response element (5'-GGTTCA-(n)5-AGGTCA-3') in the distal flanking region, which bound the nuclear hormone receptors RAR and RXR and which was required for transcriptional activation response of this promoter to RA in CYP2C22-luciferase-transfected RA-treated HepG2 cells. The cDNA-expressed CYP2C22 protein metabolized [3H]at-RA to more polar metabolites. While long-chain polyunsaturated fatty acids competed, 9-cis-RA was a stronger competitor. Our studies demonstrate that CYP2C22 is a high-abundance, retinoid-inducible, hepatic P450 with the potential to metabolize at-RA, providing additional insight into the role of the CYP2C gene family in retinoid homeostasis.


Expression of prostate-specific membrane antigen in normal and malignant human tissues.
Prostate-specific membrane antigen (PSMA) is upregulated in androgen-dependent prostate carcinoma and it has been targeted for immunotherapy and diagnosis of this cancer. However, this protein is also expressed in other tissues. The objective of this study is to investigate its expression in normal and malignant human tissues. Using monoclonal antibodies 24.4E6 (specific for residues 638-657) and 7E11.C5 (specific for the transmembrane domain of PSMA), immunohistochemical detection of PSMA was performed in surgical specimens. Prostate-specific membrane antigen was detected in the epithelium of prostate, urinary bladder, proximal tubules of kidney, liver, esophagus, stomach, small intestine, colon, breast, fallopian tubes and testicular seminiferous tubules, hippocampal neurons and astrocytes, ependyma, cortex and medulla of the adrenal gland, and ovary stroma. It was also detected in neoplasms of the prostate, kidney, urinary bladder, stomach, small intestine, colon, lung, adrenal gland, and testis. It was not detected in normal seminal vesicles or the lung. These findings demonstrate that PSMA is widely distributed in normal tissues, and, depending on the tumors, its expression is up- or down-regulated, or unchanged. The broad distribution of PSMA may make it suitable for the diagnosis and therapy of a wide variety of tumors.


Lack of an effect of standard and supratherapeutic doses of linezolid on QTc interval prolongation.
A double-blind, placebo-controlled, four-way crossover study was conducted in 40 subjects to assess the effect of linezolid on corrected QT (QTc) interval prolongation. Time-matched, placebo-corrected QT intervals were determined predose and at 0.5, 1 (end of infusion), 2, 4, 8, 12, and 24 h after intravenous dosing of linezolid 600 and 1,200 mg. Oral moxifloxacin at 400 mg was used as an active control. The pharmacokinetic profile of linezolid was also evaluated. At each time point, the upper bound of the 90% confidence interval (CI) for placebo-corrected QTcF values (i.e., QTc values adjusted for ventricular rate using the correction methods of Fridericia) for linezolid 600 and 1,200-mg doses were <10 ms, which indicates an absence of clinically significant QTc prolongation. At 2 and 4 h after the moxifloxacin dose, corresponding to the population T(max), the lower bound of the two-sided 90% CI for QTcF when comparing moxifloxacin to placebo was >5 ms, indicating that the study was adequately sensitive to assess QTc prolongation. The pharmacokinetic profile of linezolid at 600 mg was consistent with previous observations. Systemic exposure to linezolid increased in a slightly more than dose-proportional manner at supratherapeutic doses, but the degree of nonlinearity was small. At a supratherapeutic single dose of 1,200 mg of linezolid, no treatment-related increase in adverse events was seen compared to 600 mg of linezolid, and no clinically meaningful effects on vital signs and safety laboratory evaluations were noted.


Nonsteroidal Anti-inflammatory Drugs: Making the Right Choices.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed pharmacologic agents in medicine. The ability of these drugs to decrease inflammation is linked to their inhibitory effect on the synthesis of prostaglandins. This mechanism also results in toxicity that can cause gastrointestinal ulceration and bleeding, renal failure, and worsening of preexisting congestive heart failure. The superiority of one NSAID over another has not been clinically demonstrated in musculoskeletal conditions, nor has the efficacy of NSAIDs in noninflammatory rheumatic conditions been shown to be better than that of simple analgesics, such as acetaminophen. The use of these drugs, particularly in the elderly patient with osteoarthritis, should be carefully considered, and alternative, less toxic therapies should be sought whenever possible.


Visual acuity change after intravitreal triamcinolone in various types of exudative age-related macular degeneration.
The aim of this study was to compare the visual acuity change after an intravitreal high-dose injection of triamcinolone acetonide (TA) in various types of exudative age-related macular degeneration (AMD). The interventional comparative case series study included 142 patients (146 eyes) with progressive exudative AMD differentiated into the occult type (n = 78; 53.4%), minimal classic type (n = 45; 30.8%), predominantly classic type (n = 17; 11.6%), and the purely classic type (n = 6; 4.1%). Mean follow-up was 9.7 +/- 7.0 months (3-35.7 months). Single intravitreal injection of approximately 20 mg of TA. Visual acuity, intraocular pressure (IOP). Gain in visual acuity measured at 1 month (P = 0.20), 2 months (P = 0.43), and at 3 months (P = 0.38) after the intravitreal injection of triamcinolone and maximal gain in visual acuity during the whole follow-up (P = 0.81) did not vary significantly between the 4 study groups. Correspondingly, the size of a retinal pigment epithelium detachment was not significantly associated with the change in visual acuity at 1 month (P = 0.62), 2 months (P = 0.24), 3 months (P = 0.96), or the maximal gain in visual acuity during follow-up (P = 0.93). The amount of rise in IOP, compared with the baseline value (6.5 +/- 7.4 mmHg), was statistically not associated with the type of subfoveal membrane (P = 0.20; 95% confidence interval: -0.52, 2.45). The change in visual acuity and the rise in IOP in patients with exudative AMD receiving an intravitreal triamcinolone monotherapy is statistically independent of the type of subfoveal membrane, including the size of a retinal epithelium detachment.


Synthesis, characterization, and luminescence properties of a new series of Eu3+-containing macrocycles.
The synthesis and structural characterization of a series of neutral Eu(3+)-containing macrocyclic complexes, Eu(4)-Eu(7), are reported. The synthetic pathway herein allows for the size and functionality of the macrocycle to be tailored in one step from a common precursor (N,N' '-bis(p-isothiocyanatobenzylcarbamoylmethyl)diethylenetriamine-N,N'N' '-triacetic acid, (3) in high yield. The macrocyclic ligands 4-7 have within their structure a bis-amide derivative of diethylenetriaminepentaacetic acid (DTPA) functioning as the europium chelate that is bridged through thiourea groups by either a butyl (4), hexyl (5), octyl (6), or m-benzyl (7) linker. The two thiourea groups were designed into the host macrocycle to serve as hydrogen-bond donors to potential guest molecules that may alter the luminescence properties of the parent macrocycle. Characterization of the luminescence of Eu(4)-Eu(7) reveals an antenna effect from the ligand, and the luminescence lifetime data reveals the presence of one coordinated water molecule in aqueous solution.


A fresh look at meat flavor.
Hundreds of compounds contribute to the flavor and aroma of meat. Complex interactions between various compounds influence the perception of meat flavor. Inherent flavor of a meat product can be influenced by oxidation, lipid content, feeding/diet, myoglobin, and pH. Diet plays an important role in both ruminants and nonruminants. New research reveals important relationships in flavor among multiple muscles within a single animal carcass. This animal effect includes the presence of off-flavors. Diets high in polyunsaturated fatty acids may be contributing to the appearance of off-flavors in beef. Compounds associated with liver-like off-flavor notes in beef have been identified in raw tissue.


Hypothalamus but not liver retains daily expression of clock genes during hibernation in terai tree frog (Polypedates teraiensis).
Circadian clock(s) allow an organism to be in synchrony with the surrounding environment and perform daily and seasonal physiological processes, including hibernation, migration, and reproduction. To cope with adverse environmental conditions, organisms have evolved various strategies. Insects undergo diapause, while some higher animals either migrate or hibernate/aestivate during unfavorable environmental conditions. Hibernation is an energy conservation strategy used to cope with adverse environmental conditions. Limited knowledge is available on the physiology of hibernation in non-mammalian vertebrates. Some studies suggest that metabolism is altered during amphibian hibernation, but nothing is known about the circadian clock. In the present study, we investigated daily oscillation of clock genes in the brain and liver of the terai tree frog (Polypedates teraiensis) during two annual phases of life: breeding and hibernation. Adult male terai tree frogs were procured from their natural habitat on the Mizoram University campus (23°N 92°E) during their breeding and hibernation phases. Body mass and testes weight were recorded. Animals were sacrificed at six time points: ZT1, ZT5, ZT9, ZT13, ZT17, and ZT21 (ZT0, zeitgeber time 0, indicates the sunrise time at the respective time of the year; N = 5 frogs per time point). Quantitative real-time polymerase chain reaction (qPCR) was performed for clock genes (Bmal1, Clock, Per2, and Cry2) in the hypothalamus and liver. Our results showed that body and testes weights decreased during hibernation. Further, the hypothalamus retained daily clock gene oscillations during breeding and hibernation. However, the liver lost this daily oscillation during hibernation. The maintained rhythm in hypothalamus in contrast to other hibernating animals might be the result of the fact that these animals hibernate at a higher temperature and might be more alert. As the animals have no food intake during their hibernation season which might be the reason the animals loose their rhythm in liver clock genes. These results suggest that retaining daily clock gene oscillations in the hypothalamic clock could be important for internal time tracking and post-hibernation emergence.


Mammalian Per-Arnt-Sim proteins in environmental adaptation.
The Per-Arnt-Sim (PAS) domain is conserved across the kingdoms of life and found in an ever-growing list of proteins. This domain can bind to and sense endogenous or xenobiotic small molecules such as molecular oxygen, cellular metabolites, or polyaromatic hydrocarbons. Members of this family are often found in pathways that regulate responses to environmental change; in mammals these include the hypoxia, circadian, and dioxin response pathways. These pathways function in development and throughout life to regulate cellular, organ, and whole-organism adaptive responses. Remarkably, in the case of the clock, this adaptation includes anticipation of environmental change. In this review, we summarize the roles of PAS domain-containing proteins in mammals. We provide structural evidence that functionally classifies both known and unknown biological roles. Finally, we discuss the role of PAS proteins in anticipation of and adaptation to environmental change.


Health inequalities among older adults in Sweden 1991-2002.
Current research has shown a decline in health among older adults in Sweden. This study examines health inequalities among older adults in Sweden in 1991-1992 and 2000-2002 and explores the development of these inequalities during this period. A data set was constructed out of four levels of living surveys, comprising 4085 individuals aged 55 and above. Multivariate logistic regressions were used to assess the association between social class, sex, age and four different domains of self-reported health: global self-rated health, impaired mobility, musculoskeletal pain and psychological distress. Adjustments were made for period of interview. Interaction terms were also used to assess change over time. Levin's attributable risk was used to assess the magnitude of the health inequalities. The results indicate an increase in reports of all specific health problems, but not in the global health measure during the period. Significant sex differences and a clear social gradient in health were discernible during both periods. Women were more likely than men to report problems with impaired mobility, pain and psychological distress. Manual workers were significantly more likely than non-manuals to report problems in all four domains of health. However, both the sex differences and the social gradient seemed to remain constant during the period. Although it seems there are significant differences in health depending on sex and social class among older adults in Sweden, these inequalities appear to be unaffected by the general increase in ill health that has been observed in these groups over the last decade.


New discrete heavy tailed distributions as models for insurance data.
Although many data sets are discrete and heavy tailed (for example, number of claims and claim amounts if recorded as rounded values), not many discrete heavy tailed distributions are available in the literature. In this paper, we discuss thirteen known discrete heavy tailed distributions, propose nine new discrete heavy tailed distributions and give expressions for their probability mass functions, cumulative distribution functions, hazard rate functions, reversed hazard rate functions, means, variances, moment generating functions, entropies and quantile functions. Tail behaviour and a measure of asymmetry are used to compare the known and new discrete heavy tailed distributions. The better fits of the discrete heavy tailed distributions over their continuous counterparts as assessed by probability plots are illustrated using three data sets. Finally, a simulated study is performed to assess the finite sample performance of the maximum likelihood estimators used in the data application section.


Commentary: Medical subspecialty enforcement?
From its inception, the American Academy of Psychiatry and the Law (AAPL) has decided not to investigate and adjudicate complaints of unethical conduct of its members or others, but rather refers the complainant to other organizations, such as the "local district branch of the American Psychiatric Association (APA), the state licensing board, and/or the appropriate national psychiatric organization of foreign members" (AAPL Ethics Guidelines). Loss of APA membership, however, terminates one's AAPL membership upon AAPL notification. Further, the AAPL Ethics Committee "may issue opinions on general or hypothetical questions but will not issue opinions on the ethical conduct of specific forensic psychiatrists or about actual cases" (AAPL Ethics Guidelines). This referral policy has been criticized at times with various proposals for change. Candilis and colleagues have thoughtfully considered several alternative courses of action. Extending those considerations, this Commentary considers the practices of other health care professional organizations and some implications of the proposal offered by Candilis et al.