Sudden increase in skin temperature predicts venous ulcers: a case study.
Venous ulcers affect approximately 2.5 million adults with chronic venous disease (CVD). Venous ulcers are a significant health problem with a reoccurrence rate as high as 72%. There is a critical need for a prediction/prevention model of venous ulcers that includes objective methods to assess the skin. Among individuals affected by CVD, skin temperature is elevated in the lower extremities. This case study of a patient with CVD highlights the potential predictive usefulness and feasibility of measuring skin temperature with an infrared dermal thermometer as part of the standard of care for venous ulcer prevention.


Aprotinin confers neuroprotection by reducing excitotoxic cell death.
Aprotinin is used in cardiac surgery for its anti-inflammatory and hemostatic benefits. Recent reports describe the neuroprotective effects of other serine protease inhibitors via reduced excitotoxic cell death, a common pathway causing cytotoxic edema induced in various neuropathologic conditions. The purpose of this study was to investigate whether aprotinin directly protects against glutamatergic excitotoxicity in cell cultures. Mixed cortical cultures containing neuronal and glial cells were prepared from fetal mice at 13 to 15 days' gestation and plated on a layer of confluent astrocytes from 1- to 3-day-old postnatal pups. Near-pure neuronal culture containing less than 5% astrocytes was obtained from the same gestational stage and plated in multiwell vessels previously coated with poly-D-lysine and laminin. Both cultures were used at 12 to 14 days in vitro. Slowly triggered excitotoxicity was induced at 37 degrees C by 24-hour exposure to 12.5 microM N-methyl-D-aspartate or 50 microM kainate. Neuronal death was quantified by measuring the release of lactate dehydrogenase from damaged cells into the bathing medium. Data were analyzed by analysis of variance with post hoc Bonferroni comparisons. Aprotinin at a clinically relevant concentration of 100 KIU/mL significantly reduced N-methyl-D-aspartate-induced neuronal death in both pure and mixed cultures (P < .001). Aprotinin also reduced neuronal death induced by kainate from 36% to 23% in mixed cortical culture (P = .008) and from 40% to 27% in near-pure culture (P = .015), indicating that the neuroprotective effects of aprotinin are mediated directly through neurons. Aprotinin provides direct neuroprotection against glutamatergic excitotoxicity as demonstrated by reduced neuronal death in near-pure neuronal cell culture. Additional studies are needed to evaluate the potential of aprotinin to reduce neurologic injury in patients at high risk of cerebral injury, including those undergoing circulatory arrest.


Flow cytometric assessment of cell viability: a multifaceted analysis.
Flow cytometry offers the possibility to simultaneously analyze, on a cell by cell basis, different parameters related to cell viability i.e. cell size, morphology and incorporation of dyes. Different types of analysis: light absorption of unstained/stained cells, forward angle light scattering (FALS), right angle light scattering (RALS) or both, cell fluorescence based on dye retention or dye exclusion (due to erythrosin B, ethidium bromide, fluorescein diacetate, rhodamine 123) were tested and compared, with the classical Trypan blue exclusion test, for their effectiveness in the determination of cell viability. Two types of cells in monolayer cultures (L929, SIRC) and a freshly isolated suspension of mouse splenocytes were used. For each dye, the optimal dose, incubation time and conditions for analysis were determined. Viability indications by different techniques for the three type of cell line and their reliability as compared with Trypan blue were analyzed.


Formation of cyclic imide-like structures upon the treatment of calmodulin and a calmodulin peptide with heat.
Protein cyclic imide is the putative intermediate in the formation of sites of carboxyl-methylation in eukaryotic proteins. Conditions known to induce the formation of a cyclic imide in model peptides have been applied to a protein, calmodulin. Heating of calmodulin in the dry state at 100 degrees C for 24 h after lyophilization from a pH 2.0 or pH 6.0 solution produces derivatives with altered chromatographic properties in anion-exchange HPLC. At pH 6.0, complete activity of calmodulin was retained. Analysis with Fourier transform infrared (FTIR)-photoacoustic spectroscopy demonstrated the presence of a new structure in the calmodulin molecule consistent with modification of carboxylic acid groups. The conversion of calmodulin is dependent upon the absence of Ca2+ (the presence of 1 mM ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid). A peptide analogous to the calcium binding regions of calmodulin, Asp-Lys-Asp-Gly-Asn-Gly-Thr-Ile-Thr-Thr-Lys-Glu, is also converted, upon heating, to chromatographically different forms in reversed-phase chromatography. This process is also dependent upon the absence of calcium. Sequence analysis of the peptide derivatives reveals a second amino terminus, implicating peptide bond hydrolysis in the product. A dipeptide, Asp-Gly, known to form a cyclic imide structure under similar conditions is also hydrolyzed during sequence analysis consistent with cleavage occurring at the position of the cyclic imide structure. Asp3 is suggested to be the site of cyclic imide formation in the calmodulin peptide. The presence of a cyclic imide structure is also confirmed by the application of FTIR-photoacoustic spectroscopy. These data suggest that cyclic imide formation in calmodulin has been induced, possibly at one, or more, of the calcium binding loops of the protein. These modification reactions may provide a basis for future investigations of cyclic imide formation in proteins.


Ligamentous tethering and intradiscal pressure affecting the mechanical environment of scoliotic spines.
Despite several theories have been proposed to explain the progression of Adolescent Idiopathic Scoliosis (AIS), there is no consensus on the mechanical factors that control the spinal deformities. Prominent biomechanical notions focus on the geometrical asymmetry and differential growth, however, the correlation between these phenomena remains unclear. We postulate that intradiscal pressure and its connection with the supporting ligamentous structures are the reasons behind the asymmetric growth in AIS. To investigate this hypothesis, a numerical 3D patient-specific model of a scoliotic spine is constructed to carry upper body weight. Four analyses are performed: control simulation with no ligaments followed by 3 simulations, in each, a different and stiffer set of ligaments is employed. The analyses showed that intradiscal pressure is relatively high in the spine's higher-deformity region. Moreover, the stiffness effect of the ligamentous tethering correlated directly to intradiscal pressure; the stiffer the ligaments, the higher the intradiscal pressure. Due to geometrical asymmetry, the pressure is eccentric toward the concave region of deformed vertebral units. As a result, the deformed annulus fibrosus generated uplifts in the convex side of deformed vertebral units. The eccentric pressure and the uplift are opposite in location and direction creating an imbalanced mechanical environment for the spine during growth.


Synergy between prochloraz and esfenvalerate in Daphnia magna from acute and subchronic exposures in the laboratory and microcosms.
Azole fungicides can enhance the toxicity of pyrethroid insecticides on aquatic species. It is, however, unknown to what extend the synergy found under laboratory conditions for strongly sorbing compounds (Azole logK(ow): 3-4, pyrethroid logK(ow): 6-7) will also take place in the field. We therefore investigated the synergising potential of the fungicide prochloraz on the pyrethroid esfenvalerate on Daphnia magna in the laboratory and in situ in cages placed in outdoor aquatic microcosms treated with 0.17, 0.33 and 0.83 μgL(-1) esfenvalerate with and without 90 μg L(-1) prochloraz. We found that the 8-14 fold synergy observed after 2 and 7 days of exposure to mixtures in the microcosms was equivalent to or greater than the 3-7 fold synergy found in 2-day laboratory tests. Incubating new neonates in situ 7 and 14 days after pesticide addition gave EC(50) values of 0.012 ± 0.001 and <0.005μgesfenvalerateL(-1) in the mixture treatments, based on measured water column concentrations. The detection limit is more than ten-fold lower than the lowest esfenvalerate concentration observed to cause ecologically significant effects across seven long term mesocosms studies, hence, even on a longer time scale prochloraz apparently synergises the effect of esfenvalerate under field-like conditions in the microcosms. The results show that synergy found in the laboratory also takes place under field like conditions at quantitatively similar levels, and that it lasts for several weeks. More knowledge on the identification of potential synergists, their true bioavailability and the concentrations and time span within which they can cause synergy needs further study, before an overall evaluation of the occurrence and severity of synergy under field conditions can take place.


Correction: Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.
[This corrects the article DOI: 10.1371/journal.pone.0244098.].


Postoperative multiple organ failure.
Cellular damage is the pathophysiologic basis for the postoperative multiple organ failure syndrome. This damage may be caused by pre- and intraoperative shock. Postoperative organ failure is manifested when cellular repair does not occur. Three factors may contribute to this progression to multiple organ failure: inadequate resuscitation, malnutrition, and sepsis.


Gestational Weight Gain in Adolescent Compared with Adult Pregnancies: An Age-Specific Body Mass Index Approach.
To determine current trends in gestational weight gain (GWG) in adolescents, using adolescent specific body mass index (BMI), in relation to the 2009 Institute of Medicine GWG guidelines. Population-based retrospective cohort using Ohio birth records (2006-2012). Analyses were limited to primiparous women with singleton nonanomalous live births and available data on BMI and GWG. GWG percentiles were stratified by maternal age (less than 15, 15-17, 18-19, and 20-34 years old) and prepregnancy BMI category. Adolescent specific BMI definitions were used for mothers less than 19 years. A total of 1,034,552 births occurred during the study period; 326,368 were included for analysis. Less than one-quarter of women gained the recommended amount of weight (20.6%). A large proportion of pregnancies had excessive GWG: 59.8% of mothers less than 15 years of age, compared with older adolescent (59.9%, 62.6%) and adult mothers (64.6%), P < .001. Average, median, and IQRs of GWG were similar for all women within the same BMI category, regardless of age. Except in underweight women, the average GWG was at the high end or above the 2009 Institute of Medicine recommendations, for adolescents in all BMI groups, similar to adults, median 35 (IQR 24-47) pounds. Current GWG trends indicate that excessive weight gain is nearly as common in adolescents as in adult mothers.


Fetopathological aspects of holoprosencephaly.
Holoprosencephaly (HPE) is a congenital central nervous system malformation estimated to occur in 1/250 conceptuses and 1/10,000 live births. While the severe forms, which are incompatible with life, are easier to detect in the prenatal period, the milder forms can remain unrecognised. As this can have serious consequences for the pregnancy and malformation carriers it is of crucial importance to find ways of timely detection of this pathological condition. The present study AIMED at finding an association of holoprosencephaly with facial dysmorphia and anomalies of visceral organs that would alert the physician to be very careful in making the prenatal diagnosis, which may require termination of pregnancy by medical indications. The study included 15 fetuses diagnosed with holoprosencephaly out of 2095 cases analysed post-mortem in the Fetopathology Clinic at the Centre for Maternity and Neonatology in the town of Tunisia over a period of 3 years (Oct. 2006 - Oct. 2009). The fetuses were analysed macro- and microscopically. All forms of holoprosencephaly include elements of facial dysmorphism with the facial phenotypes of cyclopia, cebocephaly and ethmocephaly. It can be associated with specific internal organs anomalies, the hydrocephaly being the most common anomaly of the central nervous system. Our study suggested that holoprosencephaly can be correlated with craniofacial anomalies affecting the midfacial and medium craniovisceral structures. The anatomical variations of HPE and the phenotypic facial correlations require a systematic and targeted study of central nervous system.


Antioxidants protect against increased risk of atherosclerosis induced by exposure to cigarette smoke: Histological and biochemical study.
This study aimed to assess the dose-dependent effect of antioxidants in protection against cardiovascular changes induced by exposure to cigarette smoke. This was an experimental study, conducted at King Fahd Medical Research Center, King Abdulaziz University. This study was carried out on 57 male albino rats divided into nine groups. Rats of experimental groups were exposed to cigarette smoke from a total of 100 cigarettes per week for four weeks in a specially designed chamber. The antioxidants used (vitamin C, E, and B-carotene) were administrated at low (9, 7.2, and 0.27 mg/day) and high doses (18, 14.4, and 0.54 mg/day), respectively, through gastric feeding tubes. The lipid profile was estimated, and the carotids and heart were removed, weighed, and then processed, and the carotid intima-media thickness was measured. Statistical analysis was performed using the Statistical Package for Social Sciences. The lipid profile was significantly improved in all groups treated with low or high doses of antioxidants after or during the exposure to cigarette smoke. Improvement was marked in the group treated with a high dose of antioxidants. The histological changes, as well as the intima-medial thickness of the carotid artery induced by exposure to cigarette smoke, have been improved by treatment with antioxidants (at either low or high doses), either after or during exposure to cigarette smoke. Improvement was marked in the group treated with a low dose of antioxidant. Treatment with antioxidants could not improve degenerated cardiac muscle fibers, while they could reduce the thickness of the branches of the coronary vessels. These results indicated that antioxidants ameliorated the cigarette smoke contribution to atherosclerosis, but they could not completely reverse the changes induced by cigarette smoke. Simultaneous intake of antioxidants could ameliorate the cigarette-smoke-induced changes apart from those of the heart.


NMR-based untargeted metabolomic study of hydrogen peroxide-induced development and diapause termination in brine shrimp.
Artemia diapause has been extensively studied in embryonic biology for a long time. It has been demonstrated that hydrogen peroxide (H2O2) can increase the hatching rate in the development and diapause termination of Artemia cysts. This study used an untargeted 1H NMR-based metabolomic approach to explore the physiological regulation of H2O2 in initiating the development and terminating the diapause of Artemia cysts. This experiment was divided into two parts. In the first part, we analyzed three groups with or without H2O2 as control-0h, control-5h and H2O2 (180μM)-5h; in the second part, after 7-d incubation, the non-hatching cysts were treated with different H2O2 concentrations as low as 180μM and as high 1800μM. The results showed that arginine and proline metabolism were up-regulated after 5h, and H2O2 up-regulated valine, leucine and isoleucine biosynthesis in the development of cysts. In the second part, low H2O2 (180μM) showed alanine, aspartate and glutamate metabolism, but high H2O2 (1800μM) also up-regulated arginine and proline metabolism, as in the control group without H2O2 stimulus. These results suggest that enough H2O2 can catalyze cell transcription and translation in Artemia cysts, and it improves the cell growth rate, thus allowing embryo cells to grow again.


ER calcium discharge stimulates GDNF gene expression through MAPK-dependent and -independent pathways in rat C6 glioblastoma cells.
Glial cell line-derived neurotrophic factor (GDNF), a neurotrophic and differentiation factor, is expressed under several pathophysiological conditions but its regulatory signals have not yet been clarified. Here, we found that endoplasmic reticulum (ER) Ca(2+) discharge by thapsigargin induced GDNF mRNA as well as COX2 and GRP78 expression in rat C6 glioblastoma cells. GDNF mRNA was immediately induced and peaked at 2h by thapsigargin, and the alternative transcript consisting of exon 3 and exon 4 appeared to be most inducible. In spite of intracellular Ca(2+) perturbation, Ca(2+)-dependent PKC was not responsible for this induction. Instead, a PKCdelta-specific inhibitor, rottlerin, suppressed the thapsigargin-induced GDNF mRNA expression. On the other hand, thapsigargin transiently enhanced phosphorylation status of mitogen-activated protein kinase (MAPK) pathway, including extracellular signal-regulated kinase (Erk), p38 MAPK and c-JUN amino-terminal kinase1 (JNK1) simultaneously; whereas specific inhibitors against MEK1 and JNK only reduced the thapsigargin-induced GDNF mRNA expression. In addition, a pan-PKC inhibitor (Ro-31-8220) attenuated the thapsigargin-enhanced phosphorylation levels of Erk1/2 and JNK1, whereas rottlerin did not. Thus, the present study demonstrated that the thapsigargin-stimulated ER Ca(2+) discharge up-regulated GDNF gene expression through both MAPK-dependent and -independent pathways in C6 glioblastoma cells.


Update on the Diagnosis and Management of Familial Long QT Syndrome.
This update was reviewed by the CSANZ Continuing Education and Recertification Committee and ratified by the CSANZ board in August 2015. Since the CSANZ 2011 guidelines, adjunctive clinical tests have proven useful in the diagnosis of LQTS and are discussed in this update. Understanding of the diagnostic and risk stratifying role of LQTS genetics is also discussed. At least 14 LQTS genes are now thought to be responsible for the disease. High-risk individuals may have multiple mutations, large gene rearrangements, C-loop mutations in KCNQ1, transmembrane mutations in KCNH2, or have certain gene modifiers present, particularly NOS1AP polymorphisms. In regards to treatment, nadolol is preferred, particularly for long QT type 2, and short acting metoprolol should not be used. Thoracoscopic left cardiac sympathectomy is valuable in those who cannot adhere to beta blocker therapy, particularly in long QT type 1. Indications for ICD therapies have been refined; and a primary indication for ICD in post-pubertal females with long QT type 2 and a very long QT interval is emerging.


Strengthening local government policies to address health inequities: perspectives from Australian local government stakeholders.
With their close connection to community and increasing preventive health remit, local governments are well positioned to implement policies and programs to address health inequities. Nevertheless, there is a lack of evidence of equity-focused policy action in this sector. We aimed to understand how local government representatives approach equity in the development and implementation of health and wellbeing policies and programs, and to identify potential enablers for strengthening an equity focus. We conducted semi-structured interviews (June 2022-January 2023) with 29 health directorate representatives from 21 local governments in Victoria, Australia. Representatives were recruited from urban, regional and rural local government areas, with varying levels of socioeconomic position. Data was analysed inductively using Braun and Clarke's reflexive thematic analysis, informed by social determinants of health theory and a public policy decision making framework. Local governments approach health equity in different ways including focusing on priority populations, disadvantaged geographic areas, or by targeting the upstream determinants of health, such as housing and employment. Enabling factors for more equity-oriented local government policy action included those internal to local governments: (i) having a clear conceptualisation of equity, (ii) fostering a strong equity-centric culture, and (iii) developing organisational-wide competency in health equity. External factors related to key stakeholder groups that support and/or influence local governments included: (iv) strong support from community, (v) state government leadership and legislation, and (vi) supportive local partners, networks and NGO's. Local governments have a responsibility to implement policies and programs that improve health and reduce health inequities. Local government's capacity to leverage resources, structures, processes and relationships, internally and across sectors and community, will be key to strengthening equity-oriented local government health policies and programs.


Treatment of malignant thyroid disease.
Surgery is the primary form of therapy in the management of malignant thyroid disease. A near-total thyroidectomy is the preferred approach. Radioactive iodine is used for supplementary ablation therapy and for definitive therapy in differentiated tumors of papillary or follicular cell type. Thyroid-stimulating hormone (TSH) is administered in conjunction with radioactive iodine therapy, since tumor uptake appears to be directly related to endogenous TSH levels. Therapeutic doses of radioactive iodine range from 100 to 200 mCi of 131 I depending on tumor distribution. Adequate thyroid hormone replacement therapy resulting in the suppression of TSH is of considerable value in the prevention of tumor recurrence. Due to the possibility of late recurrence, patients should be followed for indefinite periods by means of diagnostic imaging studies at 1-2 yr intervals. Despite 30 yr of experience, the therapeutic efficacy of radioactive iodine remains controversial. However, in recent years, there has been mounting evidence indicating increased survival and decreased tumor recurrence in radioactive iodine-treated patients. External radiation therapy is reserved for anaplastic carcinoma and lymphoma, and adenocarcinomas that are refractory to radioactive iodine. Chemotherapy experience is limited; however, some reduction in the size of metastatic lesions has been observed after the administration of adriamycin.


Oxidized cholesterol bilayers. Dependence of electrical properties on degree of oxidation and aging.
Black lipid membranes made from oxidized cholesterol were examined for their specific resistance, capacitance, and physical stability, as a function of cholesterol oxidation time and of age. Membranes formed from cholesterol oxidized in n-octane were not physically stable even after 7 h of oxidation unless they were aged for at least a month. Membranes formed from cholesterol oxidized in decane and tetradecane (1 : 1) were stable immediately after 2--6 h of oxidation. Oxidation times outside this range produced unstable membranes. After 1 month storage, membranes from cholesterol solutions oxidized in decane and tetradecane from 0.75--3 h were stable. After 11 months, only the 0.75 oxidation time produced stable membranes. Storage in nitrogen retarded the aging process. After initial forming of the membrane, total membrane area and capacity increased and then stabilized, although specific capacity and resistance did not change, indicating inherent stability in the bilayer's intrinsic electrical properties. Bilayers formed soon after cholesterol oxidation had membrane capacity which ranged from 0.42 to 0.55 muF/cm2. Specific membrane resistance ranged initially from 2 . 10(6) to 37 . 10(6) omega/cm2 in 0.2 M NaCl with lower resistances in the more oxidized membranes. With aging, membrane capacity decreased gradually over 11 months to values approaching 0.1 muF/cm2 indicating membrane thickening. Membrane resistance ordinarily decreases with storage time. The rate of these changes with age is dependent on the extent of initial cholesterol oxidation and subsequent oxidation, with long term stability best in the least oxidized membranes.


Electrophoretic deposition of silicon-substituted hydroxyapatite/poly(epsilon-caprolactone) composite coatings.
Silicon-substituted hydroxyapatite/poly(epsilon-caprolactone) composite coatings were prepared on titanium substrate by electrophoretic deposition in n-butanol and chloroform mixture. The effect of the concentration of poly(epsilon-caprolactone) in suspension on the morphology and the microstructure of coatings were investigated, furthermore, the thermal behavior and in vitro bioactivity were also investigated. The results show that the coarse and accidented silicon-substituted hydroxyapatite/poly(epsilon-caprolactone) composite coatings were obtained by electrophoretic deposition when the concentration of poly(epsilon-caprolactone) in suspension was 6-16 g/l. The adsorption of poly(epsilon-caprolactone) on the surface of Si-HA particles hinders the electrophoretic deposition of Si-HA. The shear-testing experiments indicated that the addition of poly(epsilon-caprolactone) in suspension is in favor of improving the bonding strength of the coatings. After immersion in simulated body fluid for 8 days, silicon-substituted hydroxyapatite/poly(epsilon-caprolactone) composite coatings have the ability to induce the bone-like apatite formation.


Acute kidney injury after cardiac surgery: Sustained low efficiency compared to continuous renal replacement therapy.
Sustained low efficiency dialysis (SLED) has been introduced as a mode of renal replacement therapy (RRT) for treating severe cardiac surgery-associated acute kidney injury (CSA-AKI) at some hospitals; SLED is performed using intermittent hemodialysis (IHD) devices but differs from conventional IHD in its duration and intensity. However, there are limited data comparing SLED against more conventional continuous RRT methods. We conducted a retrospective cohort study to compare outcomes of patients with severe CSA-AKI after an institutional transition from continuous RRT to SLED. Following research ethics approval, we conducted a retrospective cohort study of patients with severe CSA-AKI requiring RRT. Cardiac Intensive Care Unit at the Toronto General Hospital (Toronto, Ontario, Canada) from 1 January 1999 to 31 December 2011. 351 consecutive patients with severe CSA-AKI requiring RRT after cardiac surgery. The RRT mode was continuous RRT before 31 March 2008, and SLED after 1 April 2008. The primary outcome was low-cardiac output syndrome (LCOS) and the main secondary outcome was associated costs. Propensity score matched-pairs analyses were used to compare the outcomes of patients in the continuous RRT period versus the SLED period. There were 268 patients treated with continuous RRT and 83 patients treated with SLED. The SLED group had a higher weight, higher baseline hemoglobin concentration, and higher prevalence of obstructive lung disease. In propensity score match-pairs analysis (n = 148), the SLED group experienced similar odds of low cardiac output syndrome (odds ratio [OR] 1.06, 95% CI 0.68 to 1.67), death (OR 1.09, 0.94 to 1.28), acute stroke (OR 0.97, 0.83 to 1.13), myocardial infarction (OR 0.92, 0.84 to 1.01). The use of SLED was associated with a reduced cost compared to continuous RRT. The cost differential for 83 treated patients was CAD$130,974 (CAD$178,159.50 vs CAD$309,133.50) in favor of SLED. An institutional transition from continuous RRT to SLED, was associated with a significant lower cost with the use of SLED, while maintaining comparable postoperative outcomes in CSA-AKI patients.


[Squamous cell carcinoma of the bladder in a patient with HIV and paraplegia].
In patients with spinal cord injury (SCI) the rate of squamous cell carcinomas (SCC) among bladder tumors is increased compared to the general population. An increased life expectancy is achieved by modern HIV treatment so that more AIDS-unrelated malignomas, e.g. bladder tumors, occur in these patients. Therefore, the risk for SCC in this group of patients is increased in patients with SCI and HIV but the combination of these two diseases is rare. We report the first case of SCC in a patient with SCI and HIV. Initial symptoms of bladder tumors in patients with SCI are often unspecific; therefore, in cases with new onset hematuria, recurrent urinary tract infections and changes in bladder function, cystoscopy and computed tomography (CT) scanning should be considered.


Regional variations in pediatric medication exposure: Spatial analysis of poison center utilization in western Pennsylvania.
Medication drug exposures among young children continue to rise despite current poison prevention efforts. These exposures result in increased healthcare utilization and medical costs. New tactics are needed to reduce injuries related to pediatric drug exposures. We aimed to identify cluster patterns in: (1) calls for pediatric medication drug exposures and (2) a subset of calls that resulted in medical evaluation referrals. We identified and evaluated population characteristics associated with cluster patterns. We analyzed 26,685 pharmaceutical drug exposures involving children <5 years of age based on calls reported to the Pittsburgh Poison Center from 1 January 2006 to 31 December 2010. We performed spatial statistics to assess for clustering. We used logistic regression to estimate population characteristics associated with clustering. Spatial analysis identified 22 exposure clusters and five referral clusters. Sixty-five percent of 89 ZIP codes in the clusters of drug exposure with healthcare facility (HCF) referral were not identified in the exposure clusters. ZIP codes in the HCF referral clusters were characterized as rural, impoverished, and with high rates of unemployment and school dropouts. Our principal findings demonstrate pediatric drug exposures do exist in discrete geographic clusters and with distinct socioeconomic characteristics. This study offers a starting point for subsequent investigations into the geographic and social context of pediatric medication drug exposures. This is an important step in revising pediatric poison prevention strategies.


Provisional consensus on the nomenclature and operational definition of dementia at a young age, a Delphi study.
Dementia at a young age differs from late onset dementia in pathology and care needs. This requires further research to improve the understanding of this group, support and service provision. Aim of current study is to reach consensus on the terminology and operational definition (i.e., age-related criteria and possible causes) of dementia at a young age, to aid further research. A classical Delphi technique was used to transform opinions into group consensus by using an online survey. In three rounds statements regarding (1) terminology, (2) age-related criteria, and (3) aetiologies that can be considered as causes of dementia at a young age were sent to international experts in the field to give their opinions and additional comments on the statements. Forty-four experts responded and full consensus was reached on 22 out of 35 statements. Young-onset dementia emerged as the term of preference. Provisional consensus was found for the use of age 65 at symptom onset as preferred cut-off age. Consensus was reached on the inclusion of 15 out of 22 aetiologies and categories of aetiologies as potential cause for dementia at a young age. A clear term and operational definition have been reached. Although beneficial for conducting future research to gain more insight in pathology and care needs of young people living with dementia, still consensus about some details is lacking. To reach consensus about these details and implications for use in research and clinical practice, the organisation of an in person consensus meeting is advised.


WASPs and WAVEs: from molecular function to physiology in hematopoietic cells.
The actin cytoskeleton is critically involved in a variety of cell functions. The Arp2/3 complex mediates branching of filamentous actin. The members of the Wiskott-Aldrich syndrome protein (WASP) family are major regulators of the complex. As such, the family proteins are also involved in numerous aspects of cell biology. In this short review, we first define the expanding WASP family. Next, we compare the domain structure of the members, and explain the known or proposed functions of each domain or region. Finally, we demonstrate the well-characterized roles of the proteins in specific cellular functions.


[Uretero-iliac artery fistula as a urological emergency].
Uretero-iliac artery fistulae represent a urological emergency with considerable mortality. We present 2 cases of a uretero-iliac artery fistula. Nowadays, minimally-invasive endovascular therapy seems to be the treatment of choice. For an optimal outcome, a multidisciplinary team with imminent availability of radiology, vascular surgery, urology and anaesthesia is required.


The transactivation domain of heterogeneous nuclear ribonucleoprotein K overlaps its nuclear shuttling domain.
The heterogeneous nuclear ribonucleoprotein K (hnRNP K) protein is a versatile molecule that interacts with RNA, DNA, and a number of transcription factors, implicating it in transcription, splicing, and translation processes. The underlying mechanism of transcription stimulation by hnRNP K is not well understood. To explore the possibility of a putative transactivation activity of hnRNP K, we produced constructs in which the yeast Gal4 DNA-binding domain was fused to various hnRNP K fragments in one-hybrid mammalian cells. Our results reveal that the K nuclear shuttling (KNS) domain, a well-known signal for nuclear import and export, is also responsible for the transactivation activity of hnRNP K protein. Importin alpha and beta proteins are involved in the regulation of the transactivation activity of the KNS domain via their competition for the nuclear pore complex. Site-directed mutants of serine residue 353 to alanine or aspartic acid or a series of truncated mutants of amino acids 338-363 of hnRNP K suggest the transactivation activity of KNS is primarily dependent on its amino acid composition and intact structure. Our results suggest that endogenous p53 is not required for the activity of the KNS domain, but that overexpression of exogenous p53 might affect its activity in a dose-dependent manner. We thus demonstrate the existence of a strong transactivation domain in hnRNP K and define the regulatory mechanism involved in its protein-protein interaction within the KNS domain in cells.


Reticulated multifocal fixed drug eruption due to mefenamic acid - a new morphological pattern.
Fixed drug eruption is a heterogeneous pattern of cutaneous reaction to certain drugs. Different morphological patterns of fixed drug eruption can occur. We describe a new morphology of fixed drug eruption showing a reticulated pattern as a result of ingestion of mefenamic acid and discuss the possible mechanism underlying such an appearance.


AAV-based neonatal gene therapy for hemophilia A: long-term correction and avoidance of immune responses in mice.
Hemophilia A gene therapy has been hampered by immune responses to vector-associated antigens and by neutralizing antibodies or inhibitors against the factor VIII (FVIII) protein; these 'inhibitors' more commonly affect hemophilia A patients than those with hemophilia B. A gene replacement strategy beginning in the neonatal period may avoid the development of these immune responses and lead to prolonged expression with correction of phenotype, thereby avoiding long-term consequences. A serotype rh10 adeno-associated virus (AAV) was developed splitting the FVIII coding sequence into heavy and light chains with the chicken β-actin promoter/CMV enhancer for dual recombinant adeno-associated viral vector delivery. Virions of each FVIII chain were co-injected intravenously into mice on the second day of life. Mice express sustained levels of FVIII antigen ≥5% up to 22 months of life without development of antibodies against FVIII. Phenotypic correction was manifest in all AAV-FVIII-treated mice as demonstrated by functional assay and reduction in bleeding time. This study demonstrates the use of AAV in a gene replacement strategy in neonatal mice that establishes both long-term phenotypic correction of hemophilia A and lack of antibody development against FVIII in this disease model where AAV is administered shortly after birth. These studies support the consideration of gene replacement therapy for diseases that are diagnosed in utero or in the early neonatal period.


Structure, Chaperone Activity, and Aggregation of Wild-Type and R12C Mutant αB-Crystallins in the Presence of Thermal Stress and Calcium Ion - Implications for Role of Calcium in Cataract Pathogenesis.
The current study was performed with the aim to evaluate the chaperoning ability, structural features, and aggregation propensity of wild-type and R12C mutant αB-crystallins (αB-Cry) under thermal stress and in the presence of calcium ion. The results of different spectroscopic analyses suggest that wild-type and mutant αB-Cry have dissimilar secondary and tertiary structures. Moreover, αB-Cry indicates slightly improved chaperone activity upon the R12C mutation. Thermal stress and calcium, respectively, enhance and reduce the extent of solvent-exposed hydrophobic surfaces accompanying formation of ordered and non-ordered aggregate entities in both proteins. Compared to the wild-type protein, the R12C mutant counterpart shows significant resistance against thermal and calcium-induced aggregation. In addition, in the presence of calcium, significant structural variation was accompanied by reduction in the solvent-exposed hydrophobic patches and attenuation of chaperone activity in both proteins. Additionally, gel mobility shift assay indicates the intrinsic propensity of R12C mutant αB-Cry for disulfide bridge-mediated protein dimerization. Overall, the results of this study are of high significance for understanding the molecular details of different factors that are involved in the pathomechanism of cataract disorders.


A comparison of susceptibility of two allopatric populations of Glossina pallidipes for stocks of Trypanosoma congolense.
A colony of Glossina pallidipes Austen which originated from Nguruman, Rift Valley Province, Kenya, was significantly more susceptible to infection (19.3%) with a stock of Trypanosoma congolense Broden isolated from G. pallidipes in Nguruman than a colony of the same species which originated from Shimba Hills, Coast Province, Kenya (5.6%). Male G.pallidipes from Nguruman were significantly more susceptible than females to this T.congolense stock whilst the susceptibility of both sexes of G.pallidipes from Shimba Hills did not differ significantly. All six goats on which six infected G.pallidipes fed singly (three tsetse per colony) became infected. Similarly, the G.pallidipes colony of Nguruman origin was significantly more susceptible to infection (16.4%) with a stock of T.congolense isolated from G.pallidipes in Shimba Hills than the colony of Shimba Hills origin (4.9%). The susceptibility of the sexes of G.pallidipes from both the colonies to this stock of T.congolense did not differ significantly. Again, all six goats on which six infected G.pallidipes fed singly (three tsetse per colony) became infected. If the observed differences in susceptibility of the two G.pallidipes colonies reflect transmission of trypanosomes by the two allopatric populations of tsetse in the field, then the epidemiology of congolense-trypanosomiasis in livestock must differ between these two areas of Kenya endemic for trypanosomiasis.


Myc rearrangement and concurrent high protein expression of C-Myc/Bcl2 carry an adverse prognosis in diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of non-Hodgkin lymphoma, characterized by a variety of clinicopathological, histomorphological, immunophenotypic, and molecular genetic features. The subtype of DLBCL known as double-expressor lymphoma (DEL) is associated with an adverse prognosis when treated with R-CHOP. Our study aimed to investigate the clinicopathologic features of DEL and the prognostic roles of Myc rearrangement and C-Myc expression in DEL patients. We conducted a retrospective study of 145 patients who were identified through fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) testing. We found that DEL patients were more likely to have a non-germinal center B-cell (GCB) subtype, stage III/IV disease, and a high International Prognostic Index (IPI) score. Our survival analysis indicated that Myc rearrangement and C-Myc expression were associated with poor prognosis. Although DEL patients with Myc rearrangement exhibited trends towards worse survival compared with patients without Myc rearrangement, the differences were not statistically significant (P = 0.4008). The median overall survival (OS) of DEL patients with ≥70 % C-Myc expression (DEL-C-Mychigh) was 5 months. In the DEL-C-Mychigh group, the non-GCB subtype showed nonsignificant trends towards poorer survival compared with the GCB subtype (P = 0.1042). In conclusion, our study shows that a cut-off of ≥70 % for C-Myc expression in DEL patients can improve risk stratification, and suggests that more intensive treatment regimens may be necessary to improve survival in this high-risk population.


New control of mitochondrial membrane potential and ROS formation--a hypothesis.
A new control of mitochondrial membrane potential delta(psi)m and formation of reactive oxygen species (ROS) is presented, based on allosteric ATP-inhibition of cytochrome c oxidase at high intramitochondrial ATP/ADP ratios. Since the rate of ATP synthesis by the ATP synthase is already maximal at low membrane potentials (100-120 mV), the ATP/ADP ratio will also be maximal at this delta(psi)m (at constant rate of ATP consumption). Therefore the control of respiration by the ATP/ADP-ratio keeps delta(psi)m low. In contrast, the known 'respiratory control' leads to an inhibition of respiration only at high delta(psi)m values (150-200 mV) which cause ROS formation. ATP-inhibition of cytochrome c oxidase is switched on and off by reversible phosphorylation (via cAMP and calcium, respectively). We propose that 'stress hormones' which increase intracellular [Ca2+] also increase delta(psi)m and ROS formation, which promote degenerative diseases and accelerate aging.


The TEA domain family transcription factor TEAD4 represses murine adipogenesis by recruiting the cofactors VGLL4 and CtBP2 into a transcriptional complex.
The Hippo signaling pathway is known to play an important role in multiple physiological processes, including adipogenesis. However, whether the downstream components of the Hippo pathway are involved in adipogenesis remains unknown. Here we demonstrate that the TEA domain family (TEAD) transcription factors are essential for adipogenesis in murine 3T3-L1 preadipocytes. Knockdown of TEAD1-4 stimulated adipogenesis and increased the expression of adipocyte markers in these cells. Interestingly, we found that the TEAD4 knockdown-mediated adipogenesis proceeded in a Yes-associated protein (YAP)/TAZ (Wwtr1)-independent manner and that adipogenesis suppression in WT cells involved formation of a ternary complex comprising TEAD4 and the transcriptional cofactors C-terminal binding protein 2 (CtBP2) and vestigial-like family member 4 (VGLL4). VGLL4 acted as an adaptor protein that enhanced the interaction between TEAD4 and CtBP2, and this TEAD4-VGLL4-CtBP2 ternary complex dynamically existed at the early stage of adipogenesis. Finally, we verified that TEAD4 directly targets the promoters of major adipogenesis transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and adiponectin, C1Q, and collagen domain-containing (Adipoq) during adipogenesis. These findings reveal critical insights into the role of the TEAD4-VGLL4-CtBP2 transcriptional repressor complex in suppression of adipogenesis in murine preadipocytes.


Unconventional role of lysosomes in phagocytosis.
Lysosomes are generally thought to be required only for the late stages of phagosome maturation, providing the proton pumps (V-ATPases) and hydrolases needed to acidify and degrade the ingested prey. A recent paper by Davis et al. (EMBO J. [2020], doi:10.15252/embj.2019104058) reports the involvement of lysosomes at a much earlier stage, namely in scission of phagosomes from the plasma membrane. Here we analyze these findings, highlighting a number of unexpected observations and unresolved questions.


A Portable Chip-Based NMR Relaxometry System With Arbitrary Phase Control for Point-of-Care Blood Analysis.
In this article, we present a portable NMR relaxometry system optimized for the point-of-care analysis of body liquids such as blood. The presented system is centered on an NMR-on-a-chip transceiver ASIC, a reference frequency generator with arbitrary phase control, and a custom-designed miniaturized NMR magnet with a field strength of 0.29 T and a total weight of 330 g. The NMR-ASIC co-integrates a low-IF receiver, a power amplifier, and a PLL-based frequency synthesizer on a total chip area of 1100 × 900 μm 2. The arbitrary reference frequency generator enables the use of conventional CPMG and inversion sequences, as well as modified water-suppression sequences. Moreover, it is used to implement an automatic frequency lock to correct temperature-induced magnetic field drifts. Proof-of-concept measurements on NMR phantoms and human blood samples show an excellent concentration sensitivity of v[Formula: see text] = 2.2 mM/[Formula: see text]. This very good performance renders the presented system an ideal candidate for the future NMR-based point-of-care detection of biomarkers such as the blood glucose concentration.


Object speed perception during lateral visual self-motion.
Judging object speed during observer self-motion requires disambiguating retinal stimulation from two sources: self-motion and object motion. According to the Flow Parsing hypothesis, observers estimate their own motion, then subtract the retinal corresponding motion from the total retinal stimulation and interpret the remaining stimulation as pertaining to object motion. Subtracting noisier self-motion information from retinal input should lead to a decrease in precision. Furthermore, when self-motion is only simulated visually, self-motion is likely to be underestimated, yielding an overestimation of target speed when target and observer move in opposite directions and an underestimation when they move in the same direction. We tested this hypothesis with a two-alternative forced-choice task in which participants judged which of two motions, presented in an immersive 3D environment, was faster. One motion interval contained a ball cloud whose speed was selected dynamically according to a PEST staircase, while the other contained one big target travelling laterally at a fixed speed. While viewing the big target, participants were either static or experienced visually simulated lateral self-motion in the same or opposite direction of the target. Participants were not significantly biased in either motion profile, and precision was only significantly lower when participants moved visually in the direction opposite to the target. We conclude that, when immersed in an ecologically valid 3D environment with rich self-motion cues, participants perceive an object's speed accurately at a small precision cost, even when self-motion is simulated only visually.


Successful surgical correction of symptomatic cor triatriatum dexter.
An unusual case of cor triatriatum dexter is presented. Abnormal embryologic development of the eustachian valve caused nearly complete septation of the right atrium in a 67-year-old woman. Multiple supraventricular arrhythmias prompted clinical evaluation and diagnosis. Surgical excision of the anomalous membrane resulted in complete relief from arrhythmias and a clinical cure. Cor triatriatum dexter is rare and is infrequently diagnosed before postmortem study; however, once the diagnosis is extablished, the condition is amenable to a relatively simple surgical correction. Supraventricular tachycardia has not previously been reported to be associated with cor triatriatum dexter. We believe this is the first case in which such arrhythmias led to early diagnosis and successful surgical correction.


Supportive treatment during the periprocedural period of endoscopic treatment for pancreatic fluid collections: a critical review of current knowledge and future perspectives.
Pancreatic fluid collections (PFCs) commonly develop as complications of acute pancreatitis and ductal disruption due to chronic pancreatitis. In the revised Atlanta classification, PFCs were classified based on the presence of necrosis and duration following the onset of acute pancreatitis. Interventions are required in cases of symptomatic pancreatic pseudocysts or walled-off necrosis (WON). In the management of these PFCs, endoscopic ultrasound-guided transluminal drainage and subsequent direct endoscopic necrosectomy for WON are increasingly utilized as less invasive treatment modalities compared to surgical debridement. To date, researchers have focused predominantly on the technical aspects of endoscopic therapy for symptomatic PFCs. Given the poor physical condition of patients receiving endoscopic treatment for PFCs, systemic support may have a substantial impact on the short- and long-term outcomes of these patients. A multidisciplinary approach is required to improve the clinical outcomes of patients with infected PFCs and their associated comorbidities. However, non-interventional support during the periprocedural period of endoscopic treatment of PFCs has not been fully discussed, and there have been considerable variations in the selection of treatment options between endoscopists and centers. To address these unmet needs in the clinical management of PFCs and promote future research to improve the clinical outcomes, we conducted a review of the literature within a multicenter consortium of expert endoscopists with specific expertise in the endoscopic treatment of PFCs. In this review, we summarize the current evidence on non-interventional supportive care (e.g., continuous lavage, medications, nutritional support, and antimicrobials) and propose potential topics for future research.


ATP6V1B2-related disorders featuring Lennox-Gastaut-syndrome: A case-based overview.
ATP6V1B2 (ATPase, H+ transporting, lysosomal VI subunit B, isoform 2) encodes for a subunit of a ubiquitous transmembrane lysosomal proton pump, implicated in the acidification of intracellular organelles and in several additional cellular functions. Variants in ATP6V1B2 have been related to a heterogeneous group of multisystemic disorders sometimes associated with variable neurological involvement. However, our knowledge of genotype-phenotype correlations and the neurological spectrum of ATP6V1B2-related disorders remain limited due to the few numbers of reported cases. We hereby report the case of an 18-year-old male Sicilian patient affected by a global developmental delay, skeletal abnormalities, and epileptic encephalopathy featuring Lennox-Gastaut syndrome (LGS), in which exome sequencing led to the identification of a novel de novo variant in ATP6V1B2 (NM_001693.4: c.973G > C, p.Gly325Arg). Our report provides new insights on the inclusion of developmental epileptic encephalopathies (DEEs) within the continuum group of ATP6V1B2-related disorders, expanding the phenotypic and molecular spectrum associated with these conditions.


The Case for Photodynamic Diagnosis-assisted Resection Without Intravesical Single-shot Chemotherapy.
Although there is level 1 evidence for the use of intravesical chemotherapy after the transurethral resection of bladder tumour, the decision to apply it needs to be individualised. "What benefit will the patient derive from it?"


Retraction notice to Plexin-B1 and Semaphorin 4D Cooperate to Promote Perineural Invasion in a RhoA/ROK-Dependent Manner Am J Pathol 180 (2012) 1232-1242.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article is being retracted following correspondence from the Office of Accountability and Compliance at the University of Maryland, Baltimore. An internal investigation into this manuscript by the University of Maryland, Baltimore, found evidence that there are errors with the presentation of the standard deviations and statistical significance shown in Figure 6 which are not supported by the original data, and that these inaccuracies warrant retraction to correct the scientific record. Despite extensive efforts, the journal was unable to contact Dr. Ying-hua Yang and Dr. Hua Zhou with regard to this retraction.


Dual level control of the Escherichia coli pheST-himA operon expression. tRNA(Phe)-dependent attenuation and transcriptional operator-repressor control by himA and the SOS network.
Previous studies of phenylalanyl-tRNA synthetase expression in Escherichia coli have established that the pheST operon transcription is controlled by a Phe-tRNA(Phe)-mediated attenuation mechanism. More recently, the himA gene, encoding the alpha-subunit of integration host factor, was recognized immediately downstream from pheT, possibly forming part of the same transcriptional unit. By using the in-vitro transcription and S1 mapping techniques, transcription termination after pheT could be excluded, indicating that himA can be expressed from polycistronic messenger RNAs encompassing the pheST region. However, the presence of a secondary promoter able to express himA and located within pheT is demonstrated. To further investigate the regulation of the pheST-himA operon expression, genetic fusions between various parts of this operon and the lacZ gene were constructed and studied. Our results confirm the autoregulation of himA previously described, and demonstrate that it occurs through the modulation of the secondary promoter activity within pheT. Surprisingly, it is found that the pheST promoter is also submitted to the same control. Consistent with this, DNA sequences homologous to the integration host factor binding site consensus are present at the level of both promoters. However, evidence in favor of two different repressor complexes is provided. Previously observed SOS induction of the himA expression is shown to occur through the modulation of both promoter activities. Contrasting with the other genes under SOS control, the LexA protein binding site consensus sequence could not be found in the two promoter regions. This suggests that either the LexA protein directly participates in the formation of an active holorepressor, or that the product of an SOS gene is able to inhibit the formation or the binding of such a repressor. Finally, our results indicate that the pheST-himA operon expression is controlled by two different mechanisms acting independently. (1) The phenylalanyl-tRNA synthetase and the himA product expressions are controlled by an operator-repressor type mechanism, in which the himA product and the SOS network are involved. (2) Through its partial cotranscription with pheST, himA expression is also under attenuation control. The latter control may provide a way to couple the intracellular concentration of the himA product to the functional state of the translational apparatus.


Structural studies of glucorhamnans isolated from the lipopolysaccharides of reference strains for Serratia marcescens serogroups O4 and O7, and of an O14 strain.
Partially acetylated glucorhamnans have been isolated from the lipopolysaccharides of three strains of Serratia marcescens. The polymer from the reference strain (C.D.C. 864-57) for serogroup O4 has the disaccharide repeating-unit shown below, in which acetylation at position 2 of the rhamnosyl residue is approximately 90% complete. Similar glucorhamnans from the reference strain (C.D.C. 843-57) for serogroup O7 and from a pigmented strain (NM) of serogroup O14 differ only in the configuration of the L-rhamnopyranosyl residue (beta) and the extent of O-acetylation (O7, almost stoichiometric; NM, 80-90%). Glucorhamnans of the second type have been isolated previously from the lipopolysaccharides of other strains of S. marcescens, including the reference strain for serogroup O6 and another pigmented O14 strain (N.C.T.C. 1377). In all cases, the lipopolysaccharide extracts also contained acidic glycans, but the glucorhamnans are believed to constitute the integral side-chains. (Formula: see text).


In vitro assessment of the pathogenicity of the LDLR c.2160delC variant in familial hypercholesterolemia.
Familial hypercholesterolemia (FH) is an inherited disorder with markedly elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. Although many mutations have been reported in FH, only a few have been identified as pathogenic mutations. This study aimed to confirm the pathogenicity of the LDL receptor (LDLR) c.2160delC variant in FH. In this study, the proband and her family members were systematically investigated, and a pedigree map was drawn. High-throughput whole-exome sequencing was used to explore the variants in this family. Next, quantitative polymerase chain reaction (qPCR), western blot (WB) assays, and flow cytometry were conducted to detect the effect of the LDLR c.2160delC variant on its expression. The LDL uptake capacity and cell localization of LDLR variants were analyzed by confocal microscopy. According to Dutch Lipid Clinic Network (DLCN) diagnostic criteria, three FH patients were identified with the LDLR c.2160delC variant in this family. An in-silico analysis suggested that the deletion mutation at the 2160 site of LDLR causes a termination mutation. The results of qPCR and WB verified that the LDLR c.2160delC variant led to early termination of LDLR gene transcription. Furthermore, the LDLR c.2160delC variant caused LDLR to accumulate in the endoplasmic reticulum, preventing it from reaching the cell surface and internalizing LDL. The LDLR c.2160delC variant is a terminating mutation that plays a pathogenic role in FH.


[The use of physiotherapy and antibacterial preparations in urogenital infections].
Antibacterial antibiotics only, antibiotics in combination with immunostimulators, antibiotics plus immunostimulators plus physiotherapy were administered in 132 patients with urethroprostatitis caused by mixed infection (18, 45 and 69 patients, respectively). A complete recovery was achieved only in patients who had been treated with the antibiotics, immunostimulators and physiotherapy. After antibiotics, residual infection was registered in 11.1% of the patients, clinical symptoms persisted in 6 patients; after antibiotics combined with immunostimulators in 6.7% and 4 patients, respectively.


The value of arteriography before abdominal aneurysmectomy.
We believe preoperative angiography is a safe procedure with current technics. The importance of the lateral aortogram in identifying mesenteric or celiac artery stenosis is emphasized. Sixty per cent of all patients studied showed some abnormal arteriographic finding. Significant abnormalities include (1) associated arteriosclerotic occlusions, (2) multiple aneurysms, and (3) anomalous vessels. As we consider this preoperative data of great importance in the planning of the total operation, we strongly recommend the routine use of aortography as described in evaluating all nonruptured abdominal aortic aneurysms.


Temporary epicardial pacing wire removal: is it an innocuous procedure?
The safety and efficacy of temporary pericardial pacing wires have been accepted and their use is common after cardiac operations. Complications related to pacing wire removal are unusual but it can be serious and even catastrophic. We report an unusual case of bleeding due the laceration and rent created in the saphenous vein graft wall by the metallic tip of the pacing wire at the time of pacing wire removal.


Intracardiac electrocardiography during permanent pacemaker implantation: predictors of cardiac perforation.
Intracardiac electrograms from 50 successive patients undergoing permanent pacemaker implantation have been analyzed. There were 29 male and 21 female patients aged 14 to 93 years (mean age 68.4 years). The electrograms were obtained using methods that simulated the wave form that would be detected by unipolar cardiac pacemakers. Three types of electrographic patterns were identified: qR pattern with a q/R ratio of less than 1 (type I): QR pattern with a Q/R ratio between 1 and 4.4 (type II); and Qr pattern with a Q/r ratio between 12 and 15 (type III). A type I pattern was seen in 29 patients (58 percent), type II in 18 (36 percent) and type III in 3 patients (6 percent). The duration of the follow-up period ranged from 3 weeks to 20 months (mean 9.7 months); three patients were lost to follow-up study. There were four deaths apparently unrelated to the pacemaker. Recognizable problems (either pacing or sensing failure) occurred in one patient (6 percent) with a type II pattern, in two patients (66.7 percent) with a type III pattern and in no patient with a type I pattern. On the basis of these data it is suggested that at the time of pacemaker implantation, intracardiac electrograms with a type I pattern indicating good pacing thresholds and sensing should be sought. If type II wave forms occur with good pacing thresholds and sensing then the electrode could probably be left in position. The incidence of a type III pattern is rare; when it does occur it is greatly suggestive of myocardial perforation. When this pattern is seen, the pacemaker catheter must be repositioned.


[Nuclear medicine diagnosis and therapy of distant metastases of pheochromocytoma].
Three foci, suspected of being metastases, were discovered by sonography and computed tomography in a patient twelve years after resection of a phaeochromocytoma and six years after resection of liver metastases. The findings were confirmed by scintigraphy with 131I-metaiodobenzylguanidine (MIBG) and treated with 3700 MBq of MIBG, to be repeated in the near future.


A big data approach to macrofaunal baseline assessment, monitoring and sustainable exploitation of the seabed.
In this study we produce a standardised dataset for benthic macrofauna and sediments through integration of data (33,198 samples) from 777 grab surveys. The resulting dataset is used to identify spatial and temporal patterns in faunal distribution around the UK, and the role of sediment composition and other explanatory variables in determining such patterns. We show how insight into natural variability afforded by the dataset can be used to improve the sustainability of activities which affect sediment composition, by identifying conditions which should remain favourable for faunal recolonisation. Other big data applications and uses of the dataset are discussed.


Interleukin-1 receptor antagonist polymorphism (rs2234663) and periodontitis susceptibility: a meta-analysis.
The results of recent published studies focusing on interleukin-1 receptor antagonist (IL-1RN) gene variable number of tandem repeats (VNTR) polymorphism in periodontitis susceptibility are often conflicting. We performed a meta-analysis in order to investigate the potential association of IL-1RN VNTR polymorphism with susceptibility to either chronic (CP) or aggressive (AgP) periodontitis. Nineteen studies involving a total of 2011 cases and 1719 controls were searched without any language restriction. Odds ratios (ORs) along with their 95% confidence intervals (CIs) were calculated to compare the distribution of alleles and genotypes between cases and controls. Both fixed and random effects models were used to pool the data. The IL-1RN VNTR polymorphism was marginally associated with an elevated risk of CP in overall populations (22 versus LL (L means the long alleles): OR=1.47, 95% CI 1.00-2.18, p=0.05), and the association was consistently significant in severe CP subgroup (OR=4.02, 95% CI 1.84-8.80, p<0.0005). Further stratified analysis restricted to Hardy-Weinberg equilibrium studies showed evidence for an increased risk with CP in Asians (2 allele versus L allele: OR=1.82, 95% CI 1.31-2.54, p<0.0005), however, a decreased risk with AgP in Caucasians (L2 versus LL: OR=0.50, 95% CI 0.32-0.78, p=0.002). This meta-analysis suggested that IL-1RN VNTR polymorphism might contribute to an increased risk on CP and a decreased risk on AgP. However, further well-designed studies with large sample size are needed to determine the robustness of these observations in different populations.


Implementation of an integrative movement program for residents with dementia in a VA nursing home.
Preventing Loss of Independence through Exercise (PLIÉ) is an integrative group movement program developed for adults with mild-to-moderate dementia attending day programs. However, many older adults with dementia ultimately require assistance with their activities of daily living and become residents in nursing homes or other long-term care facilities with their complex comorbidities and unique needs. We conducted a post-implementation evaluation of PLIÉ at a San Francisco Veterans Affairs (VA) nursing home to assess reach and effectiveness among residents, staff, and family members who participated in ≥ 1 PLIÉ class from 9/2018 to 6/2019. Post-implementation number of classes offered and mean attendance; anonymous satisfaction surveys (5-point Likert scales); qualitative content analysis of open-ended survey responses and clinical progress notes. Forty-five PLIÉ classes were offered over 9 months. Residents attended an average of 13 ± 12 classes with an average class size of 14 residents, 4 staff members, and 2 family members. Most survey respondents rated the program overall as "very good" or "excellent" (100 % residents, n = 15; 87 % staff, n = 14; 100 % family members, n = 8). Respondents reported improvements in themselves and/or others in four domains: (1) physical, (2) psychological, (3) social, and (4) cognitive. Physical improvements among veterans included mobility, strength, and energy. Psychological improvements included feelings of happiness/well-being, enjoyment, and self-empowerment. Social improvements included connection, social skills, and social support. Cognitive improvements included engagement, communication ability, and focus/attention. Responses were similar among resident, staff, and family member surveys and clinical progress notes. Participants frequently reported improvements in multiple domains (e.g., "The veterans are more alert and engaged, many are smiling and laughing."). Negative comments were primarily related to logistics, suggesting that the class occur more frequently. PLIÉ was successfully implemented in a VA nursing home with high attendance and satisfaction among residents, staff, and family members. Participants reported clinically meaningful physical, psychological, social, and cognitive benefits. Other long-term care facilities could potentially benefit from implementing PLIÉ to increase quality of life in residents with dementia.


Vaginal progesterone compared with intramuscular 17-alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth in singleton gestations: a systematic review and meta-analysis.
Randomized trials have found benefits of both vaginal progesterone and 17-alpha-hydroxyprogesterone caproate in the prevention of recurrent preterm birth. A previous meta-analysis directly comparing the two was limited by low-quality evidence, and national and international society guidelines remain conflicting regarding progestin formulation recommended for prevention of recurrent preterm birth. The aim of this updated systematic review with meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-alpha-hydroxyprogesterone caproate in the prevention of spontaneous preterm birth in patients with singleton gestations and previous spontaneous preterm birth. Searches were performed in MEDLINE, Ovid, Scopus, ClinicalTrials.gov, the International Prospective Register of Systematic Reviews (PROSPERO), SciELO, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) with the use of a combination of keywords and text words related to "preterm birth," "preterm delivery," "singleton," "cervical length," "progesterone," "progestogens," "vaginal," "17-alpha-hydroxy-progesterone caproate," and "intramuscular" from inception of each database to September 2021. No restrictions for language or geographic location were applied. We included all randomized controlled trials of asymptomatic singleton gestations with previous spontaneous preterm birth that were randomized to prophylactic treatment with either vaginal progesterone (ie, intervention group) or intramuscular 17-alpha-hydroxyprogesterone caproate (ie, comparison group). Post hoc sensitivity analysis was performed for studies with low risk of bias and studies with protocol registration. The primary outcome was preterm birth <34 weeks' gestation. The summary measures were reported as relative risks with 95% confidence intervals. Seven randomized controlled trials including 1910 patients were included in the meta-analysis. Patients who received vaginal progesterone had a significantly lower rate of preterm birth at <34 weeks (14.7% vs 19.9%; relative risk, 0.74; 95% confidence interval, 0.57-0.96), preterm birth at <37 weeks (36.0% vs 46.6%; relative risk, 0.76; 95% confidence interval, 0.69-0.85), and preterm birth at <32 weeks of gestation (7.9% vs 13.6%; relative risk, 0.58; 95% confidence interval, 0.39-0.86), compared with women who received intramuscular 17-alpha-hydroxyprogesterone caproate. There were no significant differences in the rate of preterm birth at <28 weeks' gestation. Adverse drug reactions were significantly lower in the vaginal progesterone group than in the 17-alpha-hydroxyprogesterone caproate group (15.6% vs 22.2%; relative risk, 0.71; 95% confidence interval, 0.54-0.92). Perinatal mortality was lower in the vaginal progesterone group than in the 17-alpha-hydroxyprogesterone caproate group (2.2% vs 4.4%; relative risk, 0.51; 95% confidence interval, 0.25-1.01). In sensitivity analysis including trials rated with at least 4 Cochrane tools as of "low risk of bias," 4 trials were included (N=575), and there was no longer a significant difference in preterm birth at <34 weeks' gestation between vaginal progesterone and 17-alpha-hydroxyprogesterone caproate (12.2% vs 13.9%; relative risk, 0.87; 95% confidence interval, 0.57-1.32). Overall, vaginal progesterone was superior to 17-alpha-hydroxyprogesterone caproate in the prevention of preterm birth at <34 weeks' gestation in singleton pregnancies with previous spontaneous preterm birth. Although sensitivity analysis of high-fidelity studies showed the same trend, findings were no longer statistically significant.


Inhibition of bacterial toxin recognition of membrane components as an anti-virulence strategy.
Over recent years, the development of new antibiotics has not kept pace with the rate at which bacteria develop resistance to these drugs. For this reason, many research groups have begun to design and study alternative therapeutics, including molecules to specifically inhibit the virulence of pathogenic bacteria. Because many of these pathogenic bacteria release protein toxins, which cause or exacerbate disease, inhibition of the activity of bacterial toxins is a promising anti-virulence strategy. In this review, we describe several approaches to inhibit the initial interactions of bacterial toxins with host cell membrane components. The mechanisms by which toxins interact with the host cell membrane components have been well-studied over the years, leading to the identification of therapeutic targets, which have been exploited in the work described here. We review efforts to inhibit binding to protein receptors and essential membrane lipid components, complex assembly, and pore formation. Although none of these molecules have yet been demonstrated in clinical trials, the in vitro and in vivo results presented here demonstrate their promise as novel alternatives and/or complements to traditional antibiotics.


Pathology of the temporomandibular joint of patients with rheumatoid arthritis--case reports of secondary amyloidosis and macrophage populations.
The pathogenetic features of rheumatoid arthritis of the temporomandibular joint (TMJ) are not well defined. In this paper the histological features of TMJs affected by rheumatoid arthritis, and the detection of secondary amyloidosis and macrophage populations in the TMJs of two patients with progressive rheumatoid arthritis are described. In two patients (64-year-old man and 61-year-old woman) with rheumatoid arthritis total TMJ replacement were performed. The surgical specimens were studied histologically. It was found that the articular cartilage had been completely replaced by proliferating fibrous tissue. Congo red staining and polarizing microscopy revealed amyloid deposition in the connective tissue of the joint space. Immunohistochemical staining showed CD 68 positive macrophages around the amyloid deposition in the proliferating soft tissue. TMJ involvement in rheumatoid arthritis followed the same destructive pathway as in other joints. Amyloid deposition and macrophage populations were detected in two TMJs affected by rheumatoid arthritis.


Current controversies in the treatment of hypertension.
Three controversies in the treatment of hypertension are reviewed. The first involves the decision whether to treat mild hypertension. Little consensus currently exists in this area and recent trial evidence is reviewed. Second, the basis of choosing specific drugs is discussed; biochemical profiling has not been overly successful, but demographic profiling and benefit profiling are to be commended. Third, the salt controversy is reviewed. On a population basis, lowering salt intake may be beneficial.


Inducing lucid dreams by olfactory-cued reactivation of reality testing during early-morning sleep: A proof of concept.
The reliable induction of lucid dreams is a challenge in lucid dream research. In a previous study by our research group we were able to induce in about 50% of the participants a lucid dream in a single sleep laboratory night by combining a wake-up-back-to-bed sleep protocol and a mnemonic technique. In the present study, we extended our previous procedure by additional presentation of an odor during sleep to reactivate memory traces about reality testing. In total 16 male participants spent a single night in the sleep lab whereas the procedure induced in two participants a lucid dream (12.5%). The induction rate stays below the success rate of our previous study and therefore odor-cueing seems not a promising technique for inducing lucid dreams. Beside the odor presentation, several other methodological changes have been made, which will be discussed and hopefully help further dream engineering to improve induction techniques.


Increased cortical BOLD signal anticipates generalized spike and wave discharges in adolescents and adults with idiopathic generalized epilepsies.
Electroencephalography-functional magnetic resonance imaging (EEG-fMRI) coregistration has recently revealed that several brain structures are involved in generalized spike and wave discharges (GSWDs) in idiopathic generalized epilepsies (IGEs). In particular, deactivations and activations have been observed within the so-called brain default mode network (DMN) and thalamus, respectively. In the present study we analyzed the dynamic time course of blood oxygen level-dependent (BOLD) changes preceding and following 3 Hz GSWDs in a group of adolescent and adult patients with IGE who presented with absence seizures (AS). Our aim was to evaluate cortical BOLD changes before, during, and after GSWD onset. Twenty-one patients with IGE underwent EEG-fMRI coregistration. EEG-related analyses were run both at the single-subject and at group level (random effect). The time-course analysis was conducted for 3 s time windows before, during, and after GSWDs, and they were included until no further BOLD signal changes were observed. Fifteen patients (nine female, mean age 28 years) had GSWDs during EEG-fMRI coregistration (262 total events, mean duration 4 s). Time-course group analysis showed BOLD increments starting approximately 10 s before GSWD onset located in frontal and parietal cortical areas, and especially in the precuneus-posterior cingulate region. At GSWD onset, BOLD increments were located in thalamus, cerebellum, and anterior cingulate gyrus, whereas BOLD decrements were observed in the DMN regions persisting until 9 s after onset. Hemodynamic changes (BOLD increments) occurred in specific cortical areas, namely the precuneus/posterior cingulate, lateral parietal, and frontal cortices, several seconds before EEG onset of GSWD. A dysfunction of these brain regions, some of which belongs to the DMN, may be crucial in generating GSWDs in patients with IGE.


Ontogeny of central serotonergic neurons in the directly developing frog, Eleutherodactylus coqui.
Embryonic development of the central serotonergic neurons in the directly developing frog, Eleutherodactylus coqui, was determined by using immunocytochemistry. The majority of anuran amphibians (frogs) possess a larval stage (tadpole) that undergoes metamorphosis, a dramatic post-embryonic event, whereby the tadpole transforms into the adult phenotype. Directly developing frogs have evolved a derived life-history mode where the tadpole stage has been deleted and embryos develop directly into the adult bauplan. Embryonic development in E. coqui is classified into 15 stages (TS 1-15; 1 = oviposition/15 = hatching). Serotonergic immunoreactivity was initially detected at TS 6 in the raphe nuclei in the developing rhombencephalon. At TS 7, immunopositive perikarya were observed in the paraventricular organ in the hypothalamus and reticular nuclei in the hindbrain. Development of the serotonergic system was steady and gradual during mid-embryogenesis. However, starting at TS 13 there was a substantial increase in the number of serotonergic neurons in the paraventricular, raphe, and reticular nuclei, a large increase in the number of varicose fibers, and a differentiation of the reticular nuclei in the hindbrain. Consequentially, E. coqui displayed a well-developed central serotonergic system prior to hatching (TS 15). In comparison, the serotonergic system in metamorphic frogs typically starts to develop earlier but the surge of development that transpires in this system occurs post-embryonically, during metamorphosis, and not in the latter stages of embryogenesis, as it does in E. coqui. Overall, the serotonergic development in E. coqui is similar to the other vertebrates.


Effects of viral pneumonia on lung macrophage lysosomal enzymes.
During viral pneumonitis in mice, lung fluid protein and free lysosomal enzyme activity are increased while macrophage lysosomal enzymes are decreased.


Structural dataset for the fast-exchanging KRAS G13D.
Cancers bearing the KRAS G13D mutation are notable for their distinct clinical behavior relative to other oncogenic KRAS mutations. We hypothesized that primary biochemical or biophysical properties of KRAS G13D might contribute to these clinical observations and as part of our study undertook structural studies using x-ray crystallography. In this data article we discuss several x-ray diffraction datasets that yielded structures of oncogenic KRAS mutants including a high resolution (1.13 Å) structure of KRAS G13D. The datasets are typical for high resolution x-ray diffraction data and allow the construction of atomic resolution, three dimensional structural models with high confidence. This data can be correlated with biochemical information such as defects in substrate binding kinetics, GTPase activities and interactions with the RAS effector RAF kinase.


Cigarette smoking and liver cancer among US veterans.
The relationship of tobacco use with risk of primary liver cancer was investigated using data from a 26-year mortality follow-up of nearly 250,000 US veterans, mostly from World War I. Significantly increased risks for liver cancer (289 deaths) were associated with most forms of tobacco use, including pipe and cigar smoking. Elevated relative risks (RRs) were seen for current cigarette smokers (RR = 2.4; 95 percent confidence interval [CI] 1.6-3.5) and former cigarette smokers (RR = 1.9, 1.2-2.9). A strong dose-response relationship (P less than 0.001) was found for cigarette smoking, with smokers of 40 or more cigarettes per day having almost a fourfold risk (RR = 3.8, 1.9-8.0). Risks were also found to increase significantly with years of cigarette use and with earlier age at the start of cigarette smoking. These results are consistent with those of other cohort and case-control studies, suggesting that cigarette smoking may be related to the risk of liver cancer.


Achilles tendinitis in Vibrio vulnificus sepsis: a rare presentation.
Vibrio vulnificus infection commonly presents as sepsis or wound infection. A case of alcoholic liver cirrhosis developed acute left heel pain and swelling 2 days after ingesting raw fish. Two sets of blood cultures indicated V. vulnificus. HLA-B27 was negative. Ultrasonography revealed left Achilles tendinitis. Fluid aspirated from the left retrocalcaneal bursa was sterile. The patient recovered completely 3 weeks after treatment. To our knowledge, V. vulnificus septicaemia with Achilles tendinitis, which may be the only indication of reactive arthritis (ReA), has not been reported previously. Prompt recognition of this life-threatening infection and adequate treatment with antibiotics is vital.


Fine afferent fibers from viscera do not terminate in the substantia gelatinosa of the thoracic spinal cord.
Transganglionic transport of horseradish peroxidase (HRP) has been used to study the anatomy of the central projection of somatic and visceral afferent fibers to the thoracic spinal cord of the cat. A dense concentration of somatic afferent fibers and terminals was found in laminae I and II of the dorsal horn and more scattered terminals were present in laminae III, IV and V and in Clarke's column. In contrast, visceral afferent fibers and terminals were found only in lamina I or reaching lamina V via a small bundle of fibers located in the lateral border of the dorsal horn. These results indicate that fine afferent fibers from viscera, unlike those of cutaneous origin, do not project to the substantia gelatinosa (lamina II) of the dorsal horn.


Synthesis, biological evaluation and quantitative structure-active relationships of 1,3-thiazolidin-4-one derivatives. A promising chemical scaffold endowed with high antifungal potency and low cytotoxicity.
With reference to recent studies reporting on the various biological properties of the thiazolidinone scaffold, we synthesized more than a hundred compounds characterized by a 1,3-thiazolidin-4-one nucleus derivatised at the C2 with a hydrazine bridge linked to (cyclo)aliphatic or hetero(aryl) moieties, and their N-benzylated derivatives. These molecules were assayed as potential anti-Candida agents and they were shown to possess comparable, and in some cases higher biological activity than well-established topical and systemic antimycotic drugs (i.e. clotrimazole, fluconazole, ketoconazole, miconazole, tioconazole, amphotericin B). Compounds endowed with the lowest MICs underwent further testing in order to assess their cytotoxic effect (CC50) on Hep2 cells, which demonstrated their relative safety. Finally, QSAR and 3-D QSAR models were used to predict putative chemical modifications of the 1,3-thiazolidin-4-one scaffold in order to design new and potential more active compounds against Candida spp.


Adherence patterns to National Comprehensive Cancer Network (NCCN) guidelines for referral to cancer genetic professionals.
Genetic predisposition is responsible for 5-10% of breast cancer, 10% of ovarian cancer and 2-5% of uterine cancer. The study objective was to compare genetic counseling and testing referral rates among women with breast cancer that met NCCN referral guidelines to the referral rates among women with gynecologic cancers and determine predictors of referral. Utilizing an institutional tumor registry database, patients from an academic women's oncology program were identified who met a subset of NCCN guidelines for genetic referral between 2004 and 2010. Patients diagnosed with ovarian cancer, breast cancer ≤50years of age, or uterine cancer <50years of age were included. A retrospective electronic chart review was conducted to evaluate for a genetic referral and uptake of genetic testing. 820 women were included (216 uterine, 314 breast, and 290 ovarian cancer). The overall genetic referral rate was 21.7%. 34% of eligible breast cancer patients were referred compared to 13.4% of uterine cancer and 14.5% of ovarian cancer patients (p<0.0001). Younger age, breast cancer diagnosis, family history and earlier stage were all significant referral predictors. The odds of being referred increased with the number of affected family members. 70.8% of referred patients, consulted with genetics. Among those who consulted with genetics, 95.2% underwent testing. Although increasing, genetic counseling remains underutilized across cancer diagnosis. Women with breast cancer are more likely to be referred than women with gynecologic cancers. Younger age, earlier stage and positive family history appear to be predictive of referral for genetic evaluation.


Functional characterization of the ABC transporters and transposable elements of an uncultured Paracoccus sp. recovered from a hydrocarbon-polluted soil metagenome.
Environmental microorganisms usually exhibit a high level of genomic plasticity and metabolic versatility that allow them to be well-adapted to diverse environmental challenges. This study used shotgun metagenomics to decipher the functional and metabolic attributes of an uncultured Paracoccus recovered from a polluted soil metagenome and determine whether the detected attributes are influenced by the nature of the polluted soil. Functional and metabolic attributes of the uncultured Paracoccus were elucidated via functional annotation of the open reading frames (ORFs) of its contig. Functional tools deployed for the analysis include KEGG, KEGG KofamKOALA, Clusters of Orthologous Groups of proteins (COG), Comprehensive Antibiotic Resistance Database (CARD), and the Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT V6) for antibiotic resistance genes, TnCentral for transposable element, Transporter Classification Database (TCDB) for transporter genes, and FunRich for gene enrichment analysis. Analyses revealed the preponderance of ABC transporter genes responsible for the transport of oligosaccharides (malK, msmX, msmK, lacK, smoK, aglK, togA, thuK, treV, msiK), monosaccharides (glcV, malK, rbsC, rbsA, araG, ytfR, mglA), amino acids (thiQ, ynjD, thiZ, glnQ, gluA, gltL, peb1C, artP, aotP, bgtA, artQ, artR), and several others. Also detected are transporter genes for inorganic/organic nutrients like phosphate/phosphonate, nitrate/nitrite/cyanate, sulfate/sulfonate, bicarbonate, and heavy metals such as nickel/cobalt, molybdate/tungstate, and iron, among others. Antibiotic resistance genes that mediate efflux, inactivation, and target protection were detected, while transposable elements carrying resistance phenotypes for antibiotics and heavy metals were also annotated. The findings from this study have established the resilience, adaptability, and survivability of the uncultured Paracoccus in the hydrocarbon-polluted soil.


Analysing features of home-based workout during COVID-19 pandemic: a systematic review.
Since the beginning of the COVID-19 pandemic, a decrease in physical activity (PA) related to home confinement has been reported worldwide. However, some individuals were able to engage in physical activities at home. Thus, in a perspective of public health, it may be useful to analyse the available evidence regarding PA adopted during home restrictions, in order to identify possible strategies to help people stay active even during emergency situations. The aim of this review was to analyse how healthy individuals spontaneously exercised at home in the course of the pandemic, in order to detect possible factors associated with this behaviour. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was registered in PROSPERO, an international prospective register of systematic reviews, with the registration number CRD42023394673. A literature search was conducted in PubMed, Scopus, and Web of Science. Cross-sectional studies published in English from the inception of each database to February 06th 2023 and focused on healthy individuals practicing spontaneous PA/exercise at home during the pandemic were considered eligible. The quality assessment was performed using the adapted Newcastle-Ottawa Quality Assessment Scale. Bibliographic information, sample size, study paricipant/population with age, gender, ethnicity, socioeconomic status, education, smart workers or not, anthropometric parameters, characteristics of at home exercises, athletic status and sedentariness, associated health-related effects, and main findings were synthetised. From 504 articles, 19 were included. Notwithstanding the differences in the studies examined, the majority of them reported that previous PA level was associated with exercise in such challenging conditions. Furthermore, technologies aimed at supporting exercise were shown to be a useful resource. Being habitually active and using digital supports may be associated with a positive attitude towards exercise at home during isolation. This suggests that in emergency situations, exercise should be promoted, also through digital media, especially among those groups who are usually less engaged in PA. Further analyses of longitudinal studies are needed to confirm these findings.


Mycobacterium marinum arthritis.
Mycobacterium marinum is an atypical acid-fast organism that is rarely associated with septic arthritis. Most often this is seen in patients with monarticular synovitis of the hands or wrists, especially in association with a history of periarticular trauma or exposure to marine environments. From tissue obtained by aspiration or synovectomy, Mycobacterium marinum can be identified by Ziehl-Nielson stain and has optimal growth in Lowenstein-Jenson medium. Therapy should consist of at least two antimycobacterial agents for a minimum 6 months. Surgical debridement also may be beneficial. The clinician must have a high index of suspicion that exposure to Mycobacterium marinum has occurred so appropriate stains and cultures can be obtained and antimycobacterial therapy initiated.


Intraoperative ketamine for reduction in postpartum depressive symptoms after cesarean delivery: A double-blind, randomized clinical trial.
Postpartum depression (PPD) is a common mental disease happens in perinatal period. Ketamine as an anesthesia and analgesia drug has been used for a long time. In recent years, ketamine is proved to have an antidepression effect with a single administration. We hypothesized that intraoperative ketamine can reduce postpartum depressive symptoms after cesarean delivery. In a randomized, double-blind, placebo-controlled study trail, healthy women scheduled for cesarean delivery were randomly assigned to receive intravenous ketamine (0.25 mg/kg diluted to 5 ml with 0.9% saline) or placebo (5 ml of 0.9% saline) within 5 min following clamping of the neonatal umbilical cord. The primary outcome was the degree of postpartum depressive symptoms, which was evaluated by Edinburgh Postnatal Depression Scale (EPDS, a threshold of 9/10 was used) at 1 week, 2 weeks, and 1 month after delivery. The secondary outcome was the numerical rating scale (NRS) score of pain at 2 days postpartum. This trail is registered in the Chinese Clinical Trial Registry, number ChiCTR1900022464. Between 26 January 2019 and 15 July 2019, 502 subjects were screened and 330 were randomly allocated: 165 (50%) to the ketamine group and 165 (50%) to the placebo group. There were significant differences in the degree of postpartum depressive symptoms between subjects in the ketamine group and the placebo group at 1 week postpartum (13.1% vs. 22.6%, respectively; p = .029). However, no difference was found between subjects in the two groups at 2 weeks (11.8% vs. 16.8%, respectively; p = .209) and 1 month postpartum (10.5% vs. 14.2%, respectively; p = .319). The NRS score of wound pain (3.0 ± 0.9 vs. 4.0 ± 1.0, respectively; p < .001) and uterine contraction pain (3.0 ± 0.9 vs. 4.1 ± 0.9, respectively; p < .001) was lower in the ketamine group at 2 days postpartum compared with placebo group. The prevalence of headache, hallucination, and dizziness was higher in the ketamine group than the placebo group during the operation. Operative intravenous ketamine (0.25 mg/kg) can reduce the postpartum depressive symptoms for 1 week. The long-time effect is remained to be seen.


Study to confirm the lack of severe cardiac side-effects following treatment with the beta-adrenergic drug fenoterol.
100 patients with premature contractions were treated with the beta-adrenergic agent fenoterol for up to 9 weeks. To rule out a detrimental effect on the myocardium, the creatine kinase isoenzyme MB, which is specific to the myocardium, was determined regularly in addition to electrocardiographic monitoring. No pathological enzyme activity was detected even in long-term tocolytic therapy with the maximum dose.


Effect of neonatal nomifensine exposure on adult behavior and brain monoamines in rats.
The aim of the study was to examine the effects of early postnatal exposure to nomifensine, an inhibitor of catecholamine uptake, on concurrent active (REM) sleep, on later alcohol related behavior and on monoamine concentrations in various brain regions of rats. For these purposes rats were given daily injections of 10 mg/kg nomifensine s.c. between the 7th and the 18th postnatal days. During the nomifensine exposure active sleep, expressed as a percentage of total sleeping time, was reduced. At one month of age, the nomifensine rats showed increased ambulation and had lower defecation scores in the open-field than the controls. Neonatal exposure to nomifensine increased voluntary intake of 10% (v/v) alcohol when the rats were 2-3 months of age. The rats, however, did not exhibit preservation in the T-maze, and similarly to control rats suppressed drinking 0.1 M lithium chloride even when thirsty. Measurement of cerebral monoamine concentrations at the age of 3 months suggested that neonatal nomifensine treatment interferes with the noradrenergic and serotonergic systems in several regions of the brain. Concentrations of noradrenaline and 5-hydroxyindoleacetic acid (5-HIAA) were decreased in the cerebral cortex and frontal cortex, concentration of 5-HIAA was decreased in the neostriatum, and concentrations of noradrenaline, 5-hydroxytryptamine (5-HT) and 5-HIAA were elevated in the lower brain stem. Taken together, these findings show that exposure to nomifensine during the 2nd and 3rd postnatal weeks suppresses neonatal active sleep, causes changes in the adult open-field behavior, and increases voluntary alcohol intake, perhaps due to a long-lasting alteration in brain monoamines.


Adult intussusceptions: Clinical presentation, diagnosis and therapeutic management.
Adult intussusception is a rare clinical entity. It is an uncommon cause of intestinal obstruction in adult. It often presents with nonspecific symptoms and preoperative diagnosis remains difficult. The purpose of this study was to determine the clinical entity and surgical approach of adult intussusception. We have conducted a retrospective descriptive study starting from 2006 until 2014. We reviewed data for all patients that had been admitted to our department for intestinal intussusception. Eight consecutive patients were admitted to our department. The mean age was 48 years old (20-71). The sex ratio was 0,6. The clinical presentation was acute in 5 cases. A computed tomography was performed in 6 cases. The diagnosis of gastrointestinal intussusception was made preoperatively in 100% of patients. All patients underwent surgery. An organic lesion was identified in 100% of the cases. In all cases, resection of the intussuscepted intestinal loop was done without intestinal reduction. All patients were well followed up and recurrences have been documented. In adults, intussusception is usually secondary to an organic cause. In the absence of signs of severity, etiologic diagnosis based on CT allows the diagnosis of the intussusception and sometimes can detect the causal lesion. Therapeutic sanction of intussusception is surgery and there is more emphasis towards resection without reduction.