Celecoxib, a COX-2 inhibitor, synergistically potentiates the anti-inflammatory activity of docosahexaenoic acid in macrophage cell line.
The anti-inflammatory properties of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and non-steroidal anti-inflammatory drugs overlap in many ways. The aim of this study was to examine the individual and synergetic anti-inflammatory effects of celecoxib, EPA and DHA in RAW-264.7 cell line. The cells were exposed to EPA, DHA, celecoxib, rosiglitazone, GW9662 alone or their combination, and stimulated with 5 μg/mL lipopolysaccharide (LPS). Nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and prostaglandin-E2 (PGE2) levels were estimated in the medium using enzyme-linked immunosorbent assays. The cyclooxygenase-2 (COX-2) and inducible Nitric Oxide Synthase (iNOS) expression were analyzed in the cell lysate by immunoblotting. Peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor-κB (NF-κB) transcription factor activation assays were performed in the nuclear extract. Combined treatment of DHA (50 μM) and celecoxib (20 μM) significantly inhibited LPS induced synthesis of NO, TNF-α, IL-6 and PGE2 levels in the cells, compared to the individual treatments. In addition, DHA and celecoxib diminished the COX-2 and iNOS expression in the cells. This was associated with increased PPARγ activity, supressed NF-κB activity in the nucleus. We determined whether GW9662, a specific PPARγ inhibitor, could abolish the anti-inflammatory effect of DHA and celecoxib. GW9662 has abolished the DHA and celecoxib induced PPARγ activation, but did not alter the NF-κB mediated anti-inflammatory effects induced by celecoxib and DHA. Interestingly, EPA did not exhibit any inhibitory effect on these parameters. Our results suggest that DHA and celecoxib exhibit anti-inflammatory effect through inhibition of NF-κB, independent of PPARγ. Co-administration of celecoxib and DHA would be promising approach for the treatment of inflammatory diseases.


N'-methylniphimycin, a novel minor congener of niphimycin from Streptomyces spec. 57-13.
A novel natural niphimycin analog, N'-methylniphimycin was isolated from the culture broth of the Streptomyces spec. 57-13. The chemical constitution was elucidated from the physico-chemical properties, NMR techniques and mass spectrometry to be a 36-membered macrolide related to azalomycin F5a, shurimycin B and RS-22C. N'-methylniphimycin displayed moderate activity against some yeasts and filamentous fungi.


Pressure limited sustained off-resonance irradiation for collision-activated dissociation in fourier transform mass spectrometry.
A theoretical evaluation of the sustained off-resonance irradiation of ions (SORI) in the presence of a collisional buffer gas in a Fourier transform ion cyclotron resonance mass spectrometer is presented. It is shown that there is an optimal pressure for a given set of irradiation parameters corresponding to the most effective dissociation. Theoretical predictions are compared with experimental results for the dissociation of electrosprayed biopolymer ions and with previously accepted view of the SORI process.


Endoscopic submandibular gland resection preserving great auricular nerve and periaural sensation.
The preservation of periaural sensation is one of the most important things to improve the postoperative quality of life after performing the surgical procedures via retroauricular approach. The aim of this study is to describe the surgical technique of endoscopic submandibular gland (SMG) resection through the potential plane between great auricular nerve (GAN) and sternocleidomastoid muscle (sub-GAN dissection) and to evaluate its technical feasibility and advantage. The present study enrolled 22 patients who underwent endoscopic SMG resection through linear hairline incision and sub-GAN dissection. The assessment was performed on the following: the cosmetic satisfaction after surgery and surgery-related variables. There was one case of a postoperative hematoma, which resolved with conservative management via a compression dressing, and one case of transient numbness at the surgical site, which spontaneously resolved within two months. In all other patients, no complications, such as seroma, skin necrosis, or marginal mandibular nerve palsy, occurred. The mean scores of pain and paresthesia evaluated with the graded scale approximated 0 (no pain or paresthesia). The cosmetic result score was as low as 1.5 ("extremely satisfied" or "satisfied"). Linear hairline incision and sub-GAN dissection were feasible to acquire the sufficient working space for endoscopic SMG resection without sensory deterioration of GAN. This procedure may be useful to apply the surgery of other upper neck masses or thyroidectomy via retroauricular approach.


Treatment of landfill leachate using immobilized Phanerochaete chrysosporium loaded with nitrogen-doped TiO₂ nanoparticles.
This study investigated the performance of immobilized Phanerochaete chrysosporium loaded with nitrogen-doped TiO2 nanoparticles in the treatment of raw landfill leachate with a very low biodegradability ratio (BOD5/COD) of 0.09. The effects of various operating parameters, such as initial chemical oxygen demand (COD) concentration, pH, temperature, and biosorbent dosage, were evaluated with respect to the removal efficiency of total organic carbon (TOC) and ammonia nitrogen (NH3-N). For the immobilized biosorbents, an optimum pH of 6.0 for TOC and 7.0 for NH3-N were found suitable for TOC and NH3-N removal at temperature of 37°C, respectively. The most superior removal efficiencies of TOC and NH3-N of landfill leachate were over 75% and 74% in 72 h at an initial COD concentration of 200 mg L(-1), respectively. In addition, heavy metals were partly removed by the immobilized biosorbents during the process of landfill leachate treatment. The species and mass percentage of organic compounds in landfill leachate after the treatment were found to have considerably declined according to the gas chromatography coupled with mass spectrometry (GC-MS) system. These results indicate that the immobilized P. chrysosporium loaded with nitrogen-doped TiO2 nanoparticles could be a convenient and efficient method for the treatment of landfill leachate.


Neuropsychological outcomes after epilepsy surgery: A comparison of stereo electroencephalography and subdural electrodes.
We analyzed the association of neuropsychological outcomes after epilepsy surgery with the intracranial electrode type (stereo electroencephalography [SEEG] and subdural electrodes [SDE]), and electrical stimulation mapping (ESM) of speech/language. Drug-resistant epilepsy patients who underwent comprehensive neuropsychological evaluation before and 1 year after epilepsy surgery were included. SEEG and SDE subgroups were matched by age, handedness, operated hemisphere, and seizure freedom. Postsurgical neuropsychological outcomes (adjusted for presurgical scores) and reliable change indices were analyzed as functions of electrode type and ESM. Ninety-nine patients aged 6-29 years were included with similar surgical resection/ablation volumes in the SEEG and SDE subgroups. Most of the neuropsychological outcomes were comparable between SEEG and SDE subgroups; however, Working Memory and Processing Speed were significantly improved in the SEEG subgroup. Undergoing language ESM was associated with significant improvements in Spelling, Letter-Word Identification, Vocabulary, Verbal Comprehension, Verbal Learning, and Story Memory scores, but a decline in Calculation scores. Intracranial evaluations with SEEG and SDE are comparable in terms of long-term postsurgical neuropsychological outcomes. Our data suggest that SEEG may be associated with improvements in working memory and processing speed, representing cognitive domains served by spatially distributed networks. Our study also supports wider use of language ESM before epilepsy surgery, preferably using other language tasks in addition to visual naming. Rather than the type of electrode, postsurgical neuropsychological outcomes are driven by whether language ESM was performed or not, with beneficial effects of language mapping.


Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism.
Secreted extracellular vesicles (EVs) influence the tumor microenvironment and promote distal metastasis. Here, we analyzed the involvement of melanoma-secreted EVs in lymph node pre-metastatic niche formation in murine models. We found that small EVs (sEVs) derived from metastatic melanoma cell lines were enriched in nerve growth factor receptor (NGFR, p75NTR), spread through the lymphatic system and were taken up by lymphatic endothelial cells, reinforcing lymph node metastasis. Remarkably, sEVs enhanced lymphangiogenesis and tumor cell adhesion by inducing ERK kinase, nuclear factor (NF)-κB activation and intracellular adhesion molecule (ICAM)-1 expression in lymphatic endothelial cells. Importantly, ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype, decreased lymph node metastasis and extended survival in pre-clinical models. Furthermore, NGFR expression was augmented in human lymph node metastases relative to that in matched primary tumors, and the frequency of NGFR+ metastatic melanoma cells in lymph nodes correlated with patient survival. In summary, we found that NGFR is secreted in melanoma-derived sEVs, reinforcing lymph node pre-metastatic niche formation and metastasis.


Diagnostic utility of FDG-PET in neurolymphomatosis: report of five cases.
Neurolymphomatosis (NL) is a rare condition involving the infiltration of lymphoma cells into the peripheral nervous system. NL can be primary or secondary in the setting of an unknown or known hematologic malignancy, respectively. Here, we report five cases in which F-18 2-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (F-18 FDG-PET/CT) had great value for diagnosing NL. Two cases were rare primary NL, and the other three were secondary NL. Clinical presentations were asymmetric sensorimotor disturbances in the extremities with or without involvement of cranial nerves. Furthermore, all patients experienced spontaneous pain in the face or affected extremities. Cerebrospinal fluid analysis was cytologically negative in two of five cases. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) detected abnormalities in the cranial nerves, nerve roots, and cauda equina in all cases except case 1 and the recurrent stage of case 2. F-18 FDG-PET/CT showed clear visualization of almost all the lymphomatous involvement of peripheral nerves and other tissues in all patients. Furthermore, F-18 FDG-PET/CT detected abnormalities including asymptomatic lesions that were not detected with MRI, and also identified the appropriate lesion for diagnostic biopsy. However, as in case 3, the lesions in the left oculomotor nerve and the cauda equina were detected only with Gd-enhanced MRI, which has superior spatial resolution. In conclusion, F-18 FDG-PET/CT is a sensitive modality that can suggest the presence of malignancy and identify appropriate places for diagnostic biopsies. It is especially useful when combined with Gd-enhanced MRI, even in patients with primary NL that is usually difficult to diagnose.


Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: does timing of administration matter?
Contrary to the approved indication for pegfilgrastim prophylaxis, some patients receive it on the same day as the last administration of chemotherapy in clinical practice, which could adversely impact risk of febrile neutropenia (FN). An evaluation of the timing of pegfilgrastim prophylaxis and FN risk was undertaken. A retrospective cohort design and data from two US private health care claims repositories were employed. Study population comprised adults who received intermediate/high-risk chemotherapy regimens for solid tumors or non-Hodgkin's lymphoma (NHL) and received pegfilgrastim prophylaxis in ≥1 cycle; all cycles with pegfilgrastim were pooled for analyses. Odds ratios (OR) for FN during the cycle were estimated for patients who received pegfilgrastim on the same day (day 1) as the last administration of chemotherapy versus days 2-4 from chemotherapy completion. The study population included 45,592 patients who received pegfilgrastim in 179,152 cycles (n = 37,095 in cycle 1); in 12 % of cycles, patients received pegfilgrastim on the same day as chemotherapy. Odds of FN were higher for patients receiving pegfilgrastim prophylaxis on the same day as chemotherapy versus days 2-4 from chemotherapy in cycle 1 (OR = 1.6, 95 % CI = 1.3-1.9, p < 0.001) and all cycles (OR = 1.5, 95 % CI = 1.3-1.6, p < 0.001). In this large-scale evaluation of adults who received intermediate/high-risk regimens for solid tumors or NHL in US clinical practice, FN incidence was found to be significantly higher among those who received pegfilgrastim prophylaxis on the same day as chemotherapy completion versus days 2-4 from chemotherapy completion, underscoring the importance of adhering to the indicated administration schedule.


Experiences of patients with cancer at health care facilities in Japan: results from a nationwide survey.
To elucidate the experience of patients with cancer from diagnosis to early survivorship in Japan using a nationwide questionnaire survey, and to inform the current progress of the cancer control programs. The survey was sent to a representative sample of adult patients with cancer identified from the national database of hospital-based cancer registries. The patients' responses were compared across three groups: patients with rare cancers, patients aged < 40 years, and patients with non-rare cancers aged ≥40 years. Of 20,488 patients invited to participate in the survey, 8935 (43.6%) responded. Respondents reported an average score of 7.9 out of 10 on global ratings of care. Patients with rare cancers experienced a longer time to diagnosis but the shortest time from diagnosis to first treatment (p < 0.05). Patients aged < 40 years rated worse for the majority of the survey items, especially on items that related to communication with medical staff and items referring to early survivorship. The care experienced by patients with cancer in Japan varies on the basis of age group and cancer type. Efforts should be directed to ensuring prompt access to diagnostic facilities for patients with rare cancers and providing sufficient support to younger patients.


Language and cognitive deficits resulting from medial and dorsolateral frontal lobe lesions.
A total of 36 patients with chronic unilateral circumscribed medial and dorsolateral frontal lobe lesions were investigated with a range of neuropsychological tests. Lateralized deficits in tasks depending on language functions were found with dorsolateral but not with medial lesions. The specific role of Broca's area could not be confirmed. Lesions of the supplementary motor area led to mild deficits in tests of "concept formation". Frontomedial lesions situated more deeply in the interhemispheric fissure resulted in memory deficits. The results are discussed on the basis of recent neurophysiological theories of brain function.


The tuberoinfundibular system of the rat as demonstrated by immunohistochemical localization of retrogradely transported wheat germ agglutinin (WGA) from the median eminence.
The origin of neuronal perikarya which project to the external zone of the median eminence (the tuberoinfundibular neuronal system) was determined in the rat after injection or diffusion of wheat germ agglutinin (WGA) into the median eminence. The retrogradely transported lectin was detected in neurons using an immunohistochemical method based on the peroxidase-antiperoxidase technique. Immunoreactive cell bodies were found both in hypothalamic and extrahypothalamic regions. Within the hypothalamus, the majority of peroxidase-positive cells were present in the dorsomedial and basolateral portions of the arcuate nucleus, regions of the periventricular nucleus, and the preoptic region, particularly at the level of the organum vasculosum of the lamina terminalis (OVLT). Within the extrahypothalamic regions, WGA-positive perikarya were found in the diagonal band of Broca, the region of the medical septum and the brainstem. Only rare cells were labeled in the ventromedial nucleus of the hypothalamus and no cells were labeled in any region of the amygdala. These data demonstrate that neurons with afferent projections to the median eminence are more widely distributed in the rat brain than previously recognized and therefore, that the concept of the tuberoinfundibular neuronal system must be expanded.


Urotensin I effects on intracellular content of cyclic AMP in the rat tail artery.
Rat tail artery strips were incubated in the presence of 4 x 10(-3) M theophylline and urotensin I (UI). At the concentrations of 1.50, 7.50 mU/ml but not of 0.75 mU/ml UI, the content of cAMP increased significantly. Cyclic AMP content and muscle tension were measured at 5--30 sec intervals during noradrenaline (NA)- and potassium chloride (KCl)-induced contractions and during subsequent urotensin I-induced relaxation. Cyclic AMP content declined initially after addition of NA but returned to baseline levels during the contraction. Significant dose-related increases in cAMP were noted upon addition of UI, prior to the onset of the relaxation response followed by a marked decrease during the relaxation response. An increase in cAMP was observed after initiation of the contractile response to KCl-contracted tissues, but no further increase in cAMP after addition of UI was detected. These findings suggest an involvement of cyclic AMP in the initial events leading to the relaxation response to urotensin I in the NA-contracted rat tail artery. Urotensin I-induced relaxation in KCl-contracted tissues appears to proceed by an alternative mechanism which does not require increased levels of cAMP.


Three-Month Psychiatric Outcome of Pediatric Mild Traumatic Brain Injury: A Controlled Study.
The objective was to clarify occurrence, phenomenology, and risk factors for novel psychiatric disorder (NPD) in the first 3 months after mild traumatic brain injury (mTBI) and orthopedic injury (OI). Children aged 8-15 years with mTBI (n = 220) and with OI but no TBI (n = 110) from consecutive admissions to an emergency department were followed prospectively at baseline and 3 months post-injury with semi-structured psychiatric interviews to document the number of NPDs that developed in each participant. Pre-injury child variables (adaptive, cognitive, and academic function, and psychiatric disorder), pre-injury family variables (socioeconomic status, family psychiatric history, and family function), and injury severity were assessed and analyzed as potential confounders and predictors of NPD. NPD occurred at a significantly higher frequency in children with mTBI versus OI in analyses unadjusted (mean ratio [MR] 3.647, 95% confidence interval [CI95] (1.264, 15.405), p = 0.014) and adjusted (MR = 3.724, CI95 (1.264, 15.945), p = 0.015) for potential confounders. In multi-predictor analyses, the factors besides mTBI that were significantly associated with higher NPD frequency after adjustment for each other were pre-injury lifetime psychiatric disorder [MR = 2.284, CI95 (1.026, 5.305), p = 0.043]; high versus low family psychiatric history [MR = 2.748, CI95 (1.201, 6.839), p = 0.016], and worse socio-economic status [MR = 0.618 per additional unit, CI95 (0.383, 0.973), p = 0.037]. These findings demonstrate that mild injury to the brain compared with an OI had a significantly greater deleterious effect on psychiatric outcome in the first 3 months post-injury. This effect was present even after accounting for specific child and family variables, which were themselves independently related to the adverse psychiatric outcome.


Assessing severity of pain in women with focal provoked vulvodynia: are von Frey filaments suitable devices?
To determine whether von Frey filaments are effective in the standardized assessment of the severity of focal provoked vulvodynia (FPV) syndrome. The data of 30 women with FPV attending monthly at our vulvovaginal disease clinic, for a collective total of 141 visits over 6 months, were analyzed. At each visit sensitivity tests at the vulvar vestibule were performed at the 5 and 7 o'clock area, totaling 282 measurements. A questionnaire, blinded to the examining physician, and a visual analogue score (VAS) of pain ranging from 1 (no pain) to 10 (maximal pain) was obtained of the discomfort felt when attempting sexual intercourse. The VAS, the investigator assessment of redness, and the 1 to 10 score result of the cotton swab touch test at 5 and 7 o'clock were superior diagnostic tools for assessing the severity of the pain when compared to the use of von Frey filaments. Although elegant because of the promise of objective, semiquantitative measurements, von Frey filaments are less suitable devices to assess severity of disease and response to treatment than are cotton swab 1 to 10 pain scores and clinical parameters like subjective pain (VAS) and objective focal redness.


Central connections of the hepatic branch of the vagus nerve: a horseradish peroxidase histochemical study.
The hepatic branch of the vagus nerve has been implicated as an important source of afferent input controlling both physiological and behavioral homeostasis. In addition, it is clear that parasympathetic efferents to the liver can significantly alter hepatic functions. In order to begin physiological studies on the nature of hepatic afferent and efferent relations, it will be necessary to understand the central anatomical organization of the components of this small visceral nerve. By carefully exposing and dissecting the hepatic branch of the vagus and applying crystalline horseradish peroxidase (HRP) to it, we were able to elucidate a predominant pattern of afferent terminations within the left subnucleus gelatinosus, the medial division of the left solitary nucleus and the left lateral edge of the area postrema. Efferent nuclei were concentrated in the left dorsal motor nucleus of the vagus (DMN) with a few scattered neurons located in the right DMN as well as the left anterior nucleus ambiguous.


Phylogenetic affinities between eukaryotic cells and a thermophilic mycoplasma.
Thermoplasma acidophilum, a thermophilic mycoplasma, has several unusual features suggesting a possible relationship to eukaryotic cells. One feature is a histone-like protein that is associated with the DNA, condensing it into subunits similar to those in eukaryotic chromatin. A second feature is an association of cytoplasmic proteins that resembles eukaryotic actin and myosin. These two components are widely distributed in different groups of eukaryotic cells, but are typically lacking in prokaryotic cells. Furthermore, T. acidophilum lacks cytochromes and respires by enzymes that apparently are not coupled to oxidative phosphorylation. This primitive type of respiration resembles that of microbodies, another feature which is represented in the cytoplasm of all groups of eukaryotic cells. Furthermore, since T. acidophilum lacks a cell wall and appears to have a primitive correlate of endocytosis, it would appear to be mechanically capable of acquiring a symbiotic mitochondrion. Thus, our observations are consistent with the symbiotic hypothesis for the origin of eukaryotic cells. We suggest that an organism similar to T. acidophilum was the host cell for the original symbiosis, becoming the nucleus and cytoplasm of modern eukaryotic cells.


Therapy of ATTR Cardiac Amyloidosis: Current Indications.
Transthyretin cardiac amyloidosis is a restrictive cardiomyopathy caused by extracellular deposition in the heart of amyloid fibrils derived from plasma transthyretin (ATTR), either in its hereditary (ATTRh) or acquired (ATTRwt) forms. Cardiac amyloidosis has a very poor prognosis if therapy is not started promptly. Therefore, it is very important to recognize cardiac amyloidosis early in order to immediately start a treatment capable of modifying the prognosis. Treatment of cardiac amyloidosis is not easy, often requiring a multidisciplinary team. New RNA-interfering drugs (such as patisiran) have been devised and are effective in the treatment of ATTRh amyloidosis. Tafamidis (a stabilizer of the native tetramer structure of TTR) is recommended to treat patients with genetic testing-proven hereditary hTTR-cardiomyopathy or wild-type TTR cardiomyopathy and NYHA Class I or II to reduce symptoms, CV hospitalization and mortality (Class I, level of evidence B). Patisiran should be considered in ATTRh cardiomyopathy with polyneuropathy. Thus, this review is intended to be a simple practical guide for the treatment of ATTR cardiac amyloidosis.


G6PD overexpression protects from oxidative stress and age-related hearing loss.
Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (G6PD-Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild-type mice during aging, together with preserved inner hair cell (IHC) and outer hair cell (OHC), OHC innervation, and a conserved number of synapses per IHC. Gene expression of antioxidant enzymes was higher in 3-month-old G6PD-Tg mice than in wild-type counterparts, whereas the levels of pro-apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL+ apoptotic cells were all lower in 9-month-old G6PD-Tg than in wild-type counterparts. Unexpectedly, G6PD overexpression triggered low-grade inflammation that was effectively resolved in young mice, as shown by the absence of cochlear cellular damage and macrophage infiltration. Our results lead us to propose that NADPH overproduction from an early stage is an efficient mechanism to maintain the balance between the production of ROS and cellular detoxification power along aging and thus prevents hearing loss progression.


Ploidy of micronucleated thyrocytes induced by methylnitrosourea injection.
Ploidy of thyroid parenchyma was studied in adult rats in the control and on day 9 after hemithyroidectomy; operated animals received 3 injections of N-nitroso-N-methylurea. The population of follicular thyrocytes is mainly diploid; total count of polyploid cells increased from 4.4% in the control to 8.5% in experimental rats. All thyrocytes containing micronuclei were tetraploid. No diploid micronucleated elements were detected. This suggests that genetically damaged thyrocytes divide by the mechanism of acytokinetic (polyploidizing) mitosis.


In vivo evaluation of intravesical paclitaxel and combined bcl-xL antisense oligodeoxynucleotide treatment for orthotopic urothelial carcinoma.
To evaluate intravesical paclitaxel monotherapy and combined treatment with antiapoptotic bcl-xL antisense oligodeoxynucleotides (AS-ODNs) on urothelial carcinoma (UC). Forty-eight FoxN(rnu) athymic nude rats with orthotopic human bladder UC were randomized to four treatment groups [1, paclitaxel; 2, paclitaxel/bcl-xL AS-ODNs; 3, bcl-xL AS-ODNs (control); 4, medium (control)]. Three consecutive instillations were applied and weekly endoscopic tumor size measurements were performed. Significant tumor size reduction was achieved in groups 1 and 2 (each P < 0.0001), whereas continuous UC growth was observed in control animals (groups 3 and 4; P < 0.0001 and P < 0.0020). Complete tumor eradication was achieved in four treated animals (groups 1 and 2). No significant difference in chemoresection effects was found between groups 1 and 2 (P = 0.2251). We present an in vivo evaluation of intravesical treatment with paclitaxel and combined bcl-xL AS-ODNs. Despite efficient tumor size reduction, no gain was observed when adding bcl-xL AS-ODNs in this experimental setting.


Correction to: Reducing macrophage numbers alleviates temporomandibular joint ankylosis.
The article "Reducing macrophage numbers alleviates temporomandibular joint ankylosis", written by Lu Zhao, E Xiao, Linhai He, Denghui Duan, Yang He, Shuo Chen, Yi Zhang and Yehua Gan, was originally published electronically on the publisher's internet portal.


Colon cancer bearing rats produce a lymphokine which induces macrophage migration inhibition (MIF) in vitro.
We studied a series of 40 rats at various stages of colorectal carcinoma, as induced by N-methyl-N-nitro-Nitrosoguanidine. Lymphokine containing supernatants were obtained simultaneously from splenic and peripheral lymphocytes, after exposure to rat colon cancer antigen in vitro. The lymphokine was found capable of performing Macrophage Migration Inhibition (MIF) when obtained from rats with: carcinoma through serosa, carcinoma of submucosa, carcinoma of the mucosa and carcinoma in situ. All control rats were free of cancer and were MIF negative. The MIF response in this study was evaluated as a marker of chemically induced colorectal carcinoma in rats in order to better understand the lymphocyte response to tumor progression from atypia to adenocarcinoma of the colon.


Evaluation of a multiplex real-time polymerase chain reaction assay for the detection of influenza and respiratory syncytial viruses.
Nasopharyngeal swabs from 424 children were used to compare the performances of the new multiplex real-time polymerase chain reaction (RT-PCR) RIDA®GENE Flu & RSV kit and monospecific RT-PCR assays in detecting respiratory syncytial and influenza viruses. The easy-to-use kit was highly sensitive and specific and is recommended for routine practice.


Controversies across continents. Report from the MS Forum Symposium, September 2002, Baltimore, USA.
The personal views of speakers from North America and Europe concerning the diagnosis and management of people with multiple sclerosis (MS) were presented at an MS Forum symposium before ACTRIM/ECTRIMS Meeting in Baltimore, USA. There were more areas of agreement than controversy and the overall impression was that MS is managed similarly across the continents. Four topics were discussed: diagnosing the clinically isolated syndrome; guidelines for using disease-modifying therapy; people who fail to respond to disease-modifying treatment; and treating the patient with rapid deterioration to disability.


Pathophysiology of gastrointestinal trichostrongyles in sheep: plasma losses and changes in plasma pepsinogen levels associated with parasite challenge of immune animals.
The pathophysiological effects of experimental larval challenge with a mixed trichostrongyle infection were measured in ewes which had previously grazed contaminated pasture. Their immune status was confirmed by low worm burdens, both before and after challenge. Despite the low worm burdens, it was evident that larval challenge was associated with marked pathophysiological disturbances and, in particular, a doubling of plasma pepsinogen levels, albumin catabolism and losses of plasma protein into the gastrointestinal tract. The concurrent timing of these changes suggested they had a common aetiology. These findings indicate that larval challenge of such animals may cause impaired production, despite low parasite burdens.


Qualitative study of yoga for Young adults in school sports.
Distress and stress-related diseases are an increasing public health problem at schools. This qualitative study was nested in a non-randomized, controlled trial studying the effects of a 10-week yoga course as an alternative for regular school sports in two secondary schools in Germany. We conducted a qualitative evaluation in 3 focus groups with 6 participants each. The focus groups were audio-recorded, transcribed verbatim, pseudonymised and analysed using qualitative content analysis. Furthermore open questions were asked in questionnaires. The analysis of the participants' interviews (mean age 19.6 ± 2.9 years, n = 10 female, n = 8 male) resulted in 4 key topics: 1. encountering yoga, 2. yoga practice, 3. effects and benefits of yoga, and 4. yoga in the school context. Yoga was very well accepted by most participants. They reported a variety of physical and psychological benefits as well as overall restorative effects. The relief of pain or other physical ailments, higher mobility and flexibility, improved posture and improved sleep were mentioned by the participants. Some participants used the new exercises and experiences (e.g. working with the breath) in their everyday life. The possibility for self-responsible action was a welcome change from the perceived pressure and heteronomy in normal (school) life. Controversial was the question of whether yoga - if it is part of school sport - should be assessed or graded, and whether it should be compulsory or voluntary. Yoga can offer both physical and psychological benefits in young adults as well as offer general regenerative effects. Yoga by sensitizing the participants to negative patterns of behaviour can encourage healthy behaviour.


Occurrence, function and evolutionary origins of '2A-like' sequences in virus genomes.
2A is an oligopeptide sequence mediating a ribosome 'skipping' effect, producing an apparent 'cleavage' of polyproteins. First identified and characterized in picornaviruses, '2A-like' sequences are found in other mammalian viruses and a wide range of insect viruses. Databases were analysed using a motif conserved amongst 2A/2A-like sequences. The newly identified 2A-like sequences (30 aa) were inserted into a reporter polyprotein to determine their cleavage activity. Our analyses showed that these sequences fall into two categories. The majority mediated very high (complete) cleavage to separate proteins and a few sequences mediated cleavage with lower efficiency, generating appreciable levels of the uncleaved form. Phylogenetic analyses of 2A-like sequences and RNA-dependent RNA polymerases (RdRps) indicated multiple, independent, acquisitions of these sequences at different stages during virus evolution. Within a virus family, 2A sequences are (probably) homologous, but diverge due to other evolutionary pressures. Amongst different families, however, 2A/2A-like sequences appear to be homoplasic.


Insulin resistance, subclinical left ventricular remodeling, and the obesity paradox: MESA (Multi-Ethnic Study of Atherosclerosis).
This study assessed whether impaired fasting glucose (IFG), insulin resistance, and waist-to-hip ratio (WHR) had effects on cardiac remodeling, independent of obesity, in the MESA (Multi-Ethnic Study of Atherosclerosis) trial. Recent studies have suggested that central obesity and insulin resistance may be primary mediators of obesity-related cardiac remodeling independent of body mass index (BMI). We investigated 4,364 subjects without diabetes in the MESA trial. IFG (100 to 125 mg/dl) or insulin resistance (by homeostatic model assessment of insulin resistance [HOMA-IR]) and WHR were used for cardiometabolic phenotyping. Multivariate linear regression analysis was used to determine the effects of the cardiometabolic markers on left ventricular (LV) remodeling, assessed primarily through the LV mass-to-volume ratio obtained by cine cardiac magnetic resonance imaging. Individuals with IFG were more likely to be older and hypertensive, with increased prevalence of cardiometabolic risk factors regardless of BMI. In each quartile of BMI, subjects with above-median HOMA-IR, above-median WHR, or IFG had a higher LV mass-to-volume ratio (p < 0.05 for all). HOMA-IR (p < 0.0001), WHR (p < 0.0001), and the presence of IFG (p = 0.04), but not BMI (p = 0.24), were independently associated with LV mass-to-volume ratio after adjustment for age, sex, hypertension, race, and dyslipidemia. Insulin resistance and WHR were associated with concentric LV remodeling independent of BMI. These results support the emerging hypothesis that the cardiometabolic phenotype, defined by insulin resistance and central obesity, may play a critical role in LV remodeling independently of BMI.


Performance Measurement Part II: A guide to developing dermatology performance measures.
Throughout the twenty-first century, national and local governments, private health sectors, health insurance companies, healthcare professionals, labor unions, and consumers have been striving to develop an effective approach to evaluate, report, and improve the quality of healthcare.1 As medicine improves and health systems grow to meet patient needs, the performance measurement system of care effectiveness must also evolve. Continual efforts should be undertaken to effectively measure quality of care to create a more informed public, improve health outcomes, and reduce healthcare costs. As such, recent policy reform has necessitated that performance systems be implemented in healthcare, with the "performance measure" being the foundation of the system in which all of healthcare must be actively engaged in to ensure optimal care for patients. The development of performance measures can be highly complex, particularly when creating specialty-specific performance measures. To help dermatologists understand the process of creating dermatology-specific performance measures to engage in creating or implementing performance measures at the local or national levels, this article in the two-part continuing medical education series reviews the types, components, and process of developing, reviewing, and implementing performance measures.


Mycobacterial persistence requires the utilization of host cholesterol.
A hallmark of tuberculosis is the ability of the causative agent, Mycobacterium tuberculosis, to persist for decades despite a vigorous host immune response. Previously, we identified a mycobacterial gene cluster, mce4, that was specifically required for bacterial survival during this prolonged infection. We now show that mce4 encodes a cholesterol import system that enables M. tuberculosis to derive both carbon and energy from this ubiquitous component of host membranes. Cholesterol import is not required for establishing infection in mice or for growth in resting macrophages. However, this function is essential for persistence in the lungs of chronically infected animals and for growth within the IFN-gamma-activated macrophages that predominate at this stage of infection. This finding indicates that a major effect of IFN-gamma stimulation may be to sequester potential pathogens in a compartment devoid of more commonly used nutrients. The unusual capacity to catabolize sterols allows M. tuberculosis to circumvent this defense and thereby sustain a persistent infection.


Antibody binding patterns in infertile males and females as detected by immunobead test, gel-agglutination test, and sperm immobilization test.
Sera from 214 infertile patients were assayed for antisperm antibodies using the IBT, GAT, and SIT. The new IBT methodology was compared with the more classical tests. Although SIT and GAT did not correlate to any particular antibody class, both were negative if IgA was present alone. The immunoglobulin class presented a preferential sperm region binding site: IgG to the head and tail, IgM to tail tip only, IgA to head and tail. Furthermore, these immunoglobulins from the serum of male patients bound differently to sperm than immunoglobulins from female serum. Finally, we were able to calculate the relative sensitivity, specificity, and predictive values for these tests.


Knowledge of Child Health and Affecting Factors Among Preschool Teachers: A Cross-Sectional Study in Chongqing, China.
This research aims to explore the health knowledge mastery of preschool teachers in Chongqing. A cross-sectional questionnaire survey of preschool teachers in Chongqing was conducted by random sampling. A total of 399 preschool teachers were included in this research. Multiple linear regression analysis was conducted to explore the influencing factors on preschool teachers' mastery of preschool child health knowledge. This research found that the average score of preschool teacher's knowledge of preschool children was only 34.01±0.78, and the accuracy of the knowledge points of continuous short-distance eye use time was the lowest, at less than 5%. The conducting of eye exercises by the kindergarten and the scores of preschool teachers were negatively correlated (β=-0.257, p<0.001); the score of health knowledge of preschool teachers of the kindergarten whose screen time met the standard was lower (β=-0.113, p=0.017); whether the time and frequency for outdoor activities of the kindergarten met the standards and the health knowledge score of preschool teachers was positively correlated (β=0.130, p<0.001 vs β=0.163, p<0.001). Male preschool teachers and teachers overweight according to BMI had higher scores for preschool health knowledge (β=-0.114, p=0.016 vs β=0.099, p=0.034). Preschool teachers in Chongqing had a poor grasp of knowledge regarding preschool children's health, and in particular, knowledge of children's exercise and eye use. Educational background and work experience may no longer indicate preparedness for teaching these topics, and suggests that supportive measures can also be directly provided at the kindergarten level in the future to increase the health knowledge of preschool teachers.


Confocal microscopic evaluation of particles at the corneal flap interface after myopic laser in situ keratomileusis.
To investigate the appearance and origin of interface particles in the cornea after myopic laser in situ keratomileusis (LASIK) using the confocal microscope. Department of Optometry and Neuroscience, UMIST, Manchester, United Kingdom. An in vivo slit-scanning, real-time confocal microscope (Tomey ConfoScan P4) fitted with an Achroplan(R) 40X/0.75 NA immersion objective (Zeiss) was used to examine the morphology of the central cornea in 6 patients (12 eyes) at the initial visit (before surgery) and 1 week and 1, 3, and 6 months after LASIK for myopia. In all eyes, several interspersed particles of variable size and brightness were observed 1 week after surgery at the flap interface. The overall density of these particles decreased with time (F = 14.34, P =.01). For analysis, the particles were divided by density into high brightness and low brightness. The low-brightness particles significantly decreased with time (F = 13.26, P =.02). The high-brightness particles remained constant in density at all postoperative visits (F = 1.3, P =.15). CONCLUSIOINS: The particles of low reflectivity may represent 1 or more types of remains. It is unclear whether the low-reflectivity particles will eventually disappear. The high-reflectivity particles may represent fine metallic debris arising from the mechanical drive mechanism and/or the disposable knife of the microkeratome. If they are metallic and magnetic, they could be cleared during surgery (immediately before flap replacement) using a specially adapted magnet.


Effects of ketosis on cocaine-induced reinstatement in male mice.
In recent years, the benefits of the ketogenic diet (KD) on different psychiatric disorders have been gaining attention, but the substance abuse field is still unexplored. Some studies have reported that palatable food can modulate the rewarding effects of cocaine, but the negative metabolic consequences rule out the recommendation of using it as a complementary treatment. Thus, the main aim of this study was to evaluate the effects of the KD on cocaine conditioned place preference (CPP) during acquisition, extinction, and reinstatement. 41 OF1 male mice were employed to assess the effects of the KD on a 10 mg/kg cocaine-induced CPP. Animals were divided into three groups: SD, KD, and KD after the Post-Conditioning test. The results revealed that, while access to the KD did not block CPP acquisition, it did significantly reduce the number of sessions required to extinguish the drug-associated memories and it blocked the priming-induced reinstatement.


DNA methylation and gene expression changes in mouse pre- and post-implantation embryos generated by intracytoplasmic sperm injection with artificial oocyte activation.
The application of artificial oocyte activation (AOA) after intracytoplasmic sperm injection (ICSI) is successful in mitigating fertilization failure problems in assisted reproductive technology (ART). Nevertheless, there is no relevant study to investigate whether AOA procedures increase developmental risk by disturbing subsequent gene expression at different embryonic development stages. We used a mouse model to explore the influence of AOA treatment on pre- and post-implantation events. Firstly, the developmental potential of embryos with or without AOA treatment were assessed by the rates of fertilization and blastocyst formation. Secondly, transcriptome high-throughput sequencing was performed among the three groups (ICSI, ICSI-AOA and dICSI-AOA groups). The hierarchical clustering and Principal Component Analysis (PCA) analysis were used. Subsequently, Igf2r/Airn methylation analysis were detected using methylation-specific PCR sequencing following bisulfite treatment. Finally, birth rate and birth weight were examined following mouse embryo transfer. The rates of fertilization and blastocyst formation were significantly lower in oocyte activation-deficient sperm injection group (dICSI group) when compared with the ICSI group (30.8 % vs. 84.4 %, 10.0 % vs. 41.5 %). There were 133 differentially expressed genes (DEGs) between the ICSI-AOA group and ICSI group, and 266 DEGs between the dICSI-AOA group and ICSI group. In addition, the imprinted gene, Igf2r is up regulated in AOA treatment group compared to control group. The Igf2r/Airn imprinted expression model demonstrates that AOA treatment stimulates maternal allele-specific mehtylation spreads at differentially methylated region 2, followed by the initiation of paternal imprinted Airn long non-coding (lnc) RNA, resulting in the up regulated expression of Igf2r. Furthermore, the birth weight of newborn mice originating from AOA group was significantly lower compared to that of ICSI group. The pups born following AOA treatment did not show any other abnormalities during early development. All offspring mated successfully with fertile controls. AOA treatment affects imprinted gene Igf2r expression and mehtylation states in mouse pre- and post-implantation embryo, which is regulated by the imprinted Airn. Nevertheless, no significant differences were found in post-natal growth of the pups in the present study. It is hoped that this study could provide valuable insights of AOA technology in assisted reproduction biology.


Cortico-cortical connections reorganize in hamsters after neonatal transection of the callosal bridge.
Neonatal hamsters were subjected to transection of the callosal bridge. Later examination of the brains showed complete or partial absence of the corpus callosum and an anomalous bilateral longitudinal bundle of fibers. In addition, aberrant commissural fibers were seen to connect heterotopically the parietal cortex with the contralateral frontal cortex through a callosal remnant over the septum, and the olfactory cortex with the opposite frontal and parietal cortices through the anterior commissure.


Use of nursing diagnoses and interventions in public health nursing practice.
To determine the frequency of use of NANDA diagnoses and the Nursing Interventions Classification in care plans written by public health nurses (PHNs) in Orange County, CA. Retrospective chart review. The frequency pattern of nursing diagnoses and nursing interventions used in care plans is consistent with the scope of practice of the PHN, whose emphasis is on health promotion and disease prevention. The most commonly used diagnoses and interventions provide evidence of a core set of interventions useful for PHN practice. Linking diagnoses and interventions allow PHNs to build a body of knowledge based on patient care and improve clinical decision-making process.


Comparative study of five different techniques for epidemiological typing of Escherichia coli O157.
A set of 47 Austrian human, food, and veterinary Escherichia coli O157:H7 isolates was used to evaluate five different epidemiological typing methods. Ribotyping using an automated microbial characterization system (RiboPrinter) was not suitable for detection of epidemiological relatedness. All but one E. Coli strain were typeable by phage typing. Random amplified polymorphic DNA-PCR fingerprinting was performed using primer M13 containing the sequence 5'-GAG GGT GGC GGT TCT-3' and primer 1247 (5'-AAGAGCCCGT-3'). Although both methods recognized only two clusters, both dendrograms grouped most of the EHEC O157 isolates into epidemiologically related subgroups. Pulsed-field gel electrophoresis of XbaI digested total DNA was a valuable subtyping system. We found that major differences can exist between results of multiple subtyping methods. E. coli O157 isolates should not be classified as epidemiologically related or nonrelated on the basis of a single typing method alone.


Characteristics of stuttering-like disfluencies in Dutch-speaking children.
The purpose of this study was to compare the characteristics of stuttering-like disfluencies in a group of native Dutch-speaking children who stutter (n=693), with a group of normally fluent children (n=79). Methods involved the observation of stuttering-like disfluencies in participants' conversational speech samples (total 77,200 words), particularly the frequency, duration and physical tension of instances of stuttering. Findings indicate that stuttering-like disfluencies exhibited by children who stutter are significantly more frequent, longer in duration and involve more physical tension when compared to those of normally fluent children. Furthermore, applying a criterion of 3% stuttering-like disfluencies to distinguish stuttering from normally fluent children resulted in a high degree of sensitivity (0.9452) and specificity (0.9747). Results were taken to suggest that characteristics of stuttering-like disfluencies of Dutch-speaking children are similar to those of English-speaking children and that talker group membership criteria for childhood stuttering can reasonably be extrapolated from the Dutch to the English language and vice versa. The reader will be able to: (1) describe characteristics of stuttering-like disfluencies, (2) define properties such as frequency, duration and physical tension for stuttering children and normally fluent children, and (3) make use of data on sensitivity and specificity of the criterion of 3% stuttering-like disfluencies to distinguish stuttering and normally fluent children.


When to start dialysis treatment: where do we stand?
Since the publication of opinion-based guidelines regarding the timing of dialysis treatment, there has been a trend toward earlier initiation. In this review, the existing guidelines and the currently published studies that evaluate them are discussed. These studies could not demonstrate a clear benefit on survival or quality of life for patients who started with relatively higher renal function. Early start of dialysis treatment should not be confused with early referral to the nephrologist. It is concluded that initiation of dialysis should not depend on a predefined magnitude of renal function, but should be tailored to the individual patient.


Association between vasomotor symptoms and sarcopenia assessed by L3 skeletal muscle index among Korean menopausal women.
To evaluate the association between vasomotor symptoms (VMS), skeletal muscle index (SMI), and sarcopenia in menopausal women. This cross-sectional study included 295 Korean menopausal women 40 to 65 years old who underwent abdominal computed tomography during routine health checkups between January 2014 and May 2016. The cross-sectional areas of adipose and skeletal muscles were measured at the L3 level using computed tomography. The SMI is defined as the sum of the skeletal muscle area (cm2)/height2 (m2). Sarcopenia was identified by an SMI of <34.9 cm2/m2. VMS were assessed using the Menopause Rating Scale. The mean age of the participants was 54.93 ± 6.20 years. VMS were reported in 160 women (54.2%). Sarcopenia was more prevalent in women without VMS (18.5%) than in those with (6.9%). Multivariate logistic regression showed that the prevalence of sarcopenia was inversely associated with the prevalence of VMS (odds ratio, 0.32; 95% CI, 0.15-0.67). Moreover, the paraspinal muscle index was positively associated with the prevalence of VMS (odds ratio, 1.06; 95% CI, 1.01-1.11) after adjusting for age, body mass index, waist circumference, adipose tissue area, history of hormone therapy, systolic and diastolic blood pressures, total cholesterol, insulin resistance, alcohol intake, and exercise. VMS are less common in women with sarcopenia than in those without and are positively associated with paraspinal muscle mass in Korean menopausal women. Further longitudinal studies are required to investigate the causal relationships and underlying mechanisms.


[Comparison between intraarterial pulsegraphy and thermodilution method for determination of cardiac output during anesthesia and operation in patients undergoing cardiac valve replacement].
Comparison of intraarterial pulsegraphy and standard thermodilution methods for determination of cardiac output (CO) in 14 patients with poor cardiac function following valve replacement operation was performed. The CO, cardiac index (CI) were moderate to high correlated between the two methods before and after valve replacement respectively. The study indicates that intraarterial pulsegraphy provides a continous method of determining CO in patients with poor cardiac function during operation.


Efficacy of a hospital-wide environmental cleaning protocol on hospital-acquired methicillin-resistant Staphylococcus aureus rates.
Environmental contamination has been associated with over half of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in hospitals. We explored if a hospital-wide environmental and patient cleaning protocol would lower hospital acquired MRSA rates and associated costs. This study evaluates the impact of implementing a hospital-wide environmental and patient cleaning protocol on the rate of MRSA infection and the potential cost benefit of the intervention. A retrospective, pre-post interventional study design was used. The intervention comprised a combination of enhanced environmental cleaning of high touch surfaces, daily washing of patients with benzalkonium chloride, and targeted isolation of patients with active infection. The rate of MRSA infection per 1000 patient days (PD) was compared with the rate after the intervention (Steiros Algorithm®) was implemented. A cost-benefit analysis based on the number of MRSA infections avoided was conducted. The MRSA rates decreased by 96% from 3.04 per 1000 PD to 0.11 per 1000 PD (P <0.0001). This reduction in MRSA infections, avoided an estimated $1,655,143 in healthcare costs. Implementation of this hospital-wide protocol appears to be associated with a reduction in the rate of MRSA infection and therefore a reduction in associated healthcare costs.


Understanding Children's Heart Surgery Data: A Cross-Disciplinary Approach to Codevelop a Website.
Risk-adjusted survival statistics after children's heart surgery are published annually in the United Kingdom. Interpreting these statistics is difficult, and better resources about how to interpret survival data are needed. Here we describe how a multidisciplinary team of mathematicians, psychologists, and a charity worked with parents of heart surgery children and other users to codevelop online resources to present survival outcomes. Early and ongoing involvement of users was crucial and considerably changed the content, scope, and look of the website, and the formal psychology experiments provided deeper insight. The website http://childrensheartsurgery.info/ was launched in June 2016 to very positive reviews.


Methylene blue-assisted lymph node dissection technique is not associated with an increased detection of lymph node metastases in colorectal cancer.
Lymph node staging is of paramount importance for prognosis estimation and therapy stratification in colorectal cancer. A high number of harvested lymph nodes is associated with an improved outcome. Methylene blue-assisted lymph node dissection effectively improves the lymph node harvest and ensures sufficient staging. Now, the effect on node positivity rate and stage-related outcome was investigated. The study cohort with advanced lymph node dissection consisted of 669 colorectal cancer cases of all stages, which were collected between 2007 and 2012. A historical collection of 663 cases investigated with conventional techniques between 2002 and 2004 served as control. Lymph node harvest was dramatically improved in the study group with mean lymph node numbers of 34 ± 17 vs 13 ± 5 (P<0.001) and sufficient staging rates of 98% vs 62% (P<0.001). However, neither the rate of nodal positive cases (37% vs 37%; P = 0.98) nor the rate of N2 cases differed between the two groups (14% vs 13%; P = 0.80). Furthermore, no differences were found concerning the outcome in both groups. The advanced lymph node dissection technique guarantees adequate histopathological lymph node staging in virtually all cases of colorectal cancer and is therefore extremely helpful. The hypothesis that it also provides a higher sensitivity in detecting metastases, however, could be not proved.


A graph theoretic approach to the development of minimal phylogenetic trees.
The problem of determining the minimal phylogenetic tree is discussed in relation to graph theory. It is shown that this problem is an example of the Steiner problem in graphs which is to connect a set of points by a minimal length network where new points can be added. There is no reported method of solving realistically-sized Steiner problems in reasonable computing time. A heuristic method of approaching the phylogenetic problem is presented, together with a worked example with 7 mammalian cytochrome c sequences. It is shown in this case that the method develops a phylogenetic tree that has the smallest possible number of amino acid replacements. The potential and limitations of the method are discussed. It is stressed that objective methods must be used for comparing different trees. In particular it should be determined how close a given tree is to a mathematically determined lower bound. A theorem is proved which is used to establish a lower bound on the lenghtof any tree and if a tree is found with a length equal to the lower bound, then no shorter tree can exist.


Magnetic resonance imaging evaluation of non ovarian adnexal lesions.
Differentiation of nonovarian from ovarian lesions is a diagnostic challenge. MRI (Magnetic Resonance Imaging) of the pelvis provides excellent tissue characterization and high contrast resolution, allowing for detailed evaluation of adnexal lesions. Salient MRI characteristics of predominantly cystic lesions and predominantly solid adnexal lesions are presented along with epidemiology and clinical presentation. Due to its excellent soft tissue resolution, MRI may be able to characterize indeterminate adnexal masses and aid the radiologist to arrive at the correct diagnosis, thus positively affect patient management.


AIR-Net: A novel multi-task learning method with auxiliary image reconstruction for predicting EGFR mutation status on CT images of NSCLC patients.
Automated and accurate EGFR mutation status prediction using computed tomography (CT) imagery is of great value for tailoring optimal treatments to non-small cell lung cancer (NSCLC) patients. However, existing deep learning based methods usually adopt a single task learning strategy to design and train EGFR mutation status prediction models with limited training data, which may be insufficient to learn distinguishable representations for promoting prediction performance. In this paper, a novel multi-task learning method named AIR-Net is proposed to precisely predict EGFR mutation status on CT images. First, an auxiliary image reconstruction task is effectively integrated with EGFR mutation status prediction, aiming at providing extra supervision at the training phase. Particularly, we adequately employ multi-level information in a shared encoder to generate more comprehensive representations of tumors. Second, a powerful feature consistency loss is further introduced to constrain semantic consistency of original and reconstructed images, which contributes to enhanced image reconstruction and offers more effective regularization to AIR-Net during training. Performance analysis of AIR-Net indicates that auxiliary image reconstruction plays an essential role in identifying EGFR mutation status. Furthermore, extensive experimental results demonstrate that our method achieves favorable performance against other competitive prediction methods. All the results executed in this study suggest that the effectiveness and superiority of AIR-Net in precisely predicting EGFR mutation status of NSCLC.


Green Synthesis, Characterization and Application of Natural Product Coated Magnetite Nanoparticles for Wastewater Treatment.
Adsorption of organic pollutants, toxic metal ions, and removal of harmful bacteria can give us clean and pure drinkable water from wastewater resources. Respective magnetite nanoparticles (MNPs) were synthesized using a cheaper and greener way in an open-air environment with the use of crude latex of Jatropha curcas (JC) and leaf extract of Cinnamomum tamala (CT). Characterization of MNPs had been performed by dynamic light scattering (DLS), Ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, powdered X-ray diffraction (XRD), and field emission scanning electron microscope (FE-SEM). The size ranges of the synthesized MNPs were observed in between 20-42 nm for JC-Fe3O4 and within 26-35 nm for CT-Fe3O4 by FE-SEM images. The effect of synthesized magnetic nanoparticles in wastewater treatment (bacterial portion), dye adsorption, toxic metal removal as well as antibacterial, antioxidant, and cytotoxic activities were studied. This purification will lead to an increase in the resources of pure drinking water in the future.


The Serbian QOLIE-AD-48: translation, cultural adaptation, and preliminary psychometric evaluation.
The goals of the work described in this article were to translate and adapt into Serbian the Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48), and to evaluate the psychometric properties of the translation. Translation/backtranslation, cultural adaptation, and pretesting were performed first. For validity, internal consistency, and sensitivity testing, the Serbian version was administered to a sample of 67 adolescents with epilepsy. All subscales (Epilepsy Impact, Memory/Concentration, Attitudes toward Epilepsy, Physical Functioning, Stigma, Social Support, School Behavior, and Health Perceptions) contributed significantly to the summary measure. Mean scores for the subscales ranged from 75.4 to 91.3, and showed a tendency to decrease as illness severity increased. Internal consistency reliability (Cronbach's alpha) was 0.92 for the entire questionnaire. The QOLIE-AD-48 Serbian version is a valid and reliable instrument for health-related quality-of-life assessment in youths with epilepsy. It can be administered in 15 minutes, and can be used in clinical practice, as well as in quality-of-life research.


Effects of season and water type on the distribution and antimicrobial resistance of Enterococcus faecalis and Ent. faecium from surface and reclaimed water.
To evaluate the safety of irrigation water sources based on phenotypic antimicrobial resistance (AMR) in Enterococcus spp., a potential environmental reservoir for AMR determinants. Eleven sites representing fresh and brackish water rivers, ponds and reclaimed water, were sampled over 2 years. Samples (n = 333) yielded 198 unique isolates of Ent. faecalis and Ent. faecium which were tested for antimicrobial susceptibility by microbroth dilution. Species distribution was influenced by water type and season. Enterococcus faecalis was more likely found in freshwater rivers and in summer, and Ent. faecium in reclaimed water and in spring. Only 11% of isolates were pansusceptible, while 48.5% and 26.3% were single (SDR) and multidrug resistant (MDR), respectively. MDR was more likely detected in Ent. faecium than Ent. faecalis. Winter isolates were more likely than summer isolates to exhibit MDR than SDR. Enterococcus faecalis and Ent. faecium in surface and reclaimed water exhibited diverse phenotypic AMR and a low-level resistance to clinically important antimicrobials such as ampicillin, vancomycin and linezolid. Single and multidrug resistance in E. faecalis and E. faecium varied by season but not water type. Antimicrobial resistance prevalence can assist decisions on the safety of irrigation water sources for fresh produce crops.


c-fos reduces growth factor requirements for mitogenic stimulation of L6 rat myoblasts.
Addition of fetal calf serum (FCS) to serum-deprived L6J1 rat myoblasts increases fos-like immunoreactivity. The nuclear immunoreactivity reached a maximum 2 h after serum addition. Effects of the c-fos protein on myoblast proliferation were analyzed in L6J1 rat myoblasts transfected with the murine c-fos gene under control of a metallothionein promoter. L6J1 myoblasts with elevated expression of transfected c-fos reached higher cell densities than neo transfected control myoblasts when approaching a stationary phase in normal culture conditions (5% FCS). The differences in cell densities were even more pronounced at low serum concentrations (0.5% FCS). c-fos transfected cells also had a faster growth rate than did control cells in serum-free medium supplemented with calcium chloride, lithium chloride, sodium selenite, hydrocortisone, and insulin. The cell morphology of c-fos transfected L6J1 myoblasts was not affected compared to control myoblasts. These results suggest that c-fos protein expression in L6J1 myoblasts is activated by serum and that mitogenic stimulation of L6J1 myoblasts is facilitated by the presence of elevated amounts of c-fos protein.


Defense proteins and immune complexes in the blood serum of women with inflammatory and neoplastic lesions of the ovary.
Blood sera of 181 women with inflammatory conditions and with benign and malignant neoplasms of the ovary and of 36 healthy women (control group) were examined by determining the levels of defense proteins: C-reactive protein (CRP), alpha 1 antitrypsin (A1AT), alpha 2 macroglobulin (A2M), components C3 (beta 1 A-globulin) and C4 (beta 1 E-globulin) of the complement, immunoglobulins M (IgM), A (IgA), and G (IgG), as well as the concentration of circulating immune complexes (IC). In women with ovarian pathology, as compared with the control group, a significant increase of all the defense proteins was found (p less than 0.05). The highest increase of the defense proteins, except in regard to A2M was observed in inflammation of the ovary. In malignant neoplasms of the ovary, the level of A2M was the highest and that of A1AT as high as in inflammatory conditions. There was also a high percentage of increased CRP values (57%). The concentration of the remaining proteins under study, although significantly higher than in the control group (p less than 0.05), was in this group the lowest in comparison with the groups of ovarian inflammation and benign neoplasms, especially with regard to component C3 of the complement and to IgM and IgG (p less than 0.05). Significantly increased values of IC (p less than 0.05) were observed in ovarian inflammation (73.2%) and in benign neoplasms (25.0%). In the group of malignant neoplasms (15.4%) and in healthy women (5.6%), the increased IC values were not statistically significant (p less than 0.05).


The prevalence of a large Hill-Sachs lesion that needs to be treated.
A large Hill-Sachs lesion has been considered a risk factor for postoperative recurrence of shoulder instability. However, there are few reports describing the prevalence of Hill-Sachs lesions that engage with the glenoid. The purpose of this study was to clarify the prevalence of engaging Hill-Sachs lesions using the concept of the glenoid track. The computed tomography images of 100 consecutive patients with unilateral recurrent anterior shoulder dislocations were assessed. An image in the plane perpendicular to the rotator cuff attachment was reconstructed from the DICOM (Digital Imaging and Communications in Medicine) data, and the maximum distance from the medial margin of the Hill-Sachs lesion to the medial margin of the rotator cuff footprint was measured. The location of the Hill-Sachs lesion in the glenoid track was assessed, and when the Hill-Sachs lesion extended medially over the glenoid track, it was defined as an "engaging Hill-Sachs lesion." Engaging Hill-Sachs lesions were observed in 7 of 100 cases (7%). There were 2 types of Hill-Sachs lesions: a large and wide type (3 cases) and a narrow but medially located type (4 cases). All cases with an engaging Hill-Sachs lesion had a large bony defect of the glenoid at the same time. In our series of consecutive 100 cases, the prevalence of engaging Hill-Sachs lesions was 7%. There were 2 types of Hill-Sachs lesions: a wide and large type and a narrow but medially located type.


Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney.
The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms alpha and beta were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific.


Application of MRI to the analysis of speech production.
Computer models of the process of speech articulation require a detailed knowledge of the vocal tract configurations employed in speech and the application of acoustic theory to calculate the sound waveform. Almost all currently available data on vocal tract dimensions come from x-ray films and are severely limited in quantity and coherence due to restrictions on radiation dosage and intersubject differences. We are using MRI techniques to obtain the pharyngeal dimensions of speakers producing sustained vowels. The fact that MRI does not employ ionizing radiation provides speech research with the opportunity to obtain comprehensive bodies of much-needed data on the articulatory characteristics of single subjects.


Bifurcation lesion treated with a single stent: a new technique.
Treatment of bifurcation lesions by percutaneous coronary interventions is one of the challenging issues for the interventional cardiologists. The overall complication rate is higher than nonbifurcation lesions. We describe a new stenting technique for the so-called true bifurcation lesions.


Through the back door: Unconventional protein secretion.
Proteins are secreted from eukaryotic cells by several mechanisms besides the well-characterized classical secretory system. Proteins destined to enter the classical secretory system contain a signal peptide for translocation into the endoplasmic reticulum. However, many proteins lacking a signal peptide are secreted nonetheless. Contrary to conventional belief, these proteins are not just released as a result of membrane damage leading to cell leakage, but are actively packaged for secretion in alternative pathways. They are called unconventionally secreted proteins, and the best-characterized are from fungi and mammals. These proteins have extracellular functions including cell signaling, immune modulation, as well as moonlighting activities different from their well-described intracellular functions. Among the pathways for unconventional secretion are direct transfer across the plasma membrane, release within plasma membrane-derived microvesicles, use of elements of autophagy, or secretion from endosomal/multivesicular body-related components. We review the fungal and metazoan unconventional secretory pathways and their regulation, and propose experimental criteria to identify their mode of secretion.


A hybrid approach of random forest and random parameters logit model of injury severity modeling of vulnerable road users involved crashes.
Vulnerable road users (VRUs) involved crashes are a major road safety concern due to the high likelihood of fatal and severe injury. The use of data-driven methods and heterogeneity models separately have limitations in crash data analysis. This study develops a hybrid approach of Random Forest based SHAP algorithm (RF-SHAP) and random parameters logit modeling framework to explore significant factors and identify the underlying interaction effects on injury severity of VRUs-involved crashes in Shenyang (China) from 2015 to 2017. The results show that the hybrid approach can uncover more underlying causality, which not only quantifies the impact of individual factors on injury severity, but also finds the interaction effects between the factors with random parameters and fixed parameters. Seven factors are found to have significant effect on crash injury severity. Two factors, including primary roads and rural areas produce random parameters. The interaction effects reveal interesting combination features. For example, even though rural areas and primary roads increase the likelihood of fatal crash occurrence individually, the interaction effect of the two factors decreases the likelihood of being fatal. The findings form the foundation for developing safety countermeasures targeted at specific crash groups for reducing fatalities in future crashes.


Scarf pin inhalation: clinical characteristics and surgical treatment.
Scarf pin inhalation is becoming a frequent accident among young Moroccan woman who wears islamic veil. The aim of the study is to highlight indications, principles and challenges of surgical removal of that particular foreign body. Twenty-eight patients were hospitalized in Thoracic Surgery department of Ibn Sina Hospital at Rabat between January 2008 and June 2013 for surgical removal of a pin scarf after unsuccessful endoscopy. Mean age was 20 years. Inhalation was accidental in all cases. Average interval between inhalation and surgery was 10 days. Penetration syndrome was found in 82% of patients. Pin was located at the left tracheo-bronchial tree in 53.5% of cases and at the right one in 46.4%. All were operated by thoracotomy. Surgery was conservative in all cases, and postoperative course was uneventful. In case of failure endoscopic treatment, surgery remains the only alternative. It must be as conservative as possible. Short interval between inhalation accident and surgery prevents parenchymal resection.


Drug monitoring of orally administered 8-methoxypsoralen in patients treated with extracorporeal photopheresis.
Recently extracorporeal photopheresis (ECP), a new therapy involving extracorporeal activation of orally administered 8-methoxypsoralen (8-MOP), has been established for the treatment of different skin diseases. The pharmacokinetic profile of 8-MOP has been pursued in a clinical study which aimed to assess the efficacy of ECP in patients with progressive systemic sclerosis and cutaneous T-cell lymphoma. However, the enormous intraindividual variations in plasma as well as buffy coat concentrations affect the efficacy of oral 8-MOP therapy. Therefore, the introduction of a liquid 8-MOP formulation enabling the direct administration of the drug into the treatment bag of the ECP device is challenging.


Lactoferrin promotes the autophagy activity during osteoblast formation via BCL2-Beclin1 signaling.
Lactoferrin, as the main component of milk, can maintain osteoblast formation, which is conducive to the prevention and treatment of osteoporosis. Lactoferrin also serves as an autophagy regulator, especially in osteoblasts. This study aimed to explore the significance of autophagy in osteoblast formation regulated by lactoferrin and the internal mechanism. In this study, we firstly explored the roles of lactoferrin in the autophagy activity of primary osteoblasts (LC3 transformation rate, autophagosome formation). Subsequently, we further investigated the effects of lactoferrin on the BCL2 expression and BCL2-Beclin1 complex. Ultimately, the significance of BCL2 overexpression and Beclin1 silencing on lactoferrin-regulated osteoblast autophagy and osteogenic parameters (ALP activity and mRNA expression of PCNA, Col1, BGLAP and OPN) was observed by gene processing, respectively. Our results showed that lactoferrin enhanced the autophagy activity of osteoblasts. Importantly, lactoferrin inhibited BCL2 expression and the co-immunoprecipitation of BCL2 and Beclin1 in osteoblasts. Moreover, lactoferrin-promoted autophagy and osteogenic parameters was reversed by BCL2 overexpression or Beclin1 silencing in osteoblasts. In conclusion, lactoferrin can inhibit BCL2 expression in osteoblasts, further enhancing Beclin1-dependent autophagy activation.


Spontaneous globe luxation associated with contact lens placement.
Globe luxation, characterized as the anterior dislocation of the eyeball beyond retracted lids, presents a dramatic clinical picture. It is an uncommon event and can produce anxiety in both the patient and the physician. The purpose of this article is to present a case of spontaneous globe luxation which occurred with attempted contact lens placement. A case report and literature review are presented. Manual reduction of the globe required conscious sedation in the emergency room. Diffuse superficial punctate keratitis resolved completely with no visual sequelae. The clinical features, epidemiology, risk factors, complications and treatments of globe luxation are presented. Eye care specialists who fit and dispense contact lenses should be aware of risk factors associated with globe luxation. A step-wise plan for management is presented, in hope of limiting patient discomfort, recurrence, and perhaps long-term visual impairment.


Macromolecular dextran sulfate facilitates extracellular matrix deposition by electrostatic interaction independent from a macromolecular crowding effect.
A faithful reconstruction of the native cellular microenvironment is instrumental for tissue engineering. Macromolecular crowding (MMC) empowers cells to deposit their own extracellular matrix (ECM) in greater amounts, and thus contributes to building tissue-specific complex microenvironments in vitro. Dextran sulfate (DxS, 500 kDa), a semi-synthetic sulfated polyglucose, was shown previously at a fractional volume occupancy (FVO) of 5.2% (v/v; 100 μg/ml) to act as a potent molecular crowding agent in vitro. When added to human mesenchymal stromal cell (MSC) cultures, DxS enhanced fibronectin and collagen I deposition several-fold also at concentrations with negligible FVO (<1% v/v). In a cell-free system, incubation of culture media supplemented with fetal bovine serum (FBS), purified fibronectin or collagen I with DxS led to a co-deposition of respective components, exhibiting a similar granular pattern as observed in cell culture. Aggregation of FBS components, fibronectin or collagen I with DxS was confirmed by dynamic light scattering, where an increase in hydrodynamic radius in the respective mixtures was observed. FBS- and fibronectin aggregates could be dissociated with increasing salt concentrations, indicating electrostatic forces to be responsible for the aggregation. Conversely, collagen I-DxS aggregates increased in size with increasing ion concentration, likely caused by charge screening of collagen I, which is net negatively charged at neutral pH, thus permitting weaker intermolecular interactions to occur. The incorporation of DxS into the ECM resulted in altered ECM topography and stiffness. DxS-supplemented cultures exhibited potentiated bioactivity, such as enhanced adipogenic and especially osteogenic differentiation under inductive conditions. We propose an alternative mechanism by which DxS drives ECM deposition via aggregation, and in an independent manner from MMC. A deeper understanding of the underlying mechanism will enable optimized engineering approaches for ECM-rich tissue constructs.


Reduced yield of pulmonary surfactant: patterns of response following administration of chemicals to rats by inhalation.
Repeated exposure of rats to trichloroethylene, carbon tetrachloride, gasoline vapour or to cigarette smoke is followed by significant reduction in the recovery of pulmonary surfactant, inhibition being evident as early as 5 days after commencement of treatment. The degree of reduction in surfactant recovery was dose-dependent and the kinetics of this reaction indicated the relative toxicities of the treatments. The results are discussed with reference to the use of surfactant recovery as an indicator of non-specific injury to respiratory tissue.


Comorbid Psoriasis and Metabolic Syndrome: Clinical Implications and Optimal Management.
To review the literature on guidance on the follow-up of psoriasis and its comorbidities and to provide practical recommendations. A PubMed search was conducted using MeSH terms and free text keywords related to "psoriasis", "obesity", "hypertension", "diabetes", "dyslipidemia", "metabolic syndrome" and "Psoriatic arthritis". The search was conducted between September 2021 and January 2022. References of selected articles were scanned to identify additional articles. Recommendations on the follow-up of hypertension, obesity, dyslipidemia, type 2 diabetes, metabolic syndrome, psoriatic arthritis, non-alcoholic fatty liver disease and inflammatory bowel disease in psoriasis patients were extracted from the included articles. These data are presented in summary tables for both adults and children. A practical and feasible approach for each comorbidity is discussed. Awareness among dermatologists for relevant psoriasis-associated comorbidities is crucial. The dermatologist should function as gatekeeper and screen for comorbidities, in order to make timely referrals when indicated.


Improving aerobic sludge granulation in sequential batch reactor by natural drying: Effluent sludge recovery and feeding back into reactor.
One of the main problems in treating high volumes of wastewater is the long startup time required aerobic granular sludge (AGS), and this issue significantly limits the broad application of advanced AGS technology. To promote rapid AGS formation in the startup phase, a method was developed involving the recovery and natural drying of effluent sludge prior to feeding it back into the sequencing batch reactor (SBR). An analysis of the process shows that supplemented naturally dried sludge swiftly promoted sludge aggregation and granular sludge formation in the reactor, and feeding the SBR with naturally dried sludge aggregates (1.75 ± 0.05 g/L seven times) significantly shortened the granulation time in the startup phase by 14 days. In addition, MLSS, SVI30, SVI30/SVI5, and the average granule size of AGS in the reactor were maintained at 4.66 g/L, 47.4 mL/g, 0.93, and 2.8 mm, respectively. When fed back into the bioreactor, the aggregates acted as nuclei/carriers in the rapid granulation and played a significant role in rendering the SBR operation stable. This approach could be used to eliminate the random granules aggregation-disintegration mechanism that occurs in the initial stage of AGS formation. The study results reveal that the removal rate of COD and NH4+-N were above 95% and 96%, respectively. Furthermore, this approach requires less energy and significantly reduces the amount of sludge produced (as the effluent sludge is reused).


Deformation of the articular cartilage and joint space of the human knee joint under static load.
In order to define the deformation of articular cartilage and the joint space under statically loaded knee joints, we studied serial sections in the frontal plane of knee joints which were frozen under the application of a load. Normal articular cartilage surfaces did not make contact even under loads of 100kg or more, leaving always a space between. The compressive deformation of articular cartilage mainly occurred at the central area near to the intercondylar notch or prominence, but the deformation of cartilage in the area covered by menisci was negligible.


TRPML1 channels initiate Ca2+ sparks in vascular smooth muscle cells.
TRPML1 (transient receptor potential mucolipin 1) is a Ca2+-permeable, nonselective cation channel localized to the membranes of endosomes and lysosomes and is not present or functional on the plasma membrane. Ca2+ released from endosomes and lysosomes into the cytosol through TRPML1 channels is vital for trafficking, acidification, and other basic functions of these organelles. Here, we investigated the function of TRPML1 channels in fully differentiated contractile vascular smooth muscle cells (SMCs). In live-cell confocal imaging studies, we found that most endosomes and lysosomes in freshly isolated SMCs from cerebral arteries were essentially immobile. Using nanoscale super-resolution microscopy, we found that TRPML1 channels present in late endosomes and lysosomes formed stable complexes with type 2 ryanodine receptors (RyR2) on the sarcoplasmic reticulum (SR). Spontaneous Ca2+ signals resulting from the release of SR Ca2+ through RyR2s ("Ca2+ sparks") and corresponding Ca2+-activated K+ channel activity are critically important for balancing vasoconstriction. We found that these signals were essentially absent in SMCs from TRPML1-knockout (Mcoln1-/- ) mice. Using ex vivo pressure myography, we found that loss of this critical signaling cascade exaggerated the vasoconstrictor responses of cerebral and mesenteric resistance arteries. In vivo radiotelemetry studies showed that Mcoln1-/- mice were spontaneously hypertensive. We conclude that TRPML1 is crucial for the initiation of Ca2+ sparks in SMCs and the regulation of vascular contractility and blood pressure.


Acute myocardial infarction in COVID-19 patients. A review of cases in the literature.
COVID-19 is an ongoing pandemic that has lasted more than a year. Patients with multiple comorbidities such as diabetes, hypertension, and smoking have been shown to be at increased risk of a more severe course and lethal outcome. Since the disease can also lead to a hypercoagulable state, several cases of acute myocardial infarction (AMI) have also been recorded. We searched PubMed/Medline for case reports of AMI occurring in COVID-19 positive patients using "acute myocardial infarction", "COVID-19", and "SARS-CoV-2" as keywords. Thirty-three articles covering 37 patients were identified, among which 30 (81.1%) were male, and 7 (18.9%) were females. The mean age of these 37 patients was 52.8 ±15.6 years. Most cases were from the United States (17 cases, 45.9%). Several comorbidities such as hypertension (16 cases, 43.2%), diabetes (14 cases, 37.8%), smoking (8 cases, 21.6%), obesity (3 cases, 8.1%), morbid obesity (1 case, 2.7%), and elevated lipid levels (4 cases, 10.8%) were also identified. The most common symptom of AMI was chest tightness (22 cases, 59.5%), while the most common symptoms for COVID-19 were dyspnoea (25 cases, 67.6%) and fever (22 cases, 59.5%). The mortality rate was 35.1%. Given the high mortality rate, physicians are encouraged to properly check for signs of cardiac dysfunction and possible AMI while treating COVID-19 positive patients with several comorbidities or previous history of AMI.


Do stillborns with no identifiable pathology have leaner cords than liveborns?
To evaluate whether stillbirths with no explanation found at autopsy have thinner cords than live, gestational-age-matched controls. Stillbirth autopsies performed at University Hospital, Newark, New Jersey, from January 1995 to October 2002 were reviewed. Cases with no explanation for the death at autopsy had their umbilical cord diameters compared to those in 3 groups of age-matched controls: stillbirths with an identifiable cause of death, liveborns with placentas submitted for pathology evaluation and liveborns from which the placentas were not submitted to pathology. Age-adjusted ANOVAs were performed for comparisons. Of 181 autopsies performed during the review period, 21 cases (11.6%) provided no information at autopsy that would explain or contribute to an understanding of the death. There was no significant difference in cord diameters between either group ofstillbirths or the pathology-submitted controls. Third-trimester placentas from liveborns without placental submission to pathology had significantly greater cord diameters (p = 0.001). This study does not support the theory that a cord accident or decreased umbilical blood flow resulting from a leaner umbilical cord can explain a significant number of stillbirths with no other findings at autopsy. However, it supports the literature in that leaner cords appear to be associated with a wide variety of adverse perinatal conditions.


Alzheimer's Disease: Related Targets, Synthesis of Available Drugs, Bioactive Compounds Under Development and Promising Results Obtained from Multi-target Approaches.
We describe herein the therapeutic targets involved in Alzheimer's disease as well as the available drugs and their synthetic routes. Bioactive compounds under development are also exploited to illustrate some recent research advances on the medicinal chemistry of Alzheimer's disease, including structure-activity relationships for some targets. The importance of multi-target approaches, including some examples from our research projects, guides new perspectives in search of more effective drug candidates. This review comprises the period between 2001 and early 2020.


Polyamines in bacteria: pleiotropic effects yet specific mechanisms.
Extensive data in a wide range of organisms point to the importance of polyamine homeostasis for growth. The two most common polyamines found in bacteria are putrescine and spermidine. The investigation of polyamine function in bacteria has revealed that they are involved in a number of functions other than growth, which include incorporation into the cell wall and biosynthesis of siderophores. They are also important in acid resistance and can act as a free radical ion scavenger. More recently it has been suggested that polyamines play a potential role in signaling cellular differentiation in Proteus mirabilis. Polyamines have also been shown to be essential in biofilm formation in Yersinia pestis. The pleiotropic nature of polyamines has made their investigation difficult, particularly in discerning any specific effect from more global growth effects. Here we describe key developments in the investigation of the function of polyamines in bacteria that have revealed new roles for polyamines distinct from growth. We describe the bacterial genes necessary for biosynthesis and transport, with a focus on Y. pestis. Finally we review a novel role for polyamines in the regulation of biofilm development in Y. pestis and provide evidence that the investigation of polyamines in Y. pestis may provide a model for understanding the mechanism through which polyamines regulate biofilm formation.


Visual mental imagery and symptoms of depression - results from a large-scale web-based study.
Mental imagery may influence the onset and maintenance of depression, but specific mechanisms have not yet been determined. Nine hundred twelve participants completed questionnaires on positive and negative mental images, as well as images of injury and death that lead to positive emotions ("ID-images"), and depressive symptomatology. The assessment was carried out online to reduce effects of social desirability. Positive images were reported by 87 % of the sample, negative images by 77 %. ID-images were present in one-third of the sample. A connection with depression severity was found for the absence of positive mental images and the presence of negative images as well as ID-images. Higher depression scores were associated with more frequent and vivid negative images, greater imagery distress, and a higher proportion of negative relative to positive images. Mental images are clearly related to depression. Future research should focus on ID-images and their connection to suicide-risk in depressed patients.


Biophysical constraints of optogenetic inhibition at presynaptic terminals.
We investigated the efficacy of optogenetic inhibition at presynaptic terminals using halorhodopsin, archaerhodopsin and chloride-conducting channelrhodopsins. Precisely timed activation of both archaerhodopsin and halorhodpsin at presynaptic terminals attenuated evoked release. However, sustained archaerhodopsin activation was paradoxically associated with increased spontaneous release. Activation of chloride-conducting channelrhodopsins triggered neurotransmitter release upon light onset. Thus, the biophysical properties of presynaptic terminals dictate unique boundary conditions for optogenetic manipulation.


Shedding the light on Pharmacists' roles during COVID-19 global pandemic.
(Background)The role of pharmacists revolves around providing the highest levels of care to society and ensuring the provision of medicine to all patients. However, with the spread of coronavirus disease 2019 (COVID -19), pharmacists as a very important part of healthcare professionals' team are responsible for fighting against the disease regardless of their setting of practice. The role of pharmacists will undergo a little change to extend and include other roles in order to ensure the safety of the community and limit the virus spread. Also, they will be required to obtain information from reliable sources, and to be up to date, so they can be reliable advisors to the community and raise their awareness. The purpose of this review is to highlight community and hospital pharmacists' roles during (COVID-19) global pandemic, and to clearly illustrate how they are contributing to maintain pharmacy services continuity, supporting other healthcare professionals, and facilitating the patient's education. Clinical pharmacists provide direct patient care through monitoring adverse drug reactions, ensuring individualized treatment, performing evidence-based practice, and evaluating drugs in clinical trials. On the other hand, community pharmacists which are the most accessible healthcare providers by the community increase their awareness regarding the preventive measures, balance medicines supply and demand, provide drive-thru and home delivery services, offer telehealth counselling, psychological support, refer suspected COVID-19 patients, and provide vaccination when available. Innovative pharmacists' roles have emerged to adapt to changes during COVID-19 pandemic, however, they may be needed in the post COVID-19 world as well.


Combined serum and bone marrow radioimmunoassays for prostatic acid phosphatase.
Combined serum and bone marrow radioimmunoassays for prostatic acid phosphatase provide a unique means for the early diagnosis and more accurate clinical staging of prostatic cancer. The combined screening technique appears to be helpful, particularly in providing a clinical assessment of the presence or absence of early, subclinical lymphatic and bone marrow metastases. Low titer elevations of bone marrow prostatic acid phosphatase by radioimmunoassay have been observed commonly in clinically understaged C prostatic cancer with normal technetium bone scans, indicating the presence of unrecognized stage D disease with bone metastases. The combined screening method also is of distinct clinical value in the early diagnosis of prostatic cancer and in monitoring the effects of specific therapy. In therapeutically responsive patients marked suppression of serum and bone marrow prostatic acid phosphatase is observed regularly with the radioimmunochemical method under study.