[The problems of cataract surgery and intraocular correction: Russian school achievements and modern trends].
The development of the safest and, at the same time, efficient methods of cataract surgery, is not only a topical task of medical science and practice, but also, taking the demographic situation into account, a solution to a social problem. The article describes the main achievements of academician S. N. Fyodorov's school in the field of cataract surgery with intraocular lense (IOL) implantation. Special attention is paid to the key components of cataract extraction technique named "small incision surgery", which is based upon the use of ultrasmall surgical approaches with self-sealing ability and no need for suturing. The main advantages and disadvantages of various types of cataract lense fragmentation, including ultrasound emulsification, mechanic and hydraulic fragmentation, and laser destruction, are described. Topical issues concerning cataract extraction technique under the conditions of complicating ophthalmopathology including the weakness of ciliary zonule system, high-degree myopia, glaucoma, pseudoexfoliative syndrome, small pupil, past injuries and eye surgery, are outlined. The paper also reflects a new qualitative step in the development of intraocular aphakia correction technique under modern conditions. Basic requirements to design parameters and IOL materials are determined from the position of reestablishing the accommodative function and fine visual functions. Ways of IOL design improvement are described especially for their application in non-standard and complicated cases.


Juvenile retinal detachment.
Among the total of 537 patients treated for retinal detachment 27 (5.02%) were under the age of 20. In 44.44 percent of the cases, there was a history of trauma. In 58.33% of the fellow eyes in this group of patients, retinal pathology was found. This pathology is considered to be a predisposing factor and trauma itself is only a trigger in causing retinal detachment.


Analysis of Stroma Labeling During Multiple Passage of a Sarcoma Imageable Patient-Derived Orthotopic Xenograft (iPDOX) in Red Fluorescent Protein Transgenic Nude Mice.
A patient-derived orthotopic xenograft (PDOX) model of undifferentiated pleomorphic sarcoma (UPS) was previously established that acquired red fluorescent protein (RFP)-expressing stroma by growth in an RFP transgenic nude mouse. In the present study, an imageable PDOX model (iPDOX) of UPS was established by orthotopic implantation in the biceps femoris of transgenic RFP nude mice. After the tumors grew to a diameter of 10 mm, they were harvested and the brightest portion of the tumors were subsequently orthotopically transplanted to both RFP and non-colored nude mice. The UPS PDOX tumor was again transplanted to RFP transgenic and non-colored nude mice, and finally a 3rd passage was made in the same manner. Five UPS tumors from each passage in both RFP and non-colored mouse models were harvested. The FV1,000 confocal microscope was used to visualize and quantitate the RFP area of the resected tumors. The average percent fluorescent area in the first passage of RFP mice was 34 ± 22%; in the second passage, 34 ± 20%; and 36 ± 11% in the third passage of RFP transgenic nude mice. The average tumor RFP area in the first passage from RFP mice to non-colored mice was 20 ± 7%; in the second passage, 28 ± 11%; in the third passage was 27 ± 13%. The present results demonstrate the extensive and stable acquisition of stroma by the UPS-tumor growing orthotopically in transgenic RFP nude mice (iPDOX). This model can be used for screening for effective drugs for individual patients and drug discovery. J. Cell. Biochem. 118: 3367-3371, 2017. © 2017 Wiley Periodicals, Inc.


Advancing the community health vulnerability index for wildland fire smoke exposure.
Wildland fire smoke risks are not uniformly distributed across people and places, and the most vulnerable communities are often disproportionately impacted. This study develops a county level community health vulnerability index (CHVI) for the Contiguous United States (CONUS) using three major vulnerability components: adaptive capacity, sensitivity, and exposure at the national and regional level. We first calculated sensitivity and adaptive capacity sub-indices using nine sensitivity and twenty adaptive capacity variables. These sub-indices were then combined with an exposure sub-index, which is based on the Community Multiscale Air Quality data (2008-2018), to develop CHVI. Finally, we conducted several analyses with the derived indices to: 1) explore associations between the level of fine particulate matter from wildland fires (fire-PM2.5) and the sub-indices/CHVI; 2) measure the impact of fire-PM2.5 on the increase in the annual number of days with 12-35 μg/m3 (moderate) and >35 μg/m3 (at or above unhealthy for sensitive groups) based on the US EPA Air Quality Index categories, and 3) calculate population size in different deciles of the sub-indices/CHVI. This study has three main findings. First, we showed that the counties with higher daily fire-PM2.5 concentration tend to have lower adaptive capacity and higher sensitivity and vulnerability. Relatedly, the counties at high risk tended to experience a greater increase in the annual number of days with 12-35 μg/m3 and >35 μg/m3 than their counterparts. Second, we found that 16.1, 12.0, and 17.6 million people out of 332 million in CONUS reside in the counties in the lowest adaptive capacity decile, highest sensitivity decile, and highest vulnerability decile, respectively. Third, we identified that the US Northwest, California, and Southern regions tended to have higher vulnerability than others. Accurately identifying a community's vulnerability to wildfire smoke can help individuals, researchers, and policymakers better understand, prepare for, and respond to future wildland fire events.


Examining health outcomes: the case of maternal epilepsy.
The paper examines the history and health outcome of a 21-year epileptic woman who was expecting her first child. At the initiation of the study period, the young woman was in her 8th month of pregnancy. Over a three month period, this study reflects upon her epileptic history/status, medical care, medication, and the health outcome of both the mother and infant following the pregnancy. The primary mode of assessment was a structured personal interview.


Targeted Therapies in HPV-positive and -negative HNSCC - Alteration of EGFR and VEGFR-2 Expression In Vitro.
Angiogenesis plays a crucial role in the formation and progression of tumor growth in head and neck squamous cell carcinoma (HNSCC). The tyrosine kinase receptors epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are essential for mediation of pro-angiogenic signals. Nilotinib, dasatinib, erlotinib and gefitinib are tyrosine kinase inhibitors and approved as targeted therapies for several tumor entities other than HNSCC. In this study, we sought to evaluate the alteration of EGFR and VEGFR-2 expression by these tyrosine kinase inhibitors with respect to the human papillomavirus (HPV)-status in squamous cell carcinoma (SCC) tumor cells. Expression patterns of EGFR and VEGFR-2 were determined by enzyme linked immunosorbent assay (ELISA) in HNSCC 11A, HNSCC 14C and p-16-positive CERV196 tumor cell lines. These cells were incubated with nilotinib, dasatinib, erlotinib and gefitinib (5-20μmol/l) and compared to a chemonaive control. The incubation time was 24, 48, 72 and 96 h. All tested substances led to a statistically significant reduction (p<0.05) of EGFR protein expression levels in HPV-negative cells compared to the negative control. Surprisingly, a statistically significant increase in VEGFR-2 expression was observed after exposure to all tested substances especially after exposure to erlotinib treatment. Nilotinib, dasatinib, erlotinib and gefitinib cause significant changes in protein expression of EGFR and VEGFR-2 in vitro. Besides the anti-angiogenic impact of the substances, as shown for the decrease of EGFR expression, we also observed an increase of VEGFR-2 expression. These contradictive effects could be interpreted as a compensatory up-regulation by the tumor cell.


Release of formaldehyde from polynoxylin and noxythiolin.
Polynoxylin and noxythiolin (Anaflex and Noxyflex) have been recommended for the treatment of certain bacterial infections. Both compounds were shown to release formaldehyde. Detailed studies with noxythiolin showed that it decomposed in solution to liberate most of its formaldehyde, and that solutions of formaldehyde of the appropriate strength gave zones of inhibition on seeded plates comparable in size with those given by noxythiolin. It is suggested that the effects observed with these compounds are caused by the formaldehyde released.


[Anaplastic Thyroid Carcinoma in a 17-Year-Old Female Patient].
Anaplastic carcinoma of thyroid gland is one of the four most malignant tumors in humans. It appears in one or two patients per million per year. It is very rare in children. A 17-year-old female patient was admitted to the Clinical Department of ENT and Head and Neck Surgery, Split University Hospital Center, for thyroid gland surgery due to rapid growth of a node in the thyroid gland left lobe. Preoperative examination indicated benign nature of changes. Total thyroidectomy with levels VI and VII neck dissection was done. Intraoperative slide of the left lobe was malignant. Positron emission tomography and computed tomography were also done. The finding was negative. The patient was examined by an ENT-oncology team and juvenile radiotherapy was administered. It was found to be carcinoma stage IVa according to TNM classification. One year after the operation, the patient was well and had no signs of illness. This case report is a contribution to the existing but scarce knowledge of anaplastic carcinoma of thyroid gland in young patients in the world.


Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels.
Gut microbiota is a potent biological modulator of many physiological and pathological states. The renin-angiotensin system (RAS), including the local gastrointestinal RAS (GI RAS), emerges as a potential mediator of microbiota-related effects. The RAS is involved in cardiovascular system homeostasis, water-electrolyte balance, intestinal absorption, glycemic control, inflammation, carcinogenesis, and aging-related processes. Ample evidence suggests a bidirectional interaction between the microbiome and RAS. On the one hand, gut bacteria and their metabolites may modulate GI and systemic RAS. On the other hand, changes in the intestinal habitat caused by alterations in RAS may shape microbiota metabolic activity and composition. Notably, the pharmacodynamic effects of the RAS-targeted therapies may be in part mediated by the intestinal RAS and changes in the microbiome. This review summarizes studies on gut microbiota and RAS physiology. Expanding the research on this topic may lay the foundation for new therapeutic paradigms in gastrointestinal diseases and multiple systemic disorders.


Voxel-based logistic analysis of PPMI control and Parkinson's disease DaTscans.
A comprehensive analysis of the Parkinson's Progression Markers Initiative (PPMI) Dopamine Transporter Single Photon Emission Computed Tomography (DaTscan) images is carried out using a voxel-based logistic lasso model. The model reveals that sub-regional voxels in the caudate, the putamen, as well as in the globus pallidus are informative for classifying images into control and PD classes. Further, a new technique called logistic component analysis is developed. This technique reveals that intra-population differences in dopamine transporter concentration and imperfect normalization are significant factors influencing logistic analysis. The interactions with handedness, sex, and age are also evaluated.


A single calcium binding site is crucial for the calcium-dependent thermal stability of thermolysin-like proteases.
Thermostable thermolysin-like proteases (TLPs), such as the TLP of Bacillus stearothermophilus CU-21 (TLP-ste), bind calcium in one double (Ca1,2) and two single (Ca3, Ca4) calcium binding sites. The single sites are absent in thermolabile TLPs, suggesting that they are determinants of (variation in) TLP stability. Mutations in the Ca3 and Ca4 sites of TLP-ste indeed reduced thermal stability, but only mutations in the Ca3 site affected the calcium-dependence of stability. The predominant effect of the Ca3 site results from the fact that the Ca3 site is part of a region of TLP-ste, which unfolding is crucial for thermal inactivation. Thermal inactivation is not caused by the absence of calcium from the Ca3 site per se, but rather by unfolding of a region of TLP-ste for which stability depends on the occupancy of the Ca3 site. In accordance with this concept is the observation that the effects of mutations in the Ca3 site could be compensated by stabilizing mutations near this site. In addition, it was observed that the contribution of calcium binding to the Ca3 was substantially reduced in extremely stable TLP-ste variants containing multiple stabilizing mutations in the Ca3 region. Apparently, in these latter variants, unfolding of the Ca3 region contributes little to the overall process of thermal inactivation.


In vivo and in vitro evidence for the involvement of tumor necrosis factor-alpha in the induction of leptin by lipopolysaccharide.
To examine the role of tumor necrosis factor-alpha (TNF alpha) in mediating leptin secretion during an immunological challenge, we studied the effects of lipopolysaccharide (LPS) and TNF alpha on leptin secretion in endotoxin-sensitive C3H/HeOuJ (OuJ) mice, endotoxin-insensitive C3H/HeJ (HeJ) mice, and primary adipocytes cultured from both. Intraperitoneal injection of LPS increased plasma concentrations of TNF alpha and leptin in OuJ mice, but not in HeJ mice, suggesting a causal relationship between the induction of TNF alpha and leptin. Consistent with this idea, i.p. injection of recombinant murine TNF alpha increased plasma leptin in both OuJ and HeJ mice. To determine whether TNF alpha induces leptin secretion by acting directly on fat cells, primary adipocytes from OuJ and HeJ mice were cultured in the presence of TNF alpha or LPS. Whereas LPS was without effect on leptin secretion by adipocytes, TNF alpha induced a marked increase in the cell supernatant leptin concentration. These data demonstrate that TNF alpha plays a role in regulating the increase in leptin caused by LPS. Moreover, they show that TNF alpha can act directly on adipocytes to stimulate leptin secretion. Our results are consistent with the emerging view that leptin is a key hormone coupling immune system activity to energy balance.


Decline of common mental disorders over time in public primary care tuberculosis patients in South Africa.
The relationship between tuberculosis and common mental disorders over time is under researched. The aim of this investigation was to estimate the prevalence of common mental disorders and its predictors among tuberculosis patients over a period of six months. A longitudinal investigation was carried out with new tuberculosis and tuberculosis retreatment patients systematically selected from 40 primary health care facilities and had screened positive for hazardous or harmful alcohol use in South Africa. Common mental disorders were measured with the Kessler-10 scale and the Primary Care Posttraumatic Stress Disorder Screen at baseline and at six months. At six months, 710 tuberculosis patients had completed the follow up. At baseline, 34.1% had severe psychological distress with a higher cut-off score (≥28), 81.1% had moderate psychological distress with a lower cut-off score (≥16), and 29.4% had posttraumatic stress disorder symptoms (two or more). At the six-month follow-up, severe psychological stress significantly reduced by 12.3%, moderate psychological distress reduced by 24.9%, and PTSD reduced by 20.0%. Multivariate logistic regression analysis using generalized estimation equation modeling across the three mental conditions found that moderate psychological distress and PTSD symptoms but not severe psychological distress significantly reduced over time. Having chronic conditions, including HIV, and sociodemographic factors (lower education and poverty) were associated with common mental disorders. The prevalence of moderate psychological distress and posttraumatic stress disorder symptoms significantly reduced over a period of six months. Mental health services should be integrated into tuberculosis treatment programs.


Youth unemployment and health effects.
Psychological and sociomedical unemployment research have become an important feature of public concern in the industrialised world. This paper focuses on research into youth unemployment and health effects from an international perspective and investigates more closely the following areas: Unemployment and health: research and the political public Youth unemployment: extent and societal coping Young and unemployed--a special problem? a. Skill utilization and social support b. Psychiatric morbidity c. Vulnerability and age d. "Americanization" of youth The demand for a "social guarantee"


A new approach of direct sample-digestion before vaporization for determination of a metal in rocks by inductively coupled plasma atomic emission spectrometry.
A new approach to sample digestion, subsequent vaporization and introduction to an inductively coupled plasma (ICP) atomic emission spectrometer was developed for the direct determination of magnesium. To each small sample cuvette made of tungsten, a ground rock sample was precisely weighed. The cuvette was situated on a tungsten boat furnace. Ammonium fluoride solution was added to the cuvette as a chemical modifier. After the on-furnace digestion has been completed, the analyte, magnesium, in the cuvette was vaporized and introduced into the ICP atomic emission spectrometer. Since the powdered samples were wet-digested in the sample cuvettes prior to vaporization, they could be analyzed by using a calibration curve prepared from aqueous standard solutions. This method was applied to the determination of magnesium in several standard reference materials with satisfactory results.


Effects of carbamazepine combined with vitamin B12 on levels of plasma homocysteine, hs-CRP and TNF-α in patients with epilepsy.
The efficacy of carbamazepine combined with vitamin B12 in epilepsy treatment by comparing levels of plasma homocysteine (Hcy), serum TNF-α and hs-CRP in patients with epilepsy before and after treatment was investigated. Fifty-eight patients with epilepsy who were admitted and received treatment in The First People's Hospital of Xuzhou were recruited as subjects, and fifty-eight healthy volunteers were recruited as the control group. Patients were treated with carbamazepine combined with vitamin B12 for a period of three months. The mRNA and protein levels of TNF-α and hs-CRP in serum were measured before and after treatment using semi-quantitative RT-PCR and western blotting, respectively. The plasma Hcy levels were measured as well. Within one year after the 3-month treatment, the frequency and duration of seizure were tracked. After treatment with carbamazepine combined with vitamin B12 for patients with epilepsy, the Hcy level was significantly higher than that before treatment and that in the control group (P<0.01). The mRNA and protein levels of TNF-α and hs-CRP in serum were significantly higher in patients than that in healthy people (P<0.01). After treatment these levels were reduced (P<0.01), but still higher than those in healthy people (P<0.05, P<0.01). After treatment, the frequency and duration of seizures were all reduced (P<0.05, P<0.01). The results suggested that carbamazepine combined with vitamin B12 was effective in treatment of epilepsy by reducing levels of TNF-α and hs-CRP in the serum, but had a risk of increasing the Hcy level.


Anti-drug Antibody Magnitude and Clinical Relevance Using Signal to Noise (S/N): Bococizumab Case Study.
Historically, the biopharmaceutical industry has used titer to characterize the magnitude of an anti-drug antibody (ADA) response. While reporting levels of antibodies in terms of titer is generally understood and accepted by regulatory and medical communities, titer values are inherently variable given the multiple serial dilutions and reporting a value either directly before or interpolated at the assay cut point on the lower plateau of the assay curve range. Using S/N is an appealing alternative approach to titer as it simplifies analysis with less dilutions, significantly reducing testing, time, and resources and provides a more precise value potentially differentiating low-level ADA responses. Current bridging electrochemiluminescence (ECL) ADA assays using Meso Scale Discovery (MSD) platform are also significantly more sensitive and drug tolerant with wider assay ranges compared to historic ELISA platforms; therefore, ADA response based on S/N may help differentiate and identify those ADA samples that are more likely to be clinically relevant. Bococizumab is a humanized monoclonal antibody targeting proprotein convertase subtilisin-kexin type 9 (PCSK9), which reduces plasma levels of low-density lipoprotein (LDL) cholesterol. Bococizumab was discontinued during Phase 3 clinical development based in part on the high rate of ADA and wide variation in LDL cholesterol responses among patients. The impact of anti-bococizumab antibodies on pharmacokinetic (PK) and pharmacodynamic (PD) endpoints was originally assessed using titer. Retrospective analysis of anti-bococizumab ADA responses using S/N ratios illustrates that S/N is an acceptable alternative to titer for characterizing the magnitude of ADA response and interpretation of clinically relevant ADA.


Postdischarge antibiotic use for prophylaxis following spinal fusion.
Despite recommendations to discontinue prophylactic antibiotics after incision closure or <24 hours after surgery, prophylactic antibiotics are continued after discharge by some clinicians. The objective of this study was to determine the prevalence and factors associated with postdischarge prophylactic antibiotic use after spinal fusion. Multicenter retrospective cohort study. This study included patients aged ≥18 years undergoing spinal fusion or refusion between July 2011 and June 2015 at 3 sites. Patients with an infection during the surgical admission were excluded. Prophylactic antibiotics were identified at discharge. Factors associated with postdischarge prophylactic antibiotic use were identified using hierarchical generalized linear models. In total, 8,652 spinal fusion admissions were included. Antibiotics were prescribed at discharge in 289 admissions (3.3%). The most commonly prescribed antibiotics were trimethoprim/sulfamethoxazole (22.1%), cephalexin (18.8%), and ciprofloxacin (17.1%). Adjusted for study site, significant factors associated with prophylactic discharge antibiotics included American Society of Anesthesiologists (ASA) class ≥3 (odds ratio [OR], 1.31; 95% CI, 1.00-1.70), lymphoma (OR, 2.57; 95% CI, 1.11-5.98), solid tumor (OR, 3.63; 95% CI, 1.62-8.14), morbid obesity (OR, 1.64; 95% CI, 1.09-2.47), paralysis (OR, 2.38; 95% CI, 1.30-4.37), hematoma/seroma (OR, 2.93; 95% CI, 1.17-7.33), thoracic surgery (OR, 1.39; 95% CI, 1.01-1.93), longer length of stay, and intraoperative antibiotics. Postdischarge prophylactic antibiotics were uncommon after spinal fusion. Patient and perioperative factors were associated with continuation of prophylactic antibiotics after hospital discharge.


ACD: Antimicrobial chemotherapeutics database.
Antimicrobial resistance is becoming a growing health problem, which has become a challenge for the physicians to control infection and also an economic burden on the healthcare. This increase in resistance to the present antimicrobial agents led the researchers to find some alternative and more efficient drugs which can fight with the resistant microorganisms more effectively. Hence, in silico approach is used to design some novel drugs against various targets of microorganisms. For effective virtual screening of the drugs, there is a need to know about the chemical structure and properties of the antimicrobial agents. Therefore, we have prepared a comprehensive database as a platform for the researcher to search for possible lead molecules. Antimicrobial chemotherapeutics database (ACD) is comprised of ~4100 synthetic antimicrobial compounds as well as ~1030 active antimicrobial peptides. The Antimicrobial peptides are mainly from biological sources but some of them are synthetic in nature. Only those compounds, which are found to be active against either bacteria (both Gram-positive and negative) or fungus, are selected for this database.The ACD database is freely available at URL: http://amdr.amu.ac.in/acd, and it is compatible with desktops, smartphones, and tablets.


The use of drains in thyroid surgery.
To evaluate the necessity and benefits of the use of drains and their limitations in thyroidectomy and assess their relationship with cost of surgery and hospital stay. We conducted a prospective randomised study on 67 patients divided into two groups. A consisted of 35 patients with drain and B, 32 patients without drain between January 2005 and June 2007. All had subtotal thyroidectomy and the technique and method of closure were the same. No anticoagulant was used and the clotting profiles were within normal range in the two groups. The sixty seven patients recruited for the study were made up of 60 females (89.6%) and 7 males (10.4%). The mean age for group A was 50.14 +/- 10.7 years, group B was 51.97 +/- 9.5 years. The P value for the mean ages of the two groups is 0.464 (p=0.05,t=3.98).There was no blood transfusion. Three patients developed features of respiratory obstruction (respiratory distress and stridor) -the first 2, one from each group was as a result of laryngeal oedema from trauma of difficult intubation. The third was from group B, as a result of hemorrhage and haematoma collection (she was one of the controlled thyrotoxic patients). Two patients (5.7%) developed wound infections in group A, which increased morbidity, hospital bill and prolonged hospital stay as compared to group B. The highest volume of drainage of 35ml was from a woman with a big goiter (120g). Average drainage was 17.7 +/- 6.9ml. The use of drains is not necessary in all cases of thyroidectomy but for cases with large cavity post extraction and copious oozing in vascular glands. Some of the limitations to the use of drains are infections, this can prolong hospital stay and thereby increase hospital bill.


Young female sex offenders: assessment and treatment issues.
Research on the characteristics and treatment of juvenile female sex offenders is limited. This article reviews the literature on female offenders and presents the results of a nationwide survey by mail of 250 mental health providers in private settings and residential treatment centers (RTCs), on approaches to diagnosing prior sexual abuse history and/or perpetration among juvenile females. Nineteen of the most experienced practitioners were also interviewed by telephone to provide further insight to the issues highlighted by the surveys. Key findings include the lack of research, tools, and literature on young female sex offenders and perceived differences between male and female offenders including history, treatment, and characteristics. Further study and awareness of this population is encouraged to address clinical needs.


In vitro fertilization. The Jamaican experience.
In June 2000, twenty-eight infertile couples were treated by in vitro fertilization and embryo transfer at our initial assisted reproduction programme carried out in conjunction with Midland Fertility Services, Aldridge, Birmingham, England. A pre-requisite for treatment was that on day 3 of the menstrual cycle the levels of follicle stimulating hormone (FSH) and oestradiol (E2) should be < 10 i mu/l and < 100 pg/ml respectively in the female partner. The ages of the women ranged from 26 to 42 years with a mean age of 35.5 years. Down regulation was carried out by using buserelin acetate 0.5 microgram subcutaneously from day 21 of the cycle for 21 days. This process was completed when the ovaries and pituitary gland were quiescent and the endometrial thickness < 4 mm in diameter. On completion of down regulation the gonadotrophin hormone, pergonal (dosage of 150-450 units) was used for ovarian hyperstimulation. A total of 294 oocytes (mean of 10.5, range 2-45) were retrieved of which 138 were fertilized (mean of 4.9, range of 0-28). Twenty-four patients each received a mean of two embryos. Five patients (20.8%) had positive pregnancy tests. Three patients (0.1%) developed ovarian hyperstimulation syndrome (OHSS), one had the severe, and two, the mild form of the syndrome. All three cases were treated successfully. The success at the initial IVF controlled ovarian hyperstimulation augers well for the future of infertile couples seeking treatment at the Fertility Management Unit, The University of the West Indies, Jamaica.


Effect of kinesthetic illusion induced by visual stimulation on ankle dorsiflexion dysfunction in a stroke patient: ABAB single-case design.
The purpose of this study was to investigate the effect of simultaneous intervention with the kinesthetic illusion induced by visual stimulation (KiNvis) and voluntary exercise on ankle dorsiflexion dysfunction in a patient with right-sided stroke hemiparesis. Within an ABAB single-case design, we conducted two phases each lasting five days. Phase A represented the baseline during which only voluntary ankle dorsiflexion (VAD) was performed. Phase B involved simultaneous performance of VAD and KiNvis. We measured the angle of ankle joint dorsiflexion (AJD), and the 10 m maximum walking speed (10MWS). AJD and 10MWS were significantly improved in phase B.


[Delayed pressure urticaria: therapeutic response to cetirizine].
We describe a 39-year-old man who suffered from delayed pressure urticaria for 2 years. His severe symptoms did not respond to antihistamine (H1 and H2) treatment and corticosteroid therapy was given despite severe side-effects. A new, nonsedating antihistamine drug, cetirizine, relieved most of his symptoms, enabled him to be weaned from corticosteroid therapy, and restored his former quality of life.


Assistive devices for the adult patient with orthopaedic dysfunction. Why physical therapists choose what they do.
The more common types of assistive devices seen in the orthopaedic setting are described. Also included are descriptions of patient factors that guide the physical therapist in deciding which of these devices to try for which patients. Examples of typical patient problems are also included to help the nurse understand the decisions that therapists make. A simple decision tree contained in this article helps further this understanding.


Individualised Versus Standardised Assessment of Quality of Life in Eating Disorders.
Individualised measures of quality of life (QoL) refer to instruments that encourage the respondent to actively elicit which areas of their life are most relevant for his/her QoL. The aim of this study is to compare individualised versus standard measures of QoL in a sample of patients with eating disorder (ED). The Schedule for the Evaluation of the Individual Quality of Life (SEIQoL) and a generic measure of QoL [World Health Organization Brief Quality of Life Assessment Scale (WHOQOL-BREF)] were applied on two occasions (one-year follow-up) to a sample of 165 patients with ED, 57 recovered patients with ED, and 349 women from the general population. The areas of 'family', 'education/career or job', 'friends', 'leisure', 'romantic partner' and 'health' were identified as the most important for their QoL for all groups, both times. The WHOQOL-BREF was more sensitive than the SEIQoL in detecting changes that occurred over time. Clinical interventions for ED should consider social components as objectives of intervention.


Sequence and analysis of the genetic locus responsible for surfactin synthesis in Bacillus subtilis.
The chromosomal region of Bacillus subtilis comprising the entire srfA operon, sfp and about four kilobases in between have been completely sequenced and functionally characterized. The srfA gene codes for three large subunits of surfactin synthetase, 402, 401 and 144 kDa, respectively, arranged in a series of seven amino acid activating domains which, as shown in the accompanying communication, recognize and bind the seven amino acids of the surfactin peptide. The srfA amino acid activating domains share homologies with similar domains of other peptide synthetases; in particular, regions can be identified which are more homologous in domains activating the same amino acid. A fourth gene in srfA encodes a polypeptide homologous to grsT. Four genes are positioned between srfA and sfp, the disruption of which does not affect surfactin biosynthesis.


Chronic activation of PPARalpha is detrimental to cardiac recovery after ischemia.
High fatty acid oxidation (FAO) rates contribute to ischemia-reperfusion injury of the myocardium. Because peroxisome proliferator-activated receptor (PPAR)alpha regulates transcription of several FAO enzymes in the heart, we examined the response of mice with cardiac-restricted overexpression of PPARalpha (MHC-PPARalpha) or whole body PPARalpha deletion including the heart (PPARalpha-/-) to myocardial ischemia-reperfusion injury. Isolated working hearts from MHC-PPARalpha and nontransgenic (NTG) littermates were subjected to no-flow global ischemia followed by reperfusion. MHC-PPARalpha hearts had significantly higher FAO rates during aerobic and postischemic reperfusion (aerobic 1,479 +/- 171 vs. 699 +/- 117, reperfusion 1,062 +/- 214 vs. 601 +/- 70 nmol x g dry wt(-1) x min(-1); P < 0.05) and significantly lower glucose oxidation rates compared with NTG hearts (aerobic 225 +/- 36 vs. 1,563 +/- 165, reperfusion 402 +/- 54 vs. 1,758 +/- 165 nmol x g dry wt(-1) x min(-1); P < 0.05). In hearts from PPARalpha-/- mice, FAO was significantly lower during aerobic and reperfusion (aerobic 235 +/- 36 vs. 442 +/- 75, reperfusion 205 +/- 25 vs. 346 +/- 38 nmol x g dry wt(-1) x min(-1); P < 0.05) whereas glucose oxidation was significantly higher compared with wild-type (WT) hearts (aerobic 2,491 +/- 631 vs. 901 +/- 119, reperfusion 2,690 +/- 562 vs. 1,315 +/- 172 nmol x g dry wt(-1) x min(-1); P < 0.05). Increased FAO rates in MHC-PPARalpha hearts were associated with a markedly lower recovery of cardiac power (45 +/- 9% vs. 71 +/- 6% of preischemic levels in NTG hearts; P < 0.05). In contrast, the percent recovery of cardiac power of PPARalpha-/- hearts was not significantly different from that of WT hearts (80 +/- 8% vs. 75 +/- 9%). This study demonstrates that chronic activation of PPARalpha is detrimental to the cardiac recovery during reperfusion after ischemia.


Evolution of hepatitis B serological markers in HIV-infected patients receiving highly active antiretroviral therapy.
Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers. After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively. Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.


Expectancy and Achievement Gaps in Educational Attainment and Subsequent Adverse Health Effects Among Adolescents With and Without Chronic Medical Conditions.
While education-based disparities in health are common, the extent to which chronic conditions contribute to education gaps and to consequent health disparities is not fully understood. As such, we sought to investigate educational aspirations, expectations, and attainment among youth with and without chronic conditions and to determine if these relationships mediated subsequent disparities in health and well-being. Longitudinal data on 3,518 youths are from the 1997-2013 Panel Study of Income Dynamics, a population-based survey. Multivariate regression was used to assess disparities in educational aspirations, expectations, and attainment by chronic conditions and the subsequent effects on health and well-being, adjusting for important potential confounders. Youth with chronic medical conditions (YCMCs) did not report significantly lower educational aspirations than their healthy peers; however, YCMC reported lower expectations for their educational attainment and fewer YCMC had earned their desired degree by the end of follow-up (e.g., ≥bachelor's degree: 19.9% for YCMC vs. 26.0% for peers, p < .05). YCMC reported significantly worse general health, lower life satisfaction, and lower psychological well-being in young adulthood than did their healthy peers. These disparities persisted after adjustment for confounders; the association between chronic disease and health was partially, but significantly, mediated by actual educational attainment. Findings suggest an important risk mechanism through which YCMC may acquire socioeconomic disadvantage as they develop and progress through educational settings. Disproportionate lags in education, from expectation to attainment, may in turn increase YCMC's susceptibility to poor health and well-being in the future.


Characterization of permeability of electrospun yarns.
We developed a novel technique enabling determination of the permeability of electrospun yarns composed of hundreds of fibers. Analyzing the wicking kinetics in a yarn-in-a-tube composite conduit, it was found that the kinetic is very specific. The liquid was pulled by the capillary pressure associated with the meniscus in the tube while the main resistance comes from the yarn. Therefore, one can separate the yarn permeability from the capillary pressure, which cannot be done in wicking experiments with single yarns. A surface tensiometer (Cahn) was employed to collect the data on wicking kinetics of hexadecane into the yarn-in-a-tube conduits. Yarns from different polymers and blends were electrospun and characterized using the proposed protocol. We showed that the permeability of electrospun yarns can be varied in a broad range from 10(-14) m(2) to 10(-12) m(2) by changing the fiber diameter and packing density. These results offer new applications of electrospun yarns as flexible micro- and nanofluidic systems.


PGC-1: The Energetic Regulator in Cardiac Metabolism.
The peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1s (PGC-1s) can induce the expression of several downstream genes that play pivotal roles in the regulation of mitochondrial biogenesis and metabolism in the heart. Moreover, PGC-1 signaling pathways have also been reported to play a critical role in cardioprotection. Given the significance of PGC-1 coactivators, we summarize the current literature on the molecular mechanisms and roles of PGC-1s in cardiac metabolism. Thus, in this review, we first introduce the basic knowledge regarding PGC-1 signaling pathways. We then discuss their roles in heart metabolism. Moreover, we describe several significant treatments that target the PGC-1 signaling pathway. This review presents the significant roles of PGC-1s in cardiac metabolism and may contribute to the promotion of PGC-1 signaling pathway as a novel therapeutic target.


Essential light chain modulates phosphorylation-dependent regulation of smooth muscle myosin.
To examine the functional role of the essential light chain (ELC) in the phosphorylation-dependent regulation of smooth muscle myosin, we replace the native light chain in smooth muscle myosin with bacterially expressed chimeric ELCs in which one or two of the four helix-loop-helix domains of chicken gizzard ELC were substituted by the corresponding domains of scallop (Aquipecten irradians) ELC. All of these myosins, regardless of the ELC mutations or regulatory light chain (RLC) phosphorylation, showed normal subunit constitutions and NH(4)(+)/EDTA-ATPase activities, both of which were similar to those of native myosin. None of the ELC mutations changed the actin-activated ATPase activity of myosin in the absence of RLC phosphorylation. However, in the presence of RLC phosphorylation, the substitution of domain 1 or 2 in the ELC significantly decreased the actin-activated ATPase activity, whereas the substitution of both of these domains did not change the activity. In contrast to myosin, the domain 2 substitution in the ELC did not affect the actin-activated ATPase activity of single-headed myosin subfragment 1. These results suggest an interhead interaction between domains 1 and 2 of ELCs which is required to attain the full actin-activated ATPase activity of smooth muscle myosin in the presence of RLC phosphorylation.


VISUAL FEEDBACK ARRAY TO ACHIEVE REPRODUCIBLE LIMB DISPLACEMENTS AND VELOCITIES IN HUMANS.
Precise and reproducible feedback is important for studies on motor control, the adaptive responses to exercise training and the limits of human neuromuscular performance. For this purpose, a custom instrumentation array was previously developed to provide human subjects with visual feedback on their contractile durations and limb velocities during knee extension exercise. The array consisted of two columns, each with 14 high-visibility light emitting diodes. One array column provided the subject with the target cadence of position change while the complementary array provided an indication of the actual rate of displacement achieved by the subject. The array design has been improved to include an onboard microcontroller-based signal generator to generate the desired protocol cadence and also the ability to easily customize and 'lock in' desired protocol parameters. The array allows for custom settings to provide feedback on the concentric and eccentric activation periods during exercise. It can also be used in clinical settings to track the active or passive ranges of motion during rehabilitation.


Engineering of a functional thermostable kanamycin resistance marker for use in Moorella thermoacetica ATCC39073.
A transformation system for Moorella thermoacetica ATCC39073 was developed using thermostable kanamycin resistant gene (kanR) derived from the plasmid pJH1 that Streptococcus faecalis harbored. When kanR with its native promoter was introduced into uracil auxotrophic mutant of M. thermoacetica ATCC39073 together with a gene to complement the uracil auxotrophy as a selection marker, it did not give kanamycin resistance due to poor transcription level of kanR. However, the use of glyceraldehyde-3-phosphate dehydrogenase promoter cloned from M. thermoacetica ATCC39073 significantly improved transcription level of kanR and resulted in the cell growth in the presence of more than 150 μg mL(-1) kanamycin. It was also demonstrated that kanR with G3PD promoter can be used as a selection marker for transformation of wild-type strain of M. thermoacetica ATCC39073.


An ergonomic study on posture-related discomfort among preadolescent agricultural workers of West Bengal, India.
In India, particularly in West Bengal, preadolescents are primarily associated with agricultural work in rural areas. Owing to poor socio-economic conditions, they are compelled to carry out a considerable number of manual, rigorous tasks in agricultural fields. The main aim of this study was to investigate postures adopted by preadolescent agricultural workers during individual agricultural activities and to analyze the causes of discomfort related to those postures. Fifty male and 50 female preadolescent agricultural workers were randomly selected and a detailed posture analysis was performed with the Ovako Working Posture Analysis System (OWAS). It was observed that those workers worked continuously in awkward postures during certain agricultural activities. Consequently they suffered from discomfort in different parts of their body. Even though they were very young, they were likely to suffer from serious musculoskeletal disorders in the future.


Selective Magnetic Nanoheating: Combining Iron Oxide Nanoparticles for Multi-Hot-Spot Induction and Sequential Regulation.
The contactless heating capacity of magnetic nanoparticles (MNPs) has been exploited in fields such as hyperthermia cancer therapy, catalysis, and enzymatic thermal regulation. Herein, we propose an advanced technology to generate multiple local temperatures in a single-pot reactor by exploiting the unique nanoheating features of iron oxide MNPs exposed to alternating magnetic fields (AMFs). The heating power of the MNPs depends on their magnetic features but also on the intensity and frequency conditions of the AMF. Using a mixture of diluted colloids of MNPs we were able to generate a multi-hot-spot reactor in which each population of MNPs can be selectively activated by adjusting the AMF conditions. The maximum temperature reached at the surface of each MNP was registered using independent fluorescent thermometers that mimic the molecular link between enzymes and MNPs. This technology paves the path for the implementation of a selective regulation of multienzymatic reactions.


[Analgesic effect and side-effects of buprenorphine in acute coronary heart disease. A randomized double-blind comparison with morphine].
The analgetic effect and the side effects of buprenorphine (Temgesic) and morphine were compared in a double blind randomised study in 76 patients with suspected acute coronary heart disease. In 68 patients the acute coronary heart disease could be proven, in 61 patients the protocols could be entirely analysed. In 7 of 30 patients on buprenorphine and in 10 of 31 on morphine the analgetic effect was not sufficient (n.s.). The observed side effects were hypotension, bradycardia, nausea, vomiting, vertigo, reduction in respiratory rate and sedation. There were no significant differences in the rate of these side effects in the two groups. The average reduction in respiratory rate was more prominent in the buprenorphine group (-8 vs. -3/min. p less than 0.001) but we found no significant difference in both groups in the number of patient with a respiratory rate less than 12/min. We conclude that buprenorphine is safe for use in the pain therapy of patients with acute coronary heart disease and has a similar analgetic effect and profile of side effects as morphine. It can be used as an alternative to morphine in acute coronary heart disease.


Preventing recurrence of postpartum depression by regulating sleep.
Women are at a high risk of recurrence of depression in the postpartum period. Given the circumscribed duration of the risk period and knowledge of its triggers, postpartum depression should be easily preventable. However, prophylactic drug studies have reported contradictory findings partly due to the heterogeneity of the disorder. Currently, there are no studies on the efficacy of psychotherapy in the prevention of postpartum depression in women with major depressive or bipolar disorder. This review evaluates the results of controlled medication and psychotherapeutic studies in the prevention of depression in women with major depressive disorder or bipolar disorder; it further suggests that the management of sleep loss/insomnia may be an effective strategy in the prevention of postpartum depression. A thorough understanding of the clinical course of the antecedent mood disorder and historical treatment response is necessary before the implementation of strategies for the prevention of postpartum depression. Targeting disturbed and/or insufficient sleep - a common and early transdiagnostic symptom of peripartum psychiatric disorders - may be a more effective intervention for the prevention of postpartum depression and psychiatric comorbidities in some individuals than the traditional approach of antidepressant use.


MicroRNA-200c as a Prognostic Biomarker for Pancreatic Cancer.
MicroRNA (miRNA) regulates messenger RNA stability and translation. In cancer biology, miRNA affects the growth and metastasis of cancer cells by controlling epithelial-mesenchymal transition (EMT). MiR-200 family (200a/200b/ 200c/141) and miR-205 are associated with the regulation of EMT. We investigated the prognostic role of EMT-related miRNAs in pancreatic cancer. We analyzed miR-200 family and miR-205 expression in tissue samples of 84 patients who underwent radical resection for pancreatic cancer. Patients were followed from the date of diagnosis until death or censoring. The mean overall survival was 25.0 ± 2.0 months (2-140 months). The R0 resection rate was obtained in 84.5% (n=71) of patients. The relative expressions of miR-200a/200b/200c/141 and miR-205 were 266.9 ± 57.3/18.5 ± 2.2/0.7 ± 0.1/27.2 ± 6.6 folds and 0.1 ± 0.1 compared with human pancreatic ductal epithelial cells, respectively. Overall survival was longer in the low miR-200c expression group than in the high expression group (35 vs. 19 months, p=0.013). Multivariate analysis confirmed that patients with low miR-200c expression survived longer than the high expression group (hazard ratio, 1.771; 95% CI, 1.081-2.900; p=0.023). There was a trend toward longer disease-free survival in low miR-200c group without statistical significance (p=0.061). The expression of miR-200c may be an important prognosis factor in pancreatic cancer, and it could be a novel therapeutic target of pancreatic cancer.


Three new coordination geometries of homoleptic Zn complexes of curcuminoids and their high antiproliferative potential.
To our previously reported first crystal structure of a homoleptic zinc curcuminoid complex with square pyramidal geometry, we add herein three new geometries of homoleptic type complexes i.e. octahedral, trigonal-pyramidal, and trigonal-bipyramidal. Octahedral geometry was observed in the new pseudo-polymorph of the DAC-Zn complex resulting from crystallization in DMF, while square-pyramidal geometry was obtained in DMSO. Improving crystallinity involved suppressing the phenolic interactions by etherification and esterification. The complete characterization of these complexes was carried out using SCXRD, IR, MS, EA, liquid, and solid-state NMR. Moreover, the cytotoxic activity of all complexes was evaluated. The IC50 values for the DiMeOC-Zn (7) complex were 8 or 22 times higher than for cisplatin in the U251 and HCT-15 cell lines, indicating a high antiproliferative and therapeutic potential.


[Case of fatal aconite poisoning, and its background].
Two people out of three who accidentally ate boiled aconite leaves died in 2012. This was a typical case of aconite poisoning in Japan: Aconite (Aconitum spp.) was mistakenly collected instead of Anemone flaccida, an edible wild plant. The leaves of these plants are quite similar to each other. Chemical analyses of the aconite plant left at the scene suggested intake of a fatal amount of aconitine alkaloids by each person. The collector, who died, had missed the botanical differences between the two plants, even though he owned a wild plant guidebook. A. flaccida should be collected with its flowers in order to aid positive indentification and avoid aconite poisoning.


Circulating adiponectin levels and risk of endometrial cancer: Systematic review and meta-analysis.
Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were -1.96 (-2.60, -1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (-0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (-0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of -2.27 (-4.36, -0.18) and P<0.05, however, no association was observed in premenopausal endometrial cancer cases with an SMD (95% CI) of -1.52 (-3.49, 0.45) and P>0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer.


Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without affecting systemic viral loads in human CD34+ engrafted mice.
HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.


Total arterial revascularization and concomitant aortic valve replacement.
The safety of total arterial revascularization with a left internal thoracic artery-radial artery T-graft was evaluated in patients with at least two-vessel coronary artery disease and aortic valve stenosis requiring concomitant aortic valve replacement. From June 2001 to January 2005, 18 patients underwent aortic valve replacement and total arterial revascularization, while 101 had aortic valve replacement and conventional grafting. By matching age, sex, left ventricular ejection fraction, and number of distal anastomoses, 1:2 matched groups were generated: 15 patients with a left internal thoracic-radial artery T-graft, and 30 with left internal thoracic artery and additional vein grafts. Aortic cross clamp and cardiopulmonary bypass times were similar in both groups. There were no significant differences in postoperative data between the groups. Early mortality was 0% in the T-graft group and 2% in those with conventional grafts. Follow-up ranged from 2 to 50 months. Event-free survival was 100% in the T-graft group and 90% in the conventional graft group. Total arterial grafting with a left internal thoracic-radial artery T-graft can be performed in selected patients with aortic valve stenosis requiring simultaneous aortic valve replacement.


Permanently polarized hydroxyapatite, an outstanding catalytic material for carbon and nitrogen fixation.
Hydroxyapatite (HAp) is a well-known ceramic material widely used in the biomedical field. This review summarizes the very recent developments on permanently polarized HAp (pp-HAp), a HAp variety with tuned electrical properties that confer remarkable catalytic activity. pp-HAp is obtained by applying a thermal stimulation polarization process (TSP), which consists on a DC electric voltage of 500 V at 1000 °C, to previously sintered HAp. The TSP not only increases the crystallinity, reducing the defects in the crystal lattice, but also creates charges that accumulate at the crystalline boundaries and at the surface of microscopic grains, boosting the electrical conductivity. Finally, the successful utilization of pp-HAp in the catalytic fixation of carbon and nitrogen from CO2 and N2 gases, respectively, is reported and the formation of different products of chemical interest (e.g. amino acids, ethanol and ammonium) as a function of the reaction conditions (i.e. feeding gases and presence/absence of UV illumination) and catalyst plasticity is discussed. pp-HAp exhibits important advantages with respect to other consolidated catalysts, which drastically increases the final energetic net balance of the reactions.


Obesity, oxidative stress, and fibrosis in chronic kidney disease.
Obesity in combination with diabetes and hypertension likely is contributing to the increasing incidence of chronic kidney disease (CKD) in the 21st century worldwide and requires novel insights and strategies for treatment. There is an increasing recognition that the kidney has an important role in the complex inter-organ communication that occurs with the development of inflammation and fibrosis with obesity. Inhibition of the adiponectin-AMPK pathway has now become established as a critical pathway regulating both inflammation and pro-fibrotic pathways for both obesity-related kidney disease and diabetic kidney disease. AMPK regulates NFκB activation and is a potent regulator of NADPH oxidases. Nox4 in particular has emerged as a key contribtor to the early inflammation of diabetic kidney disease. AMPK also regulates several transcription factors that contribute to stimulation of the transforming growth factor-beta (TGF-β) system. Another key aspect of AMPK regulation is its control of mammalian target of rapamycin (mTOR) and mitochondrial biogenesis. Inhibition of PGC-1α, the transcriptional co-activator of mitochondrial biogenesis is being recognized as a key pathway that is inhibited in diabetic kidney disease and may be linked to inhibition of mitochondrial function. Translation of this concept is emerging via the field of urine metabolomics, as several metabolites linked to mitochondria are consistently downregulated in human diabetic kidney disease. Further studies to explore the role of AMPK and related energy-sensing pathways will likely lead to a more comprehensive understanding of why the kidney is affected early on and in a progressive manner with obesity and diabetes.


Localization of a moving target using a fly eye sensor.
An optical sensor based on the visual system of the common housefly (Musca domestica) has been developed by the researchers at the Wyoming Image and Signal Processing Research (WISPR) Laboratory. This optical sensor shows promising peformance for detection of an edge in real-time, with minimal processing overhead. An application of this sensor might be the deflection measurement of a moving target, such as the wing of an aircraft under test. In this paper, we have investiaged the possibility of localizing an edge, and hence the target, using the fly eye sensor, which is an important part of the deflection measurement process. A simulation program has been developed for this purpose, which simulates the sensor output, for a moving object on the target plane at a specified distance from the sensor. After successfully simulating the sensor output, it has been found that the location of an edge changes with the change in sensor to target distance, and their relative orientation. It also changes for the limited movement of the target, withing the field of view (FOV) of the sensor. On the contrary, the target-background contrast scenario, and shifting of the target normal to the target movement direction, do not affect the edge localization process. This paper shows and edge can be precisely detected for a target a aspecified distance from the sensor with proper sensor-target orientation, when the target moves all the way across the FOV of the sensor.


The sharing of radiological images by professional mixed martial arts fighters on social media.
Mixed martial arts is a sport that has recently enjoyed a significant increase in popularity. This rise in popularity has catapulted many of these "cage fighters" into stardom and many regularly use social media to reach out to their fans. An interesting result of this interaction on social media is that athletes are sharing images of their radiological examinations when they sustain an injury. To review instances where mixed martial arts fighters shared images of their radiological examinations on social media and in what context they were shared. An Internet search was performed using the Google search engine. Search terms included "MMA," "mixed martial arts," "injury," "scan," "X-ray," "fracture," and "break." Articles which discussed injuries to MMA fighters were examined and those in which the fighter themselves shared a radiological image of their injury on social media were identified. During our search, we identified 20 MMA fighters that had shared radiological images of their injuries on social media. There were 15 different types of injury, with a fracture of the mid-shaft of the ulna being the most common. The most popular social media platform was Twitter. The most common imaging modality X-ray (71%). The majority of injuries were sustained during competition (81%) and 35% of these fights resulted in a win for the fighter. Professional mixed martial artists are sharing radiological images of their injuries on social media. This may be in an attempt to connect with fans and raise their profile among other fighters.


[Effects of Gut Microbiota on Stress Response and Behavioral Phenotype of the Host].
Gut microbiota are involved in host patho-physiological functions; however, little is known about whether or not they can affect brain function. Several recent works including ours have shown that gut microbiota play a critical role in the determination of stress response and behavioral phenotype of the host. We here review recent advances in this area, i.e. the interaction between gut microbiota and the brain-gut axis, based on our series of experimental data.


An experimental investigation of the indirect transfer and deposition of gunshot residue: further studies carried out with SEM-EDX analysis.
Experiments were undertaken in order to explore the potential for gunshot residue (GSR) particles to undergo tertiary transfer, and to be deposited on individuals in the vicinity of a firearm discharge. Samples were taken from hands following a series of test-firings. SEM-EDX with automated detection and analysis software was used to determine the presence of GSR on these samples. As many as 22 particles were found to have undergone tertiary transfer via a series of handshakes following a firearm discharge. In one run, a particle measuring 49.19 μm was recovered from a tertiary transfer recipient. Significant numbers of particles were also recovered from bystanders, with as many as 36 being detected on a sample taken from an individual who was in the proximity of a firearm discharge. The implications of these observations for forensic investigations are considered. In particular, the need to prevent unwanted transfer during the collection phase is highlighted, and the importance of acknowledging the possibility of secondary and tertiary transfers when reconstructing firearms incidents is also stressed. Experimental studies offer a means of improving our understanding of the dynamics of GSR transfer and deposition, and assisting the forensic reconstruction of firearms incidents.


Understanding Service Utilization in Cases of Elder Abuse to Inform Best Practices.
Elder abuse (EA) case resolution is contingent upon victims accepting and pursuing protective service interventions. Refusal/underutilization of services is a major problem. This study explored factors associated with extent of EA victim service utilization (SU). Data were collected from a random sample of EA cases (n = 250) at a protective service program in New York City. In cases involving financial abuse, higher SU was associated with females, poor health, perceived danger, previous help-seeking, and self or family referral. In physical abuse cases, higher SU was associated with family referral and previous help-seeking; lower SU was related to Hispanic race/ethnicity, being married, and child/grandchild perpetrator. In emotional abuse cases, higher SU was associated with self or family referral, victim-perpetrator gender differential, perceived danger, and previous help-seeking; lower SU was related to child/grandchild perpetrator. Findings carry implications for best practices to retain and promote service use among elder victims of abuse.


Changing folding and binding stability in a viral coat protein: a comparison between substitutions accessible through mutation and those fixed by natural selection.
Previous studies have shown that most random amino acid substitutions destabilize protein folding (i.e. increase the folding free energy). No analogous studies have been carried out for protein-protein binding. Here we use a structure-based model of the major coat protein in a simple virus, bacteriophage φX174, to estimate the free energy of folding of a single coat protein and binding of five coat proteins within a pentameric unit. We confirm and extend previous work in finding that most accessible substitutions destabilize both protein folding and protein-protein binding. We compare the pool of accessible substitutions with those observed among the φX174-like wild phage and in experimental evolution with φX174. We find that observed substitutions have smaller effects on stability than expected by chance. An analysis of adaptations at high temperatures suggests that selection favors either substitutions with no effect on stability or those that simultaneously stabilize protein folding and slightly destabilize protein binding. We speculate that these mutations might involve adjusting the rate of capsid assembly. At normal laboratory temperature there is little evidence of directional selection. Finally, we show that cumulative changes in stability are highly variable; sometimes they are well beyond the bounds of single substitution changes and sometimes they are not. The variation leads us to conclude that phenotype selection acts on more than just stability. Instances of larger cumulative stability change (never via a single substitution despite their availability) lead us to conclude that selection views stability at a local, not a global, level.


Rab11-FIP3 and FIP4 interact with Arf6 and the exocyst to control membrane traffic in cytokinesis.
The dual Rab11/Arf binding proteins, family of Rab11-interacting proteins FIP3 and FIP4 function in the delivery of recycling endosomes to the cleavage furrow and are, together with Rab11, essential for completion of abscission, the terminal step of cytokinesis. Here, we report that both FIP3 and FIP4 bind Arf6 in a nucleotide-dependent manner but exhibit differential affinities for Rab11 and Arf6. Both FIP3 and FIP4 can form ternary complexes with Rab11 and Arf6. Arf6 is localised to the furrow and midbody and we show that Arf6-GTP functions to localise FIP3 and FIP4 to midbodies during cytokinesis. Exo70p, a component of the Exocyst complex, also localises to the furrow of dividing cells and interacts with Arf6. We show that depletion of Exo70p leads to cytokinesis failure and an impairment of FIP3 and Rab11 localisation to the furrow and midbody. Moreover, Exo70p co-immunoprecipitates FIP3 and FIP4. Hence, we propose that FIP3 and FIP4 serve to couple Rab11-positive vesicle traffic from recycling endosomes to the cleavage furrow/midbody where they are tethered prior to fusion events via interactions with Arf6 and the Exocyst.


Associations among trauma, posttraumatic stress disorder, cannabis use, and cannabis use disorder in a nationally representative epidemiologic sample.
Research in community and clinical samples has documented elevated rates of cannabis use and cannabis use disorders (CUDs) among individuals with trauma exposure and posttraumatic stress disorder (PTSD). However, there is a lack of research investigating relations between, and correlates of, trauma and cannabis phenotypes in epidemiologic samples. The current study examined associations between trauma (i.e., lifetime trauma exposure and PTSD) and cannabis phenotypes (i.e., lifetime cannabis use and CUD) in a nationally representative sample. Participants were individuals who participated in Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,396; 52.4% women; age, M = 48.0 years, SD = 16.9). Lifetime DSM-IV Criterion A trauma exposure was significantly associated with lifetime cannabis use (OR = 1.215) but was only marginally associated with CUD (OR = 0.997). Within the trauma-exposed sample, lifetime PTSD showed a significant association with CUD (OR = 1.217) but was only marginally associated with lifetime cannabis use (OR = 0.992). Partially consistent with hypotheses, lifetime trauma was associated with greater odds of lifetime cannabis use, whereas PTSD was associated with greater odds of CUD. Longitudinal research investigating patterns of onset of these events/disorders is needed.


Symmetry and Topology of Twin Boundaries and Five-Fold Twin Boundaries in Soft Crystals.
Heteroclusters constructed by tethering dissimilar nanoclusters using organic linkers resemble lipids and self-assemble into cubosomes, namely, microparticles of soft crystals composed of unique nanochannel lattices with a defined symmetry and topology. The internal porous crystal structures can be accurately characterized using transmission electron microscopy. We herein describe twin boundaries and five-fold twin boundaries in cubosomes with a double-diamond Pn3̅m structure. Our analysis indicates a clear distinction in the conformation of the skeletal unit: a centrosymmetric staggered conformation with point group D3d for the normal skeletal unit and a mirror-symmetric eclipsed one with point group D3h for the skeletal unit on the twin boundary. This symmetry distinction causes the channels to change direction and elongate slightly as they pass through the twin boundary, but the topology is maintained. For cubosomes containing five-fold twin boundaries, one of the channels is in the center of the particles seamlessly connecting the five blocks. Our conclusion is that the two distinct channel systems are still continuous. This fundamental understanding will contribute to the development of soft crystals with defined shapes and special inner nanostructures for advanced applications.


Secular change in running performance of Japanese adolescents: A longitudinal developmental study.
A 5-year longitudinal cohort study of the running development of Japanese adolescents was conducted at a secondary school in Tokyo from 1968 to 1994. The purpose was to investigate changes in the pattern of development over time. The test items were an endurance run (1,500 m for boys and 1,000 m for girls) and a dash (50 m for both sexes). The total number of subjects was 512 boys and 516 girls in the endurance run, and 825 boys and 895 girls in the dash. These students entered the first grade of the school from 1968 to 1989 at the age of 12 years, and were followed for the next 5 years. In the analyses, a quadratic regression model was used to characterize intra-individual, age-related changes in running performance. The model fit the observed data, and the validity of the model was confirmed. Secular changes in the running development of boys were minimal over the last 30 years. Changes in girls, however, had three different patterns: 1) an overall decrease in performance with an almost unchanged estimated performance in the first grade, 2) a greater decrease in the late-teenage years, and 3) a decrease in the age of maximal performance. Secular changes in physical growth (stature and body mass index) could not fully explain the secular changes in the running development of girls, suggesting that the underlying causes may be social and cultural. Am. J. Hum. Biol. 10:765-779, 1998. © 1998 Wiley-Liss, Inc.


Osteoarthritis-related changes in human articular cartilage. An immunologic study.
We report the use of immunologic methods for detecting specific alterations in human osteoarthritic cartilage. Monoclonal antibodies with specificities for proteoglycans and link proteins have been used to define immunogenic sites in these molecules. We have identified 1 site in the protein core, 1 site in the link proteins, and another site that is common to both proteoglycan and link proteins, which are not modified in osteoarthritic cartilage. In addition, an antigenic determinant in link proteins that is altered in osteoarthritic cartilage has been identified. These results suggest that the structure of the ternary complex (hyaluronic acid binding region-link proteins-hyaluronic acid) could be altered in osteoarthritic cartilage. These modifications may be due to a genetic defect or to partial enzymatic degradation of these sites.


A fast, simple, and cost-effective method of expanding patient-derived xenograft mouse models of pancreatic ductal adenocarcinoma.
Patient-derived xenograft (PDX) mouse models of cancer have been recognized as better mouse models that recapitulate the characteristics of original malignancies including preserved tumor heterogeneity, lineage hierarchy, and tumor microenvironment. However, common challenges of PDX models are the significant time required for tumor expansion, reduced tumor take rates, and higher costs. Here, we describe a fast, simple, and cost-effective method of expanding PDX of pancreatic ductal adenocarcinoma (PDAC) in mice. We used two established frozen PDAC PDX tissues (derived from two different patients) and implanted them subcutaneously into SCID mice. After tissues reached 10-20 mm in diameter, we performed survival surgery on each mouse to harvest 90-95% of subcutaneous PDX (incomplete resection), allowing the remaining 5-10% of PDX to continue growing in the same mouse. We expanded three consecutive passages (P1, P2, and P3) of PDX in the same mouse. Comparing the times required for in vivo expansion, P2 and P3 (expanded through incomplete resection) grew 26-60% faster than P1. Moreover, such expanded PDX tissues were successfully implanted orthotopically into mouse pancreases. Within 20 weeks using only 14 mice, we generated sufficient PDX tissue for future implantation of 200 mice. Our histology study confirmed that the morphologies of cancer cells and stromal structures were similar across all three passages of subcutaneous PDX and the orthotopic PDX and were reflective of the original patient tumors. Taking advantage of incomplete resection of tumors associated with high local recurrence, we established a fast method of PDAC PDX expansion in mice.


Batch and continuous cultivation of Pseudomonas fluorescens at increased pressure.
The effect of increased total pressure and partial pressures of oxygen and carbon dioxide on the growth of Pseudomonas fluorescens was investigated in an airlift reactor. In batch cultivations bacterial growth was completely inhibited with air at 8 bars total pressure. The same effect was observed with aeration by pure oxygen at 1.15 bars. Carbon dioxide partial pressure did not show inhibitory effects. Continuous experiments confirm the assumption that growth inhibition at higher total pressure is caused by the increase in oxygen partial pressure. Incubation of P. fluorescens at higher oxygen partial pressure led to an increase of bacterial productivity during subsequent continuous cultivation at ambient pressure (1 bar) with air. Maximum productivity was increased by about 75% after aeration with pure oxygen. This effect is probably the result of metabolic adaption of the bacterial cells to high oxygen partial pressure.


Effect of isobutylmethylxanthine and related drugs on the receptor response (ERG; a-wave) of the frog retina at various extracellular calcium concentrations.
Various drugs known or expected to increase the levels of cyclic nucleotides in cells were applied to isolated superfused frog retinae, and their influence on the aspartate-isolated a-wave was studied. Isobutylmethylxanthine (IBMX), triacetylguanosine (TAG), and dimethylaminopurine (DAMP) strongly influenced the responses elicited from dark-adapted retinae by flashes of light: With all three drugs the response amplitude was increased, and latency and time to peak were prolonged. If, on the other hand, the retinae were light-adapted by background light of various intensities, the drugs showed different effects on the response amplitude: IBMX either did not influence the amplitude at all or even caused a decrease (4 of 6 experiments), DAMP decreased the amplitude and TAG caused an increase of the amplitude in 2 of 3 experiments. But latency and time to peak were still prolonged by all three drugs. When dark-adapted retinae were superfused with IBMX or TAG Ringer solution and simultaneously calcium concentration was raised, different effects of calcium on the three measured parameters of the a-wave were observed: By increasing the extracellular calcium concentration the increase of the amplitude caused by drugs was reversed, down or even below the control level, whereas latency and time to peak remained prolonged. Thus, both an increased calcium level and light adaptation had the same effect, namely to reverse only that part of the drug effect concerning the amplitude but not latency or time to peak of the response. The data suggest that calcium and cyclic nucleotides act through different ways in the rod cells.


Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells.
The antidyslipidemic drug nicotinic acid (niacin) has been used for decades. One of the major problems of the therapeutical use of nicotinic acid is a strong cutaneous vasodilation called flushing, which develops in almost every patient taking nicotinic acid. Nicotinic acid-induced flushing has been shown to be mediated by the nicotinic acid receptor GPR109A and to involve the formation of vasodilatory prostanoids. However, the cellular mechanisms underlying this short-term effect are unknown. Here, we show that epidermal Langerhans cells are essential for the cutaneous flushing response induced by nicotinic acid. Langerhans cells respond with an increase in [Ca(2+)](i) to nicotinic acid and express prostanoid synthases required for the formation of the vasodilatory prostanoids prostaglandin E(2) and prostaglandin D(2). Depletion of epidermal Langerhans cells but not of macrophages or dendritic cells abrogates nicotinic acid-induced flushing. These data unexpectedly identify epidermal Langerhans cells as essential mediators of nicotinic acid-induced flushing and may help to generate new strategies to suppress the unwanted effects of nicotinic acid. In addition, our results suggest that Langerhans cells besides their immunological roles are also involved in the local regulation of dermal blood flow.


[Examining the properties of hepatic cytosol and the efficiency of its use in the Biological Support Liver apparatus].
Clinical trials showed the minimum efficiency of various detoxifying methods (dialysis, charcoal adsorption, plasma exchange) in terms survival in acute hepatic insufficiency. Attempts were made to provide hepatic functions through ex vivo perfusion of the whole liver and tissue sections, but these methods remain a challenge to immune responses and blood clotting. This led to the development of the extracorporeal liver support systems and early clinical results encouraged further work in this area. The liver support system consists of a bioreactor containing a liver homogenate, a transfer mechanism, and a dialyzer that connects 2 closed contours. The apparatus is connected to the patient's blood system by means of an arteriovenous or venovenous shunt. The contact time of a liver homogenate and a patient's blood in the dialyzer and the diffusion rate of molecules of chemical substances determine the detoxifying and metabolic effects. Laboratory studies have demonstrated that the detoxifying activation method has high effects (increased biotransformation, decreased blood ammonia levels), decreases the intensity of pathological processes, normalizes blood components (higher levels of ATP, glucose, amino acids, vitamin C). Model and experimental studies of the efficiency of the method lead to the conclusion that it is expedient to apply it in medical practice.


In vitro evaluation of Bifidobacterium strains of human origin for potential use in probiotic functional foods.
The present study investigated some in vitro properties for probiotic use of four strains of bifidobacteria isolated from faeces of healthy children (Bifidobacterium longum 51A, Bifidobacterium breve 1101A, Bifidobacterium pseudolongum 1191A and Bifidobacterium bifidum 1622A). In vitro tests were carried out to compare growth rate, aerotolerance, antagonistic activity against pathogens, antimicrobial susceptibility profile and cell wall hydrophobicity. Mean doubling time of B. longum 51A was shorter compared to the other strains. All strains were aerotolerant up to 72 h of exposure to oxygen. In vitro antagonism showed that B. longum 51A and B. pseudolongum 1191A were able to produce inhibitory diffusible compounds against all pathogenic bacteria tested, but not against Candida albicans. B. longum 51A was sensitive to all the antimicrobials tested, except neomycin. The hydrophobic property of the cell wall was highest for B. bifidum 1622A. Based on these parameters, B. longum 51A showed the best potential for probiotic use among the tested strains, presenting the greatest sensitivity to antimicrobials, the best growth rate and the highest capacity to produce antagonistic substances against various pathogenic microorganisms.


DNA hypermethylation is associated with invasive phenotype of malignant melanoma.
Tumor cell invasion is one of the key processes during cancer progression, leading to life-threatening metastatic lesions in melanoma. As methylation of cancer-related genes plays a fundamental role during tumorigenesis and may lead to cellular plasticity which promotes invasion, our aim was to identify novel epigenetic markers on selected invasive melanoma cells. Using Illumina BeadChip assays and Affymetrix Human Gene 1.0 microarrays, we explored the DNA methylation landscape of selected invasive melanoma cells and examined the impact of DNA methylation on gene expression patterns. Our data revealed predominantly hypermethylated genes in the invasive cells affecting the neural crest differentiation pathway and regulation of the actin cytoskeleton. Integrative analysis of the methylation and gene expression profiles resulted in a cohort of hypermethylated genes (IL12RB2, LYPD6B, CHL1, SLC9A3, BAALC, FAM213A, SORCS1, GPR158, FBN1 and ADORA2B) with decreased expression. On the other hand, hypermethylation in the gene body of the EGFR and RBP4 genes was positively correlated with overexpression of the genes. We identified several methylation changes that can have role during melanoma progression, including hypermethylation of the promoter regions of the ARHGAP22 and NAV2 genes that are commonly altered in locally invasive primary melanomas as well as during metastasis. Interestingly, the down-regulation of the methylcytosine dioxygenase TET2 gene, which regulates DNA methylation, was associated with hypermethylated promoter region of the gene. This can probably lead to the observed global hypermethylation pattern of invasive cells and might be one of the key changes during the development of malignant melanoma cells.


Interventions that Enhance Breastfeeding Initiation, Duration, and Exclusivity: A Systematic Review.
The purpose of this review was to evaluate breastfeeding interventions trialed to date and recommend directions for future needs in breastfeeding research. A literature review was conducted using PubMed, CINAHL Plus, and PsycINFO databases to identify studies that evaluated efficacy or effectiveness of breastfeeding interventions on breastfeeding initiation, duration, or exclusivity as a primary, secondary, or tertiary outcome. Combinations of search terms included breastfeeding, feeding behavior, prenatal/patient education, health promotion, social support, perinatal/prenatal/intrapartum/postnatal care, and postpartum period. Six studies were included in this review, using PRISMA guidelines. Acquisition of knowledge and skills, emotional support by healthcare providers, and self-efficacy over maternal confidence in her ability to breastfeed were factors the intervention studies relied on to affect breastfeeding practices. Although these factors were addressed in the studies, breastfeeding mothers had difficulty transferring what they gained from interventions into their real-life breastfeeding practices as evidenced by the highest drop-off rate of exclusive breastfeeding in the early postpartum. There were conceptual limitations to the reviewed studies: (1) lack of understanding of maternal perception of infant behavior and (2) perceived insufficient milk as a remaining primary reason for breastfeeding discontinuation. There were methodological limitations: (1) lack of theory-based interventions and (2) lack of intervention fidelity. Future studies involving breastfeeding should focus on the causes of the problems driven by theory-based interventions integrated with intervention fidelity.


In search of missing links in otology. III. Development of a new animal model for cholesteatoma.
An experimental study was conducted in chinchillas regarding the pathogenesis of acquired cholesteatoma (keratoma). The placement of a chemically modified gelatin membrane from the external auditory canal to the promontory through a tympanic membrane perforation stimulated squamous epithelial cell migration. Cholesteatoma formation with the presence of keratin debris and inflammatory reactions was observed in the middle ear and anterior bulla in 53.5% of the experimental animals. These experimental findings show for the first time the presence of epithelial migration and true cholesteatoma formation in the middle ear of chinchillas in an experimental model with deliberate perforation of the tympanic membrane. Erosion of the cochlear walls was observed in areas with granulation tissue and cholesteatoma. The importance and significance of the migration of squamous epithelium and of the middle ear inflammatory reaction in the genesis of acquired cholesteatomas are discussed.


New subgroup of Bacteroidetes and diverse microorganisms in Tibetan plateau glacial ice provide a biological record of environmental conditions.
We recovered microorganisms from five ice core samples from three glaciers (Puruogangri, Malan, and Dunde) located in the Tibetan Plateau in China and analyzed their small subunit rRNA gene sequences. Most of the bacterial sequences were unknown previously; the most closely related known sequences were from bacteria of the Proteobacteria, Bacteroidetes, and Actinobacteria phyla. Chlorophyta, Streptophyta, Ciliophora, and fungal groups were represented among the 18S rRNA gene sequences that we obtained. The most abundantly represented glacial bacteria were Bacteroidetes, and Chlamydomonas was the predominant eukaryote. Comparative analysis showed that the Bacteroidetes sequences obtained from this study were highly similar to one another but most were only distantly related to previously characterized Bacteroidetes (<92% identity). We propose that our Bacteroidetes sequences represent two novel subgroups: one at the family level and one at the genus level. The unique ice environment and the high abundance of Bacteroidetes, combined with the coexistence of a high abundance of psychrophilic Chlamydomonas, strongly suggests that there is a viable ecosystem on the surface of Tibetan glaciers. Comparisons of microbial community structures in the five ice samples showed distinct differences, likely due to environmental differences in the locations in which the samples were obtained.


A scoring system predicting acute radiation dermatitis in patients with head and neck cancer treated with intensity-modulated radiotherapy.
We created a scoring system incorporating dosimetric and clinical factors to assess the risk of severe, acute skin reactions in patients undergoing intensity-modulated radiation therapy (IMRT) to treat head and neck cancer (HNC). A total of 101 consecutive patients who received definitive IMRT or volumetric modulated arc therapy (VMAT) with a prescription dose of 70 Gy to treat HNC between 2013 and 2017 in our hospital were enrolled. Skin V5Gy, V10Gy, V20Gy, V30Gy, V40Gy, V50Gy, and V60Gy values delivered 5 mm within the body contour were compared between patients with Grades 1-2 and Grade 3 dermatitis. A scoring system was created based on logistic regression analysis (LRA) that identified the most significant dosimetric and clinical factors. The V60Gy was significantly associated with radiation dermatitis grade in both LRA and recursive partitioning analysis (RPA). A scoring system incorporating the V60Gy, concurrent chemotherapy status, age, and body mass index was used to divide all patients into three subgroups (0-1, 2-3, and 4-6 points) in the RPA. The incidence of Grade 3 dermatitis significantly differed among the subgroups (0, 20.5, and 58.6%, respectively, P < 0.01). A risk analysis model incorporating dose-volume parameters successfully predicted acute skin reactions and will aid in the appropriate management of radiation dermatitis.


Clinical Comparison of MEBO and Hyaluronic Acid Gel in the Management of Pain after Free Gingival Graft Harvesting: A Randomized Clinical Trial.
This study aimed to compare the effect of MEBO versus 0.2% hyaluronic acid gel (Gengigel®) applied to the palatal donor site on postoperative pain reduction and wound healing after free gingival graft harvesting. Methodology. Thirty-nine patients with different mucogingival defects were included in this study for harvesting a free gingival graft (FGG) for soft tissue augmentation. Patients were randomly assigned into three equal groups: group I (MEBO), group II (0.2% HA Gengigel®), and group III (control). Postoperative pain was recorded by using the Visual Analogue Scale (VAS). Analgesic consumption was recorded for 7 days postoperatively. Wound size was measured at baseline and on days 3, 7, 14, and 21. Postoperative healing of the palatal wound was assessed by the VAS score for color match on days 3, 7, 14, 21, and 42. Results of this study showed significant postoperative pain reduction for the three groups; MEBO showed statistically significant less VAS score compared to the other two groups, while HA showed statistically significant less VAS score compared to the control group. Both MEBO and HA showed statistically significant less total analgesic consumption. No statistically significant difference was observed between groups for wound size. MEBO showed statistically significant higher VAS for color match. Both treatment modalities could reduce postoperative pain following harvesting of FGG and improve the palatal wound healing. However, MEBO showed better outcomes in terms of postoperative pain and color match.


Quinolone resistance in veterinary isolates of Salmonella.
Twenty-seven nalidixic acid-resistant (MIC > or = 256 mg/L) isolates of salmonella from veterinary sources were also less susceptible to fluoroquinolones (range of MICs of ciprofloxacin, 0.12-2 mg/L). Six isolates were cross-resistant to one or more chemically unrelated antibacterial agents. The concentrations of enrofloxacin that inhibited DNA synthesis by 50% were similar to the MIC values for 23 of 27 isolates, suggesting a mutation in gyrA. Insertion of pNJR3-2 (gyrA) in nine of 20 isolates increased susceptibility to quinolones, suggesting that resistance was due to mutation in gyrA. Five of 27 isolates had reduced levels of accumulation of enrofloxacin. Two of the five also had increased susceptibility to quinolones when pNJR3-2 was introduced. None of the outer membrane protein profiles of the resistant isolates differed from those of sensitive control strains. Three of 27 isolates had differences in lipopolysaccharide profiles compared to control strains. Although the MIC of ciprofloxacin was less than the recommended UK break point concentrations for most isolates, the increasing incidence of quinolone-resistance in salmonella from veterinary sources is a matter of concern.


Treatment of endocrine disorders in the neuroscience intensive care unit.
This review discusses concepts and treatments associated with the most clinically relevant areas of acute endocrine dysfunction amongst patients with common diseases in neuroscience intensive care units (Neuro ICUs). We highlight the following points:• While a thorough work-up for hyponatremia when it is present is always warranted, subarachnoid hemorrhage (SAH) patients who are in a time window concerning for cerebral vasospasm and who are hyponatremic with high urine output are generally thought to have cerebral salt wasting. These patients are typically treated with a combination of continuous hypertonic saline infusion and fludrocortisone.• Diabetes insipidus (DI) is often seen in patients fulfilling death by neurological criteria, as well as in patients with recent pituitary surgery and less often in SAH and traumatic brain injury patients who are not brain dead. Patients with DI in the Neuro ICU often cannot drink to thirst and may require a combination of desmopression/vasopressin administration, aggressive fluid repletion, and serum sodium monitoring.• Diagnosing adrenal insufficiency immediately following pituitary injury is complicated by the fact that the expected atrophy of the adrenal glands, due to lack of a stimulus from pituitary adrenocorticotropic hormone, may take up to 6 weeks to develop. Cosyntropin testing can be falsely normal during this period.• Both hyperglycemia (glucose >200 mg/dL) and hypoglycemia (glucose <50 mg/dL) are strongly associated with neurological morbidity and mortality in ICUs and should be avoided. Glucose concentrations between 120-160 mg/dL can serve as a reasonable target for insulin infusion protocols.• There is no data to suggest that treatment of abnormal thyroid function tests in nonthyroidal illness syndrome/sick euthyroid leads to benefits in either mortality or morbidity. True myxedema coma is a rare clinical diagnosis that is treated with intravenous levothyroxine accompanied by stress-dose steroids.


[Enterococcal infections. Clinical findings and treatment considering antibiotic resistance in Denmark].
Enterococcus has become a more frequent cause of serious infections over the last 10-15 years. The infections are primarily nosocomial, owing to compromised immunity in the patients and excessive use of antibiotics in the hospitals. The rise is marked in the USA, where the enterococci furthermore tend to become multiresistant. Abroad, many enterococci have developed resistance to all available antibiotics, and their spread is now controllable only by strict hygienic precautions. No increase in enterococcal infections has been noted in Denmark, and very few clinical isolates of vancomycin-resistant enterococci have been found. Because of the worldwide relevance, we present a review of enterococcal infections with the focus on endocarditis and bacteraemia. However, we would emphasise that the classic combination of a penicillin and an aminoglycoside still provides adequate treatment of enterococcal infections in Denmark.