The role of hepatitis B virus surface protein in inducing Sertoli cell ferroptosis.
Hepatitis B virus infection could result in male infertility with sperm defects and dysfunction. Sertoli cells are essential for testis function and play a crucial role in spermatogenesis. Sertoli cell death contributes to spermatogenesis impairment, leading to poor sperm quality. Ferroptosis has been implicated as a mechanism of Sertoli cell death. The issue in studying the relationship between hepatitis B virus and Sertoli cell ferroptosis has not yet been addressed. To explore the mechanisms underlying ferroptosis in hepatitis B virus-exposed Sertoli cells. Human Sertoli cells were treated in vitro with levels of 25, 50, and 100 μg/mL of hepatitis B virus surface protein (HBs). Cell viability and levels of glutathione, malondialdehyde, cellular ferrous ion (Fe2+ ), lipid peroxidation, and N6-methyladenosine in Sertoli cells were detected. The level of glutathione peroxidase 4, transferrin receptor 1, ferritin heavy chain, tripartite motif (TRIM) 37, methyltransferase like 3, and insulin-like growth factor 2 mRNA binding protein 2 was examined. Cell transfection was carried out to alter expression of ferroptosis-related proteins. qPCR and immunoblotting were performed to measure protein expression level. Immunoprecipitation was applied to determine the protein and protein-RNA interaction. Luminescence analysis was performed to identify the target of methyltransferase like 3. HBs exposure triggered ferroptosis featured with increased intracellular Fe2+ ion, reduced cell viability and expression of glutathione peroxidase 4 in Sertoli cells. HBs treatment significantly increased TRIM37 expression, which suppressed glutathione peroxidase 4 expression through ubiquitination. TRIM37 silencing attenuated the effect of HBs exposure-regulated cell viability and ferroptosis. HBs upregulated N6-methyladenosine modification in TRIM37 3'-UTR by increasing methyltransferase like 3 expression. The binding of N6-methyladenosine reader insulin-like growth factor 2 mRNA binding protein 2 and TRIM37 3'-UTR enhanced the stability of TRIM37 mRNA. HBs can decrease human Sertoli cell viability by promoting ferroptosis induced by the loss of glutathione peroxidase 4 activity through TRIM37-mediated ubiquitination of glutathione peroxidase 4. The findings highlight the role of TRIM37/glutathione peroxidase 4 signaling responsible for ferroptosis regulation in hepatitis B virus-infected Sertoli cells.


Something old, something new: indoor endotoxin, allergens and asthma.
Endotoxin and allergen exposure have been explored in the context of asthma for more than a century. Building upon a pyramid of knowledge are recent observations that provide new insights to the effect of these exposures on the development of asthma. Some of these studies challenge some previously held concepts of the role of these exposures in asthma inception. Indoor allergens are well established as the basis of inflammation in sensitised asthmatics, contributing to disease severity. Then does greater exposure to indoor allergens cause allergen sensitisation and asthma as well? While risk of sensitisation to house dust mites generally increases with higher levels of exposure, this does not seem to hold for cats, where higher levels of cat allergen exposure are associated with less sensitisation. Indeed, several recent studies suggest that early childhood exposure to animals, as indoor pets or in farming stables, are associated with a lower prevalence of asthma, hay fever, and inhalant allergen sensitisation. Endotoxin in asthma provides a similar paradox. Endotoxin is a potent immune-stimulatory component of the bacterial cell wall of all gram-negative bacteria. As such, endotoxin is ubiquitous in our environment. Endotoxin exposure has been well demonstrated to underlie "Monday Asthma" or byssinosis in cotton workers, and has since emerged as a frequent cause of asthma-like symptoms in a wide range of occupational settings. Asthmatics are particularly sensitive to inhaled endotoxin, and inhalation induces both immediate and sustained airflow obstruction. The paradox of endotoxin exposure is that higher levels of exposure in early life might mitigate the development of allergy and persistent asthma. With endotoxin exposure being significantly higher in homes with animals and in farming households, where allergy and asthma are less likely to develop, endotoxin and other microbial exposures in early life may keep allergen sensitisation and asthma from developing by promoting Th1-type immune development. These observations, consistent with the "Hygiene Hypothesis" of allergy and asthma, are an encouraging glimpse of the potential for early immune modulatory approaches to asthma therapy and prevention.


Percutaneous vertebroplasty--a technique to treat refractory spinal pain in the setting of advanced metastatic cancer: a case series.
We present three cases of severe movement-related spinal pain in patients with advanced metastatic carcinomas successfully treated with percutaneous vertebroplasty (PV). These patients had multi-symptom burden and progressive metastasis. Their movement-related pain was incapacitating and refractory to a variety of more conservative interventions. PV is a minimally invasive technique to stabilize vertebral compression fractures, thereby decreasing spinal pain in this setting. Its use in the setting of advanced cancer with severe movement-related pain has not been previously clarified in the palliative care literature. In summary, PV is a technique with a favorable risk: benefit ratio even in the setting of advanced metastatic cancer. The keys to successful utilization of PV in this patient population are careful patient assessment and selection as outlined in the report, in addition to an experienced care team approach.


Recent advances of bioresponsive polymeric nanomedicine for cancer therapy.
A bioresponsive polymeric nanocarrier for drug delivery is able to alter its physical and physicochemical properties in response to a variety of biological signals and pathological changes, and can exert its therapeutic efficacy within a confined space. These nanosystems can optimize the biodistribution and subcellular location of therapeutics by exploiting the differences in biochemical properties between tumors and normal tissues. Moreover, bioresponsive polymer-based nanosystems could be rationally designed as precision therapeutic platforms by optimizing the combination of responsive elements and therapeutic components according to the patient-specific disease type and stage. In this review, recent advances in smart bioresponsive polymeric nanosystems for cancer chemotherapy and immunotherapy will be summarized. We mainly discuss three categories, including acidity-sensitive, redox-responsive, and enzyme-triggered polymeric nanosystems. The important issues regarding clinical translation such as reproducibility, manufacture, and probable toxicity, are also commented.


MicroRNA-204-GSDMD interaction regulates pyroptosis of fibroblast-like synoviocytes in ankylosing spondylitis.
Ankylosing spondylitis (AS) is a disease characterized by inflammation of the sacroiliac joint and the attachment point of the spine. This study aimed to investigate the effect of microRNA (miR)-204-targeted GSDMD on fibroblast-like synoviocytes (FLSs) in AS. miR-204, GSDMD, pyrolysis-related genes (Caspase-1, Caspase-11 and NLRP3) in synovial tissues from AS patients were tested by RT-qPCR. Online website prediction and dual luciferase reporter gene assay were conducted to verify the binding relationship between miR-204 and GSDMD. FLSs were isolated from AS patients and transfected with miR-204- or GSDMD-related oligonucleotides, siRNA and plasmids to explore their roles in pyroptosis of FLSs. Intracellular [Ca2+] was detected by laser scanning confocal microscopy, reactive oxygen species (ROS) by DCFH-DA and pyrolysis by AO/EB staining and flow cytometry. Decreased miR-204 and elevated GSDMD were found in synovial tissue of patients with AS. miR-204 could directly target GSDMD and inhibit GSDMD protein expression. FLSs treated with miR-204 mimic inhibited the pyroptosis rate and Caspase-1/PI double-positive cells and reduced [Ca2+], ROS, NLRP3, Caspase-1 and Caspase-11 levels in FLSs. Up-regulating GSDMD blocked the effect of miR-204 overexpression on FLSs. Altogether, up-regulated miR-204 suppresses pyroptosis of FLSs in AS via suppressing GSDMD, which may help us to understand the mechanism of AS deeply.


RP-HPLC separation of the diastereomers of technetium-99m labelled tropanes and identity confirmation using radio-LC-MS.
99mTc-TRODAT-1 (technetium(V)-oxo-2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]]amino]-ethanethiolato(3-)) and 99mTc-TRODAT-M, the 4-methylphenyl derivative of 99mTc-TRODAT-1, are at this moment being evaluated in clinical trials as imaging agents for the central nervous dopamine transporter system. Both compounds are formed as a mixture of two major diastereomers. As the tracer concentration in preparations for clinical investigations is very low (30-150 pmol/ml), identification of these 99mTc-complexes was, up to now, carried out indirectly using X-ray diffraction analysis of the corresponding rhenium complexes which can be synthesized in gram amounts. In this study, we developed a convenient and practical reversed phase HPLC-method for purification and isolation of the respective diastereomers of 99mTc-TRODAT-1 and three of its derivatives using mixtures of solvents which are compatible with biological studies, i.e. aqueous buffers and ethanol. Furthermore, direct identity confirmation of the 99mTc-complexes using radio-LC-MS was successfully elaborated.


Cancer Cure and Consequences on Survivorship Care: Position Paper from the Italian Alliance Against Cancer (ACC) Survivorship Care Working Group.
A multidisciplinary panel of experts and cancer patients developed a position paper to highlight recent evidence on "cancer cure" (ie, the possibility of achieving the same life expectancy as the general population) and discuss the consequences of this concept on follow-up and rehabilitation strategies. The aim is to inform clinicians, patients, and health-care policy makers about strategies of survivorship care for cured cancer patients and consequences impacting patient lives, spurring public health authorities and research organizations to implement resources to the purpose. Two identifiable, measurable, and reproducible indicators of cancer cure are presented. Cure fraction (CF) is >60% for breast and prostate cancer patients, >50% for colorectal cancer patients, and >70% for patients with melanoma, Hodgkin lymphoma, and cancers of corpus uteri, testis (>90%), and thyroid. CF was >65% for patients diagnosed at ages 15-44 years and 30% for those aged 65-74 years. Time-to-cure was consistently <1 year for thyroid and testicular cancer patients and <10 years for patients with colorectal and cervical cancers, melanoma, and Hodgkin lymphoma. The working group agrees that the evidence allows risk stratification of cancer patients and implementation of personalized care models for timely diagnosis, as well as treatment of possible cancer relapses or related long-term complications, and preventive measures aimed at maintaining health status of cured patients. These aspects should be integrated to produce an appropriate follow-up program and survivorship care plan(s), avoiding stigma and supporting return to work, to a reproductive life, and full rehabilitation. The "right to be forgotten" law, adopted to date only in a few European countries, may contribute to these efforts for cured patients.


Photonic enhancement in photoluminescent metal halide perovskite-photonic crystal bead hybrids.
We report two photonic crystal-perovskite nanocrystal microbead hybrids with photoluminescence matching that of the parent nanocrystals but with increased photoluminescence quantum yields. Time-resolved photoluminescence spectroscopy quantifies the radiative enhancement afforded by the photonic environment of the microbeads. The reported hybrids also demonstrate markedly better resistance to degradation in water over 30 days of immersion.


Mechanistic effects of IVIg in neuroinflammatory diseases: conclusions based on clinicopathologic correlations.
The mechanisms of action of IVIg on immunoregulatory and neuroinflammatory network have been predominantly based on in vitro experiments and animal studies, rather than direct effects on human tissues. Based on clinicopathologic correlations and tissues obtained before and after IVIg therapy, the better documented and clinically-relevant in-vivo actions of IVIg include effects on: a) Antibodies. An extracted antigen-specific anti-immunoglobulin (idiotypic) fraction appears partially responsible for its effect in myasthenia gravis and GBS; b) Complement. Sera from Dermatomyositis (DM) patients responding to IVIg, inhibit complement consumption and intercept MAC formation leading to disappearance of MAC deposits in the repeated muscle biopsies and normalization of muscle tissue; c) Genes. In repeated muscle biopsies from DM patients who improved after IVIg, but not from Inclusion-Body-Myositis (IBM) who did not improve, there is a 2-fold alteration of 2206 tissue genes associated with inflammation, fibrosis, tissue remodeling and regeneration; and d) degenerative-proinflammatory molecules and β-amyloid, implicated in neurodegenerative CNS diseases and IBM. In repeated muscle biopsies of IBM patients who did not respond to IVIg, the mRNA or protein expression for chemokines, IFN-γ, TGF-ß, IL-10, Ubiquitin and aB-crystallin is reduced, but not for the key molecules ICOS, ICOSL, IL-6, IL1-β, perforin, APP, nitric oxide synthase and nitrotyrosine, in spite of good IVIg penetration in muscles. Collectively, the selective effectiveness of IVIg in human diseases seems to correlate in vivo with inhibition of causative inflammatory mediators. Study of accessible tissues before and after therapy and clinicopathologic correlations, may help explain the differential effect of IVIg in autoimmune or neuroinflammatory diseases.


Cytotoxic responses to unfractionated extracts from digestive glands of mussels.
The contamination of bivalve molluscs by lipophylic toxins is mainly detected by the use of unfractionated extracts from contaminated material in mouse bioassays. The development of alternate detection methods based on the use of cultured cells is hampered by difficulties related to the complexity of matrices including toxic compounds obtained from contaminated material. In this paper we have used unfractionated lipid extracts prepared from the digestive gland of mussels, which gave a negative response by the mouse bioassay, and have investigated their effects on functioning of MCF-7 cells. We show that altered growth was induced after addition of lipid extracts corresponding to less than 1mg of digestive gland per ml of culture medium. The cytotoxic effect was also confirmed by the analysis of the effect of the unfractionated extracts on four selected proteins, which were used as markers of general (actin), regulatory (mitogen activated protein kinase isoforms ERK1 and ERK2), as well as differentiative (alpha isoform of estrogen receptor) functions of the MCF-7 human breast cancer cell line.


Lumbar spine endplate fractures: Biomechanical evaluation and clinical considerations through experimental induction of injury.
Lumbar endplate fractures were investigated in different experimental scenarios, however the biomechanical effect of segmental alignment was not outlined. The objectives of this study were to quantify effects of spinal orientation on lumbar spine injuries during single-cycle compressive loads and understand lumbar spine endplate injury tolerance. Twenty lumbar motion segments were compressed to failure. Two methods were used in the preparation of the lumbar motion segments. Group 1 (n = 7) preparation maintained pre-test sagittal lordosis, whereas Group 2 (n = 13) specimens had a free-rotational end condition for the cranial vertebra, allowing sagittal rotation of the cranial vertebra to create parallel endplates. Five Group 1 specimens experienced posterior vertebral body fracture prior to endplate fracture, whereas two sustained endplate fracture only. Group 2 specimens sustained isolated endplate fractures. Group 2 fractures occurred at approximately 41% of the axial force required for Group 1 fracture (p < 0.05). Imaging and specimen dissection indicate endplate injury consistently took place within the confines of the endplate boundaries, away from the vertebral periphery. These findings indicate that spinal alignment during compressive loading influences the resulting injury pattern. This investigation identified the specific mechanical conditions under which an endplate breach will take place. Development of endplate injuries has significant clinical implication as previous research identified internal disc disruption (IDD) and degenerative disc disease (DDD) as long-term consequences of the axial load-shift that occurs following a breach of the endplate. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1084-1091, 2016.


Nasopharyngeal aspirates in children with severe community-acquired pneumonia collected within 3 days before bronchoscopy can partially reflect the pathogens in bronchoalveolar lavage fluids.
There is little evidence about consistency between nasopharyngeal and pulmonary pathogens in children with severe pneumonia. This study aims to compare the difference of pathogens between nasopharyngeal aspirates (NPAs) collected before bronchoscopy and bronchoalveolar lavage fluids (BALFs) in children with severe community-acquired pneumonia (SCAP). NPAs and BALFs were collected form pediatric SCAP cases hospitalized from January 2018 to March 2019. NPAs were colleced within 3 days before bronchoscopy. Samples were detected by direct immunofluorescence assay (DFA) for seven respiratory viruses and by routine bacterial culture in the clinical microbiology laboratory. Respiratory syncytial virus (RSV), Adenovirus (ADV), Influenza virus types A, B (IV-A and IV-B), Parainfluenza virus 1-3 (PIV1-3) were detected with a commercial assay. The virological and bacteriological detention results of NPAs were compared with the results of BALFs. In total 204 cases with mean age of 3.4 ± 2.8 years (IQR, 1 month-14 years) were included in the study. Both NPA and BALF were collected from those cases. The positive rates of pathogen in NPAs and BALFs were 25.0% (51/204) and 36.7% (75/204), respectively (x2 = 6.614, P = 0.010). Respiratory viruses were found in 16.1% (33/204) from NPAs and 32.3% (66/204) from BALFs (x2 = 14.524, P < 0.001). RSV and ADV were the two most frequent detected viruses in NPAs and BALFs. High consistentcy of pathogens between NPAs and BALFs was observed, and 96.9% (32/33) viruses detected in NPAs were also found in BALFs. While bacteria were isolated from 12.7% (26/204) and 10.7% (22/204) of the two kinds of samples, respectively (x2 = 0.378, P = 0.539). In addition, Haemophilus influenzae (HI) was the dominant germ in both samples. The DFA method used to detect seven respiratory viruses from NPAs collected within 3 days before bronchoscopy can partially reflect the pathogens in the lungs in children with SCAP.


Frequency of CYP2B6 Alleles in Major Iranian Ethnicities, Affecting Response to Efavirenz.
Efavirenz is an antihuman immunodeficiency virus (HIV) drug metabolized by cytochrome P450 2B6 (CYP2B6) enzyme. Cytochrome P450 2B6 is an enzyme that in humans is encoded by the CYP2B6 gene. Polymorphisms of this gene play a crucial role in the metabolism of drugs such as Efavirenz. This study aims to evaluate the frequency of three clinically significant CYP2B6 polymorphisms (CYP2B6 ∗ 6 (516G > T), CYP2B6 ∗ 4 (785A > G), and CYP2B6 ∗ 5 (1459C > T)) in three major Iranian ethnicities. One hundred forty-seven participants from three main Iranian ethnicities were included in this study. After DNA extraction, CYP2B6 ∗ 6 (516G > T), CYP2B6 ∗ 4 (785A > G), and CYP2B6 ∗ 5 (1459C > T) were genotyped using tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR). The frequency of the mutated allele in the Iranian population for CYP2B6 ∗ 6 (516G > T) was 41.50 (95% CI: 35.81, 47.36), which was significantly lower than in Kurds (59.62, 95% CI: 45.10, 72.99). Similarly, Kurds had a higher frequency of mutated allele of CYP2B6 ∗ 5 (1459C > T) (46.15%, 95% CI: 32.23, 60.53) than in Iranians (24.49%, 95% CI: 19.68, 29.82). The frequency of A and G alleles of CYP2B6 ∗ 4 (785A > G) was 62.59% (95% CI: 56.78, 68.13) and 37.41 (95% CI: 31.87, 43.22), respectively. Kurds are at higher risk of adverse drug reactions (ADRs) and insufficient anti-HIV response compared to other Iranians.


Dracunculiasis in tribal region of southern Rajasthan, India: a case report.
Although the Rajasthan state was declared rid off from dracunculiasis in 1997, nevertheless two cases in succession 2002 and 2003 were reported and the present is third one which is being reported from Dungarpur district of Rajasthan, India.


Lymph node sharing between pancreas, gut, and liver leads to immune crosstalk and regulation of pancreatic autoimmunity.
Lymph nodes (LNs) are critical sites for shaping tissue-specific adaptive immunity. However, the impact of LN sharing between multiple organs on such tailoring is less understood. Here, we describe the drainage hierarchy of the pancreas, liver, and the upper small intestine (duodenum) into three murine LNs. Migratory dendritic cells (migDCs), key in instructing adaptive immune outcome, exhibited stronger pro-inflammatory signatures when originating from the pancreas or liver than from the duodenum. Qualitatively different migDC mixing in each shared LN influenced pancreatic β-cell-reactive T cells to acquire gut-homing and tolerogenic phenotypes proportional to duodenal co-drainage. However, duodenal viral infections rendered non-intestinal migDCs and β-cell-reactive T cells more pro-inflammatory in all shared LNs, resulting in elevated pancreatic islet lymphocyte infiltration. Our study uncovers immune crosstalk through LN co-drainage as a powerful force regulating pancreatic autoimmunity.


Adhesive and tough hydrogels promoted by quaternary chitosan for strain sensor.
As a flexible material, hydrogels have attracted considerable attention in the exploration of various wearable sensor devices. However, the performance of the existing hydrogels is often too single, which limits its further application. Here, a conductive hydrogel with adhesiveness, toughness, self-healing and anti-swelling properties was successfully prepared by adding 2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) to the polyacrylic acid/ferric ionic (PAA/Fe3+) cross-linking system. Based on the existence of three types of non-covalent interactions in the hydrogel system, including electrostatic interaction, coordination interaction and hydrogen bonds, the hydrogel possessed excellent mechanical properties (tensile stress and strain were 827 kPa and 1652 %, respectively), self-healing properties (self-healing efficiency reached 83.3 % at room temperature) and anti-swelling properties. In addition, the introduction of HACC also successfully gave the hydrogel outstanding adhesiveness. Moreover, the existence of iron ions provided sensitive conductivity to the hydrogel, which could be used as a flexible sensor for directly monitoring various motions. Therefore, this simple strategy for preparation of multifunctional hydrogels would expand the application of a new generation of hydrogel-based sensors.


Positive side effects in trauma-focusing PTSD treatment: Reduction of attendant symptoms and enhancement of affective and structural regulation.
Trauma-focusing treatments such as eye movement desensitization and reprocessing (EMDR) are highly effective in reducing the core symptoms of posttraumatic stress disorder (PTSD), for example, intrusive memories and flashbacks, hyperarousal, and avoidance. Additionally, suffering from PTSD is often accompanied by a broader set of mental comorbidities and complaints such as depression, anxiety disorders or somatization, and disturbed self-regulation abilities. According to the Adaptive Information Processing model (Shapiro, 2001), the processing of pathogenic memories can help not only to reduce the PTSD symptoms but also accompanying complaints additionally. In an eye movement desensitization and reprocessing treatment study of 116 patients suffering from PTSD, we targeted the course of additional symptoms and structural skills using the Symptom Checklist-90 SCL-90, Beck Depression Inventory, Toronto Alexithymia Scale-20, and Hannover Selbstregulationsinventar in a pre-post design. The results showed that apart from alleviating the PTSD symptoms, exposure-based treatment of pathogenic memories led to a significant decrease in accompanying symptoms such as depression, anxiety, and somatization. Furthermore, patients improved their structural abilities with regard to emotional perception and differentiation, controlling impulses, tolerating frustration, and regulating self-esteem. PTSD core symptoms and comorbid complaints are closely interlinked and can be seen as a traumatic-stress cluster, which is accompanied by significant impairments in self- and emotion regulation. Therefore, treatment concepts should explicitly foster emotional processing and structural abilities to target the posttraumatic stress responses entirely. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Influence of Drugs on Mild Cognitive Impairment in Parkinson's Disease: Evidence from the PACOS Study.
polytherapy and the anticholinergic activity of several drugs negatively influence cognition in the elderly. However, little is known on the effect on Mild Cognitive Impairment (MCI) in Parkinson's Disease (PD). patients with PD belonging to the baseline PACOS cohort with full pharmacological data have been included in this study. MCI diagnosis was made according to the MDS level II criteria. Polytherapy was defined as patients assuming ≥6 drugs. The anticholinergic burden has been calculated using the Anticholinergic Drug Scale (ADS). Molecules have been classified according to the ATC classification. Association with MCI has been assessed with a multivariate logistic regression analysis with MCI as the dependent variable. pharmacological data were available for 238 patients (mean age 64.7±9.7). One hundred (42.0%) were diagnosed with MCI. No association was found in the full multivariate model (correcting for age, sex, disease duration, education, UPDRS-ME, LEDD-DAs) with either polytherapy or the ADS. Concerning drug classes, anti-hypertensive medications were positively associated with PD-MCI (OR 2.02;95%CI 1.04-3.89; p=0.035) while gastroprotective agents were negatively associated (OR 0.51; 95%CI 0.27-0.99; p=0.047). the magnitude of polytherapy and anticholinergic drugs burden does not appear to modulate MCI risk in PD, probably due to cautious prescription patterns. The effect of antihypertensive and gastroprotective agents on PD-MCI risk, while needing further confirmations, could be relevant for clinical practice.


Mycobacterium fortuitum keratitis.
Two of four cases of Mycobacterium fortuitum keratitis occurred after corneal surgery with contact lens wear, one was associated with extended contact lens wear alone, and one occurred after a foreign body injury. All cases were characterized by pain, conjunctival hyperemia, stromal inflammation, and ulceration. Diagnosis was made by culture and acid-fast staining of corneal scrapings. On the basis of published experience with amikacin for the treatment of nonocular M. fortuitum infections, three patients were treated with topical amikacin. Two patients responded clinically, but histopathologic examination of a penetrating keratoplasty specimen in one of the two disclosed persistent infection. One patient was cured of early disease by debridement alone. Rapid diagnosis and absence of corticosteroid use were the two most important determinants of successful therapy. In advanced cases, infection may be cured and useful vision restored by penetrating keratoplasty.


Hypoxia as a Modulator of Inflammation and Immune Response in Cancer.
A clear association between hypoxia and cancer has heretofore been established; however, it has not been completely developed. In this sense, the understanding of the tumoral microenvironment is critical to dissect the complexity of cancer, including the reduction in oxygen distribution inside the tumoral mass, defined as tumoral hypoxia. Moreover, hypoxia not only influences the tumoral cells but also the surrounding cells, including those related to the inflammatory processes. In this review, we analyze the participation of HIF, NF-κB, and STAT signaling pathways as the main components that interconnect hypoxia and immune response and how they modulate tumoral growth. In addition, we closely examine the participation of the immune cells and how they are affected by hypoxia, the effects of the progression of cancer, and some innovative applications that take advantage of this knowledge, to suggest potential therapies. Therefore, we contribute to the understanding of the complexity of cancer to propose innovative therapeutic strategies in the future.


What's new in FGF23 research?
FGF23 is a hormone that regulates phosphate and vitamin D metabolism by binding to Klotho-fibroblast growth factor (FGF) receptor complex. Excess actions of FGF23 cause several kinds of hypophosphatemic diseases. The mechanism of overproduction of FGF23 in some of these diseases is becoming clear, whereas it is not yet completely understood. Several specific methods to inhibit FGF23 actions have been reported as candidates for new therapies for these FGF23-related hypophosphatemic diseases. On the other hand, many epidemiological studies indicated the association between high FGF23 levels and several adverse events in cardiovascular system, kidney, bone and mortality. FGF23 was recently shown to induce ventricular hypertrophy in a Klotho-independent manner. However, it is not yet shown whether this Klotho-independent action of FGF23 can explain all the results of epidemiological studies.


Secondary structure of human leukocyte interferon from Raman spectroscopy.
Raman spectra were taken of human alpha (leukocyte) interferon subtype A (HuIFN-alpha A) purified from extracts of transformed Escherichia coli. Quantitative analysis of the conformationally sensitive amide I band indicates that IFN (interferon)-alpha A is 75 +/- 5% helical and 7 +/- 4% beta-strand. An independent analysis of the amide III spectrum indicates 71 +/- 5% helix and 10 +/- 6% beta-strand. These results differ with a recently proposed three-dimensional model based on secondary structure predictions derived from sequence and with circular dichroism measurements. The Raman spectrum of IFN-alpha A is compared with the spectra of several other helical proteins: hemerythrin, intestinal calcium-binding protein, melittin, and insulin.


Regional structural characterization of the brain of schizophrenia patients.
We study morphologic characteristics and age-related changes in patients with schizophrenia to investigate whether abnormal neurodevelopment and brain structure have a role in the pathophysiological course of this disease. Our data consist of a set of cranial magnetic resonance images of 46 patients with schizophrenia and age- and sex-matched healthy controls. We deformed a template brain image to our set of subject images. Jacobian fields of these deformations were reduced to sets of 52 normalized region volumes for each subject by using a neuroanatomic atlas. Normalized regional volumes of the control and patient groups were compared by using Student t-test, and age correlation of each region volume was calculated for the two groups. All results were corrected for multiple comparisons by using permutation testing. We used a classifier based on support vector machines and a feature selection method to determine our ability to discriminate brains of controls from those of patients. Analysis of normalized region volumes shows enlargement of the third ventricle in patients. The age-correlation study showed a significant positive correlation in the third ventricle and right thalamus of controls, but not patients. Using an average of 6.5 features, our classifier was able to correctly identify 72% of patients and 70% of controls. In addition to enlargement of the third ventricle, brains of patients with schizophrenia show a different pattern of age-related changes.


The TOR pathway participates in the regulation of growth development in juvenile spotted drum (Nibea diacanthus) under different dietary hydroxyproline supplementation.
Commonly used aquatic feed naturally contains low-level or no hydroxyproline (Hyp). This study was conducted to evaluate the effects of dietary Hyp inclusion on growth performance, body composition, amino acid profiles, blood biochemistry, and the expression of target of rapamycin (TOR) pathway-related genes in juvenile Nibea diacanthus. Fish with similar size (initial body weight, 133.00 ± 2.14 g) were fed six isonitrogenous and isolipidic practical diets supplemented with graded levels of Hyp (0, 5, 10, 15, 20, and 25 g kg-1 of dry matter) for 8 weeks. The results indicated that growth performance and feed utilization were improved with increased levels of dietary Hyp (P < 0.05), and the optimum amount of dietary Hyp estimated from SGR as 16.6 g kg-1. The crude protein of whole body and swim bladder and the amino acid composition of muscle and swim bladder were significantly (P < 0.05) affected by the addition of dietary Hyp, which reflects the important role of feed composition in animal body composition. In addition, the expression levels of mammalian target of rapamycin (TOR) and ribosomal protein S6 kinase1 (S6K1) genes in the liver, muscle, and swim bladder increased with increasing Hyp content of diets, while the mRNA expression level of eukaryotic translation initiation factor 4E-binding protein (4E-BP) gene in these tissues decreased. These results indicated that Hyp improved fish growth and the ability to synthesize proteins, most likely through the TOR pathway. It is suggested that dietary Hyp supplementation is particularly necessary for application in aquatic feed.


Clinical and socioeconomic impact of pediatric seasonal and pandemic influenza.
Influenza is frequent among otherwise healthy day-care and school-aged children. Recent studies have demonstrated its significant effect on various outcome factors, including significantly more school and parental work absenteeism, and secondary illnesses among family members. Other studies have shown that the potential benefit of vaccinating children against influenza extends to other members of their families, thus supporting earlier economic modeling analyses of immunization programs. Although there are some differences in the clinical and socio-economic impact of seasonal and pandemic influenza, the benefits of vaccination are similar in both cases. The vaccination of otherwise healthy children may significantly reduce direct and indirect influenza-related costs, which supports the recommendation to make wider use of influenza vaccine in healthy children of any age in order to reduce the burden of infection on the community.


Effect of angiotensin converting enzyme inhibitor (lisinopril) on insulin sensitivity and sodium transport in mild hypertension.
The purpose of this study was to determine whether antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril would alter cell Na+ transport kinetics, metabolic parameters associated with insulin resistance, or both in young adults with mild hypertension. Sixteen young adults (mean age 29 +/- 4 years) were treated with placebo for 8 weeks, then with lisinopril for 12 weeks. Metabolic risk factors examined included plasma lipid levels, plasma insulin concentration during an oral glucose tolerance test, and insulin sensitivity determined by an euglycemic hyperinsulinemic clamp procedure. Red blood cells were assayed for Na+/H+ exchange, Na+/Li+ exchange, Na(+)-K+ pump activity, and Na(+)-K(+)-Cl- cotransport before and during treatment. Blood pressure decreased from 142 +/- 4/98 +/- 2 mm Hg before treatment to 131 +/- 3/85 +/- 1 mm Hg during lisinopril treatment (P < .001). During lisinopril treatment, there was a significant reduction in total cholesterol (from 177 +/- 8 to 161 +/- 8 mg/dL, P < .008), in low density lipoprotein-cholesterol (from 107 +/- 7 to 91 +/- 7 mg/dL, P < .002), and in insulin at 60 min into the oral glucose tolerance test (from 132 +/- 18 to 99 +/- 15 microU/mL, P < .05). There was a marginally significant increase in insulin sensitivity during lisinopril treatment (P < .08). The assays of cell Na+ transport showed a significant reduction in maximal activity (Vmax) for Na+/H+ exchange (from 33.7 +/- 3.8 to 19.7 +/- 2.6 mmol/L cell/h, P < .003).(ABSTRACT TRUNCATED AT 250 WORDS)


More of what? Dissociating effects of conceptual and numeric mappings on interpreting colormap data visualizations.
In visual communication, people glean insights about patterns of data by observing visual representations of datasets. Colormap data visualizations ("colormaps") show patterns in datasets by mapping variations in color to variations in magnitude. When people interpret colormaps, they have expectations about how colors map to magnitude, and they are better at interpreting visualizations that align with those expectations. For example, they infer that darker colors map to larger quantities (dark-is-more bias) and colors that are higher on vertically oriented legends map to larger quantities (high-is-more bias). In previous studies, the notion of quantity was straightforward because more of the concept represented (conceptual magnitude) corresponded to larger numeric values (numeric magnitude). However, conceptual and numeric magnitude can conflict, such as using rank order to quantify health-smaller numbers correspond to greater health. Under conflicts, are inferred mappings formed based on the numeric level, the conceptual level, or a combination of both? We addressed this question across five experiments, spanning data domains: alien animals, antibiotic discovery, and public health. Across experiments, the high-is-more bias operated at the conceptual level: colormaps were easier to interpret when larger conceptual magnitude was represented higher on the legend, regardless of numeric magnitude. The dark-is-more bias tended to operate at the conceptual level, but numeric magnitude could interfere, or even dominate, if conceptual magnitude was less salient. These results elucidate factors influencing meanings inferred from visual features and emphasize the need to consider data meaning, not just numbers, when designing visualizations aimed to facilitate visual communication.


Study of Common Illnesses Before and After Vaccination: A Risk interval Approach.
To compare the proportion of children who developed a specified illness in the 7 day post-vaccination window, with the background rate of the same event in the 7 day pre-vaccination window. Risk interval approach (Self-controlled case-series). Well Baby Clinic of Christian Medical College, Vellore. 1602 healthy infants and under-six children presenting for routine vaccination. Episode of any illness. The interviewer enquired about any adverse event or illness experienced by the child for each day of the week preceding the administration of age-appropriate vaccines. A second interview (telephonic) was conducted by the same interviewer one week following vaccine administration to enquire about adverse event(s) experienced by the child for each day of the subsequent week using a similar protocol. With multiple vaccines delivered at appropriate ages, common childhood illnesses that could be reported as adverse events following immunization, except fever (RR=5.7, 95% CI=4.50-7.35), occurred at higher rates pre-vaccination. Risk Ratios of fever following whole cell (RR=9.3, 95% CI=6.43-13.52) and acellular (RR=8.5, 95% CI=3.82-18.91) vaccines were similar, with both showing a decreasing trend with increasing age. The gastrointestinal adverse event profile [diarrhea (RR=0.6, 95% CI=0.14-2.51) and vomiting (RR=1.0, 95% CI=0.14-7.10)] for rotavirus vaccine was similar pre- and post-immunization. Since most adverse events to vaccines are also common childhood illnesses, estimating the background rates of common illnesses is important to accurately ascertain a causal relationship.


Trends and Outcomes in Patients with Dementia Undergoing Spine Fusions: A Matched Nationwide Inpatient Sample Analysis.
The aim of our study was to define the trends and outcomes in patients with a preexisting diagnosis of dementia who underwent spine fusions using a large national database. The Nationwide Inpatient Sample database was queried using the International Classification of Diseases, Ninth Revision and Tenth Revision, from 1998 to 2018. We included patients who underwent spine fusions with or without the diagnosis of dementia. Outcomes were trends, complications, length of stay (LOS), discharge disposition, and mortality. A cohort of 4495 patients (N = 1,390,657; 0.32%) with dementia who underwent spine fusions was identified. There was an increasing trend of spine fusions in patients with the diagnosis of dementia. Most patients with dementia were white (77% vs. 69%), with ≥3 comorbidities (70% vs. 23%), had Medicare insurance (83% vs. 34%) compared with patients without dementia (P < 0.0001). Overall, 38% of patients had complications after spine fusions compared with 21% of patients without dementia during the study period. Median LOS was significantly longer in patients with dementia compared with patients without dementia (6 vs. 4 days). Patients with dementia were less likely to be discharged home (19% vs. 40%) and incurred higher in-hospitalization charges ($139,101 vs. $101,629) compared with patients without dementia. No differences in terms of in-hospital mortality were noted across the cohorts (1.4% vs. 1.6%). Patients with dementia had 1.5 times longer LOS and 1.4 times higher index hospitalization charges and were 2.5 times more likely to have complications and 71% less likely to be discharged home, with no difference in mortality compared with patients without dementia after spine fusions.


Effect of magnesium supplementation on emergence delirium and postoperative pain in children undergoing strabismus surgery: a prospective randomised controlled study.
The benefits of intraoperative magnesium supplementation have been reported. In this prospective, randomized study, the effects of magnesium supplementation during general anaesthesia on emergence delirium and postoperative pain in children were evaluated. A total of 66 children aged 2 to 5 years who underwent strabismus surgery were assigned to the magnesium or to the control group. Preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale. After anaesthesia induction, the magnesium group received an initial loading dose of 30 mg/kg magnesium sulphate over 10 min and, then, continuous infusion of 10 mg/kg per h until 10 min before the end of the surgery. The control group received an equal volume of normal saline via the same regimen. The Paediatric Anaesthesia Emergence Delirium (PAED) score, pain score, and respiratory events were assessed at the postanaesthetic care unit. Data obtained from 65 children were analyzed. The PAED and pain scores of the two groups did not differ significantly. There were 26 of 33 (78.8%) and 27 of 32 (84.4%) children with emergence delirium in the control and the magnesium groups, respectively (odds ratio 0.69, 95% CI 0.19-2.44; p = 0.561). The preoperative anxiety score was not significantly correlated with the PAED score. The incidence of respiratory events during the emergence period did not differ significantly between the two groups. Magnesium supplementation during anaesthesia had no significant effects on the incidence of emergence delirium or postoperative pain in children undergoing strabismus surgery. ClinicalTrials.gov ( NCT03132701 ). Prospectively registered May 8, 2017.


Co-expression of four penaeidins in transgenic rice seeds: an alternative strategy for substitute antibiotic agricultural products.
The co-expression of multiple antimicrobial peptides (AMPs) in genetically modified (GM) crops can give plants a broader antibacterial spectrum and lower the pathogen risk of drug resistance. Therefore, four penaeidins (shrimp-derived AMPs) were fused and encoded in an artificial gene (PEN1234), driven by the seed-specific promoter Pzein, with the aim of co-expression in seeds of transgenic rice. The resistant rice plants, acquired via Agrobacterium-mediated transformation and glufosinate screening, were identified by PCR and the modified disk-diffusion method, and eight GM lines with high AMP content in the seeds were obtained. Among them, the PenOs017 line had the largest penaeidin content, at approximately 251-300 μg/g in seeds and 15-47 μg/g in roots and leaves. The AMPs in the seeds kept their antibacterial properties even after the seed had been boiled in hot water and could significantly inhibit the growth of methicillin-resistant Staphylococcus aureus, and AMPs in the leaves could effectively inhibit Xanthomonas oryzae pv. Oryzae. The results indicate that PenOs017 seeds containing AMPs are an ideal raw-material candidate for antibiotic-free food and feed, and may require fewer petrochemical fungicides or bactericides for disease control during cultivation than conventional rice.


Stimulation of the hexosemonophosphate-pentose pathway by pyrroline-5-carboxylate in cultured cells.
delta 1-Pyrroline-5-carboxylic acid, an intermediate in the interconversions of proline, ornithine, and glutamate, is a potent stimulator of glucose oxidation through the hexosemonophosphate-pentose pathway. The effect is observed in cultured human fibroblasts, Chinese hamster ovary cells (CHO-K1), and rabbit kidney cells (LLC-RK1). In human fibroblasts, the magnitude of the stimulation of the hexosemonophosphate-pentose pathway is dependent on the concentration of added pyrroline-5-carboxylate and the effect is observed over a wide range of glucose concentrations. The mechanism of the effect is related to the generation of oxidizing potential in the form of NADP+ by pyrroline-5-carboxylate reductase concomitant with the conversion of pyrroline-5-carboxylate to proline. In LLC-RK1 cells, a cell line unique in having proline oxidase activity, proline also stimulated hexosemonophosphate-pentose pathway activity. Although pyrroline-5-carboxylate markedly stimulated the hexosemonophosphate-pentose pathway, it has no effect on glucose metabolism in the Embden-Meyerhof pathway or the tricarboxylic acid cycle. Since the hexosemonophosphate-pentose pathway is a source of ribose-5-phosphate, the precursor of phosphoribosyl pyrophosphate, the effect of pyrroline-5-carboxylate on the hexosemonophosphate-pentose pathway may link amino acid and nucleic acid metabolism.


Characteristics of Retained Foreign Bodies in the Tongue: A Retrospective Study of 35 Cases.
There are only a few case reports of foreign bodies (FBs) in the tongue. Delayed diagnosis or misdiagnosis is commonly reported. The purpose of this study was to identify the demographic, clinical, and radiological features that might facilitate the diagnosis of retained FBs in the tongue. A retrospective case series was performed. Clinical and imaging data of patients with FBs in the tongue at Wuhan University Hospital of Stomatology were reviewed. The outcome variable was a preliminary, radiological, intraoperative, or pathological diagnosis. Covariates included age, sex, FB-related history, symptoms and signs, duration, and computed tomography (CT) imaging features. Descriptive statistics were computed for each study variable. Thirty-five patients were included. The sample's mean age was 54.5 ± 11.2 years, included 19 males (54.3%). Eighty percent of the patients reported FB-related history with a mean duration of 4 weeks. More than 70% of the patients presented with tongue swelling. Approximately half of the 35 cases were preliminarily misdiagnosed, and 15 of them were initially suspected to be tumors. After CT examinations, 33 of the 35 cases were diagnosed as FB. Characteristic CT imaging feature of the FB was a radiopaque line. Most FBs were located at the anterior two-thirds and marginal area of the tongue and in an oblique direction. The depth of FB was 0.61 ± 0.42 cm. The superficial ends of most FBs were close to the surface of the dorsum and the tongue margin. The possibility of a retained FB should be included in the differential diagnosis of a nonhealing wound or tongue enlargement when a radiopaque line is present on CT images of patients presenting with or without FB-related history. It may be easier to detect a FB in the tongue when a CT imaging postprocessing protocol, including thin-slice reconstruction and multiplanar reformation visualization and careful interpretation, is used.


Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study.
Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by difficulties in social communication, unusually restricted, repetitive behavior and interests, and specific abnormalities in language and perception. The precise etiology of ASD is still unknown and probably heterogeneous. In a subgroup of patients, toxic environmental exposure might lead to an imbalance between oxidative stress and anti-oxidant systems. Previous serum and postmortem studies measuring levels of glutathione (GSH), the main cellular free radical scavenger in the brain, have supported the hypothesis that this compound might play a role in the pathophysiology of autism. Using the method of single-voxel proton magnetic resonance spectroscopy (MRS), we analyzed the GSH signal in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) of 24 ASD patients with normal or above average IQs and 18 matched control subjects. We hypothesized that we would find decreased GSH concentrations in both regions. We did not find overall group differences in neurometabolites including GSH, neither in the dorsal ACC (Wilks' lambda test; p = 0.429) nor in the DLPFC (p = 0.288). In the dACC, we found a trend for decreased GSH signals in ASD patients (p = 0.076). We were unable to confirm our working hypothesis regarding decreased GSH concentrations in the ASD group. Further studies combining MRS, serum, and cerebrospinal fluid measurements of GSH metabolism including other regions of interest or even whole brain spectroscopy are needed.


Different types of physical exercise in brain activity of older adults: A systematic review.
To verify the effects of different modalities of physical exercise on brain activity of older adults. Systematic searches were conducted according to the PICOS strategy and the following databases were searched: PubMed, Web of Science, PsycInfo and Scielo. Two independent evaluators performed the initial selection from reading the title and abstract based on the stipulated eligibility criteria. The searches resulted in 1935 titles, of which 97 were duplicated and 1793 were excluded based on reading the titles and abstracts. This phase resulted in 45 articles for detailed analysis. At this stage, 35 articles were excluded because they did not meet the eligibility criteria. The information for qualitative analysis was extracted from 10 articles that met the criteria. There was improvement in the brain activity of older adults regardless of the type of physical exercise performed (aerobic, neuromuscular, flexibility or neuromotor), but with a discrete advantage for balance and coordination exercises (neuromotor).


Synthesis and in vitro anti-bacterial evaluation of tetracyclic-ortho-fused 4H-naphtho[1',2'-5,6]pyrano[3,4-d](1,2,3)selenadiazole and its derivatives.
Synthesis of new heterocyclic compounds 3a-e containing naphthopyran and selenadiazole as the heterocyclic sub-units in the molecule is achieved using high yielding synthetic protocol. These molecules 3a-e have shown moderate anti-bacterial activity against some gram-positive and gram-negative bacterias.


Residents' perception of their skill levels in the clinical management of adolescent health problems.
Residents in six specialty training programs completed a 126-item questionnaire designed to assess their skill or confidence to manage adolescent health issues. The residency programs studied were family practice, internal medicine, pediatrics, emergency medicine, obstetrics/gynecology, and combined medicine/pediatrics. Although almost three-fourths of the residents were at least moderately interested in adolescent health care and 90% expected to care for adolescents, only 26% believed an adolescent rotation should be required during training. Residents generally considered themselves unskilled to manage adolescents in the areas of sexuality, handicapping conditions, and psychosocial problems. Significant differences in perceived skills were found among the specialty programs on 45% of the items presented. Resident training appears to be needed in the areas of adolescent growth and development, counseling, and sexuality.


STAT4 is a target of the hematopoietic zinc-finger transcription factor Ikaros in T cells.
STAT4 is a transcription factor activated in response to IL-12, and is involved in Th1 cell development. The molecular mechanisms controlling the transcription of the STAT4 gene are however, unclear. Sequence comparison of the 5' flanking regions of human, mouse and pufferfish (Fugu rubripes) Stat4 genes revealed a high frequency of Ikaros (Ik) binding elements in all three species. We then investigated the role of Ik binding elements in the human STAT4 promoter using Jurkat T cells. Transactivation, electrophoretic mobility shift assay and RNA interference-mediated gene knockdown experiments revealed that Ik is involved in the regulation of STAT4 in human T cells.


Analysis of clinical effect of the four-step pouch approach in ocular plastic surgery.
To investigate the clinical effect of the four-step pouch plastic surgery in ocular plastic surgery. Patients with ocular plastic surgery admitted to our hospital from January 2018 to October 2019 were selected as the study subjects. The patients were divided into the observation group (n=41) and the control group (n=43) according to the different surgical modalities received. The traditional skin approach of lower eyelid, and the four-step pouch plastic surgery were used as the control group and observation group, respectively. The operation time, postoperative recovery time of the eye skin, clinical effect, postoperative complications, and satisfaction rate were compared between the two groups. The operation time was compared between the two groups, indicating no significant difference (P > 0.05). The postoperative recovery time of the eye skin was significantly shorter in the observation group than the control group (P < 0.05). The total clinical effective rate (95.12%) was significantly higher in the observation group than that in the control group (79.07%) (P < 0.05). The total incidence of complications (7.32%) was significantly lower in the observation group than that in the control group (25.58%) (P < 0.05). The overall satisfaction rate was significantly higher in the observation group than the control group (P < 0.05). The clinical effect of four-step pouch plastic surgery in ocular plastic surgery is significant.


Repolarization indicates electrical instability in ventricular arrhythmia originating from papillary muscle.
Cardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood. Ventricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity. RT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients.


Adenosquamous-cell carcinoma in ulcerative colitis. Report of a case.
Three adenosquamous carcinomas and 2813 adenocarcinomas of the colon proximal to a line 7 cm craniad to the dentate line were treated between 1946 and 1986. Of these, one adenosquamous carcinoma and 42 adenocarcinomas were associated with ulcerative colitis. Therefore it was calculated that adenosquamous carcinoma occurs 0.07 percent as frequently as adenocarcinoma of the colon in the general hospital population and 2.4 percent as frequently in patients with ulcerative colitis, a 33-fold increase. It is concluded that, although adenosquamous-cell carcinoma of the colon is a rare tumor, its frequency in relation to adenocarcinoma increases in the presence of ulcerative colitis.


Extraluminal Recanalization of Bile Duct Anastomosis Obstruction after Liver Transplantation.
This report describes extraluminal recanalization of bile duct anastomosis obstruction after living donor liver transplantation. The procedure was performed in 5 patients in whom negotiation of the biliary anastomotic obstruction by retrograde endoscopic approach and percutaneous intraluminal recanalization had failed. Extraluminal puncture from the donor bile duct to the recipient side bile duct was made with the stiff back end of a 0.035-inch hydrophilic guide wire. After recanalization, a percutaneous transhepatic biliary drainage catheter was placed through the created tract. In all 5 patients, extraluminal recanalization was achieved without major complication, and endoscopic plastic stents were subsequently placed along the tract.


Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitus.
Oxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and require association with subunit p22phox (encoded by the CYBA gene). Increased expression of p22phox was described in animal models of diabetic nephropathy. In the opposite direction, glutathione is one of the main endogenous antioxidants whose plasmatic concentrations were reported to be reduced in diabetes patients. The aim of the present investigation was to test whether functional single nucleotide polymorphisms (SNPs) in genes involved in the generation of NADPH-dependent O₂•⁻ (-675 T → A in CYBA, unregistered) and in glutathione metabolism (-129 C → T in GCLC [rs17883901] and -65 T → C in GPX3 [rs8177412]) confer susceptibility to renal disease in type 1 diabetes patients. 401 patients were sorted into two groups according to the presence (n = 104) or absence (n = 196) of overt diabetic nephropathy or according to glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease (MDRD) equation: ≥ 60 mL (n = 265) or < 60 mL/min/1.73 m² (n = 136) and were genotyped. No differences were found in the frequency of genotypes between diabetic and non-diabetic subjects. The frequency of GFR < 60 mL/min was significantly lower in the group of patients carrying CYBA genotypes T/A+A/A (18.7%) than in the group carrying the T/T genotype (35.3%) (P = 0.0143) and the frequency of GFR < 60 mL/min was significantly higher in the group of patients carrying GCLC genotypes C/T+T/T (47.1%) than in the group carrying the C/C genotype (31.1%) (p = 0.0082). Logistic regression analysis identified the presence of at least one A allele of the CYBA SNP as an independent protection factor against decreased GFR (OR = 0.38, CI95% 0.14-0.88, p = 0.0354) and the presence of at least one T allele of the GCLC rs17883901 SNP as an independent risk factor for decreased GFR (OR = 2.40, CI95% 1.27-4.56, p = 0.0068). The functional SNPs CYBA -675 T → A and GCLC rs17883901, probably associated with cellular redox imbalances, modulate the risk for renal disease in the studied population of type 1 diabetes patients and require validation in additional cohorts.


Genetic heterogeneity in patients with pantothenate kinase-associated neurodegeneration and classic magnetic resonance imaging eye-of-the-tiger pattern.
We performed a detailed molecular study in two unrelated families with pantothenate kinase-associated neurodegeneration (PKAN) and the specific magnetic resonance imaging (MRI) eye-of-the-tiger pattern. In the first family with classic PKAN, linkage analysis using polymorphic markers from the PANK2 region ruled out linkage with this locus, and no mutation of the PANK2 gene was found. In the second family with atypical PKAN, we identified a novel homozygous C-to-T transition at nucleotide 1069 of the PANK2 gene, which resulted in an arginine to tryptophane substitution at codon 357. As far as we are aware, this is the first case of classic PKAN with the specific MRI eye-of-the-tiger pattern not carrying a PANK2 mutation. Therefore, the present observation reinforces the notion of the phenotypic and genetic heterogeneity in PKAN.


Baseline series fragrance markers fail to predict contact allergy.
Negative patch test results with fragrance allergy markers in the European baseline series do not always predict a negative reaction to individual fragrance substances. To determine the frequencies of positive test reactions to the 26 fragrance substances for which labelling is mandatory in the EU, and how effectively reactions to fragrance markers in the baseline series predict positive reactions to the fragrance substances that are labelled. The records of 1951 eczema patients, routinely tested with the labelled fragrance substances and with an extended European baseline series in 2011 and 2012, were retrospectively reviewed. Two hundred and eighty-one (14.4%) (71.2% females) reacted to one or more allergens from the labelled-fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were cinnamyl alcohol (48; 2.46%), Evernia furfuracea (44; 2.26%), and isoeugenol (40; 2.05%). Of the 203 patients who reacted to any of the 26 fragrances in the labelled-fragrance substance series, only 117 (57.6%) also reacted to a fragrance marker in the baseline series. One hundred and seven (52.7%) reacted to either fragrance mix I or fragrance mix II, 28 (13.8%) reacted to Myroxylon pereirae, and 13 (6.4%) reacted to hydroxyisohexyl 3-cyclohexene carboxaldehyde. These findings confirm that the standard fragrance markers fail to identify patients with contact allergies to the 26 fragrances.


The Impact of Hospital Characteristics on the Availability of Radiology Services at Critical Access Hospitals.
Although all critical access hospitals (CAHs) provide basic medical and radiographic imaging services, it remains unclear how CAHs provide additional imaging services given relatively low patient volumes and high resource costs. The aim of this study was to examine whether CAHs with more resources or access to resources through affiliation with larger systems are more likely to offer other imaging services in their communities. Linking data from the American Hospital Association's annual hospital surveys and the American Hospital Directory's annual surveys from 2009 to 2011, multivariate logistic regressions were performed to estimate the likelihood of individual CAHs with greater financial resources or network affiliations providing specific imaging services (MRI, CT, ultrasound, mammography, and PET/CT), while adjusting for the number of beds, personnel, inpatient revenue share, case mix, rural status, year, and geographic location. Hospital total expenditures were positively associated with the provision of MRI (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.07-1.19), mammography (OR, 1.11; 95% CI, 1.01-1.16), and PET/CT (OR, 1.04; 95% CI, 1.01-1.06). Network affiliation was positively associated with the availability of MRI (OR, 1.75; 95% CI, 1.27-2.39), CT (OR, 2.17; 95% CI, 1.15-4.09), ultrasound (OR, 2.03; 95% CI, 1.17-3.52), and mammography (OR, 2.00; 95% CI, 1.47-2.71). Rural location was negatively associated with the availability of PET/CT (OR, 0.65; 95% CI, 0.49-0.88). Total hospital expenditures and network participation are important determinants of whether CAHs provide certain imaging services. Encouraging CAHs' participation in larger systems or networks may facilitate access to highly specialized services in rural and underserved areas.


Does learning to count involve a semantic induction?
We tested the hypothesis that, when children learn to correctly count sets, they make a semantic induction about the meanings of their number words. We tested the logical understanding of number words in 84 children that were classified as "cardinal-principle knowers" by the criteria set forth by Wynn (1992). Results show that these children often do not know (1) which of two numbers in their count list denotes a greater quantity, and (2) that the difference between successive numbers in their count list is 1. Among counters, these abilities are predicted by the highest number to which they can count and their ability to estimate set sizes. Also, children's knowledge of the principles appears to be initially item-specific rather than general to all number words, and is most robust for very small numbers (e.g., 5) compared to larger numbers (e.g., 25), even among children who can count much higher (e.g., above 30). In light of these findings, we conclude that there is little evidence to support the hypothesis that becoming a cardinal-principle knower involves a semantic induction over all items in a child's count list.


Development of the spatio-chromatic visual evoked potential (VEP): a longitudinal study.
Most prior visual evoked potential (VEP) research on the development of color vision has employed pattern-reversing stimuli that are not optimal for producing chromatic responses. We measured infant VEPs using low spatial frequency, onset-offset stimuli, modulated along the three axes of a cone-based color space (Derrington et al. [J. Physiol 1984;357, 241-265.]). Three color-normal infants were tested in a longitudinal design over the first postnatal year. One red/green color-deficient infant was also tested at 197 days. We found that VEP responses to S-axis (tritan) stimuli have their initial onset later than responses to red/green (L-M) or achromatic stimuli, and that developmental changes in VEP waveforms are more complex and longer lasting for chromatic than for achromatic stimuli. Possible mechanisms underlying these changes are discussed.


Outcomes of a Presurgical Optimization Program for Elective Hernia Repairs Among High-risk Patients.
Preoperative optimization is an important clinical strategy for reducing morbidity; however, nearly 25% of persons undergoing elective abdominal hernia repairs are not optimized with respect to weight or substance use. Although the preoperative period represents a unique opportunity to motivate patient health behavior changes, fear of emergent presentation and financial concerns are often cited as clinician barriers to optimization. To evaluate the feasibility of evidence-based patient optimization before surgery by implementing a low-cost preoperative optimization clinic. This quality improvement study was conducted 1 year after a preoperative optimization clinic was implemented for high-risk patients seeking elective hernia repair. The median (range) follow-up was 197 (39-378) days. A weekly preoperative optimization clinic was implemented in 2019 at a single academic center. Referral occurred for persons seeking elective hernia repair with a body mass index greater than or equal to 40, age 75 years or older, or active tobacco use. Data analysis was performed from February to July 2020. Enrolled patients were provided health resources and longitudinal multidisciplinary care. The primary outcomes were safety and eligibility for surgery after participating in the optimization clinic. The hypothesis was that the optimization clinic could preoperatively mitigate patient risk factors, without increasing patient risk. Safety was defined as the occurrence of complications during participation in the optimization clinic. The secondary outcome metric centered on the financial impact of implementing the preoperative optimization program. Of the 165 patients enrolled in the optimization clinic, most were women (90 patients [54.5%]) and White (145 patients [87.9%]). The mean (SD) age was 59.4 (15.8) years. Patients' eligibility for the clinic was distributed across high-risk criteria: 37.0% (61 patients) for weight, 26.1% (43 patients) for tobacco use, and 23.6% (39 patients) for age. Overall, 9.1% of persons (15 patients) were successfully optimized for surgery, and tobacco cessation was achieved in 13.8% of smokers (8 patients). The rate of hernia incarceration requiring emergent surgery was 3.0% (5 patients). Economic evaluation found increased operative yield from surgical clinics, with a 58% increase in hernia-attributed relative value units without altering surgeon workflow. In this quality improvement study, a hernia optimization clinic safely improved management of high-risk patients and increased operative yield for the institution. This represents an opportunity to create sustainable and scalable models that provide longitudinal care and optimize patients to improve outcomes of hernia repair.


Hydrolea zeylanica improves cognitive impairment in high-fat diet fed-streptozotocin-induced diabetic encephalopathy in rats via regulating oxidative stress, neuroinflammation, and neurotransmission in brain.
Type2 diabetes mellitus is a progressive metabolic disorder characterized by β-cell dysfunction with the increase in hepatic glucose synthesis and insulin resistance which leads to microvascular complications like diabetic encephalopathy that impairs cognitive dysfunctions, and dementia. The green and leafy vegetables of Hydrolea zeylanica are used in diet as rich source of nutrition, dietary fibers in reducing malnutrition and keeps in control the blood sugar level to treat diabetes related vascular complications. This study investigated the effect of hydroalcohol extracted fraction of leaves of H. zeylanica (HHZ) on high-fat diet fed-streptozotocin (HFD/STZ)-induced diabetes encephalopathy in experimental rats, and quantified the flavonoids, nutrients contents by HPLC analysis. HHZ demonstrated potential cellular antioxidant protection in ORAC, CAP-e tests. HHZ showed mixed competitive inhibition towards acetylcholinesterase (AChE), and butyrylcholineserase (BChE) activities, and exhibited dose dependent inhibition to both neurotransmitter activities. After 4 weeks administration of HHZ (oral, 300, and 400 mg/kg b.w.) in HFD/STZ-induced diabetic rats, HHZ-400 significantly (p < 0.001) improved the learning and memory impairment with the reduction in serum glucose and elevation in insulin level in encephalopathy rats. It also significantly (p < 0.001) improved oxidative (MDA, SOD, CAT, and GSH), and proinflammatory markers (TNF-α, IL-6, and hs-CRP) with the reduction in cholinesterase (AChE, BChE) and β-secretase (BACE1, BACE2) activities as evidenced by histological architecture of cortex in diabetic encephalopathy rats. Diet rich source of flavonoids e.g., quercetin, caffeic acid, rutin, gallic acid, and ferulic acid, nutrients, and vitamins in H. zeylanica enhanced the cellular antioxidant protection by reducing oxidative stress, neuroinflammation and neurotransmission in the brain of diabetic encephalopathy rats.


Aza-Dipyrrinate Stabilized Compounds with a Low-Valent Main Group Element.
The possibility of using aza-dipyrromethene (a-DPM) ligands to stabilize compounds containing low-valent main group elements is demonstrated through the isolation of germylenes, a-DPM(p-tol)GeCl (2), a-DPM(Naph)GeCl (6), and a-DPM(Naph)GeN(TMS)2 (7) (tol=tolyl, Naph=naphthyl). Because of the presence of the a-DPM ligand, these germylenes exhibit an absorption maximum at around 640 nm, a highly red-shifted value previously unknown for germylenes.


A cell-based bioluminescence reporter assay of human Sonic Hedgehog protein autoprocessing to identify inhibitors and activators.
The Sonic Hedgehog (SHh) precursor protein undergoes biosynthetic autoprocessing to cleave off and covalently attach cholesterol to the SHh signaling ligand, a vital morphogen and oncogenic effector protein. Autoprocessing is self-catalyzed by SHhC, the SHh precursor's C-terminal enzymatic domain. A method to screen for small molecule regulators of this process may be of therapeutic value. Here, we describe the development and validation of the first cellular reporter to monitor human SHhC autoprocessing noninvasively in high-throughput compatible plates. The assay couples intracellular SHhC autoprocessing using endogenous cholesterol to the extracellular secretion of the bioluminescent nanoluciferase enzyme. We developed a WT SHhC reporter line for evaluating potential autoprocessing inhibitors by concentration response-dependent suppression of extracellular bioluminescence. Additionally, a conditional mutant SHhC (D46A) reporter line was developed for identifying potential autoprocessing activators by a concentration response-dependent gain of extracellular bioluminescence. The D46A mutation removes a conserved general base that is critical for the activation of the cholesterol substrate. Inducibility of the D46A reporter was established using a synthetic sterol, 2-α carboxy cholestanol, designed to bypass the defect through intramolecular general base catalysis. To facilitate direct nanoluciferase detection in the cell culture media of 1536-well plates, we designed a novel anionic phosphonylated coelenterazine, CLZ-2P, as the nanoluciferase substrate. This new reporter system offers a long-awaited resource for small molecule discovery for cancer and for developmental disorders where SHh ligand biosynthesis is dysregulated.


Substance P Receptor Antagonist Suppresses Inflammatory Cytokine Expression in Human Disc Cells.
Laboratory study. To evaluate whether blockade of the Substance P (SP) NK1R attenuates its proinflammatory effect on human intervertebral disc cells (IVD), and to evaluate the signaling pathways associated with SP. SP and its receptors are expressed in human IVD cells, and cause upregulation of inflammatory mediators; however, the effects of blocking these receptors have not been studied in human IVD cells. Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were expanded in monolayer, and then suspended in alginate beads. The alginate beads were treated with culture medium first containing a high affinity NK1R antagonist (L-760735) at different concentrations, and then with medium containing both NK1R antagonist and SP at 2 concentrations. Ribonucleic acid was isolated and transcribed into cDNA. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate expression of interleukin (IL)-1β, IL-6, and IL-8. Western blot analysis was performed to examine levels of the phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB p65). The cells were pretreated with specific inhibitors of p38 (SB203580), ERK1/2 (PD98059), and p65 (SM7368) and then stimulated with SP. We detected expression of NK1R, neurokinin receptor 2 (NK2R), and neurokinin receptor 3 (NK3R) in AF and NP cells. Treatment of disc cells with the NK1R antagonist was able to suppress expression of IL-1β, IL-6, and IL-8 in a dose-dependent manner. SP stimulation increased phosphorylation of p38-MAPK and ERK1/2, but not of NFκB p65. This indicates that p38-MAPK and ERK1/2 control SP-induced cytokine expression independently from NF-kB p65. Inhibition of p38 and ERK1/2 activation reduced SP-induced IL-6 production in human disc cells. NK1R is responsible for the proinflammatory effect of SP on IVD cells and this effect can be blocked by preventing binding of SP to NK1R. This study shows for the first time that SP mediates signaling in disc cells through NK1R and that SP activates the proinflammatory p38-MAPK and ERK1/2 pathways. 4.


Hemodynamic Effects of High-dose Levothyroxine and Methylprednisolone in Brain-dead Potential Organ Donors.
Hormonal replacement therapy is administered to many brain-dead organ donors to improve hemodynamic stability. Previous clinical studies present conflicting results with several randomized studies reporting no benefit. Consecutive adult donors (N = 199) were randomized to receive high-dose levothyroxine, high-dose methylprednisolone, both (Combo), or no hormonal therapy (Control). Vasopressor requirements using the vasoactive-inotropic score (VIS) were assessed at baseline, 4 h, and at procurement. Crossover to the Combo group was sufficient to require separate intention-to-treat and per-protocol analyses. In the intention-to-treat analysis, the mean (±SD) reduction in VIS from baseline to procurement was 1.6 ± 2.6, 14.9 ± 2.6, 10.9 ± 2.6, and 7.1 ± 2.6 for the levothyroxine, methylprednisolone, Combo, and Control groups, respectively. While controlling for the baseline score, the reduction in VIS was significantly greater in the methylprednisolone and Combo groups and significantly less in the levothyroxine group compared with controls. Results were similar in the per-protocol analysis. High-dose methylprednisolone alone or in combination with levothyroxine allowed for significant reduction in vasopressor support in organ donors. Levothyroxine alone offered no advantage in reducing vasopressor support. Organ yield, transplantation rates, and recipient outcomes were not adversely affected.


Important Technical Details During Uniportal Video-Assisted Thoracoscopic Major Resections.
Since it was first performed in 2010, lobectomy via a single port-uniportal video-assisted thoracoscopic surgery (VATS)-has become increasingly popular among surgeons. However, this most minimally invasive surgical approach requires a different skill set compared with even conventional multiportal VATS. For those beginning to learn uniportal VATS, the technical challenges can seem considerable. This article shares some tips and tricks from experienced uniportal VATS practitioners that will help those wishing to learn the approach, and covers the principles of operative setup and instrumentation as well as specific pointers on surgery for each lung lobe.


Control of the heart rate by sympathetic nerves in cats.
Pre- and postganglionic sympathetic nerves were electrically stimulated and heart rate was recorded in chloralose-anaesthetised cats. The vagal nerves and white rami were cut on both sides. Electrical stimulation was performed with a 15- or 30-s train of 0.2-ms pulses at a frequency of 30 Hz. The control heart rate was 150 beats/min. Heart rate was increased when the T3 white ramus on the left (52 beats/min above control) and T3, T4 white rami on the right side (100 beats/min above control) were stimulated electrically. The magnitude of the heart rate increase declined when the neighbouring thoracic white rami were stimulated. The increase of the heart rate was caused by group B preganglionic fibres. Electrical stimulation of the sympathetic fibres in the right vagus nerve and the right inferior cardiac nerve increased the heart rate by 92 beats/min and by 67 beats/min above the control level respectively. Electrical stimulation of the left inferior cardiac nerve, the left middle cardiac nerve and the sympathetic fibres in the left vagus nerve resulted in an increase of the heart rate of 43 beats/min, 30 beats/min and 49 beats/min from the control level respectively. This indicates that a majority of the preganglionic cardiac sympathetic fibres, whose activity influences the heart rate, originate from the T3 and T4 segments of the spinal cord. The majority of the postganglionic cardiac sympathetic fibres which affect the heart rate are located in the vagal nerves.


Tailoring cryo-electron microscopy grids by photo-micropatterning for in-cell structural studies.
Spatially controlled cell adhesion on electron microscopy supports remains a bottleneck in specimen preparation for cellular cryo-electron tomography. Here, we describe contactless and mask-free photo-micropatterning of electron microscopy grids for site-specific deposition of extracellular matrix-related proteins. We attained refined cell positioning for micromachining by cryo-focused ion beam milling. Complex micropatterns generated predictable intracellular organization, allowing direct correlation between cell architecture and in-cell three-dimensional structural characterization of the underlying molecular machinery.


Diacylglyceride lipase activity in rod outer segments depends on the illumination state of the retina.
We have demonstrated that the competition between phosphatidic acid (PA) and lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P) for lipid phosphate phosphatases (LPP) generates different levels of diacylglycerol (DAG) depending on the illumination state of the retina. The aim of the present research was to determine the diacylglyceride lipase (DAGL) activity in purified rod outer segments (ROS) obtained from dark-adapted retinas (DROS) or light-adapted retinas (BLROS) as well as in ROS membrane preparations depleted of soluble and peripheral proteins. [2-(3)H]monoacylglycerol (MAG), the product of DAGL, was evaluated from [2-(3)H]DAG generated by LPP action on [2-(3)H]PA in the presence of either LPA, S1P or C1P. MAG production was inhibited by 55% in BLROS and by 25% when the enzymatic assay was carried out in ROS obtained from dark-adapted retinas and incubated under room light (LROS). The most important events occurred in DROS where co-incubation of [2-(3)H]PA with LPA, S1P or C1P diminished MAG production. A higher level of DAGL activity was observed in LROS than in BLROS, though this difference was not apparent in the presence of LPA, S1P or C1P. DAGL activity in depleted DROS was diminished with respect to that in entire DROS. LPA, S1P and C1P produced a similar decrease in MAG production in depleted DROS whereas only C1P significantly diminished MAG generation in depleted BLROS. Sphingosine and ceramide inhibited MAG production in entire DROS and stimulated its generation in BLROS. Sphingosine and ceramide stimulated MAG generation in both depleted DROS and BLROS. Under our experimental conditions the degree of MAG production depended on the illumination state of the retina. We therefore suggest that proteins related to phototransduction phenomena are involved in the effects observed in the presence of S1P/sphingosine or C1P/ceramide.


AS-1 cyanophage infection inhibits the photosynthetic electron flow of photosystem II in Synechococcus sp. PCC 6301, a cyanobacterium.
In Synechococcus sp. cells AS-1 cyanophage infection gradually inhibits the photosystem II mediated photosynthetic electron flow whereas the activity of photosystem I is apparently unaffected by the cyanophage infection. Transient fluorescence induction and flash-induced delayed luminescence decay studies revealed that the inhibition may occur at the level of the secondary acceptor, QB of photosystem II. In addition, the breakdown of D1-protein is inhibited, comparable to DCMU-induced protection of D1-protein turnover, in AS-1-infected cells.


Chlamydial infections in duck farms associated with human cases of psittacosis in France.
Five severe cases of psittacosis in individuals associated with duck farms were notified in France between January and March 2006. Diagnostic examination included serology and/or molecular detection by PCR from respiratory samples. As a consequence, we investigated all duck flocks (n=11) that were housed in the three farms where human infections occurred. While serology by complement fixation test was negative for all samples, cloacal and/or tracheal chlamydial excretion was detected by PCR in all three units. Notably, one duck flock was tested strongly positive in 2 of the 3 affected farms, and Chlamydophila (C.) psittaci strains were isolated from cloacal and/or tracheal swab samples from both farms. Human samples and duck isolates exhibited the same PCR-RFLP restriction pattern, which appeared to be an intermediate between genotypes A and B. Analysis of ompA gene sequences and comparison to those of the type strains showed that the isolates could not be strictly assigned to any of the generally accepted genotypes of C. psittaci. Further analysis by MLVA of the PCR-positive human samples revealed two distinct patterns, which were related to previously isolated C. psittaci duck strains.


Prey nutritional quality and the effectiveness of chemical defenses against tropical reef fishes.
Many coral-reef seaweeds and sessile invertebrates produce both secondary chemicals and mineral or fibrous skeletal materials that can reduce their susceptibility to consumers. Although skeletal materials often have been assumed to function as physical defenses, their deterrent effectiveness may derive from their reduction of prey nutritional quality as well as from noxiousness of the skeletal material itself. To test the relative importance of prey nutritional quality and chemical defenses in susceptibility to predation, we offered reef fishes on Guam a choice of artificial foods varying in nutritional quality (4% versus 22% protein) and in secondary chemistry (spanning approximately natural concentration ranges). Field feeding assays were performed with pachydictyol A from the pantropical brown seaweed genus Dictyota, manoalide from the Micronesian sponge Luffariella variabilis, and a brominated diphenyl ether from the Micronesian sponge Dysidea sp. The results indicated that chemical defenses were less effective in high- than in low-quality foods. In paired assays with metabolite-free controls, all three compounds at natural concentrations significantly reduced feeding by reef fishes only in assays using low-quality food, and not in assays with high-quality food. When fishes were offered an array of artificial foods varying in both food quality and metabolite concentration, food quality significantly affected fish feeding in all three cases, while secondary chemistry was significant in only one. Thus differences in nutritional quality, within the natural range among reef organisms, can be comparable to or greater in importance than secondary chemistry in affecting feeding preferences of their consumers. Reduced nutritional quality may be an important selective advantage of producing indigestible structural materials, in addition to their roles as physical support and defense, in coral reef organisms.


Histopathology in botryomycosis-like panophthalmitis due to Staphylococcus aureus. A light microscopic and electron microscopic study. A case report.
A Swedish farmer's wife aged 46 developed a unilateral panophthalmitis 6 weeks after a visit to Gambia in Africa. Vitreous puncture revealed growth of Staphylococcus aureus, but in spite of adequate treatment the eye had to be enucleated 5 weeks after the onset of symptoms. Gram-positive microorganisms in botryomycosis-like granules in the vitreal abscesses were at first suspected to be Histoplasma capsulatum. Electron microscopic examination revealed microorganisms, consistent with staphylococci. There was extensive proliferation of mesosomes, most probably due to the intense treatment. The poor nutrition and slow resorption of the dead microorganisms from the avascular vitreous did possibly also play a part in the proliferation of the mesosomes.


Determinants of muscle function and health-related quality of life in patients with endogenous hypercortisolism: a cross-sectional study.
Prospective data on determinants of muscle strength impairment and quality of life in patients with various subtypes and severity of endogenous hypercortisolism are lacking. Single-center cross-sectional study, 2019 to 2022. Patients with Cushing syndrome (CS) and mild autonomous cortisol secretion (MACS) were assessed with clinical and biochemical severity scores, muscle function (nondominant hand grip strength and sit-to-stand test), and quality of life (Short Form-36 [SF36] and CushingQoL). Referent subjects were recruited from the local population undergoing abdominal imaging for reasons other than suspected adrenal disorder. Of 164 patients, 81 (49%) had MACS, 14 (9%) had adrenal CS, 60 (37%) had pituitary CS, and 9 (5%) had ectopic CS. Median age was 53 years (interquartile range: 42-63 years), and 126 (77%) were women. The SF36 mental component score was similarly low in patients with MACS vs CS, but physical component score was lower in CS when compared to MACS (mean of 34.0 vs 40.5, P = .001). Compared to MACS, patients with CS had lower scores on the standardized CushingQoL (mean of 47.1 vs 34.2, P < .001). Compared to referent subjects, patients with MACS demonstrated reduced muscle strength, similar to patients with CS (mean sit to stand Z-score of -0.47 vs -0.54, P = .822). Clinical severity (r = -0.22, P = .004) but not biochemical severity was associated with sit-to-stand test performance. Both patients with overt CS and MACS demonstrate reduced muscle strength and low quality of life. The clinical severity score utilized is associated with both physical and psychosocial components of CushingQoL and with the physical component of SF36.


Differential effects of a gram-negative and a gram-positive infection on autogenous and prosthetic grafts.
A canine model was developed to study the differential response of a gram-negative and a gram-positive bacterial infection on autogenous and prosthetic grafts. After replacing segments of the femoral arteries of 15 dogs with autogenous vein in one groin and polytetrafluoroethylene in the contralateral groin, 10(8) colony-forming units of nonmucin-producing Staphylococcus epidermidis (five dogs), Pseudomonas aeruginosa (five dogs), or sterile saline solution (five dogs) were directly inoculated onto the grafts. The grafts were examined 7 to 10 days after implantation. None of the control dogs exhibited inflammatory signs, and no grafts or anastomoses disrupted. S. epidermidis was unrecoverable from either graft material in any of the animals, although histologic evaluation confirmed neutrophils and bacteria in four of five animals in the vein and polytetrafluoroethylene groups. No dog inoculated with S. epidermidis had graft or anastomotic disruption. By contrast, P. aeruginosa was recovered from both types of grafts in all inoculated animals. Neutrophils, bacteria, and microabscesses were observed in all of these animals. In addition, three of five polytetrafluoroethylene grafts and all five vein grafts disrupted either at the anastomoses or in the body of the vein graft. Therefore S. epidermidis is a less virulent organism that may persist in graft walls despite negative cultures, whereas P. aeruginosa is a highly virulent organism that can disrupt native artery, vein grafts, and anastomoses. The graft material appears to be less important than the bacteria in determining the outcome of infection.


[Osteosynthesis of metastatic fractures of bronchial origin. Analysis of a series of 18 cases].
The authors present a series of 18 femoral and humeral metastases of bronchial origin treated by surgery. They study the results and recommend "closed wound" osteosynthesis, underlying the antalgic character of the intervention which does not modify the already limited survival.


[Study of the consistency of a system for preoperative planning digital in total arthroplasty of the hip].
Check the agreement of a preoperative digital templating, compared with the final result in the postoperative radiograph. The study was carried out on a 55 total hip prosthesis. A templating-software Neteous (Socincer, Gijón, Spain) was used. Agreement was measured using the Kappa Index for the stem offset or Lin Index for others variables: stem size, cup size, femoral neck length, and the distance from the center of rotation of the femoral head to the lesser trochanter. The percentage of accurate hits was also described. Stem size: The exact success or error of only one size was of 61.6%. Quantitatively the Lin Index was 0.64 (substantial). Horizontal offset: satisfactory agreement was obtained (Kappa index of 0.75). In 6 cases (10.90%) was changed to lateralized during surgery, for more joint stability. Size of the cup: the agreement obtained was 0.67 (substantial) with a hit grade of 43.6%. Prosthetic neck length: the exact hit or error of only one size were found in 50.9%, moderate level of agreement. Distance from the center of rotation to the lesser trochanter: was observed for almost perfect agreement with Lin Index of 0.95. The exact percentage of hits or gap error less than 5mm was 74.5%. In ours hands, the preoperative templating software analyzed, has provided acceptable agreement rates, when compared with the postoperative result. But it takes more works verified by independent observers.


Prevalence and factors associated with teenage pregnancy among parturients in Mbale Regional Referral Hospital: a cross sectional study.
In Uganda, 12% of the audited maternal deaths occur among teenagers. The prevalence and factors associated with teenage pregnancy in health facilities is not well documented. We determined the prevalence and factors associated with teenage pregnancy in Mbale Regional Referral Hospital. We conducted a cross sectional study between July and September 2019.We consecutively enrolled and collected information from 427 respondents. Associated factors were determined using logistic regression, a P-value < 0.05. The prevalence of teenage pregnancy was 20.6% [95% CI : (17.0% - 24.7%)]. Rural residence [(AOR: 2.8 (1.08 - 7.09)], primary level of education [(AOR: 9.57 (3.48 - 26.3)], unhappy feelings about the current pregnancy [(AOR: 3.57(1.05 - 12.15)], primiparity [(AOR: 21.05 (7.36 - 60.15)] increased the likelihood of teenage pregnancy. While, history of ever use of contraceptives [(AOR: 0.32 (0.12 - 0.84)], age at coitarche [(AOR: 0.68 (0.54 - 0.85)], grand multiparity [(AOR: 0.06 (0.01 - 0.51)], and exposure to sex education at home [(AOR: 0.37 (0.15 - 0.89)] decreased its likelihood. The prevalence of teenage pregnancy was high. It was associated with being resident in rural area, low level of education and ever use of contraception. Promotion of reproductive health education may prevent teenage pregnancy.


Opioid Use and Associated Patient Satisfaction With Pain Control After Endoscopic Surgery and Robotic-Assisted Radical Prostatectomy.
To evaluate patient reported measures in patients undergoing endourologic procedures and robotic assisted radical prostatectomy (RARP) to demonstrate the efficacy of non-opioid postoperative pain management strategies. A prospective cohort study performed at an academic medical center included a patient telephone questionnaire and chart review. Opioid prescriptions, opioid use, and patient reported outcomes were recorded. Bivariate analyses were used to compare patients who did and did not use opioids in the RARP cohort while overall trends were reported for the endourologic procedures. Of the 68 patients undergoing endoscopic intervention, 14 (21%) were prescribed an opioid and 6 (9%) reported any opioid use. 58 (85%) reported their pain was very well or well controlled while 9 reported their pain was poorly controlled. 59 (87%) were satisfied or very satisfied with their pain control. Fifty-three (93%) of the 57 patients undergoing RARP received an opioid prescription and only 23 reported any opioid use. All but 1 patient reported that their pain was well or very well controlled and almost all (54) of the patients were satisfied with their level of pain control. 36 (63%) reported their pain was less than expected while only 7 (12%) reported it was more than expected. Most patients undergoing endourologic procedures do not use postoperative opioids and report favorable outcomes regarding their pain control. Similarly, after RARP, most patients do not use opioids even when they are prescribed and are satisfied with their pain control.