FADE OUT HIV: An Educational Intervention Allying Black Community Barbers, Their Clients, and Community Clinicians.
Black individuals in the United States are less likely to use medication to prevent HIV (pre-exposure prophylaxis, or PrEP) than White individuals and are significantly more likely to receive a new HIV diagnosis. Because of America's long history of unethical medical and research practices and ongoing prejudice and bias, Black Americans have mistrust towards the medical community. This distrust, along with the social determinants of health, leads to low participation in health care. Health interventions at culturally "safe" and familiar venues are a popular strategy to engage Black Americans in health care. In the United States, barbershops are staples of the Black community and the utility of barbershops as a venue for delivering interventions has been successfully explored. We describe FADE OUT HIV, a program designed to increase barberknowledge of prevalence of HIV in the Black community; facilitatediscussions between Black barbers and their Black clients about HIVexposure, prevention, and treatment; provide free HIV tests forbarbers' clients; and educate community clinicians via live andenduring webcasts about HIV prevention and treatment. Clinician education was designed to facilitate HIV screening and ensure that the barber clients would be referred to clinicians who were knowledgeable about HIV. The learning objectives of the education were focused on barriers that prevent HIV screening and PrEP uptake and strategies to overcome these barriers, monitoring recommendations for people using PrEP, the benefits and limitations of new and in-development PrEP, and the importance of rapid initiation of antiretroviral therapy (ART). As a result of this programme, 308 HIV tests were administered to barber clients at hosted events in Los Angeles and clinician knowledge and competence increased by 33% and 34%, respectively.


[Vulvar carcinoma--retrospective study of 47 cases (epidemiology, etiology and long-term results].
To evaluate the incidence of vulvar carcinoma, epidemiological signs and therapeutic results in patients with vulvar malignancies during the stated time period. Retrospective clinical study. Department of Obstetrics and Gynaecology, First Faculty of Medicine, Charles University and General Faculty Hospital, Prague. An analysis of the available clinical documentation of the patients of the oncological outpatient service of the Department of Obstetrics and Gynaecology. Vulvar carcinoma represents 4% of all malignant tumours of female genital tract. It concerns predominantly elder women (the average age is 74.2 years). The overall 5-year survival, with no regard to the stage of the disease, is 39.1% in our group. This low figure is due to the high age of the group and to the inappropriate therapeutic approach owed to the internal comorbidity, advanced age and the fact that the majority of cases are diagnosed in advanced stage. In spite of good access, the introduction of screening program is unlikely due to the age distribution, biological behaviour and difficulties in diagnostic of premalignant lesions. With regard to the increasing incidence of in situ carcinoma whose ethiopathogenesis is affected by HPV infection, it is necessary to pay more attention to vulva lesions in terms of an early histopathological verification. The treatment of the external genital tract malignancies should be concentrated to the centers with the greatest experience of their management.


Continuous myocloni and tonic spasms in a 2-month-old infant with enterovirus 71 brain stem encephalitis.
Brain stem encephalitis is a cardinal presentation of central nervous system involvement in enterovirus 71 infection, and manifests as myoclonus, ataxia, tremor, and autonomic dysfunction. A 2-month-old infant with enterovirus 71 brain stem encephalitis demonstrated continuous myocloni and tonic spasms. On admission, the patient's myoclonus, which mainly involved the shoulders and the arms, was considerably worse during wakefulness and occurred once or twice a minute. Several hours after admission, the myoclonic jerks steadily worsened, appeared ceaselessly every 1 to 2 seconds, and were intermixed with tonic spasms of all four extremities accompanied by crying. Video electroencephalography revealed a normal background without epileptiform discharges and no ictal electroencephalographic changes during the myoclonic jerks and tonic spasms. Complete remission was achieved without complications after completion of a 3-day immunoglobulin therapy. This case suggests that the brain stem may be a major origin site for not only myoclonus but also tonic spasm.


Nurse-led chest drain removal in a cardiac high dependency unit.
Within the cardiac high dependency unit it is currently a member of the surgical team who makes the decision for a patient's chest drain to be removed after cardiac surgery. This has often resulted in delays in discharging one patient and therefore in admitting the next. A pilot study was carried out using a working standard that had been developed, incorporating an algorithmic model. The results have enabled nursing staff in a cardiac high dependency unit to undertake this responsibility independently.


Influenza defective interfering viral RNA is formed by internal deletion of genomic RNA.
The 3'- and 5'-terminal nucleotide sequences of the defective interfering (DI) RNAs present in a preparation of DI influenza virus were determined. It was found that all DI RNAs possessed identical terminal sequences for at least the first 13 nucleotides at the 5' end and at least the last 12 nucleotides at the 3' end. The sequence of the DI RNAs is (5')A-G-U-A-G-A-A-A-C-A-A-G-G-...-C-C-U-G-C-U-U-U-C-G-C-U-OH(3'). In addition, the same sequences were present at the 3' and 5' termini of the viral polymerase genes (P1, P2, and P3) from which these DI RNAs originate. These results indicate that DI RNAs of influenzing virus are formed by an internal deletion of the genomic RNA.


Identification of sensitive indicators in immune response for leprosy affected patients: An observational clinical study of safety and immunogenicity of influenza vaccine.
Cured leprosy patients have special physical conditions, which could pose challenges for safety and immunogenicity after immunization. We performed an observational clinical study aimed to identify the safety and immunogenicity of influenza vaccine in cured leprosy patients. A total of 65 participants from a leprosarium were recruited into leprosy cured group or control group, and received a 0.5 ml dose of the inactivated split-virion trivalent influenza vaccine and a follow-up 28 days proactive observation of any adverse events. Hemagglutination and hemagglutination inhibition test was performed to evaluate serum antibody titer, flow cytometry was conducted to screen of cytokines level. The total rate of reactogenicity was 0.0% [0/41] in leprosy cured group and 37.5% [9/24] in control group. The seroconversion rate for H1N1 was difference between leprosy cured group and control group (41.83% vs 79.17%, P = .0082), but not for H3N2 (34.25% vs 50.00%, P = .4468). At day 0, leprosy cured group have relatively high concentration of interleukin-6, interleukin-10, tumor necrosis factor, interferon-γ, and interleukin-17 compared to control group. The interleukin-2 concentration increased 2 weeks after vaccination compared to pre-vaccination in leprosy cured group, but declined in control group (0.92 pg/ml vs -0.02 pg/ml, P = .0147). Leprosy cured group showed a more rapid down-regulation of interleukin-6 when influenza virus was challenged compared to control group (-144.38 pg/ml vs -11.52 pg/ml, P < .0001). Subgroup analysis revealed that the immunization administration declined interleukin-17 concentration in Tuberculoid type subgroup, but not in Lepromatous type subgroup or control group. Clinically cured leprosy patients are relatively safe for influenza vaccine. Leprosy cured patient have immune deficit in producing antibody. Interleukin-6 and interleukin-17 were 2 sensitive indicators in immune response for leprosy affected patients. The identification of indicators might be help management of leprosy and used as predictive markers in leprosy early symptom monitoring.


[Clonal hematopoiesis in aplastic anemia].
Aplastic anemia (AA) is an autoimmune-mediated bone marrow failure syndrome. While AA is not a malignant disease, clonal hematopoiesis is commonly detected via next-generation sequencing and single nucleotide polymorphism (SNP) array. Clonal hematopoiesis in AA has been confirmed by the detection of classic X chromosome skewing, PNH clones, UPD6p, and various mutations. The most frequent genetic events in AA are UPD6p and somatic mutations in BCOR/BCORL1, PIGA, DNMT3A, and ASXL1. While some mutations are common between patients with AA and healthy elderly donors, UPD6p and PIGA mutations are specific to clonal cells in AA, which need to manage their highly autoimmune extrinsic environment. During the evolution of AA into myelodysplastic syndrome (MDS), additional genetic events are frequently acquired that provide MDS cells with intrinsic survival benefits. Hematopoietic cells in AA appear to achieve clonal expansion by their escape from recognition and cytotoxicity by CD8 T-cells, accounting for the distinct landscape of genetic events observed in AA.


Direct comparison of amplitude and geometric measures of spectral inhomogeneity using phase-cycled 2D-IR spectroscopy.
Two-dimensional infrared (2D-IR) spectroscopy provides access to equilibrium dynamics with the extraction of the frequency-fluctuation correlation function (FFCF) from the measured spectra. Several different methods of obtaining the FFCF from experimental spectra, such as the center line slope (CLS), ellipticity, phase slope, and nodal line slope, all depend on the geometrical nature of the 2D line shape and necessarily require spectral extent in order to achieve a measure of the FFCF. Amplitude measures, on the other hand, such as the inhomogeneity index, rely only on signal amplitudes and can, in principle, be computed using just a single point in a 2D spectrum. With a pulse shaper-based 2D-IR spectrometer, in conjunction with phase cycling, we separate the rephasing and nonrephasing signals used to determine the inhomogeneity index. The same measured data provide the absorptive spectrum, needed for the CLS. Both methods are applied to two model molecular systems: tungsten hexacarbonyl (WCO6) and methylcyclopentadienyl manganese tricarbonyl [Cp'Mn(CO)3, MCMT]. The three degenerate IR modes of W(CO)6 lack coherent modulation or noticeable intramolecular vibrational redistribution (IVR) and are used to establish a baseline comparison. The two bands of the MCMT tripod complex include intraband coherences and IVR as well as likely internal torsional motion on a few-picosecond time scale. We find essentially identical spectral diffusion, but faster, non-equilibrium dynamics lead to differences in the FFCFs extracted with the two methods. The inhomogeneity index offers an advantage in cases where spectra are complex and energy transfer can mimic line shape changes due to frequency fluctuations.


Mediating Effects of Specific Types of Coping Styles on the Relationship between Childhood Maltreatment and Depressive Symptoms among Chinese Undergraduates: The Role of Sex.
Although childhood maltreatment is known to be associated with depressive symptoms, few studies have investigated the mediating effect of different types of coping styles on this association. It is unknown whether the impacts vary by sex. We investigated the mediating effects of different coping styles on the relationship between childhood maltreatment and depressive symptoms among Chinese undergraduates, as well as the role of sex in the mediated pathways. A total of 7643 college freshmen and sophomores (5665 females, 1978 males; 4215 freshmen, 3428 sophomores; mean age, 19.67 years) from two colleges in China completed a standard questionnaire on the details of childhood maltreatment, depressive symptoms, and coping styles. Childhood maltreatment was significantly correlated with all coping styles and depressive symptoms studied (p < 0.001). Problem solving, self-blame, help seeking, problem avoidance, and rationalization mediated the relationship between childhood maltreatment and depressive symptoms. The estimated ratio of the effect of childhood maltreatment on the occurrence of depressive symptoms can be explained by the mediation of problem solving, self-blame, help seeking, problem avoidance, and rationalization, which accounted for 15.1%, 25.6%, 7.4%, 1.6% and 1.6% of the total effect, respectively. Sex differences were found to have mediating effects on coping styles in terms of the relationship between childhood maltreatment and depressive symptoms. The findings illustrate the need to focus on coping styles and to employ sex-specific methods to effectively help college students reduce depressive symptoms associated with childhood maltreatment.


Annual Performance of a Two-Speed, Dedicated Dehumidification Heat Pump in the NIST Net-Zero Energy Residential Test Facility.
A 2715 ft2 (252 m2), two story, residential home of the style typical of the Gaithersburg, Maryland area was constructed in 2012 to demonstrate technologies for net-zero energy (NZE) homes (or ZEH). The NIST Net-Zero Energy Residential Test Facility (NZERTF) functions as a laboratory to support the development and adoption of cost-effective NZE designs, technologies, construction methods, and building codes. The primary design goal was to meet the comfort and functional needs of the simulated occupants. The first annual test period began on July 1, 2013 and ended June 30, 2014. During the first year of operation, the home's annual energy consumption was 13039 kWh (4.8 kWh ft-2, 51.7 kWh m-2), and the 10.2 kW solar photovoltaic system generated an excess of 484 kWh. During this period the heating and air conditioning of the home was performed by a novel air-source heat pump that utilized a reheat heat exchanger to allow hot compressor discharge gas to reheat the supply air during a dedicated dehumidification mode. During dedicated dehumidification, room temperature air was supplied to the living space until the relative humidity setpoint of 50% was satisfied. The heat pump consumed a total of 6225 kWh (2.3 kWh ft-2, 24.7 kWh m-2) of electrical energy for cooling, heating, and dehumidification. Annual cooling efficiency was 10.1 Btu W-1h-1 (2.95 W W-1), relative to the rated SEER of the heat pump of 15.8 Btu W-1h-1 (4.63 W W-1). Annual heating efficiency was 7.10 Btu W-1h-1 (2.09 W W-1), compared with the unit's rated HSPF of 9.05 Btu W-1h-1 (2.65 W W-1). These field measured efficiency numbers include dedicated dehumidification operation and standby energy use for the year. Annual sensible heat ratio was approximately 70%. Standby energy consumption was 5.2 % and 3.5 % of the total electrical energy used for cooling and heating, respectively.


Quantifying the mechanical properties of human skin to optimise future microneedle device design.
Microneedle devices are a promising minimally invasive means of delivering drugs/vaccines across or into the skin. However, there is currently a diversity of microneedle designs and application methods that have, primarily, been intuitively developed by the research community. To enable the rational design of optimised microneedle devices, a greater understanding of human skin biomechanics under small deformations is required. This study aims to develop a representative stratified model of human skin, informed by in vivo data. A multilayer finite element model incorporating the epidermis, dermis and hypodermis was established. This was correlated with a series of in-vivo indentation measurements, and the Ogden material coefficients were optimised using a material parameter extraction algorithm. The finite element simulation was subsequently used to model microneedle application to human skin before penetration and was validated by comparing these predictions with the in-vivo measurements. Our model has provided an excellent tool to predict micron-scale human skin deformation in vivo and is currently being used to inform optimised microneedle designs.


Separation of tautomeric forms of [2-nitrophloroglucinol-H]- by an in-electrospray ionization source hydrogen/deuterium exchange approach.
Here we report the observation that, depending on the solvent used for the electrospray, 2-nitrophloroglucinol undergoes a deprotona- tion from different sites forming two tautomeric gas phase ions. Those ions differ bythe collision-induced dissociation [CID] spectra and by the gas phase hydrogen/deuterium (H/D) exchange kinetic. We performed H/D exchange in the electrospray ionization (ESI) source by saturation ESI region with vapors of deuterated solvent (D20). It was observed that [2-nitrophloroglucinol-H]- exchanges two -OH hydrogens when MeOD is used as the spray solvent but when the spray solvent is 50:50 MeOD/DO20 we observed an additional two H/D exchanges at the aromatic ring. We propose that the reaction occurs via a keto-enolt tautomerization mechanism which was found to be energetically favorable.


Typing of food-borne Listeria monocytogenes by polymerase chain reaction-restriction enzyme analysis and amplified fragment length polymorphism.
The applicability of polymerase chain reaction-restriction enzyme analysis (PCR-REA) and amplified fragment length polymorphism (AFLP) for typing of food borne Listeria monocytogenes strains was tested. A panel of 43 L. monocytogenes strains isolated from food, mostly serovars 1/2b or 1/2a, were analysed by the optimized PCR-REA oriented to inlA and inlB genes and by AFLP. By PCR-REA, five types of profiles were obtained. By AFLP, the strains were separated into 11 types and 18 subtypes forming two major clusters. PCR REA was a relatively straightforward method for typing food-borne L. monocytogenes with a moderate discrimination power. AFLP was a more complex but a highly discriminative and reproducible method.


[Apollonia, patron saint of dentistry].
Apollonia's short trajectory and her martyrdom in the times of Emperor Decius in the 3rd century, is here reported. The artists who painted the saint are quoted, offering a small biography about their trajectory and principals works. Bernardino Luini, painting is studied with more detail, mentioning the similar characteristics of his Saint Apollonia with those of some of the personages painted by Leonardo da Vinci.


[Study of molecular mechanism for a blood sample with A3 phenotype].
OBJECTIVE To explore the molecular mechanism for a blood sample with mixed-field hemagglutination upon determination of ABO blood group. METHODS Serological techniques were employed to identify the erythrocyte phenotype. The A and B antigens were detected by flow cytometry. The preliminary genotype of ABO gene was assayed with sequence-specific primer-polymerase chain reaction (PCR-SSP). Exons 6 and 7 of the ABO gene were amplified with PCR and analyzed by direct sequencing. Haplotypes of the ABO gene were analyzed by cloning sequencing as well. RESULTS The serological reaction pattern has supported an O phenotype when all the tubes were centrifuged for the first time. However, a mixed-field hemagglutination of red blood cells (RBCs) with anti-A antibodies was present after the tube was centrifuged five times later. A antigens were detected on the surface of partial red blood cells of the sample by flow cytometry. PCR- SSP results have shown that the preliminary ABO genotype was A/O. Analysis of the fragments of exons 6 and 7 of the ABO gene has indicated that heterozygosis lied as follows: 261G/A, 425T/T, 467C/T, 646A/T, 681A/G, 745C/T, 771C/T, 829A/G, conjecturing the genotype to be A307/O02, which was confirmed by haplotype sequence analysis. Compared with A101 allele, A307 allele has two missense mutations, 467C> T and 745C> T, which have resulted in substitutions Pro156Leu and Arg249Trp in the A glycosyltransferase polypeptide chain. CONCLUSION A variant allele (A307) has been identified for the first time in mainland China, which is responsible for the formation of A3 phenotype.


Frequency of Irritable Bowel Syndrome Among Healthcare Personnel.
This study aims to investigate the frequency of irritable bowel syndrome (IBS) among healthcare professionals. A total of 394 healthcare professionals and 207 individuals who were selected as a control group were included in the study. A questionnaire form containing Rome III diagnostic criteria was administered to health workers and the control group. The study groups were evaluated according to age, gender, occupation, profession, presence of chronic disease, drug usage, smoking, awareness of IBS, alarm symptoms, and the type of IBS they have. Irritable bowel syndrome was diagnosed in 44 healthcare workers and 10 control group participants. Of the 44 healthcare professionals with IBS, 6 had alternate, 13 had constipated-dominant, and 25 had diarrhea-dominant IBS. Of the 10 persons in the control group who were diagnosed as having IBS, 5 were diarrhea-dominant and 5 were constipated-dominant type. Irritable bowel syndrome was more frequent in healthcare professionals than in the control group. Healthcare workers are more prone to IBS due to their stressful working environment.


Induction of continuous ambulatory peritoneal dialysis after retroperitoneoscopic nephrectomy.
Induction of continuous ambulatory peritoneal dialysis (CAPD) as treatment of end-stage renal disease is difficult for patients requiring nephrectomy with traditional surgery, and usually hemodialysis is selected for these patients. In a 61-year-old woman with end-stage renal failure a left renal tumor was diagnosed by abdominal ultrasonography, enhanced computed tomography and magnetic resonance imaging. Following an urology consultation, we decided to perform left kidney nephrectomy. We estimated that she had to undergo dialysis permanently after nephrectomy. She desired to be treated by CAPD, however, we decided after allowing for a postoperative period for complete healing of the peritoneum to avoid complications. This is why during the interim period between surgery and induction of CAPD she underwent hemodialysis (HD) in a local outpatient HD center and in our hospital. We selected a retroperitoneoscopic approach for nephrectomy. Pathology evaluation revealed a renal cell carcinoma. 4 months after nephrectomy, CAPD catheter implantation was performed by using laparoscopy and CAPD was started. At the present time, the patient is doing well on CAPD. To our knowledge, there are no clear indications regarding initiation of peritoneal dialysis after nephrectomy. The retroperitoneoscopic approach for nephrectomy allows for initiation of peritoneal dialysis after nephrectomy within a relative short postoperative period.


Nonequilibrium evolution of volatility in origination and extinction explains fat-tailed fluctuations in Phanerozoic biodiversity.
Fluctuations in biodiversity, large and small, pervade the fossil record, yet we do not understand the processes generating them. Here, we extend theory from nonequilibrium statistical physics to describe the fat-tailed form of fluctuations in Phanerozoic marine invertebrate richness. Using this theory, known as superstatistics, we show that heterogeneous rates of origination and extinction between clades and conserved rates within clades account for this fat-tailed form. We identify orders and families as the taxonomic levels at which clades experience interclade heterogeneity and within-clade homogeneity of rates, indicating that families are subsystems in local statistical equilibrium, while the entire system is not. The separation of timescales between within-clade background rates and the origin of major innovations producing new orders and families allows within-clade dynamics to reach equilibrium, while between-clade dynamics do not. The distribution of different dynamics across clades is consistent with niche conservatism and pulsed exploration of adaptive landscapes.


Mechanism of interaction of the double-stranded RNA (dsRNA) binding domain of protein kinase R with short dsRNA sequences.
The dsRNA-activated protein kinase (PKR) plays a major role in the cellular response to viral infection. PKR contains an N-terminal dsRNA binding domain (dsRBD) and a C-terminal kinase domain. The dsRBD consists of two tandem copies of a conserved double-stranded RNA binding motif, dsRBM1 and dsRBM2. dsRNA binding is believed to activate PKR by inducing dimerization and subsequent autophosphorylation reactions. We have characterized the function of the dsRBD by assessing the binding of dsRBM1 and dsRBD to a series of dsRNA sequences ranging from 15 to 45 bp. For dsRBM1, the binding stoichiometries agree with an overlapping ligand binding model where the motif binds to multiple faces of the dsRNA duplex and overlaps along the helical axis. Similar behavior is observed for a dsRBD containing both dsRBM1 and dsRBM2 for sequences up to 30 bp; however, the binding affinity is enhanced 30-fold. Longer dsRNA sequences exhibit lower-than-expected stoichiometries, indicating a change in binding mode. NMR spectroscopy was used to define the regions of the dsRBD that interact with dsRNA. dsRNA binding induces exchange broadening of cross-peaks in 1H-15N HSQC spectra. For a 20 bp dsRNA, the resonances most affected map to the known dsRNA binding regions of dsRBM1 as well as the N-terminus of dsRBM2. For a longer 40 bp sequence, additional regions of dsRBM2 exhibit enhanced broadening. These data support a model in which dsRBM1 plays the dominant role in binding short dsRNA sequences and dsRBM2 makes additional interactions with the longer sequences capable of activating PKR.


A DNA sequence obtained by replacement of the dopamine RNA aptamer bases is not an aptamer.
A unique specificity of the aptamer-ligand biorecognition and binding facilitates bioanalysis and biosensor development, contributing to discrimination of structurally related molecules, such as dopamine and other catecholamine neurotransmitters. The aptamer sequence capable of specific binding of dopamine is a 57 nucleotides long RNA sequence reported in 1997 (Biochemistry, 1997, 36, 9726). Later, it was suggested that the DNA homologue of the RNA aptamer retains the specificity of dopamine binding (Biochem. Biophys. Res. Commun., 2009, 388, 732). Here, we show that the DNA sequence obtained by the replacement of the RNA aptamer bases for their DNA analogues is not able of specific biorecognition of dopamine, in contrast to the original RNA aptamer sequence. This DNA sequence binds dopamine and structurally related catecholamine neurotransmitters non-specifically, as any DNA sequence, and, thus, is not an aptamer and cannot be used neither for in vivo nor in situ analysis of dopamine in the presence of structurally related neurotransmitters.


Rapid determination of triclosan in personal care products using new in-tube based ultrasound-assisted salt-induced liquid-liquid microextraction coupled with high performance liquid chromatography-ultraviolet detection.
This paper describes the development of a novel, simple and efficient in-tube based ultrasound-assisted salt-induced liquid-liquid microextraction (IT-USA-SI-LLME) technique for the rapid determination of triclosan (TCS) in personal care products by high performance liquid chromatography-ultraviolet (HPLC-UV) detection. IT-USA-SI-LLME method is based on the rapid phase separation of water-miscible organic solvent from the aqueous phase in the presence of high concentration of salt (salting-out phenomena) under ultrasonication. In the present work, an indigenously fabricated home-made glass extraction device (8-mL glass tube inbuilt with a self-scaled capillary tip) was utilized as the phase separation device for USA-SI-LLME. After the extraction, the upper extractant layer was narrowed into the self-scaled capillary tip by pushing the plunger plug; thus, the collection and measurement of the upper organic solvent layer was simple and convenient. The effects of various parameters on the extraction efficiency were thoroughly evaluated and optimized. Under optimal conditions, detection was linear in the concentration range of 0.4-100ngmL(-1) with correlation coefficient of 0.9968. The limit of detection was 0.09ngmL(-1) and the relative standard deviations ranged between 0.8 and 5.3% (n=5). The applicability of the developed method was demonstrated for the analysis of TCS in different commercial personal care products and the relative recoveries ranged from 90.4 to 98.5%. The present method was proven to be a simple, sensitive, less organic solvent consuming, inexpensive and rapid procedure for analysis of TCS in a variety of commercially available personal care products or cosmetic preparations.


Case of thyroid hemiagenesis and ectopic lingual thyroid presenting as goitre.
We report an extremely rare case of thyroid hemiagenesis with ectopic lingual thyroid. Case report and review of the world literature concerning thyroid hemiagenesis with ectopic lingual thyroid and heredity. Ectopic thyroid is an uncommon embryological aberration characterised by the presence of thyroid tissue in a site other than its usual, pretracheal location. The lingual thyroid is the most common manifestation of benign ectopic thyroid tissue, but is still a rare clinical entity. Thyroid hemiagenesis is also a very rare abnormality, in which one thyroid lobe fails to develop. We report a case of left thyroid hemiagenesis and goitre in the right lobe in a 26-year-old woman with an ectopic lingual thyroid. To our knowledge, this is the first report in the world literature of thyroid hemiagenesis with ectopic lingual thyroid.


[Perspective on transition from pediatric to adult health care for patients with neurological disease: current situation and issues].
An improvement in efficacy treatment and development of the social support system has led to many patients with neurological disease being able to reach adulthood. Therefore health care for life from pediatrics to adulthood has become necessary. The Special Committee for Measures Against Transition from Pediatric to Adult Health Care of the Japanese Society of Neurology officially started to examine the current situation and issues of transition from pediatric to adult health care in July 2020. Pediatric neurologists and adult neurologists have an awareness of this issue of constructing a better transition from pediatric to adult health care. However, there are some tasks that need to be resolved in the medical system. We intend to improve the understanding of transition and assessment of medical service fees for transition in cooperation with the Japanese Society of Neurology and the Japanese Society of Child Neurology.


Sex differences in the administration-time-dependent effects of low-dose aspirin on ambulatory blood pressure in hypertensive subjects.
Previous studies have revealed sex differences in blood pressure (BP) regulation, pathophysiology of hypertension, and treatment responses to medication. On the other hand, low-dose aspirin has been shown to reduce BP when administered at bedtime, as opposed to upon awakening, in hypertensive subjects and pregnant women at risk for preeclampsia. The purpose of this research was to investigate the potential sex differences in the administration-time-dependent influence of aspirin on BP. We studied 130 men and 186 women with untreated mild hypertension, 44.1 +/- 13.2 yrs of age, randomized to receive aspirin (100 mg/day) either on awakening or at bedtime daily for three months. BP was measured for 48 h before and after treatment. With ASA on awakening, ambulatory BP was unchanged in men and slightly but significantly elevated in women (1.7/1.4 mmHg in the 48 h SBP/DBP means, respectively; p < 0.023). BP was significantly reduced after aspirin at bedtime and to a larger extent in women (-8.0/-5.6 mmHg in SBP/DBP) than men (5.5/3.4 mmHg, respectively; p < 0.009 between men and women). Factors influencing a stronger response of BP to aspirin at bedtime included female sex, elevated fasting glucose, and high glomerular filtration rate. This study corroborates the significant administration-time-dependent effect of low-dose aspirin on ambulatory BP in subjects with untreated mild hypertension, while documenting significant sex differences in the BP response to aspirin. Accordingly, results indicate that bedtime is the optimal time for aspirin ingestion in both men and women. This timed administration of low-dose aspirin could provide a cost-effective valuable approach for BP control and potential added cardiovascular protection, especially in hypertensive women.


Oxidative stress regulates IL-4 gene expression in mast cells through the reduction of histone deacetylase.
Many proinflammatory cytokines are regulated by the acetylation and deacetylation of the core histone. Since dysregulation of T helper 2 cytokine production is a key in the pathogenesis of allergic diseases, we examined the role of histone deacetylase (HDAC) on interleukin (IL)-4 gene expression in mast cells. We also examined whether oxidative stress has any impact on HDAC activity. In vitro study. Academic research laboratory. An IgE-sensitized mast cell line (RBL-2H3 cells) was treated with varying concentrations of the HDAC inhibitors trichostatin A (TSA) and H2O2 and stimulated with antigens. The amount of IL-4 gene expression was quantified by real-time polymerase chain reaction. Quantitative measurement of IL-4 in the cell supernatant was performed using enzyme-linked immunosorbent assay. Moreover, HDAC activity was measured with the use of a nonisotopic assay that utilized an HDAC Fluorescent Activity Assay Kit. IL-4 mRNA expression was induced by antigens in IgE-sensitized RBL-2H3 cells. Pretreatment with TSA and H2O2 enhanced IL-4 mRNA expression up to 5-fold in a dose-dependent manner. Furthermore, HDAC activity in RBL-2H3 cells was reduced after treatment with H2O2. Our results suggest that oxidative stress may up-regulate IL-4 gene expression in mast cells via a decrease in HDAC activity.


A Novel Staphylococcus Podophage Encodes a Unique Lysin with Unusual Modular Design.
Drug-resistant staphylococci, particularly Staphylococcus aureus and Staphylococcus epidermidis, are leading causes of hospital-acquired infections. Bacteriophages and their peptidoglycan hydrolytic enzymes (lysins) are currently being explored as alternatives to conventional antibiotics; however, only a limited diversity of staphylococcal phages and their lysins has yet been characterized. Here, we describe a novel staphylococcal phage and its lysins. Bacteriophage Andhra is the first reported S. epidermidis phage belonging to the family Podoviridae. Andhra possesses an 18,546-nucleotide genome with 20 open reading frames. BLASTp searches revealed that gene product 10 (gp10) and gp14 harbor putative catalytic domains with predicted peptidase and amidase activities, characteristic functions of phage lysins. We purified these proteins and show that both Andhra_gp10 and Andhra_gp14 inhibit growth and degrade cell walls of diverse staphylococci, with Andhra_gp10 exhibiting more robust activity against the panel of cell wall substrates tested. Site-directed mutagenesis of its predicted catalytic residues abrogated the activity of Andhra_gp10, consistent with the presence of a catalytic CHAP domain on its C terminus. The active site location combined with the absence of an SH3b cell wall binding domain distinguishes Andhra_gp10 from the majority of staphylococcal lysins characterized to date. Importantly, close homologs of Andhra_gp10 are present in related staphylococcal podophages, and we propose that these constitute a new class of phage-encoded lysins. Altogether, our results reveal insights into the biology of a rare family of staphylococcal phages while adding to the arsenal of antimicrobials with potential for therapeutic use. IMPORTANCE The spread of antibiotic resistance among bacterial pathogens is inciting a global public health crisis. Drug-resistant Staphylococcus species, especially S. aureus and S. epidermidis, have emerged in both hospital and community settings, underscoring the urgent need for new strategies to combat staphylococcal infections. Bacterial viruses (phages) and the enzymes that they use to degrade bacterial cell walls (lysins) show promise as alternative antimicrobials; however, only a limited variety of staphylococcal phages and their lysins have yet been identified. Here, we report the discovery and characterization of a novel staphylococcal phage, Andhra. We show that Andhra encodes two lysins (Andhra_gp10 and Andhra_gp14) that inhibit growth and degrade the cell walls of diverse staphylococci, including S. aureus and S. epidermidis strains. Andhra and its unique lysins add to the arsenal of antimicrobials with potential for therapeutic use.


[Importance of atrial rhythm disease in geriatrics].
13 patients aged between 69 and 85 suffering from atrial rhythm disease were examined. Special attention was paid to the relationships between this syndrome and acute cerebral vascular pathology. The series shows the high frequency in arrhythmic atrial disease of episodes of incipient loss of consciousness or authentic syncopal phenomena. Fully 11 patients were subjected.....ed to definitive endocardial stimulation owing to the intensity of the symptomatology. On the basis of these observations, stress is laid on the importance of atrial rhythm disease as a cause of acute cerebral ischaemia in the elderly subject


Branch Retinal Vein Occlusion, Macular Ischemia, and Intravitreal Anti-VEGF Therapy.
To report a case with ischemic macular edema (ME) due to an acute branch retinal vein occlusion (BRVO) which was treated with repeated intravitreal anti-VEGF injections. Retrospective case presentation. A 66-year-old female patient was treated with repeated intravitreal anti-VEGF injections due to ischemic ME following an acute BRVO. Over a period of 2.5 years best corrected visual acuity increased from 0.06 to 0.6 (decimal notation) accompanied by a reduction in central retinal thickness from 546 to 292 µm. Overall 17 anti-VEGF injections were administered to treat repeated recurrence of ME. Macular ischemia did not worsen during this profound intravitreal anti-VEGF therapy. Intravitreal anti-VEGF therapy can be a beneficial treatment strategy even in ischemic ME following an acute BRVO.


A review of pulmonary neutrophilia and insights into the key role of neutrophils in particle-induced pathogenesis in the lung from animal studies of lunar dusts and other poorly soluble dust particles.
The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of toxicity. Some investigators have postulated that oxidative stress from particle surface reactive oxygen species (psROS) on the dust produces the toxicopathology in the lungs of dust-exposed animals. This postulate was tested concurrently with the studies to elucidate the toxicity of lunar dust (LD), which is believed to contain psROS due to high-speed micrometeoroid bombardment that fractured and pulverized lunar surface regolith. Results from studies of rats intratracheally instilled (ITI) with three LDs (prepared from an Apollo-14 lunar regolith), which differed 14-fold in levels of psROS, and two toxicity reference dusts (TiO2 and quartz) indicated that psROS had no significant contribution to the dusts' toxicity in the lung. Reported here are results of further investigations by the LD toxicity study team on the toxicological role of oxidants in alveolar neutrophils that were harvested from rats in the 5-dust ITI study and from rats that were exposed to airborne LD for 4 weeks. The oxidants per neutrophils and all neutrophils increased with dose, exposure time and dust's cytotoxicity. The results suggest that alveolar neutrophils play a critical role in particle-induced injury and toxicity in the lung of dust-exposed animals. Based on these results, we propose an adverse outcome pathway (AOP) for particle-associated lung disease that centers on the crucial role of alveolar neutrophil-derived oxidant species. A critical review of the toxicology literature on particle exposure and lung disease further supports a neutrophil-centric mechanism in the pathogenesis of lung disease and may explain previously reported animal species differences in responses to poorly soluble particles. Key findings from the toxicology literature indicate that (1) after exposures to the same dust at the same amount, rats have more alveolar neutrophils than hamsters; hamsters clear more particles from their lungs, consequently contributing to fewer neutrophils and less severe lung lesions; (2) rats exposed to nano-sized TiO2 have more neutrophils and more severe lesions in their lungs than rats exposed to the same mass-concentration of micron-sized TiO2; nano-sized dust has a greater number of particles and a larger total particle-cell contact surface area than the same mass of micron-sized dust, which triggers more alveolar epithelial cells (AECs) to synthesize and release more cytokines that recruit a greater number of neutrophils leading to more severe lesions. Thus, we postulate that, during chronic dust exposure, particle-inflicted AECs persistently release cytokines, which recruit neutrophils and activate them to produce oxidants resulting in a prolonged continuous source of endogenous oxidative stress that leads to lung toxicity. This neutrophil-driven lung pathogenesis explains why dust exposure induces more severe lesions in rats than hamsters; why, on a mass-dose basis, nano-sized dusts are more toxic than the micron-sized dusts; why lung lesions progress with time; and why dose-response curves of particle toxicity exhibit a hockey stick like shape with a threshold. The neutrophil centric AOP for particle-induced lung disease has implications for risk assessment of human exposures to dust particles and environmental particulate matter.


SNPSTR: a database of compound microsatellite-SNP markers.
There has been widespread and growing interest in genetic markers suitable for drawing population genetic inferences about past demographic events and to detect the effects of selection. In addition to single nucleotide polymorphisms (SNPs), microsatellites (or short tandem repeats, STRs) have received great attention in the analysis of human population history. In the SNPSTR database (http://www.imperial.ac.uk/theoreticalgenomics/data-software) we catalogue a relatively new type of compound genetic marker called SNPSTR which combines a microsatellite marker (STR) with one or more tightly linked SNPs. Here, the SNP(s) and the microsatellite are less than 250 bp apart so each SNPSTR can be considered a small haplotype with no recombination occurring between the two individual markers. Thus, SNPSTRs have the potential to become a very useful tool in the field of population genetics. The SNPSTR database contains all inferable human SNPSTRs as well as those in mouse, rat, dog and chicken, i.e. all model organisms for which extensive SNP datasets are available.


Role of Fatty Acid Binding Protein 4 (FABP4) in Kidney Disease.
Accumulating evidences indicated that obesity and metabolic syndrome were independent risk factors for the development and progression of kidney diseases. Apart from inflammation, lipotoxicity, and hemodynamic factors, adipokines have been proposed to play crucial roles in the relationship between kidney diseases and metabolic disorders. As one of the key adipokines, fatty acid binding protein 4 (FABP4), which is mainly expressed in adipocytes and macrophages, has recently been shown to be associated with renal dysfunction and kidney damage. Both clinical and experimental studies have proposed circulating FABP4 as a novel predictor for renal injuries, and it might also be a predictor for cardiovascular events in patients with end stage renal disease (ESRD). FABP4 has also been detected in the glomerular cells and epithelial tubular cells in mouse and human kidneys, and the expression of FABP4 in these cells has been involved in the pathogenesis of kidney diseases. In addition, experimental studies suggested that inhibition of FABP4 had protective effects on renal damage. Here, we reviewed current knowledge regarding the role of FABP4 in pathophysiological insights as well as its potential function as a predictor and therapeutic target for kidney diseases.


Effects of daily variation in outdoor particulates and ambient acid species in normal and asthmatic children.
Evidence suggests that the respiratory health of children may be adversely affected by daily variation in outdoor pollutants, particularly ozone and particulates. However, data from the UK are sparse and the contribution of different particulate fractions and acid species, together with the identification of those individuals most at risk, are not clear. One hundred and sixty two 9 year old children were enrolled from two inner city locations and recorded daily symptoms and twice daily peak expiratory flow (PEF) over 8 week periods in the winter and summer. Their results were analysed with daily pollutant levels at appropriate lags using regression models which corrected for trends, weather, pollen, and autocorrelation. Pollutant levels were generally low, especially in the summer. Multiple statistically significant associations were noted between health outcomes and pollutant concentrations, but no consistent patterns in identified effects were apparent between pollutants, lags, direction of observed effect, or location. There was no evidence to suggest that subgroups with atopy or pre-existing wheeze are more sensitive to pollutant effects. These data do not suggest that adverse health outcomes are associated with daily variations in pollutants [corrected]. No evidence was found to indicate that particulates or individual acid and anion species are more closely related to adverse health outcomes than other pollutants.


Factors Leading to a Poor Functional Outcome in Spinal Meningioma Surgery: Remarks on 173 Cases.
Spinal meningiomas are common spinal tumors, in most cases benign and with a good surgical prognosis. However, specific location, infiltration of spinal cord, vascular encasement, or spinal root involvement can bring a less favorable prognosis. To correlate these data with clinical/functional outcome. Two hundred twenty-four consecutive patients with spinal meningiomas treated from 1976 to 2013 in our institution were analyzed; among these, 51 were excluded for incomplete clinical data or follow-up. The remaining 173 cases were classified in regards to sex, age, symptoms, axial location, Simpson grade resection, and functional pre-/postoperative status. Most recurring onset symptoms were pain (32.9%) and motor deficit (31.8%); thoracic spine was the most severely affected (69.8%). Functional improvement on the follow-up was observed in 86.7% of cases; 6.4% of patients resulted stable and 6.9% worsened. A low functional grade before surgery was connected to a lesser improvement after. Anterolateral meningiomas were the most represented (42.2%); a gross total resection (Simpson grades I and II) was conducted in 98.8%, and a macroscopically complete removal without dural resection or coagulation (Simpson grade III) was performed in 1.2%. Of the meningiomas, 98.3% were classified as WHO grade I. Recurrence rate was 2.3%, and 7 cases presented complications (4 of 7 required surgical procedure). We can affirm that negative prognostic factors in our study were anterior or anterolateral axial location, prolonged presentation before diagnosis, WHO grade >I, Simpson grade resections II and III, sphincter involvement, and worse functional grade at onset.


Brdt Bromodomains Inhibitors and Other Modern Means of Male Contraception.
Compared to efficient and secure female contraception, a vasectomy and condoms are the only options for men. The choice of male contraceptive methods is limited, so contraception mainly rests on the shoulders of women. Several concepts are considered: testosterone administration--inhibiting pituitary secretion of lutropin (LH) and follicle stimulating hormone (FSH), progestogen--affecting the secretion of gonadotropin and gonadoliberin (GnRH) antagonists. New potential targets for non-hormonal male contraception were discovered: glyceraldehyde-3-phosphate-dehydrogenase (GAPDHS)--specific to male germ cells and voltage-gated cation channel (CatSper). Both are responsible for sperm motility. Drugs such as thioridazine used in schizophrenia treatment and phenoxybenzamine (antihypertensive activity) exhibit a contraceptive effect. Similar action exhibits an analogue of lonidamine--adjudin and an antagonist of retinoic acid receptors (BMS-189453). Researchers are working on a contraceptive vaccine, whose active ingredient is epididymal protease inhibitor (Eppin). Another promising method acts by blocking Bromodomain testis-specific proteins (Brdt) involved in the process of spermatogenesis. JQ1-the Brdt inhibitor causes reversible infertility without affecting the endocrine signaling pathways. A recent discovery of Juno as the binding partner for Izumo1 identifies these proteins as the cell-surface receptor pair, essential for gamete recognition and this interaction can be inhibited by an anti-Juno monoclonal antibody. Our review shows that the situation of men can change and investigators are close to the optimal solution. In the near future men will be able to choose the best contraceptive suited to their needs.


[Sar1]angiotensin II receptor-mediated stimulation of protein synthesis in chick heart cells.
Cardiac hypertrophy is a process that occurs in response to various mechanical or hormonal stimuli. Stimulation of the renin-angiotensin system is involved in the process of cardiac hypertrophy through mechanisms related to increased peripheral vascular resistance and increased cardiac afterload. In this study we determined whether [Sar1]angiotensin II (ANG II) directly stimulated protein synthesis and cell growth in embryonic chick myocytes in cell culture. Eighteen-day-old embryonic chick myocytes in subconfluent cell culture, incubated in a chemically defined serum-free media, showed a significant increase in total protein content, 18.5, 26.2, and 22.2%, respectively, when exposed to [Sar1]ANG II (1 microM/day) for 5, 7, and 9 days, respectively. The increase in total protein resulted in part from an increase in the fractional protein synthesis rate of 21.7, 16.5, and 14.9% at 5, 7, and 9 days, respectively. Total DNA and RNA levels did not change significantly following a 4-day exposure to [Sar1]ANG II in subconfluent culture. The relative rate of protein synthesis, determined by pulse labeling for 3 h with [3H]phenylalanine, showed increases of 23.4, 22.9, and 17.8% over control after 4, 5, and 6 days of exposure to [Sar1]ANG II. The incorporation of [3H]phenylalanine was blocked by the specific ANG II-receptor antagonist [Sar1,Ile8]ANG II. The data demonstrate a receptor-mediated increase in the rate of protein synthesis in cultured chick myocytes in response to [Sar1]ANG II, with a resultant increase in total cellular protein. This angiotensin peptide appears to directly stimulate protein synthesis in cultured embryonic chick myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)


Phase I safety, tolerability, and pharmacokinetic study of recombinant human mannan-binding lectin.
Mannan-binding lectin (MBL), a human plasma protein, plays an important role in the innate immune defence. MBL recognizes microorganisms through surface carbohydrate structures. Due to genetic polymorphisms, MBL plasma concentrations range from 5 to 10,000 ng/mL. Approximately 30% of the human population have low levels of MBL (below 500 ng/mL). MBL deficiency is associated with increased susceptibility to infections in immunosuppressed individuals, e.g., during chemotherapeutically induced neutropenia. Replacement therapy with MBL may be beneficial in this patient group, and recombinant human MBL (rhMBL) is in development as a novel therapeutic approach. To assess the safety, tolerability, and pharmacokinetics of rhMBL, a placebo-controlled double-blinded study was performed in MBL-deficient healthy male subjects. rhMBL was administered as both single intravenous (i.v.) infusions (0.01, 0.05, 0.1, and 0.5 mg/kg) and repeated i.v. infusions (0.1 or 0.3 mg/kg given at 3-day intervals). There were no difference in incidence and type of adverse events reported in the study between the groups of subjects receiving rhMBL and the placebo group. All adverse events reported as drug-related were mild and no serious adverse events were recorded. There were no clinically significant changes in laboratory evaluations, ECG or vital signs, and no anti-MBL antibodies were detected following rhMBL administration. After single i.v. doses of rhMBL the maximal plasma levels increased in a dose-dependent manner reaching a geometric mean of 9710 ng/mL+/-10.5% in the highest dose group (0.5 mg/kg), with an elimination half-life of approximately 30 h. No rhMBL accumulation in plasma was observed following repeat dosing. Administration of rhMBL restored the ability to activate the MBL pathway of the complement system without non-specific activation of the complement cascade. In conclusion, no safety or tolerability concern was raised following rhMBL administration no signs of immunogenicity detected, and an rhMBL plasma level judged sufficient to achieve therapeutic benefit (>1000 ng/mL) can be achieved.


Paediatric laser dentistry. Part 4: Soft tissue laser applications.
Lasers can provide effective soft tissues applications in children. All the wavelengths produce incision and vaporisation of oral tissues, together with a high bactericidal effect. The haemosthatic effect varys according to the wavelength used, and the choice of a visibile, near, medium or far infrared laser allows a better interaction with specific targets, gingiva, mucosa, frenum, or oral pathology.


Efficiency of Dinucleosides as the Backbone to Pre-Organize Multi-Porphyrins and Enhance Their Stability as Sandwich Type Complexes with DABCO.
Flexible linkers such as uridine or 2'-deoxyuridine pre-organize bis-porphyrins in a face-to-face conformation, thus forming stable sandwich complexes with a bidentate base such as 1,4-diazabicyclo[2.2.2]octane (DABCO). Increased stability can be even greater when a dinucleotide linker is used. Such pre-organization increases the association constant by one to two orders of magnitude when compared to the association constant of DABCO with a reference porphyrin. Comparison with rigid tweezers shows a better efficiency of nucleosidic dimers. Thus, the choice of rigid spacers is not the only way to pre-organize bis-porphyrins, and well-chosen nucleosidic linkers offer an interesting option for the synthesis of such devices.


[Facial pains as symptoms of mental disorders].
One hundred seventeen patients, aged 16-75 years, with orofacial pains were studied. Borderline psychic disorders were detected in 106 cases, schizophrenia--in 11 cases. Facial pain was characterized by (1) polymorphism of sensations changing their site and duration, (2) absence of orofacial sensory deficits, (3) symptoms "mosaic"--a combination of separate signs specific for various "organic" facial pain, (4) absence of objective changes in oral cavity and facial region, (5) key role of psychoemotional factors in pain recurrence and intensification, (6) non-opioid analgesics and carbamazepine inefficacy. A systematics for facial pains of psychic genesis, comprising two groups of disorders, was elaborated. The first group includes facial pain and odontalgia in borderline psychic disorders--neurotic (somatoform, hypochondriac and hysteric) disorders, affective ones (mild depressive episodes and dystimia) and paranoic personality disorder. The second group comprises orofacial cenesthopathies in neurotic-like (schizotypal disorders) and paranoid types of schizophrenia.


Determination of the concentration of cathepsin B by SPRI biosensor in children with appendicitis, and its correlation with proteasomes.
Cathepsin B (CatB) belongs to a family of lysosomal cysteine proteases and plays an important role in intracellular proteolysis. The concentration of CatB and 20S proteasome was evaluated in the serum of children with appendicitis, before and after surgery, on a basis of an innovative method for determining biomolecules concentration - surface plasmon resonance imaging (SPRI) biosensor. Forty-two children with acute appendicitis, who were treated at the Department of Pediatric Surgery (Medical University of Bialystok, Poland), were randomly included into the study (age: 5-17 years, mean age: 11.5 ±1 year). There were 15 girls and 27 boys in the study group. Eighteen healthy, age-matched subjects, admitted for planned surgeries, served as controls. Exclusion criteria were the following: severe preexisting infections, immunological or cardiovascular diseases that required longterm medication, and complicated cases of appendicitis with perforation of the appendix and/or peritonitis. The CatB concentrations in the blood plasma of patients with acute appendicitis were elevated before surgery, they were the highest 24 h after surgery, and were above the range of concentrations measured in controls; the difference was statistically significant. The CatB concentration measured 72 h after the operation was decreased, but still did not reach the normal range when compared with the concentration measured in controls (p < 0.05). Cathepsin B concentration may reflect the metabolic response to acute state of inflammation, surgical intervention in the abdominal cavity and the process of gradual ebbing of the inflammation. The method of operation - classic open appendectomy or laparoscopic appendectomy - does not influence the general trend in the CatB concentration in children with appendicitis. There is a strong positive correlation between the CatB and 20S proteasome concentrations 24 h after surgery. The SPRI method can be successfully used for determining the concentration of active forms of enzymes presented in lysosomes in the diagnosis of inflammatory conditions in the abdominal cavity.


Combination of a subcutaneous ICD in a patient with a baroreceptor activation device: Feasibility, safety, and precautions: A Case Report.
We present a case of a patient with a baroreflex activation therapy (BAT) receiving a subcutaneous implantable cardioverter defibrillator (S-ICD). We anticipated two possible hazardous interactions between the two devices. Stimulation by the BAT could be adjudicated as noise and result in underdetection of ventricular arrhythmias or it might be misinterpreted as ventricular arrhythmias and lead to inappropriate shocks. Postop ensing occurred, the upper limit of pulse width of the BAT was limited because of noise detection by the S-ICD, but the upper limit of amplitude was limited by patient's discomfort. In this patient, the combination of a BAT and an S-ICD was safe.


Influence of mass transfer limitations on determination of the half saturation constant for hydrogen uptake in a mixed-culture CH(4)-producing enrichment.
There is strong evidence in the literature supporting the existence of significant mass transfer limitations on the kinetics of exogenous H(2) consumption by methanogens. The half saturation constant for H (2) uptake by a mixed-culture, CH(4) producing enrichment was measured using an experimental protocol that avoided internal mass transfer limitations. The value obtained was two orders of magnitude smaller than any other previously reported. A mathematical model for acetogenic syntrophic associations was developed to check the capacity of H(2) as electron transporter between syntrophic partners. It was found that H(2) diffusion could account for the rate of transport of electrons between the syntrophic microorganisms and that formate is not a necessary intermediate. The possibility that formate may be an intermediate in this system was not ruled out. A Monod-type kinetic equation was modified to include the observed H(2) threshold effect. This modified equation was used to predict the CH(4)-production rate in a batch-fed digester. The results show that the external and internal H(2) pools are kinetically coupled.


Evaluation of Early Postoperative Neurological Complications Following Living Donor Liver Transplantation.
Liver transplantation is one of the best treatment options for end-stage liver disease. In Turkey, living donor liver transplantation (LDLT) is performed more frequently than cadaveric transplantation, because organ donation is unpopular in our country. Neurological complications contribute to poor postoperative outcomes after liver transplantation. In the present study, we aimed to evaluate the outcomes of LDLT patients in whom such complications developed early during postoperative follow-up in the intensive care unit. Of 217 LDLTs performed between August 2011 and August 2012, neurology consultations were arranged for 29 patients (13.36%) because of development of new-onset neurological symptoms and/or findings in patients with neurologically uneventful preoperative histories. We retrospectively collected data on age, gender, primary disease, Model for End-Stage Liver Disease (MELD) score, and postoperative hospitalization duration of those who survived. The indications for neurological consultation and diagnoses were categorized into acute confusion/encephalopathy, epileptic seizures, leukoencephalopathy, and focal neurological deficits. The immunosuppressive treatment regimens prescribed were also considered. The outcomes of the 2 groups (with and without neurological complications) were compared. The mean patient age was 44.52±16.24 years, and males predominated (65.5%, n=19). Acute confusion/encephalopathy was the most frequent complication (62.1%, n=18), followed by epileptic seizures (27.6%, n=8), cerebrovascular disease (6.9%, n=2), and leukoencephalopathy (3.4%, n=1). Statistically significant between-group differences in age (44.5±16.2 vs. 34.33±20.98 years; p<0.001), and proportions of patients with a disease of viral etiology (55.17% vs. 35.63%, p<0.05), were evident. Mortality was significantly higher in the group with neurological complications (65.5% vs. 37.32%, p<0.05). The duration of postoperative hospitalization was also significantly longer in this group (29.80±15.04 vs. 10.00±5.47 days; p<0.05). Mortality was significantly higher and the duration of postoperative hospitalization significantly longer in LDLT patients with new-onset neurological complications than in those without such complications.


Associations among SNPs in two addictive genes, food addiction, and antioxidant markers in recreationally active young women.
Introduction: food addiction is associated with genetic polymorphisms and decreased antioxidant intake. Objectives: this study determined the associations among food addiction, dopamine receptor 2 (DRD2) and toll-interleukin 1 receptor (TIR) domain-containing adaptor protein (TIRAP rs625413) gene polymorphisms, antioxidant capacities, and zinc levels among recreationally active Turkish women. Methods: the Yale Food Addiction Scale was used to evaluate the food addiction status. Serum antioxidant capacities and zinc levels were evaluated by blood analyses. Deoxyribonucleic acid (DNA) extraction was performed using peripheral blood leukocytes, and the polymorphism status of the DRD2 Taq 1A and TIRAP genes was investigated using a commercial kit. Results: the frequencies of the heterozygous genotypes of DRD2 Taq 1A and TIRAP were 23.1 % and 31.4 %, respectively, and the frequency of risk allele homozygous genotypes was 3.2 %. Most participants (94.4 %) had a nonpolymorphic/wild (CC) genotype in both genes; however, 11.5 % of the participants had a food addiction. The differences between serum antioxidant capacities, zinc levels, and body mass indices of those with and without food addiction were statistically significant. However, there were no differences in the serum zinc and antioxidant levels among the different genotypes. Conclusion: food addiction in young Turkish women was not associated with DRD2 Taq 1A or TIRAP polymorphisms but was associated with serum antioxidant capacities and zinc levels. Further studies on different loci of the same genes or genotypes of different genes with larger sample sizes are warranted.


Functional Role of G9a Histone Methyltransferase in Cancer.
Post-translational modifications of DNA and histones are epigenetic mechanisms, which affect the chromatin structure, ultimately leading to gene expression changes. A number of different epigenetic enzymes are actively involved in the addition or the removal of various covalent modifications, which include acetylation, methylation, phosphorylation, ubiquitination, and sumoylation. Deregulation of these processes is a hallmark of cancer. For instance, G9a, a histone methyltransferase responsible for histone H3 lysine 9 (H3K9) mono- and dimethylation, has been observed to be upregulated in different types of cancer and its overexpression has been associated with poor prognosis. Key roles played by these enzymes in various diseases have led to the hypothesis that these molecules represent valuable targets for future therapies. Several small molecule inhibitors have been developed to specifically block the epigenetic activity of these enzymes, representing promising therapeutic tools in the treatment of human malignancies, such as cancer. In this review, the role of one of these epigenetic enzymes, G9a, is discussed, focusing on its functional role in regulating gene expression as well as its implications in cancer initiation and progression. We also discuss important findings from recent studies using epigenetic inhibitors in cell systems in vitro as well as experimental tumor growth and metastasis assays in vivo.


Accreditation Council for Graduate Medical Education Hand Surgery Milestones V2.0 Development and Implementation: What Fellowship Directors, Faculty, and Fellows Need to Know.
Milestones have been in effect for Accreditation Council for Graduate Medical Education-accredited hand surgery fellowships since 2015. In 2016, the Accreditation Council for Graduate Medical Education began an improvement process to make the milestones easier to read, understand, and assess. This article looks at the process used for hand surgery, makes comparisons between the two versions, and discusses the resulting changes. A representative group of hand surgery faculty and fellows worked together to review the milestones data and identify necessary changes. Working iteratively in large and small groups, the milestones were edited, and a supplemental guide was developed. The new hand surgery milestones have fewer patient care subcompetencies, yet include the same overarching themes. The medical knowledge subcompetencies have been reduced to four, and they now focus on key dimensions of knowledge development instead of pure anatomical knowledge. Systems-based practice, practice-based learning and improvement, professionalism, and interpersonal and communication skills include subcompetencies harmonized with all other accredited programs. Finally, the supplemental guide was created as an aid to clinical competency committees to provide clear understanding of the intent of the milestones. The guide includes examples for individual milestones, ideas for how to assess each subcompetency, and resources for faculty and fellows alike. The new hand surgery milestones were designed to be clearer and easier for clinical competency committees to evaluate and for faculty and fellows to understand. The accompanying supplemental guide is a new addition that will help individual programs better understand how to implement these changes. The new hand surgery milestones can be found at https://www.acgme.org/globalassets/pdfs/milestones/handsurgerymilestones.pdf.


Brugada Phenocopy Induced by Hypovolemic Hyponatremia.
Brugada syndrome (BrS) is a hereditary channelopathy caused by an autosomal dominant mutation in the cardiac sodium channel gene SCN5A alpha subunit. In individuals without structural heart disease, the risk of sudden cardiac death (SCD) increases in this channelopathy with ST-segment elevation in V1-3 precordials. Brugada phenocopy (BrP) is a condition in which transient ST-segment elevations are observed, mimicking BrS electrocardiographic changes, which can occur with electrolyte and metabolic disorder scenarios. In this study, we share a case of BrP that occurred due to hypovolemic hyponatremia and recovered spontaneously with the correction of electrolyte disturbance.


Learning and Doing: An Interview with Bill Wood.
THE Genetics Society of America's Elizabeth W. Jones Award for Excellence in Education recognizes significant and sustained impact on genetics education. As well as having made major contributions to biochemistry and developmental genetics, the 2016 awardee William B. Wood has been a pioneer in the reform of science teaching. Wood's leadership has been crucial in several national initiatives and programs, including the development of the influential National Academies Summer institutes on Undergraduate Education in Biology. He has also catalyzed change in education through his service as Editor-in-Chief of CBE-Life Sciences Education, a peer-reviewed journal published by the American Society for Cell Biology, in editorial partnership with the GSA.


Metaplastic carcinoma of the breast (carcinosarcoma variant): a case report.
A case of a female patient aged 60 yrs, with metaplastic carcinoma of the breast which is a rare neoplasm is presented. Although it is a tumor of the ductal type, the predominant component of the neoplasm has an appearance other than glandular pattern and more in keeping with other cell types. Metaplastic carcinoma runs a very aggressive course and bears an unfavourable prognosis.


Multiple Electrolyte and Metabolic Emergencies in a Single Patient.
While some electrolyte disturbances are immediately life-threatening and must be emergently treated, others may be delayed without immediate adverse consequences. We discuss a patient with alcoholism and diabetes mellitus type 2 who presented with volume depletion and multiple life-threatening electrolyte and metabolic derangements including severe hyponatremia (serum sodium concentration [SNa] 107 mEq/L), hypophosphatemia ("undetectable," <1.0 mg/dL), and hypokalemia (2.2 mEq/L), moderate diabetic ketoacidosis ([DKA], pH 7.21, serum anion gap [SAG] 37) and hypocalcemia (ionized calcium 4.0 mg/dL), mild hypomagnesemia (1.6 mg/dL), and electrocardiogram with prolonged QTc. Following two liters of normal saline and associated increase in SNa by 4 mEq/L and serum osmolality by 2.4 mosm/Kg, renal service was consulted. We were challenged with minimizing the correction of SNa (or effective serum osmolality) to avoid the osmotic demyelinating syndrome while replacing volume, potassium, phosphorus, calcium, and magnesium and concurrently treating DKA. Our management plan was further complicated by an episode of significant aquaresis. A stepwise approach was strategized to prioritize and correct all disturbances with considerations that the treatment of one condition could affect or directly worsen another. The current case demonstrates that a thorough understanding of electrolyte physiology is required in managing complex electrolyte disturbances to avoid disastrous outcomes.


Observations on the relationships between plasma free fatty acids, ketones and bicarbonate in acute hyperglycaemia.
Some of the initial biochemical findings, obtained from 141 randomly-selected cases of acute hyperglycaemia (admission plasma glucose > 20 mmol/L) were examined. When viewed in terms of their initial plasma bicarbonate concentration, three groups were identifiable. Plasma concentrations of free fatty acids (FFA), acetone and the sum of 3-hydroxybutyrate (3OHB) and lactate were different between these groups. However, there were no differences in plasma glucose or lactate concentrations. It was further observed that the relationship between the plasma FFA/albumin molar ratio, and ketone concentration could be described by a rectangular hyperbola, and the initial anion gap was linearly related to the sum of the 3OHB and lactate concentrations.


A miRNA signature for an environmental heterocyclic amine defined by a multi-organ carcinogenicity bioassay in the rat.
Heterocyclic amines (HCAs) produced during high-temperature cooking have been studied extensively in terms of their genotoxic/genetic effects, but recent work has implicated epigenetic mechanisms involving non-coding RNAs. Colon tumors induced in the rat by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) have altered microRNA (miRNA) signatures linked to dysregulated pluripotency factors, such as c-Myc and Krüppel-like factor 4 (KLF4). We tested the hypothesis that dysregulated miRNAs from PhIP-induced colon tumors would provide a "PhIP signature" for use in other target organs obtained from a 1-year carcinogenicity bioassay in the rat. Downstream targets that were corroborated in the rat were then investigated in human cancer datasets. The results confirmed that multiple let-7 family members were downregulated in PhIP-induced skin, colon, lung, small intestine, and Zymbal's gland tumors, and were associated with c-myc and Hmga2 upregulation. PhIP signature miRNAs with the profile mir-21high/mir-126low/mir-29clow/mir-215low/mir-145low were linked to reduced Klf4 levels in rat tumors, and in human pan-cancer and colorectal cancer. It remains to be determined whether this PhIP signature has predictive value, given that more than 20 different genotoxic HCAs are present in the human diet, plus other agents that likely induce or repress many of the same miRNAs. Future studies should define more precisely the miRNA signatures of other HCAs, and their possible value for human risk assessment.


Wedge filling and interface delocalization in finite Ising lattices with antisymmetric surface fields.
Theoretical predictions by Parry et al. for wetting phenomena in a wedge geometry are tested by Monte Carlo simulations. Simple cubic LxLxL(y) Ising lattices with nearest neighbor ferromagnetic exchange and four free LxL(y) surfaces, at which antisymmetric surface fields +/-H(s) act, are studied for a wide range of linear dimensions (4</=L</=320, 30</=L(y)</=1000), in an attempt to clarify finite size effects on the wedge filling transition in this "double-wedge" geometry. Interpreting the Ising model as a lattice gas, the problem is equivalent to a liquid-gas transition in a pore with quadratic cross section, where two walls favor the liquid and the other two walls favor the gas. For temperatures T below the bulk critical temperature T(c) this boundary condition (where periodic boundary conditions are used in the y direction along the wedges) leads to the formation of two domains with oppositely oriented magnetization and separated by an interface. For L,L(y)--> infinity and T larger than the filling transition temperature T(f)(H(s)), this interface runs from the one wedge where the surface planes with a different sign of the surface field meet (on average) straight to the opposite wedge, so that the average magnetization of the system is zero. For T<T(f)(H(s)), however, this interface is bound either to the wedge where the two surfaces with field -H(s) meet (then the total magnetization m of the system is positive) or to the opposite wedge (then m<0). The distance l(0) of the interface midpoint from the wedges is studied as T-->T(f)(H(s)) from below, as is the corresponding behavior of the magnetization and its moments. We consider the variation of l(0) for T>T(f)(H(s)) as a function of a bulk field and find that the associated exponents agree with theoretical predictions. The correlation length xi(y) in the y direction along the wedges is also studied, and we find no transition for finite L and L(y)--> infinity. For L--> infinity the prediction l(0) proportional, variant (H(sc)-H(s))(-1/4) is verified, where H(sc)(T) is the inverse function of T(f)(H(s)) and xi(y) proportional, variant (H(sc)-H(s))(-3/4), respectively. We also find that m vanishes discontinuously at the filling transition. When the corresponding wetting transition is first order we also obtain a first-order filling transition.


Metal-Free [2 + 1 + 2]-Cycloaddition of Tosylhydrazones with Hexahydro-1,3,5-triazines To Form Imidazolidines.
A novel protocol toward imidazolidines has been accomplished using tosylhydrazones and hexahydro-1,3,5-triazines as the substrates under metal-free reaction conditions. Importantly, the role of LiOtBu has been confirmed not only to release the diazo but also to promote the cycloaddition. Further mechanistic investigations reveal that the reaction proceeds through a stepwise [2 + 1 + 2] process.


Oxygen reduction electrocatalyst of Pt on Au nanoparticles through spontaneous deposition.
A straightforward one-step spontaneous deposition approach for growth of Pt atomic shell on Au nanoparticles and the superior activity and durability of the resulted Pt-on-Au nanoparticles for the oxygen reduction reaction (ORR) are reported. Transmission electron microscopy, X-ray photoelectron spectroscopy, energy-dispersive spectrometry, and electrochemical measurements indicate that Pt can be spontaneously deposited on Au surface upon simply dispersing carbon-supported Au nanoparticles in PtCl42–-containing solution, without introducing any extraneous reducing agents or any pre/post-treatments. The deposited Pt atoms are uniformly distributed on the surface of Au nanoparticles, with coverage tunable by the concentration of PtCl42– and temperatures. An approximate monolayer of Pt forms at temperature of ca. 80 °C and PtCl42– concentrations of above 10–4 mol/L. The obtained Pt-on-Au core–shell nanoparticles catalyze the ORR with specific and mass activities of Pt that are 3.5 times higher than that of pure Pt nanoparticles. Moreover, they exhibit no visible activity degradation after undergoing long-term oxidization/reduction cycling in O2-saturated acid media, therefore showing great prospect as durable cathode electrocatalysts in proton-exchange membrane fuel cells.


Primary prevention in hypertension. Valid conclusions from observational studies.
Relatively few observational (i.e., nonexperimental) studies have been conducted to examine the role of antihypertensive drug therapy in the primary prevention of coronary heart disease. To draw valid conclusions from experimental or observational studies, internal validity should be ensured. In particular, similarity of "extraneous" effects, of information, and of prognosis between the treatment groups compared in a particular study is needed. Because allocation of participants to antihypertensive drug therapy in observational studies is nonrandomized by definition, special efforts should be made to achieve comparability of prognosis, that is, to avoid "confounding by indication." Follow-up and case-control studies, the two main types of observational studies, also offer certain advantages over randomized clinical trials, particularly when different classes of drugs are compared. Although few valid observational studies on the efficacy of drug therapy for hypertension in the primary prevention of first coronary events have been published, the available data suggest that beta-blockers might confer greater protection than other drug regimens. However, more evidence is needed to confirm these findings. It is concluded that observational studies could play an increasing role in the assessment of the role of antihypertensive therapy in the primary prevention of coronary heart disease when the inherent potentials and pitfalls of these studies are appreciated.


Ecology of breastfeeding in the United States: An applied perspective.
Breastfeeding initiation and duration have followed distinct cycles in the United States. Despite recent increases, breastfeeding rates still fall short of public health goals. This paper takes an applied perspective to examine the potential role of human biologists in enhancing the promotion of breastfeeding in the United States. The conceptual model of breastfeeding held by policy makers and public health professionals is distinguished from that of human biologists. An integrated model is proposed that incorporates the sociodemographic factors of the public health model with the components of breastfeeding structure and early mother-infant interaction of the human biology model. It is suggested that human biologists can contribute to the more effective promotion of breastfeeding by promoting inclusion of a wide range of anthropological research on infant feeding, clarifying the vocabulary of infant feeding, and expanding their own research to include participation in the development and testing of breastfeeding interventions. Am. J. Hum. Biol. 10:221-228, 1998. © 1998 Wiley-Liss, Inc.


Distribution of forebrain diffuse axonal injury following inertial closed head injury in miniature swine.
Diffuse axonal injury (DAI) is one of the most frequently encountered types of brain damage resulting from closed head injury. This study was designed to verify whether DAI could be produced in miniature swine by rapid acceleration and deceleration of the head in the coronal plane. Hanford miniature swine (16-19 kg) were anesthetized with 3% isoflurane and their heads accelerated rapidly once through a 60-105 degrees arc in the coronal plane, producing only transient post-traumatic unconsciousness without prolonged coma. All animals made a good recovery and were sacrificed between 6 h and 10 days after injury. The response of forebrain projection systems to this injury was studied using neurofilament immunohistochemistry with antisera to nonphosphorylated (SMI-32) and phosphorylated (SMI-31) epitopes common to heavy (200 kDa) and medium (160 kDa) neurofilament proteins. In 9 of 12 animals, lesions characterized by foci of SMI-32 positive axonal retraction balls were present at the white matter/gray matter junction at the crests of gyri in the dorsolateral regions of the frontal, parietal, and temporal cortices and along margins of the lateral ventricles. A high density of pyramidal neuron perikarya in layers III and V within cortical gyri associated with subcortical DAI were intensely positive for SMI-31 immunohistochemistry. These results validate the use of miniature swine in studies of axonal injury and demonstrate that axonal injury analogous to that seen in the mildest form of DAI (grade I) can be produced in these animals without producing prolonged coma.


Fixed-Level Frequency Threshold Testing for Ototoxicity Monitoring.
Hearing loss from ototoxicity is often most pronounced at high frequencies. To improve patient monitoring and compliance, high-frequency testing methods should be short and easy to administer. We evaluated the repeatability and accuracy of a Békésy-like, fixed-level frequency threshold (FLFT) technique. This test takes less than a minute and could provide a rapid and effective way to determine the highest audible frequency. We hypothesized the FLFT test would be repeatable in normal-hearing subjects, and accurate when compared with Békésy fixed-frequency audiometry in the sensitive region for ototoxicity (SRO). Twenty-nine normal-hearing subjects (20 females, 9 males) performed 2 different automated audiometry tests at least 4 times over a period of no less than 3 weeks. Ages ranged from 23 to 35 years (average = 28 years). Subjects completed testing under Sennheiser HDA-200 headsets. Initial fixed-frequency audiometry thresholds were obtained at frequencies ranging from 0.5 to 20 kHz to identify each subject's highest audible frequency, which was used to determine the SRO. The SRO was defined as the seven frequencies at and below the highest audible frequency in 1/6-octave steps. These frequencies were monitored with fixed-frequency audiometry. At each session, the FLFT test was administered at 80 dB SPL. Subjects used a Békésy-style tracking method to determine the frequency threshold. All testing was completed in a sound booth (single wall, Industrial Acoustics Company) using a computerized, laptop-based, system. FLFT repeatability was calculated as the root mean square difference from the first test session. FLFT accuracy was calculated as the difference from the highest audible frequency determined from fixed-frequency audiometry interpolated to 80 dB SPL level. The FLFT average RMSD for intersession variability was 0.05 ± 0.05 octaves. The test showed no learning effect [F(3,78) = 0.7; p = 0.6]. The overall intersession variability for SRO fixed-frequency audiometry thresholds at all frequencies was within clinically acceptable test-retest variability (10 dB) at 5.8 dB (range 2.7 to 9.9 dB). The SRO fixed-frequency audiometry therefore served as a repeatable basis of comparison for accuracy of the FLFT test. The mean absolute difference between the fixed-frequency audiometry and FLFT-determined highest audible frequency was 0.03 octaves. The FLFT and the highest audible frequency via fixed-frequency audiometry at 80 dB SPL were not different statistically (p = 0.12). The FLFT took approximately 30 seconds to complete, compared with approximately 4.5 min for fixed-frequency audiometry SRO and 20 to 25 min for a traditional ototoxic audiometric assessment. The Békésy-style FLFT was repeatable within 1/12 octave (1 step size in the testing procedure). The FLFT agreed well with the highest audible frequency determined via fixed-frequency audiometry at 80 dB SPL. The FLFT test is amenable to automatic and self-administration and may enable quick, accurate, noise-tolerant ototoxicity, and high-frequency hearing monitoring.


Heterocephalacria mucosa sp. nov., a new basidiomycetous yeast species isolated from a mangrove forest in Thailand.
Strains of yeast were isolated under a nitrogen-depleted culture condition from decaying tree bark (strain N-12.1) and from mangrove forest water (strain 1-7W.1) sampled at different locations within a mangrove forest site in Ranong province, Thailand. They were found to be genetically and phenotypically different from any currently recognised yeast species. Phylogenetic analysis of nucleotide sequence of three genes, the internal transcribed spacer region 1 and 2 plus 5.8S ribosomal RNA gene (ITS), D1/D2 domain of the large subunit ribosomal RNA gene (LSU D1/D2) and the small subunit of the ribosomal RNA gene (SSU), revealed that these two strains were related to but distinguished from Heterocephalacriaarrabidensis. Several distinct physiological characteristics of these two strains were detected, namely inability to assimilate glycerol, dl-lactic acid, succinic acid, citric acid, d-gluconic acid, and ability to grow well at 25 °C, which were different from those of H. arrabidensis. Accordingly, the name Heterocephalacria mucosa sp. nov., is proposed to accommodate this novel species. The MycoBank number is MB 828624.


Prevention of common healthcare-associated infections in humanitarian hospitals.
Humanitarian medical organizations focus on vulnerable patients with increased risk for healthcare-associated infections (HAIs) and are obligated to minimize them in inpatient departments (IPDs). However, in doing so humanitarian groups face considerable obstacles. This report will focus on approaches to reducing common HAIs that the authors have found to be helpful in humanitarian settings. HAIs are common in humanitarian contexts but there are few interventions or guidelines adapted for use in poor and conflict-affected settings to improve prevention and guide surveillance. Based on existing recommendations and studies, it appears prudent that all humanitarian IPDs introduce a basic infection prevention infrastructure, assure high adherence to hand hygiene with wide accessibility to alcohol-based hand rub, and develop pragmatic surveillance based on clinically evident nosocomial infection. Although microbiology remains out of reach for most humanitarian hospitals, rapid tests offer the possibility of improving the diagnosis of HAIs in humanitarian hospitals in the decade ahead. There is a dearth of new studies that can direct efforts to prevent HAIs in IPDs in poor and conflict-affected areas and there is a need for practical, field-adapted guidelines from professional societies, and international bodies to guide infection prevention efforts in humanitarian environments.


Flexible intramedullary nailing in simple bone cysts of the proximal humerus: prospective study for high-risk cases of pathologic fracture.
We designed and evaluated a modified cyst index using the Picture Archiving and Communication System software for treating simple bone cysts of the proximal humerus by preventive intramedullary flexible nail insertion in symptomatic children or adolescents. From January 2007 to December 2009, cases with a cyst index of at least 4 were enrolled in the study. Of 20 total cases, 19 were prospectively followed-up for at least 2 years. The mean patient age was 10.6 years (range, 7-15 years) and the mean modified cyst index was 6.56 (range, 4.95-8.25). The mean cyst healing period was 8.7 months (range, 4-30 months) and the mean follow-up period was 31.05 months (range, 24-42 months). Seventeen lesions (89%) were classified as completely healed and two (11%) were classified as healed with residual radiolucency. In all cases, no angular deformity was found on the final follow-up radiograph. Therefore, preventive flexible intramedullary nail insertion before the occurrence of a pathologic fracture because of simple bone cysts with a modified cyst index of at least 4 in the proximal humerus is an excellent treatment option. Therapeutic Level IV.


Effect of free fall on higher plants.
The influence of exposure to the free fall state on the orientation, morphogenesis, physiology, and radiation response of higher plants is briefly summarized. It is proposed that the duration of the space-flight experiments has been too brief to permit meaningful effects of free fall on general biochemistry, growth and development to appear. However, two types of significant effect did occur. The first is on differential growth, i.e. tropism and epinasty, resulting from the absence of a normal geostimulus. For these phenomena it is suggested that ground-based experiments with the clinostat would suffice to mimic the effect of the free fall state. The second is an apparent interaction between the radiation response and some flight condition, yielding an enhanced microspore abortion, a disturbed spindle function, and a stunting of stamen hairs. It is suggested that this apparent interaction may be derived from a shift in the rhythm of the cell cycle, induced by the free fall.


Update on Identification and Treatment of Infants and Toddlers With Suspected Childhood Apraxia of Speech.
The purpose of this tutorial is to (a) provide an updated review of the literature pertaining to proposed early features of childhood apraxia of speech (CAS), (b) discuss the findings of recent treatment studies of infants and toddlers with suspected CAS (sCAS), and (c) present evidence-based strategies and tools that can be used for the identification of and intervention for infants and toddlers with sCAS or at high risk for the disorder. Since Davis and Velleman's (2000) seminal work on assessment and intervention in infants and toddlers with sCAS, limited research has guided clinicians in the complex task of identifying and treating early speech motor difficulties prior to a definitive diagnosis of CAS. Following the structure of Davis and Velleman, we explore the proposed early characteristics of CAS with reference to contemporary research. Next, we describe the limited treatment studies that have investigated intervention for infants and toddlers at risk of or suspected of having CAS. Finally, we present practical suggestions for integrating this knowledge into clinical practice. Many of the originally proposed correlates of CAS in infants and toddlers now have research supporting their presence. However, questions remain about the developmental trajectory of the disorder. Although limited in number and restricted by lack of experimental control, emerging treatment studies can help guide clinicians in providing appropriate intervention to infants and toddlers with sCAS who need not wait for a definitive diagnosis to initiate intervention.


Designing supramolecular liquid-crystalline hybrids from pyrenyl-containing dendrimers and arene ruthenium metallacycles.
The association of the arene ruthenium metallacycle [Ru4(p-cymene)4(bpe)2(donq)2][DOS]4 (bpe = 1,2-bis(4-pyridyl)ethylene, donq = 5,8-dioxydo-1,4-naphtoquinonato, DOS = dodecyl sulfate) with pyrenyl-functionalized poly(arylester) dendrimers bearing cyanobiphenyl end-groups is reported. The supramolecular dendritic systems display mesomorphic properties as revealed by polarized optical microscopy, differential scanning calorimetry and small-angle X-ray scattering measurements. The multicomponent nature of the dendrimers and of the corresponding host-guest supramolecules (i.e., end-group mesogens, dendritic core, pyrene unit, aliphatic spacers, and metallacycle) leads to the formation of highly segregated mesophases with a complex multilayered structure due to the tendency of the various constitutive building-blocks to separate in different organized zones. The pyrenyl dendrimers exhibit a multilayered smectic A-like phase, thereafter referred to as LamSmA phase to emphasize this unaccustomed morphology. As for the corresponding Ru4-metallacycle adducts, they self-organize into a multicontinuous thermotropic cubic phase with the Im3̅m space group symmetry. This represents a unique example of liquid-crystalline behavior observed for such large and complex supramolecular host-guest assemblies. Models of their supramolecular organizations within both mesophases are proposed.


Activity of temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam against carbapenem-non-susceptible Enterobacteriaceae without carbapenemase production.
Treatment options for multidrug-resistant Gram-negative infections are scarce and therefore alternatives with a narrow spectrum or new agents are sought. Antimicrobial susceptibility to temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam was determined using Etest and disk diffusion according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology. A total of 77 carbapenem-nonsusceptible Enterobacteriaceae were studied, including Klebsiella pneumoniae (26%), Escherichia coli (26%), Enterobacter cloacae (26%), and Enterobacter aerogenes (22%). Several phenotypic tests, PCRs followed by sequencing and a microbiological bioassay excluded carbapenemase production in all isolates. Antimicrobial susceptibility rates were low for temocillin (15.6%, minimum inhibitory concentration [MIC] range 2 to >1,024 μg/ml), moderate for mecillinam (59.7%, MIC range 0.25 to >256 μg/ml), and excellent for ceftazidime/avibactam (100%, zone diameter range 19 to 32 mm, median 25 mm). 5.2% of the isolates were susceptible to ceftazidime alone (zone diameter range 6 to 32 mm). In this study, mecillinam exhibited moderate and ceftazidime/avibactam excellent in vitro antimicrobial activity against carbapenem-nonsusceptible Enterobacteriaceae without carbapenemase production. Ceftazidime/avibactam was able to restore previously reduced susceptibility to ceftazidime in all isolates, thus potentiating its activity. Temocillin only exhibited low in vitro antimicrobial activity against the isolates. Further evaluation of mecillinam and ceftazidime/avibactam with regard to the potential clinical utility against infections caused by these pathogens has to be performed.


Field evolution of coexisting superconducting and magnetic orders in CeCoIn5.
We present nuclear magnetic resonance (NMR) measurements on the three distinct In sites of CeCoIn5 with a magnetic field applied in the [100] direction. We identify the microscopic nature of the long range magnetic order (LRO) stabilized at low temperatures in fields above 10.2 T while still in the superconducting (SC) state. We infer that the ordered moment is oriented along the c axis and map its field evolution. The study of the field dependence of the NMR shift for the different In sites indicates that the LRO likely coexists with a modulated SC phase, possibly that predicted by Fulde, Ferrell, Larkin, and Ovchinnikov. Furthermore, we discern a field region dominated by strong spin fluctuations where static LRO is absent and propose a revised phase diagram.


Spontaneous arterio-venous fistulae of the vertebral artery. Diagnostic and therapeutic considerations.
Spontaneous arterio-venous fistulae of the vertebral artery are rare. These lesions mainly affect the upper cervical area, and are usually asymptomatic, or may present as small, often pulsatile, cervical masses with vascular murmurs. The authors report on two cases in which the presumptive diagnosis, suggested by venous digital subtraction angiography, was then confirmed by selective angiography. In both cases an intravascular approach with detachable balloons and particulate substances was carried out, with good anatomical and functional results. Problems related to diagnosis, pathophysiology of symptoms, indications for treatment and embolization techniques are discussed.