[Clinical value of the gonadotropic hormone releasing hormone (GHRH) test in the diagnosis of growth deficiency].
Many stimulation tests are available for the assessment of growth hormone release from the pituitary in clinical practice. Three of the most common tests are insulin-hypoglycaemia, arginine stimulation and spontaneous hGH nocturnal peaks and profiles. In this study we compared the Growth hormone releasing-hormone (GHRH)-test in a dose of 1 microgram/kg b.w. with these three other tests for evaluation of the somatotropic function of the pituitary. Each of these four tests was performed in 29 children with short stature due to growth failure of various etiologies and height-deficits (-SDS) of -3.0 +/- 0.5 SE. The peak plasma hGH levels of all patients after GHRH stimulation did not correlate with the respective peak values during insulin (r = 0.02) and arginine (r = 0.28) stimulation and with peak levels during the spontaneous nocturnal hGH profile (r = 0.18). The diagnostic value of the GHRH test alone is thus still questionable in establishing the diagnosis of a hypothalamic GHRH/GH defect, because some of these patients do not react to the first GHRH dose as one might expect, but only after a few days of repeated injections of GHRH (priming). The tolerance of intravenous injections of GHRH was excellent. The mean plasma GH response to GHRH was higher (p less than 0.05) in the group of children with constitutional short stature than in GH deficient patients, but there were overlaps in this group with normal volunteers and other groups of patients with growth failure.


Understanding factors that influence the decision to be vaccinated against influenza and pertussis in pregnancy: A qualitative study.
To identify how pregnant women perceive pertussis and influenza and the factors that influence their decision to be vaccinated. Suffering from influenza during pregnancy increases complications in the pregnant woman, foetus and newborn. Pertussis in children under six months of age causes severe complications. Maternal vaccination against influenza and pertussis is effective and safe. However, vaccination rates are insufficient. We conducted a qualitative descriptive study, using semi-structured interviews. This research adheres to the COREQ guidelines and checklist. We carried out 18 semi-structured face-to-face interviews with pregnant women, using intentional sampling and thematic analysis. We identified an overarching theme, 'factors that influenced participants' decision to be vaccinated or not', which was composed of four subthemes that were in turn made up of 12 categories. The factors that influenced participants' decision to be vaccinated against influenza and pertussis were related to their knowledge of and their perception of risk for these diseases. Participants perceived the risk of pertussis to be greater, and they focused their concern on the newborn. The recommendations and convictions of nurse-midwives were the most important factors encouraging vaccination. Participants trusted their nurse-midwives and most reported that they would have been vaccinated if their midwife had recommended it. Other factors were linked to lack of information, fear and concerns about economic interests. The convictions and actions of the nurse-midwife in recommending vaccination to pregnant women are decisive. Strategies to improve vaccination rates should be directed to helping health professionals understand how their practice affects the final decision of pregnant women. Understanding the factors that limit vaccination rates among pregnant women provides valuable information to nurse-midwives that can help to improve vaccination strategies and practices. Increased maternal vaccination rates would reduce morbidity and mortality among pregnant women and newborns.


A novel computational framework for deducing muscle synergies from experimental joint moments.
Prior experimental studies have hypothesized the existence of a "muscle synergy" based control scheme for producing limb movements and locomotion in vertebrates. Such synergies have been suggested to consist of fixed muscle grouping schemes with the co-activation of all muscles in a synergy resulting in limb movement. Quantitative representations of these groupings (termed muscle weightings) and their control signals (termed synergy controls) have traditionally been derived by the factorization of experimentally measured EMG. This study presents a novel approach for deducing these weightings and controls from inverse dynamic joint moments that are computed from an alternative set of experimental measurements-movement kinematics and kinetics. This technique was applied to joint moments for healthy human walking at 0.7 and 1.7 m/s, and two sets of "simulated" synergies were computed based on two different criteria (1) synergies were required to minimize errors between experimental and simulated joint moments in a musculoskeletal model (pure-synergy solution) (2) along with minimizing joint moment errors, synergies also minimized muscle activation levels (optimal-synergy solution). On comparing the two solutions, it was observed that the introduction of optimality requirements (optimal-synergy) to a control strategy solely aimed at reproducing the joint moments (pure-synergy) did not necessitate major changes in the muscle grouping within synergies or the temporal profiles of synergy control signals. Synergies from both the simulated solutions exhibited many similarities to EMG derived synergies from a previously published study, thus implying that the analysis of the two different types of experimental data reveals similar, underlying synergy structures.


Role of Sn as a Process Control Agent on Mechanical Alloying Behavior of Nanocrystalline Titanium Based Powders.
In this study, the effects of Sn as a process control agent (PCA) on the final powder sizes, morphology, homogenization and alloying process of a new titanium alloy were investigated. Two kinds of powders, Ti10Ta8Mo and Ti10Ta8Mo3Sn (wt %), were prepared using a mechanical alloying process. For the Ti10Ta8Mo3Sn (wt %) alloy, the Sn element was used as PCA to enhance the milling process in the planetary ball mill. The milling process of both compositions was carried out with 200 rpm for 10, 15, 20, 40, 60, 80 and 100 h. The results confirmed that using Sn as a process control agent can result in a relatively good size distribution and better yield performance compared to samples without Sn addition. The phase analysis using X-ray diffraction proved the formation of the α nanocrystalline phase and the partial phase transformation from α to nanocrystalline β phases of both alloy compositions. The Scaning Electron Micoscope- Backscattered Electrons SEM-BSE results confirmed that the use of Sn as the PCA can provide a better homogenization of samples prepared by at least 60 h of ball milling. Furthermore, the presence of Sn yielded the most uniform, spheroidal and finest particles after the longest milling time.


Superfast assembly and synthesis of gold nanostructures using nanosecond low-temperature compression via magnetic pulsed power.
Gold nanostructured materials exhibit important size- and shape-dependent properties that enable a wide variety of applications in photocatalysis, nanoelectronics and phototherapy. Here we show the use of superfast dynamic compression to synthesize extended gold nanostructures, such as nanorods, nanowires and nanosheets, with nanosecond coalescence times. Using a pulsed power generator, we ramp compress spherical gold nanoparticle arrays to pressures of tens of GPa, demonstrating pressure-driven assembly beyond the quasi-static regime of the diamond anvil cell. Our dynamic magnetic ramp compression approach produces smooth, shockless (that is, isentropic) one-dimensional loading with low-temperature states suitable for nanostructure synthesis. Transmission electron microscopy clearly establishes that various gold architectures are formed through compressive mesoscale coalescences of spherical gold nanoparticles, which is further confirmed by in-situ synchrotron X-ray studies and large-scale simulation. This nanofabrication approach applies magnetically driven uniaxial ramp compression to mimic established embossing and imprinting processes, but at ultra-short (nanosecond) timescales.


Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011.
Neuromuscular blocking drugs (NMBDs) are the most common cause of intraoperative anaphylaxis in Western Australia. Differences in the rates of anaphylaxis between individual agents have been surmised in the past, but not proven, and are an important consideration if agents are otherwise equivalent. We estimated a rate of anaphylaxis to NMBDs by analysing cases of NMBD anaphylaxis referred to the only specialized diagnostic centre in Western Australia over a 10 yr period. Exposure was approximated by analysing a 5 yr period of NMBD ampoule sales data. Agents were also ranked according to the prevalence of cross-reactivity in patients with previous NMBD anaphylaxis. Rocuronium was responsible for 56% of cases of NMBD anaphylaxis, succinylcholine 21%, and vecuronium 11%. There was no difference in the severity of reactions for different NMBDs. Rocuronium had a higher rate of IgE-mediated anaphylaxis compared with vecuronium (8.0 vs 2.8 per 100,000 exposures; P=0.0013). The prevalence of cross-reactivity after NMBD anaphylaxis suggested that succinylcholine also has a high risk of triggering anaphylaxis. Cisatracurium had the lowest prevalence of cross-reactivity in patients with known anaphylaxis to rocuronium or vecuronium. Rocuronium has a higher rate of IgE-mediated anaphylaxis compared with vecuronium, a result that is statistically significant and clinically important. Cisatracurium had the lowest rate of cross-reactivity in patients who had previously suffered anaphylaxis to rocuronium or vecuronium.


Osteoid in bones of elderly patients without bone disease.
Bone samples were taken at post-mortem examination by Jamshidi needles from 88 elderly patients who were known to have normal bone biochemistry in life. The extent of osteoid in these samples is quantitatively described. In patients with normal creatinines the relative osteoid area ranges from 0 to 3.7% and trabecular osteoid surface percentage ranges from 0 to 23%, but higher values were seen in those with raised creatinines. Osteoid extent did not vary with age, sex or time of year. Descriptions of other series of control bone biopsies in the literature are reviewed and it is suggested that relative osteoid area greater than 3.5% or osteoid surfaces greater than 25% should be considered excess osteoid.


Assessing children's and parents' opinions on salivary sampling for therapeutic drug monitoring.
This paper describes preliminary development and pilot testing of a questionnaire to assess opinions on saliva sampling for therapeutic drug monitoring (TDM) in paediatric patients. Less distressing alternatives are needed for sampling body fluids from children and young people for TDM to obtain results that are as accurate as those attained from blood samples. Two versions of a salivary sampling questionnaire were developed, one for young children and one for older children and young people and administered to two cohorts of 15 children and young people aged from eight to 19 years, and their parents. Questionnaire refinement based on feedback from the first was undertaken before administration tothe second. Data were analysed thematically. Where saliva sampling is a viable alternative to blood sampling, it should be offered in-clinic as well as at home to provide opportunities for direct communication with clinicians if that is the preferred option for children and young people. The questionnaire has potential value for assessing preferences in clinical scenarios involving where saliva sampling may be indicated. Ongoing research is needed to inform item development and refinement, and to investigate questionnaire validity and psychometric performance.


Community integration programs and interventions for people with spinal cord injury: a scoping review.
The focus of this scoping review was to identify the extent, range, and nature of studies that have been published regarding community integration programs and interventions that support people during the transition home from hospital following spinal cord injury. Four electronic databases and one search engine were searched for articles published between 2010 and 2020. Grey literature and manual searches were also done. Of the 16 articles included, 8 were published in peer-reviewed journals. Two of these did not include an evaluation. Study designs included but were not limited to pilot studies (n = 2); mixed methods evaluations (n = 2); single-site randomized controlled trials (n = 3); and, non-randomized single-arm study design (n = 1). The articles were from the United States (n = 12), Canada (n = 2), Australia (n = 1), and the United Kingdom (n = 1). The majority of interventions focused on addressing health-related educational needs, followed by community mobility. Goal setting and promoting self-efficacy were identified as important components, and the importance of involvement of people with lived experience was also highlighted. There was a lack of focus on management of relationships, including addressing sexuality needs. This review highlights the need for further empirical evaluation of implemented programs and interventions in this area, particularly in countries other than the USA, to inform service development.IMPLICATIONS FOR REHABILITATIONSuccessful community integration is an important outcome of spinal cord injuries rehabilitation.The majority of published programs focus on health-related educational needs, followed by community mobility.It is recommended that goal setting and promoting self-efficacy are included in programs.It is recommended that people with lived experience of spinal cord injuries are involved in interventions.It is recommended that programs include a focus on management of relationships, including addressing sexuality needs.


Immunoglobulin G Antibodies to SARS-CoV-2 Among Healthcare Workers at a Tertiary Care Center in South India.
Introduction Healthcare workers (HCWs) are at risk of exposure to SARS-CoV-2. Seroprevalence in this group may offer insights into trends to monitor and revise strategies to prevent transmission. Methods A cross-sectional study was conducted in two phases among healthcare workers at a tertiary care center to detect IgG antibodies to SARS-CoV-2. Seropositivity was calculated during both phases, and possible associations were determined using regression analysis. Results A total of 382 and 168 HCWs took part in the two phases, respectively. IgG antibodies were detected in 13 of 382 (3.4%; 95% confidence interval (CI): 2%-5.7%) and 71 of 168 (42.3%) participants in the first and second phases, respectively. Receiving at least one dose of vaccine (p < 0.001) and age (p = 0.028) were factors associated with the presence of antibodies, while gender, job type, exposure to COVID-19 cases, and comorbidities were not associated with seropositivity. Conclusion Serosurveys among HCWs may help identify transmission patterns and redesign infection control practices in the healthcare setting.


[Effects of duration on the equal loudness contours of short and brief tones: 40 phones equal loudness contours. Preliminary experiments (author's transl)].
Loudness balances have been obtained between 10-, 20-, 100- and 1,000-ms tones of different frequencies (62.5, 125, 250, 500, 1,000, 2,000, 4,000, 8,000 and 12,000 Hz), and a constant reference tone of 1,000 Hz and 1,000 ms duration at 40 dB SPL. The absolute thresholds were also measured on the same observers at each duration. Progressive shifts of the equal loudness contours appear when the durations become shorter, in the same direction as the corresponding shifts of the threshold curves; the shifts of the equal loudness contours and the corresponding shifts of the threshold curves do not however appear completely similar; some differences may also exist between tones of differing frequencies. These experiments were preliminary ones; some problems arise, in relation with the technique used; improvements appear necessary.


On the genetic contribution to selected multifactorial diseases with autoimmune characteristics.
The genetics of multifactorial diseases characterized by autoimmune phenomena are elusive so far. Yet, it is clear that the genetic contribution to a given clinically defined autoimmune disease entity is mostly variable and highly complex. On the basis of two basically different model diseases, Wegener's Granulomatosis and multiple sclerosis, approaches are discussed to unravel at least certain genetic predisposition factors. Major difficulties in these analyses arise from (in)exact definition of the clinical phenotype (disease entity), the vast number of potential candidate genes, the small to modest contribution of each genetic variation to disease risk and the combinatorial possibilities.


Synthesis and conformational analysis of hybrid α/β-dipeptides incorporating S-glycosyl-β(2,2)-amino acids.
We synthesized and carried out the conformational analysis of several hybrid dipeptides consisting of an α-amino acid attached to a quaternary glyco-β-amino acid. In particular, we combined a S-glycosylated β(2,2)-amino acid and two different types of α-amino acid, namely, aliphatic (alanine) and aromatic (phenylalanine and tryptophan) in the sequence of hybrid α/β-dipeptides. The key step in the synthesis involved the ring-opening reaction of a chiral cyclic sulfamidate, inserted in the peptidic sequence, with a sulfur-containing nucleophile by using 1-thio-β-D-glucopyranose derivatives. This reaction of glycosylation occurred with inversion of configuration at the quaternary center. The conformational behavior in aqueous solution of the peptide backbone and the glycosidic linkage for all synthesized hybrid glycopeptides was analyzed by using a protocol that combined NMR experiments and molecular dynamics with time-averaged restraints (MD-tar). Interestingly, the presence of the sulfur heteroatom at the quaternary center of the β-amino acid induced θ torsional angles close to 180° (anti). Notably, this value changed to 60° (gauche) when the peptidic sequence displayed aromatic α-amino acids due to the presence of CH-π interactions between the phenyl or indole ring and the methyl groups of the β-amino acid unit.


Molecular iodine catalyzed cross-dehydrogenative coupling reaction between two sp3 C-H bonds using hydrogen peroxide.
A useful method for molecular iodine catalyzed oxidative C-C bond formation between tertiary amines and a carbon nucleophile using hydrogen peroxide as the terminal oxidant is reported. This is the first report of a molecular iodine catalyzed cross-dehydrogenative coupling (CDC) reaction between two sp(3) C-H bonds.


Isolating spectral cues in amplitude and quasi-frequency modulation discrimination by reducing stimulus duration.
This study investigated the psychophysical effects of distortion products in a listening task traditionally used to estimate the bandwidth of phase sensitivity. For a 2000 Hz carrier, estimates of modulation depth necessary to discriminate amplitude modulated (AM) tones and quasi-frequency modulated (QFM) were measured in a two interval forced choice task as a function modulation frequency. Temporal modulation transfer functions were often non-monotonic at modulation frequencies above 300 Hz. This was likely to be due to a spectral cue arising from the interaction of auditory distortion products and the lower sideband of the stimulus complex. When the stimulus duration was decreased from 200 ms to 20 ms, thresholds for low-frequency modulators rose to near-chance levels, whereas thresholds in the region of non-monotonicities were less affected. The decrease in stimulus duration appears to hinder the listener's ability to use temporal cues in order to discriminate between AM and QFM, whereas spectral information derived from distortion product cues appears more resilient.


C1orf194 deficiency leads to incomplete early embryonic lethality and dominant intermediate Charcot-Marie-Tooth disease in a knockout mouse model.
Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy and shows clinical and genetic heterogeneity. Mutations in C1orf194 encoding a Ca2+ regulator in neurons and Schwann cells have been reported previously by us to cause CMT disease. In here, we further investigated the function and pathogenic mechanism of C1or194 by generating C1orf194 knockout (KO) mice. Homozygous mutants of C1orf194 mice exhibited incomplete embryonic lethality, characterized by differentiation abnormalities and stillbirth on embryonic days 7.5-15.5. Heterozygous and surviving homozygous C1orf194 KO mice developed motor and sensory defects at the age of 4 months. Electrophysiologic recordings showed decreased compound muscle action potential and motor nerve conduction velocity in the sciatic nerve of C1orf194-deficient mice as a pathologic feature of dominant intermediate-type CMT. Transmission electron microscopy analysis revealed demyelination and axonal atrophy in the sciatic nerve as well as swelling and loss of mitochondrial matrix and other abnormalities in axons and Schwann cells. A histopathologic examination showed a loss of motor neurons in the anterior horn of the spinal cord and muscle atrophy. Shorter internodal length between nodes of Ranvier and Schmidt-Lanterman incisures was detected in the sciatic nerve of affected animals. These results indicate that C1orf194 KO mice can serve as an animal model of CMT with a severe dominant intermediate CMT phenotype that can be used to investigate the molecular mechanisms of the disease and evaluate the efficacy of therapeutic strategies.


Development of a novel positive psychology-based intervention for couples post-stroke.
Stroke provides challenges for survivors and partner caregivers. Stroke survivors and caregivers are interconnected in their emotional health, including depression, a common stroke sequelae. The purpose of this study was to develop and test the feasibility of a dyadic positive psychology-based intervention (PPI) for couples coping poststroke. Community-dwelling couples consisted of 1 partner who had a stroke ≥6 months ago and a cohabiting partner caregiver. One or both partner(s) had to report depressive symptoms. The PPI consisted of 1 brief face-to-face training session and an 8-week self-administered intervention in which participants were instructed to engage in at least 2 activities alone and 2 together each week. Two dyads were randomly assigned to a waitlist control to test feasibility of this process. Baseline, postintervention, and 3-month follow-up assessments and post-program feedback were obtained. Descriptive statistics were used to analyze sample characteristics, recruitment and retention rates, adherence, key pre- and postintervention outcomes, and satisfaction with the intervention. Eleven of 20 couples responding to recruitment letters were enrolled in the study. Ten of 11 dyads completed the program. All participants engaged in activities for at least 6 of 8 weeks. Feedback data indicated participant satisfaction with the intervention, and key outcome measures demonstrated adequate variability. The self-administered dyadic PPI is feasible for implementation with couples poststroke. The PPI represents a first step in a novel dyadic approach in this population. Recruitment, enrollment and attrition rates, and feedback will be used to inform a larger randomized trial. (PsycINFO Database Record


[Photodynamic Therapy].
Photodynamic therapy( PDT) is a method consider "medical treatment" in which a drug( i.e., photosensitizer) is incorporated into a tumor and a laser beam of a wavelength corresponding thereto generates a reaction consider "elicits a phototoxic reaction that kills the tumor cells". It is a less invasive treatment that has a tumor-selective cell killing effect and has been established as a standard therapy for centrally located early stage lung cancer. Most patients with centrally located early stage lung cancer are heavy smokers, and cardiopulmonary function is often deteriorated owing to pulmonary emphysema or heart disease. Centrally located early stage lung cancer is known to occur frequently as synchronous or metachronous neoplasm. Taking the patient's background into consideration, PDT that does not affect the pulmonary function may be considered as a promising treatment. Herein, we outline the current applications of PDT and its future prospects.


Small animal PET: a review of what we have done and where we are going.
Small animal research is an essential tool in studying both pharmaceutical biodistribution and disease progression over time. Furthermore, through the rapid development ofin vivoimaging technology over the last few decades, small animal imaging (also referred to as preclinical imaging) has become a mainstay for all fields of biologic research and a center point for most preclinical cancer research. Preclinical imaging modalities include optical, MRI and MRS, microCT, small animal PET, ultrasound, and photoacoustic, each with their individual strengths. The strong points of small animal PET are its translatability to the clinic; its quantitative imaging capabilities; its whole-body imaging ability to dynamically trace functional/biochemical processes; its ability to provide useful images with only nano- to pico- molar concentrations of administered compounds; and its ability to study animals serially over time. This review paper gives an overview of the development and evolution of small animal PET imaging. It provides an overview of detector designs; system configurations; multimodality PET imaging systems; image reconstruction and analysis tools; and an overview of research and commercially available small animal PET systems. It concludes with a look toward developing technologies/methodologies that will further enhance the impact of small animal PET imaging on medical research in the future.


Sexual harassment at work. Introduction.
This article introduces the special section on sexual harassment at work. It discusses the importance of sexual harassment as a continuing, chronic occupational health psychology problem to which the public health and preventive medicine notions of prevention may be applied. The article discusses the dilemmas in conducting and reviewing research on harassment, briefly examining some alternative methods of inquiry. The three articles in this section are introduced and the contrasting legal views of the problems in Europe and the United States are addressed. The preventive management of sexual harassment is suggested.


Multiple sclerosis: relapses, resource use, and costs.
Relapses can have a major impact on the lives of people with multiple sclerosis (MS), and yet relapse-related healthcare costs have received little attention. This has limited cost-effectiveness analyses of treatments for MS and hampered decision-making regarding the funding of MS healthcare services. To describe health/social care resource use and costs according to the frequency, severity, and endurance of MS relapses. Data from the prospective, longitudinal UK South West Impact of Multiple Sclerosis cohort were used. A total of 11,800 questionnaires from 1441 people with MS were available, including data on relapses, contacts with health/social care professionals, and other MS-related resource use. The mean (SD) 6-monthly MS-related health/social care cost for individuals who reported a relapse was £519 (£949), compared to £229 (£366) for those who had not did report a relapse. Care costs varied widely dependent on the characteristics of the relapse. The mean (SD) cost when a relapse was not treated with steroids was £381 (£780), whilst the equivalent cost was £3579 (£1727) when a relapse resulted in hospitalization. The impact of relapses on health and social care resources and costs differs according to their frequency, length, and severity. The data provided here can be used in cost-effectiveness analyses and to inform decision-making regarding healthcare provision for people with this condition.


Hemoglobin Philly (beta 35 tyrosine phenylalanine): studies in the molecular pathology of hemoglobin.
An abnormal unstable hemoglobin, hemoglobin Philly, was found in three members of a family, each of whom had evidence of a chronic hemolytic state. The presence of the mutant protein was suggested by the rapid appearance of inclusion bodies upon incubation of erythrocytes with brilliant cresyl blue and by the increased heat precipitability of the hemoglobin. However, no abnormal hemoglobin could be demonstrated by electrophoresis or column chromatography. Sulfhydryl titration of the hemolysates with p-mercuribenzoate indicated that there was an average of four reactive sulfhydryl groups per hemoglobin molecule instead of the usual two. The total number of hemoglobin sulfhydryl groups was normal; six groups were measured when denatured globin was reacted with 5,5'-dithiobis[2-nitrobenzoic acid]. This indicated that the increased sulfhydryl reactivity was due to an increased availability to p-mercuribenzoate of the usually unreactive hemoglobin cysteines at beta112 and alpha104. After treatment for (1/2) hr with 4-5 moles of p-mercuribenzoate per mole of hemoglobin, electrophoresis revealed that 30-35% of the hemoglobin had been dissociated into alpha- and beta-chains. Normal hemolysates revealed negligible splitting after 72 hr of similar treatment. The alpha- and beta-chains of hemoglobin Philly were separated from the unsplit hemoglobin A by carboxymethyl cellulose chromatography. Fingerprint and amino acid analyses revealed that tyrosine beta35 was replaced by phenylalanine. In hemoglobin Philly there is loss of the normal hydrogen bond between the tyrosine hydroxyl group and the carboxyl group of aspartic acid alpha126 at the alpha(1)beta(1) contact. This shifts the equilibrium from hemoglobin tetramers toward monomers, exposing the beta112 and alpha104 cysteines. In the cell, precipitation of the unstable monomers may contribute to erythrocyte destruction.


Isolated arthroscopic partial meniscectomy. Functional radiographic evaluation at five years.
Fifty patients who underwent isolated arthroscopic partial meniscectomy with a minimum followup of 5 years were analyzed retrospectively. To analyze the factors associated with a satisfactory or an unsatisfactory clinical result, we looked at the patient's age, duration of symptoms, type of meniscal lesion, and articular cartilage abnormalities. The patients were graded with a functional knee score (Lysholm-Gillquist), and activity level before surgery and at followup was determined. The data also included radiographic evaluation of 29 of the 50 patients. Tibiofemoral alignment was measured, and osteoarthritic changes were graded and correlated with the type of meniscal abnormality and functional result. Eighty-two percent of our patients had satisfactory knee function, and the activity level was maintained. The factors associated with a satisfactory result after a partial meniscectomy included age less than 40 years, symptoms less than 12 months duration, type of tear, and chondromalacia less than grade II. Fairbank's changes were present in 50% of the patients, with significant grade III and IV changes identified in 30%. Although the radiographic changes did not necessarily correlate with the functional result, we felt that the changes were significant and indicative of abnormal stress transfer to articular cartilage and bone.


Get Your Facts Right: Preschoolers Systematically Extend Both Object Names and Category-Relevant Facts.
There is an ongoing debate over the extent to which language development shares common processing mechanisms with other domains of learning. It is well-established that toddlers will systematically extend object labels to similarly shaped category exemplars (e.g., Markman and Hutchinson, 1984; Landau et al., 1988). However, previous research is inconclusive as to whether young children will similarly extend factual information about an object to other category members. We explicitly contrast facts varying in category relevance, and test for extension using two different tasks. Three- to four-year-olds (N = 61) were provided with one of three types of information about a single novel object: a category-relevant fact ('it's from a place called Modi'), a category-irrelevant fact ('my uncle gave it to me'), or an object label ('it's called a Modi'). At test, children provided with the object name or category-relevant fact were significantly more likely to display systematic category extension than children who learnt the category-irrelevant fact. Our findings contribute to a growing body of evidence that the mechanisms responsible for word learning may be domain-general in nature.


Immunohistological evidence of lymphokine production and lymphocyte activation antigens in tuberculin reactions.
Evidence of lymphokine elaboration and lymphocyte activation was sought in tuberculin skin test reactions at 24 and 48, or 48 and 96 h in patients with active, culture-proven, pulmonary tuberculosis. Through the use of frozen sections, immunoperoxidase techniques and monoclonal antibodies, anti-interleukin 2 positive cells were found to constitute 0.4% to 0.6% of the dermal infiltrate, and keratinocyte Ia expression at 96 h was consistent with a marker for interferon-gamma production. Cells bearing the interleukin 2 receptor more than doubled in prevalence from 24 to 48 or 96 h but cells staining with Ta1, an antibody identifying activated lymphocytes, were 10% of the cells of the infiltrate at all three times. One-half of the cells of the infiltrate were OKM1-positive, presumably macrophages, perhaps reflecting the presence of active tuberculosis.


Virulent spores of Bacillus anthracis and other Bacillus species deposited on solid surfaces have similar sensitivity to chemical decontaminants.
To compare the relative sensitivity of Bacillus anthracis and spores of other Bacillus spp. deposited on different solid surfaces to inactivation by liquid chemical disinfecting agents. We prepared under similar conditions spores from five different virulent and three attenuated strains of B. anthracis, as well as spores of Bacillus subtilis, Bacillus atrophaeus (previously known as Bacillus globigii), Bacillus cereus, Bacillus thuringiensis and Bacillus megaterium. As spore-surface interactions may bias inactivation experiments, we evaluated the relative binding of different spores to carrier materials. The survival of spores deposited on glass, metallic or polymeric surfaces were quantitatively measured by ASTM standard method E-2414-05 which recovers spores from surfaces by increasing stringency. The number of spores inactivated by each decontaminant was similar and generally within 1 log among the 12 different Bacillus strains tested. This similarity among Bacillus strains and species was observed through a range of sporicidal efficacy on spores deposited on painted metal, polymeric rubber or glass. The data obtained indicate that the sensitivity of common simulants (B. atrophaeus and B. subtilis), as well as spores of B. cereus, B. thuringiensis, and B. megaterium, to inactivation by products that contain either: peroxide, chlorine or oxidants is similar to that shown by spores from all eight B. anthracis strains studied. The comparative results of the present study suggest that decontamination and sterilization data obtained with simulants can be safely extrapolated to virulent spores of B. anthracis. Thus, valid conclusions on sporicidal efficacy could be drawn from safer and less costly experiments employing non-pathogenic spore simulants.


Poly(A)-containing RNA in embryonic chick tissues.
Cytoplasmic and nuclear RNA is prepared from chick embryo skin, muscle and brain at 13 days of incubation. The concentration and labelling of RNA is measured after oligo(dT) chromatography. Skin, muscle and brain contain respectively 4.8, 3.6 and 5.6% cytoplasmic RNA with a poly(A) segment. The corresponding figures for nuclear poly(A)-containing RNA are 13, 16 and 9.4%. In skin, incorporation of [3H]uridine in RNA lacking poly(A) exceeds the rate of incorporation into muscle and brain RNA by about 2.5- and 5-fold, respectively. By contrast, no such large differences in rates of incorporation between the tissues are observed with poly(A)-containing RNA.


Quality of life in women with urinary incontinence is impaired and comparable to women with chronic diseases.
To evaluate the quality of life in women with urinary incontinence (categorised by urodynamic findings). Prospective cohort study on patients. Urogynaecology unit of a university teaching hospital in Hong Kong. PATIENTS. Female patients presenting to our clinic from July 2008 to December 2009 and having their urinary incontinence categorised by urodynamic study. Patient's quality of life was assessed using the Medical Outcomes Study Short Form, Urogenital Distress Inventory Short Form, and Incontinence Impact Questionnaire Short Form. Their quality of life was compared according to their urodynamic category and a subgroup analysis was performed on patients having continence surgery for urodynamic stress incontinence. Among the 223 women studied, 46% had urodynamic stress incontinence, 18% had detrusor overactivity, 2% had both urodynamic stress incontinence and detrusor overactivity, and 34% had no urodynamic abnormality. In all, the Medical Outcomes Study Short Form scoring was lower than normal local population. The Medical Outcomes Study Short Form score in detrusor overactivity group was significantly lower than urodynamic stress incontinence group in vitality and mental health domains. Detrusor overactivity group also had higher scores in Incontinence Impact Questionnaire Short Form in travel, social and emotional health subscales and total score (46.3 vs 29.1; P<0.01). Women with urodynamic stress incontinence and required continence surgery had higher scores in Incontinence Impact Questionnaire Short Form. Women with urinary incontinence had impaired quality of life and it was comparable to other chronic medical diseases. Women with detrusor overactivity have more impaired quality of life than women with urodynamic stress incontinence. Severity of urodynamic stress incontinence did not correlate with quality of life. Women who opted for continence surgery had poorer quality of life.


Co-creating digital educational resources to enhance quality in student nurses' clinical education in nursing homes: Report of a co-creative process.
To report a methodological, co-creative approach for developing an interactive digital educational resource to enhance the quality of student nurses' clinical education in nursing homes and to elucidate the lessons learned from this approach. This study applied a co-design methodology that builds on participatory design principles. Co-creating the digital educational resource included multiple sequential and interactive phases inspired by the design thinking framework. Workshops were employed as the primary co-creative activity. Seven separate homogenous or joint heterogeneous workshops were conducted with student nurses, nurse educators, registered nurse mentors and e-learning designers (n = 36) during the active stakeholder engagement phases to inform the educational content, design and functionality of the digital educational resource. These were informed by, and grounded in, learning theory and principles. Co-creative approaches in nursing education are an essential avenue for further research. We still lack systematic knowledge about the impact and benefits of co-created initiatives, stakeholders' motivations, barriers, facilitators to participation and the role of context in supporting effective co-creative processes to increase the quality of nursing education. This paper demonstrates how digital educational initiatives to enhance quality in clinical nursing education can be co-created with key stakeholders through a novel methodological approach inspired by design thinking. To date, the methodological development process of co-created educational interventions has received limited attention and compared with the content and theoretical underpinnings of such interventions, has rarely been addressed. Therefore, this paper facilitates knowledge exchange and documents vital aspects to consider when co-creating digital educational initiatives incorporating multistakeholder perspectives. This promotes a stronger academic-practice partnership to impact and enhance the quality of clinical nursing education in nursing homes. Student nurses, nurse educators, and registered nurse mentors worked alongside researchers and e-learning designers in the co-creative process.


Plasms renin acitivity in coarctation of aorta before and after surgery.
Plasma renin acitivity was measured in II cases of coarctation of the aorta before and after operation. The values of plasma renin activity in the recumbent position before operation were significantly lower than in the control group. After surgery plasma renin activity rose to normal levels. There was no correlation between plasma renin activity levels and arterial blood pressure. The renin-angiotensin system seems not to be involved directly in the maintenance of hypertension in patients with aortic coarctation.


Latent herpes simplex virus type 1 DNA is not extensively methylated in vivo.
The methylation pattern of herpes simplex virus type 1 (HSV-1) DNA, present in the central nervous system of latently infected mice, was examined by digestion of the DNA with methylation-sensitive restriction endonucleases and Southern blot hybridization. Using the enzymes SmaI, XmaI, SalI and SacII, the data indicate no extensive methylation of latent HSV-1 DNA in vivo. Thus, extensive methylation of the viral genome is not a necessary condition for, or a consequence of maintaining, the latent state in vivo.


Artemisinin-Resistant Plasmodium falciparum with High Survival Rates, Uganda, 2014-2016.
Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014-2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage-specific P. falciparum susceptibility to artemisinin. We conducted 4 cross-sectional surveys to assess artemisinin sensitivity in Gulu, Uganda. Among 194 isolates, survival rates (ratio of viable drug-exposed parasites to drug-nonexposed controls) were high (>10%) for 4 isolates. Similar rates have been closely associated with delayed parasite clearance after drug treatment and are considered to be a proxy for the artemisinin-resistant phenotype. Of these, the PfKelch13 mutation was observed in only 1 isolate, A675V. Population genetics analysis suggested that these possibly artemisinin-resistant isolates originated in Africa. Large-scale surveillance of possibly artemisinin-resistant parasites in Africa would provide useful information about treatment outcomes and help regional malaria control.


Unusual contents of a scrotal swelling.
Pseudomyxoma peritonei is an uncommon tumour, usually arising from the appendix. It occasionally presents as a hernia, particularly in men. Here, the case of a 56-year-old male with pseudomyxoma peritonei presenting as a left inguinal hernia is presented, and a brief discussion of the literature on its diagnosis and management is given. The case highlights the importance of carefully evaluating patients with ascites and abdominal wall hernias.


Time-and-motion tool for the assessment of working time in tuberculosis laboratories: a multicentre study.
Implementation of novel diagnostic assays in tuberculosis (TB) laboratory diagnosis requires effective management of time and resources. To further develop and assess at multiple centres a time-and-motion (T&M) tool as an objective means for recording the actual time spent on running laboratory assays. Multicentre prospective study conducted in six European Union (EU) reference TB laboratories. A total of 1060 specimens were tested using four laboratory assays. The number of specimens per batch varied from one to 60; a total of 64 recordings were performed. Theoretical hands-on times per specimen (TTPS) in h:min:s for Xpert® MTB/RIF, mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping, Ziehl-Neelsen staining and manual fluorescence microscopy were respectively 00:33:02 ± 00:12:32, 00:13:34 ± 00:03:11, 00:09:54 ± 00:00:53 and 00:06:23 ± 00:01:36. Variations between laboratories were predominantly linked to the time spent on reporting and administrative procedures. Processing specimens in batches could help save time in highly automated assays (e.g., line-probe) (TTPS 00:14:00 vs. 00:09:45 for batches comprising 7 and 31 specimens, respectively). The T&M tool can be considered a universal and objective methodology contributing to workload assessment in TB diagnostic laboratories. Comparison of workload between laboratories could help laboratory managers justify their resource and personnel needs for the implementation of novel, time-saving, cost-effective technologies, as well as identify areas for improvement.


Randomized controlled trial of laparoscopic Nissen versus Lind fundoplication for gastro-oesophageal reflux disease.
To compare the effect of laparoscopic Nissen and Lind fundoplication on gastro-oesophageal reflux disease by means of a prospective randomized controlled trial. One hundred and twenty-one patients were randomized to undergo either Nissen (61) or Lind (60) fundoplication. Initial enrollment and subsequent clinical appointments were undertaken 1, 3, 6 and 12 months after the procedure using a standardized questionnaire. Ambulatory pH monitoring and manometry were undertaken both preoperatively and at approximately 3 months post-procedure. The mean operating time was similar in both groups (44.8 versus 45 min). One operation in the Lind group was converted to open surgery. Postoperative dysphagia symptoms at 3 and 6 months were higher in the Nissen fundoplication group than in the Lind group (3 months p=0.003; 6 months p=0.020). The time taken to return to work was statistically longer in the Nissen group: at 1 month, 9 of 40 versus 2 of 45 patients had not returned to full activities (p=0.013). Three individuals required re-operation in the Nissen group and 4 individuals in the Lind group because of dysphagia caused by mechanical obstruction. Both procedures demonstrated good Visick scores at 12 months; the Nissen group having 33 (97%) patients with a Visick score of 1 or 2, and the Lind group having 38 (100%) patients with a Visick score of 1 or 2. Both operations provide good quantitative and qualitative control of gastro-oesophageal reflux. Operation time and postoperative comparators were similar in both groups. There were no statistically significant differences between the groups at 1 year.


Effectiveness of PCR primers for the detection of occult hepatitis B virus infection in Mexican patients.
Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HVB) DNA in the liver of HBsAg negative individuals with or without detectable viral DNA in serum. OBI is a diagnostic challenge as it is characterized by a very low viral load, intermittently detectable through time. Individuals with OBI can develop chronic hepatic disease, including liver cirrhosis and hepatocellular carcinoma. The aim of this work was to produce tools to improve OBI detection of the HVB genotypes prevalent in Mexico. We designed and tested primers to detect OBI in serum samples by nested and real-time PCR. Conserved sites in the viral genome were determined by alignment of the most frequent HBV genotypes in Mexico (H, G/H, F and D) and primers spanning the entire viral genome were designed for first round and nested PCR. Primers were tested in serum samples of 45 patients not co-infected with hepatitis C virus or with HIV, out of a group of 116 HBsAg (-)/anti-HBc (+) individuals. Primers were also tested in a control group with chronic HBV. Nested PCR products obtained from HBsAg (-)/anti-HBc (+) were sequenced and used to design primers for real-time PCR (SYBR Green). The most effective primer pairs to detect HBV products by nested PCR targeted ORF regions: PreS2/P, S/P, X/PreC, and C; while by real-time PCR they targeted ORF regions PreS2/P, S/P, X, and C. Out of the 45 HBsAg (-)/anti-HBc (+) patients tested, the viral genome was detected in 28 (62.2%) and 34 (75.5%), with nPCR and real-time PCR respectively. Primers designed for real-time PCR detected up to 75.5% of suspected OBI Mexican patients, with or without liver disease, which represents an improvement from previous PCR strategies.


Impact, regulation and health policy implications of physician migration in OECD countries.
BACKGROUND: In the face of rising demand for medical services due to ageing populations, physician migration flows are increasingly affecting the supply of physicians in Organisation for Economic Co-operation and development (OECD) countries. This paper offers an integrated perspective on the impact of physician migration on home and host countries and discusses international regulation and policy approaches governing physician migration. METHODS: Information about migration flows, international regulation and policies governing physician migration were derived from two questionnaires sent to OECD countries, a secondary analysis of EUROSTAT Labour Force Surveys, a literature review and official policy documents of OECD countries. RESULTS: OECD countries increasingly perceive immigration of foreign physicians as a way of sustaining their physician workforce. As a result, countries have entered into international agreements regulating physician migration, although their success has been limited due to the imposition of licensing requirements and the protection of vested interests by domestic physicians. OECD countries have therefore adopted specific policies designed to stimulate the immigration of foreign physicians, whilst minimising its negative impact on the home country. Measures promoting immigration have included international recruitment campaigns, less strict immigration requirements and arrangements that foster shared learning between health care systems. Policies restricting the societal costs of physician emigration from developing countries such as good practice guidelines and taxes on host countries have not yet produced their expected effect or in some cases have not been established at all. CONCLUSIONS: Although OECD countries generally favour long-term policies of national self-sufficiency to sustain their physician workforce, such policies usually co-exist with short-term or medium-term policies to attract foreign physicians. As this is likely to continue, there is a need to create a global framework that enforces physician migration policies that confer benefits on home and host countries. In the long term, OECD countries need to put in place appropriate education and training policies rather than rely on physician migration to address their future needs.


Changes in the activities of NADP+-linked dehydrogenases during ontogenesis in the chicken.
Changes in the activities of glucose-6-phosphate dehydrogenase [EC 126.96.36.199], 6-phosphogluconate dehydrogenase [EC 18.104.22.168] and cytoplasmic and mitochondrial "malic" enzyme [EC 126.96.36.199] and NADP+- linked isocitrate dehydrogenase [EC 126.96.36.199] were measured in the liver, heart, lung and brain during ontogenesis in the chicken. In the liver the cytoplasmic malic enzyme was constant during embryonal development, increasing suddenly and markedly thereafter and isocitrate dehydrogenase increased in the embryo and decreased after hatching while their mitochondrial isoenzymes showed parallel but less marked changes. Activities of the other dehydrogenases were essentially unchanged. In the heart only cytoplasmic isocitrate dehydrogenase showed important changes, increasing three-fold during growth after hatching. In the lung, glucose-6-phosphate dehydrogenase and cytoplasmic malic enzyme attained their maximum activities respectively at 16 to 18 d and 14 d of development. Mitochondrial malic enzyme did not change, while isocitrate dehydrogenase reached its maximum between 14 and 18 d. In the brain cytoplasmic malic enzyme was activated only after hatching, while its mitochondrial isoenzyme and isocitrate dehydrogenase showed discontinuous variations of an insignificant magnitude. Other activities were unchanged.


A New Way to Trace SARS-CoV-2 Variants Through Weighted Network Analysis of Frequency Trajectories of Mutations.
Early detection of SARS-CoV-2 variants enables timely tracking of clinically important strains in order to inform the public health response. Current subtype-based variant surveillance depending on prior subtype assignment according to lag features and their continuous risk assessment may delay this process. We proposed a weighted network framework to model the frequency trajectories of mutations (FTMs) for SARS-CoV-2 variant tracing, without requiring prior subtype assignment. This framework modularizes the FTMs and conglomerates synchronous FTMs together to represent the variants. It also generates module clusters to unveil the epidemic stages and their contemporaneous variants. Eventually, the module-based variants are assessed by phylogenetic tree through sub-sampling to facilitate communication and control of the epidemic. This process was benchmarked using worldwide GISAID data, which not only demonstrated all the methodology features but also showed the module-based variant identification had highly specific and sensitive mapping with the global phylogenetic tree. When applying this process to regional data like India and South Africa for SARS-CoV-2 variant surveillance, the approach clearly elucidated the national dispersal history of the viral variants and their co-circulation pattern, and provided much earlier warning of Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). In summary, our work showed that the weighted network modeling of FTMs enables us to rapidly and easily track down SARS-CoV-2 variants overcoming prior viral subtyping with lag features, accelerating the understanding and surveillance of COVID-19.


Permanent cardiac sarcomere changes in a rabbit model of intrauterine growth restriction.
Intrauterine growth restriction (IUGR) induces fetal cardiac remodelling and dysfunction, which persists postnatally and may explain the link between low birth weight and increased cardiovascular mortality in adulthood. However, the cellular and molecular bases for these changes are still not well understood. We tested the hypothesis that IUGR is associated with structural and functional gene expression changes in the fetal sarcomere cytoarchitecture, which remain present in adulthood. IUGR was induced in New Zealand pregnant rabbits by selective ligation of the utero-placental vessels. Fetal echocardiography demonstrated more globular hearts and signs of cardiac dysfunction in IUGR. Second harmonic generation microscopy (SHGM) showed shorter sarcomere length and shorter A-band and thick-thin filament interaction lengths, that were already present in utero and persisted at 70 postnatal days (adulthood). Sarcomeric M-band (GO: 0031430) functional term was over-represented in IUGR fetal hearts. The results suggest that IUGR induces cardiac dysfunction and permanent changes on the sarcomere.


[Met]enkephalin-Arg6-Gly7-Leu8-immunoreactive nerves in guinea-pig and rat lungs: distribution, origin, and co-existence with vasoactive intestinal polypeptide immunoreactivity.
[Met]Enkephalin-Arg6-Gly7-Leu8 is an endogenous opioid peptide, first isolated from the bovine adrenal medulla. Because this octapeptide is specifically contained in the amino acid sequence of preproenkephalin A but not in other opioid precursors like preproopiomelanocortin or preproenkephalin B, [Met]enkephalin-Arg6-Gly7-Leu8 has been regarded as a specific marker for preproenkephalin A and its derivatives. In this study, we examined the occurrence and origin of [Met]enkephalin-Arg6-Gly7-Leu8-immunoreactive nerves in the guinea-pig and rat lung by immunohistochemical techniques, using a specific antiserum against this peptide. In addition, we investigated the possible co-existence of [Met]enkephalin-Arg6-Gly7-Leu8 and vasoactive intestinal peptide immunoreactivity in neuronal elements of the respiratory tract. In both species, [Met]enkephalin-Arg6-Gly7-Leu8 immunoreactivity was localized in nerve fibers chiefly distributed to the trachea and major bronchi, where they were prevalent in smooth muscle bundles, in the lamina propria, around airway glands, and in the walls of pulmonary vessels, but were absent in airway epithelium. Slight differences in the distribution pattern of immunoreactive nerve fibers were noted between the two species: immunoreactive nerve fibers in the smooth muscle bundles were much more abundant in guinea-pigs than in rats, while those in the mucous glands were richer in rats than in guinea-pigs. Neither chemical sympathectomy by 6-hydroxydopamine, nor chemical sensory denervation by capsaicin, changed the density or distribution of [Met]enkephalin-Arg6-Gly7-Leu8-immunoreactive nerve fibers in the airway, suggesting an intrinsic source for these nerve fibers. Colchicine injection into the tracheal wall, to promote the accumulation of neuropeptides in nerve cell bodies, led to the visualization of [Met]enkephalin-Arg6-Gly7-Leu8 immunoreactivity in some neuronal cell bodies within airway ganglia. Immunostaining for [Met]enkephalin-Arg6-Gly7-Leu8 and for vasoactive intestinal polypeptide on serial adjacent sections of airway ganglia obtained from colchicine-treated tracheae, demonstrated the co-existence of these immunoreactivities in a population of nerve cell bodies in these ganglia. The immunohistochemical localization of immunoreactive [Met]enkephalin-Arg6-Gly7-Leu8 in nerve elements in guinea-pig and rat lungs provides a morphological basis for the possibility that preproenkephalin A-related opioid peptides may have a neuromodulatory role in mammalian airways and pulmonary vessels.


Diffusion of inositol 1,4,5-trisphosphate but not Ca2+ is necessary for a class of inositol 1,4,5-trisphosphate-induced Ca2+ waves.
Combining a realistic model of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ oscillations with the diffusion of IP3 and buffered diffusion of Ca2+, we have found that diffusion of Ca2+ plays only a minor role in a class of agonist-induced Ca2+ wave trains. These waves are primarily kinematic in nature, with variable wavelengths and speeds that depend primarily on the phase differences between oscillators at different spatial points. The period is set by the steady-state value of IP3, while the wave speed approximately equals the wavelength/period. Ca2+ diffusion, which is much slower than that of IP3 because of endogenous buffers, is shown to have only a small effect on the wave trains and not to be necessary for the apparent wave propagation. Diffusion of IP3 sets the phase gradient responsible for these wave trains, which consist primarily of localized cycles of Ca2+ uptake and release. Our results imply a possible previously undisclosed role for IP3 in cell signaling.


Use of micro and macroalgae extracts for the control of vector mosquitoes.
Mosquitoes are one of the most dangerous vectors of human diseases such as malaria, dengue, chikungunya, and Zika virus. Controlling these vectors is a challenging responsibility for public health authorities worldwide. In recent years, the use of products derived from living organisms has emerged as a promising approach for mosquito control. Among these living organisms, algae are of great interest due to their larvicidal properties. Some algal species provide nutritious food for larvae, while others produce allelochemicals that are toxic to mosquito larvae. In this article, we reviewed the existing literature on the larvicidal potential of extracts of micro- and macroalgae, transgenic microalgae, and nanoparticles of algae on mosquitoes and their underlying mechanisms. The results of many publications show that the toxic effects of micro- and macroalgae on mosquitoes vary according to the type of extraction, solvents, mosquito species, exposure time, larval stage, and algal components. A few studies suggest that the components of algae that have toxic effects on mosquitoes show through synergistic interaction between components, inhibition of feeding, damage to gut membrane cells, and inhibition of digestive and detoxification enzymes. In conclusion, algae extracts, transgenic microalgae, and nanoparticles of algae have shown significant larvicidal activity against mosquitoes, making them potential candidates for the development of new mosquito control products.


The Immunological Regulation Roles of Porcine β-1, 4 Galactosyltransferase V (B4GALT5) in PRRSV Infection.
B4GALT5, also known as β-1, 4 galactosyltransferase V, is one of the members of β-1, 4 galactosyltransferase gene (B4GALT) family, which was concerned with embryonic development, tumor generation, other malignant diseases. In this study, we firstly cloned porcine B4GALT (pB4GALT5) from porcine alveolar macrophages, and predicted the structural domain and function of seven porcine β-1, 4 galactosyltransferase (I-VII) based on transcriptome analysis of PRRSV infected cells. Additionally, the upregulated porcine B4GALT5 expression was detected from PRRSV infected porcine alveolar macrophage (PAM) cells. The PRRSV proliferation were slightly inhibited in overexpression of pB4GALT5 transfected cells, the interaction of B4GALT5 and GP5 of PRRSV was firstly be detected by Co-IP, and the co-location between B4GALT5 and GP5 were also observed in golgi membranes by confocal microscopy. A significant increasing mRNA transcription, including inflammatory cytokines (IFN-α, IL-6, IL-18, IL-1β, TNF-α) and some cell surface glycosylated protein involved in antigen present (MHC-I/II), cell adhesion and migration (chemokine MCP-1 and receptor CCR2; LFA-1, ICAM-1) were upregulated in B4GALT5 overexpressed PRRSV infected cells. Our results demonstrated that the regulation of pB4GALT5 plays an important roles in PRRSV proliferation and modification function in viral infection cells. And these results will make achievements by supporting the research of latent mechanisms of β-1, 4 galactosyltransferase V in antiviral immunity.


An integrated system for optical and electrical detection of single molecules/particles inside a solid-state nanopore.
Nanopore techniques have proven to be useful tools for single-molecule detection. The combination of optical detection and ionic current measurements enables a new possibility for the parallel readout of multiple nanopores without complex nanofluidics and embedded electrodes. In this study, we developed a new integrated system for the label-free optical and electrical detection of single molecules based on a metal-coated nanopore. The entire system, containing a dark-field microscopy system and an ultralow current detection system with high temporal resolution, was designed and fabricated. An Au-coated nanopore was used to generate the optical signal. Light scattering from a single Au-coated nanopore was measured under a dark-field microscope. A lab-built ultralow current detection system was designed for the correlated optical and electrical readout. This integrated system might provide more direct and detailed information on single analytes inside the nanopore compared with classical ionic current measurements.


Adaptation Shapes Local Cortical Reactivity: From Bifurcation Diagram and Simulations to Human Physiological and Pathological Responses.
Human studies employing intracerebral and transcranial perturbations suggest that the input-output properties of cortical circuits are dramatically affected during sleep in healthy subjects as well as in awake patients with multifocal and focal brain injury. In all these conditions, cortical circuits react to direct stimulation with an initial activation followed by suppression of activity (Off-period) that disrupts the build-up of sustained causal interactions typically observed in healthy wakefulness. The transition to this stereotypical response has important clinical implications, being associated with loss of consciousness or loss of functions. Here, we provide a mechanistic explanation of these findings by means of simulations of a cortical-like module endowed with activity-dependent adaptation and mean-field theory. First, we show that fundamental aspects of the local responses elicited in humans by direct cortical stimulation can be replicated by systematically varying the relationships between adaptation strength and excitation level in the network. Then, we reveal a region in the adaptation-excitation parameter space of crucial relevance for both physiological and pathologic conditions, where spontaneous activity and responses to perturbation diverge in their ability to reveal Off-periods. Finally, we substantiate through simulations of connected cortical-like modules the role of adaptation mechanisms in preventing cortical neurons from engaging in reciprocal causal interactions, as suggested by empirical studies. These modeling results provide a general theoretical framework and a mechanistic interpretation for a body of neurophysiological measurements that bears critical relevance for physiological states as well as for the assessment and rehabilitation of brain-injured patients.


Very Low Levels of Physical Activity in Older Patients During Hospitalization at an Acute Geriatric Ward: A Prospective Cohort Study.
Lack of activity during hospitalization may contribute to functional decline. The purpose of this study was to investigate (1) the time spent walking during hospitalization by geriatric patients referred to physical and/or occupational therapy and (2) the development in time spent walking during hospitalization. In this observational study, 24-hr accelerometer data (ActivPal) were collected from inclusion to discharge in 124 patients at an acute geriatric ward. The median time spent walking was 7 min per day. During the first quartile of hospitalization, the patients spent 4 (IQR:1;11) min per day walking, increasing to 10 (IQR:1;29) min during the last quartile. Improvement in time spent walking was primarily observed in the group able to perform the Timed Up & Go task at admission. When walking only 7 min per day, patients could be classified as inactive and at risk for functional decline; nonetheless, the physical activity level increased significantly during hospitalization.


Treatment options in responding to drug misuse problems.
Reducing both the supply of and demand for drugs is a major theme in efforts to control the drug problem. It is essential to recognize that demand-reduction efforts are critical to enable supply-reduction efforts to have realizable goals. The initial goal of any intervention must be the limitation of harm to the individual and society. The primary goal is to reduce the prevalence of drug misuse within the community. The provision of a wide range of integrated approaches is essential if demand-reduction programmes are to be successful in contacting drug misusers, maintaining that contact and successfully assisting the individual through treatment, rehabilitation and social reintegration. The article summarizes the more common approaches to the treatment, rehabilitation and social reintegration of drug-dependent persons.


Improvement of J(sc) in a Cu2ZnSnS4 Solar Cell by Using a Thin Carbon Intermediate Layer at the Cu2ZnSnS4/Mo Interface.
Back contact modification plays an important role in improving energy conversion efficiency of Cu2ZnSnS4 (CZTS) thin film solar cells. In this paper, an ultrathin carbon layer is introduced on molybdenum (Mo)-coated soda lime glass (SLG) prior to the deposition of CZTS precursor to improve the back contact and therefore enhance CZTS solar cell efficiency. By introducing this layer, the short circuit current (Jsc) and device conversion efficiency increase for both nonvacuum (sol-gel) and vacuum (sputtering) methods. Specifically, for the sol-gel based process, Jsc increases from 13.60 to 16.96 mA/cm(2) and efficiency from 4.47% to 5.52%, while for the sputtering based process, Jsc increases from 17.50 to 20.50 mA/cm(2) and efficiency from 4.10% to 5.20%. Furthermore, introduction of this layer does not lead to any deterioration of either open circuit voltage (Voc) or fill factor (FF).


Conductive Nanowires Templated by Molecular Brushes.
In this paper, we report the fabrication of conductive nanowires using polymer bottle brushes as templates. In our approach, we synthesized poly(2-dimethylamino)ethyl methacrylate methyl iodide quaternary salt brushes by two-step atom transfer radical polymerization, loaded them with palladium salt, and reduced them in order to form metallic nanowires with average lengths and widths of 300 and 20 nm, respectively. The obtained nanowires were deposited between conductive gold pads and were connected to them by sputtering of additional pads to form an electric circuit. We connected the nanowires in an electric circuit and demonstrated that the conductivity of these nanowires is around 100 S·m(-1).


Relationship between physical activity and inflammation among apparently healthy middle-aged and older US adults.
Physical activity has been associated with a reduced risk of coronary heart disease, but the mechanism underlying this association is unclear. Because coronary heart disease is increasingly seen as an inflammatory process, it might be reasonable to hypothesize that physical activity reduces risk of coronary heart disease by reducing or preventing inflammation. The study examined the relationship between physical activity and elevated inflammation as indicated by a high C-reactive protein level, white blood cell count, or fibrinogen level. Study subjects were 3638 apparently healthy US men and women 40 years and older who participated in the Third National Health and Nutrition Examination Survey. More frequent physical activity was independently associated with a lower odds of having an elevated C-reactive protein level. Compared with those engaging in physical activity 0 to 3 times per month, the odds of having an elevated C-reactive protein level was reduced among those engaging in physical activity 4 to 21 times per month (odds ratio, 0.77; 95% confidence interval, 0.58-1.02) and 22 or more times per month (odds ratio, 0.63; 95% confidence interval, 0.43-0.93) (P for trend,.02). Similar associations were seen for white blood cell count and fibrinogen levels. More frequent physical activity is independently associated with a lower odds of having elevated inflammation levels among apparently healthy US adults 40 years and older, independent of several confounding factors. The results suggest that the association between physical activity and reduced coronary heart disease risk may be mediated by anti-inflammatory effects of regular physical activity.


Enhancement of human monocyte tumoricidal activity by recombinant M-CSF.
Activated monocytes are an important component of immunologic defense against neoplastic disease. A variety of agents capable of inducing tumoricidal activity have been described, including bacterial LPS, IFN-gamma, IL-1, IL-2, TNF, and GM-CSF. We now show that pretreatment of monocytes with recombinant human macrophage-specific colony stimulating factor (M-CSF) augments the tumoricidal activity of human peripheral blood monocytes induced by other activating agents. Monocytes were preincubated for three days with M-CSF at 10(3) U/ml, washed, and treated for an additional two days with secondary activators. Tumoricidal activity was measured in a 6-h 51Cr-release assay using NK-resistant WEHI 164 cells that had been treated with actinomycin D. Pretreatment of monocytes with M-CSF significantly increased tumoricidal activity induced by LPS, IFN gamma, LPS plus IFN gamma, and LPS plus PMA. Pretreatment with IL-1, IL-2, IL-3, IL-4, or GM-CSF was not as effective as M-CSF in increasing tumoricidal activity. Enhanced tumoricidal activity was directly correlated to the increased TNF production resulting from M-CSF pretreatment. TNF antiserum completely blocked tumoricidal activity, demonstrating that TNF was responsible for the M-CSF-mediated increase in tumor cell lysis. M-CSF pretreatment also enhanced non-TNF mediated tumoricidal activity by monocytes, as seen by increased killing of the TNF-resistant target P815. This study demonstrated that in addition to the role of M-CSF in the proliferation and differentiation of monocyte/macrophage precursors, M-CSF also augments an effector function of mature blood monocytes.


Inhibitory effect of galanin on basal and pentagastrin-stimulated gastric acid secretion in rats.
The dose-dependent effects of galanin on basal and pentagastrin-stimulated gastric acid secretion in pentobarbital-anesthetized rats were examined. Intravenous infusion of galanin at doses of 0.31, 0.62, 1.25, 1.87, 3.11, and 6.22 nmol/kg-1/h-1 into pentagastrin-stimulated rats produced a diminution in gastric acid secretion which was maximal (54.7%) at the level of the 1.87 nmol/kg-1/h-1 dose. Furthermore, the effect was biphasic, since both lower and higher doses of peptide were less effective. At the optimum concentration of 1.87 nmol/kg-1/h-1 galanin also inhibited basal gastric acid secretion. We conclude that endogenous galanin might be involved in the physiologic regulation of gastric acid secretion.


[Advance in di-n-butyl phthalate].
Di-n-butyl phthalate is ubiquitous because it is widely used in plastic and cosmetic production. In this paper, the research progress on the exposure, metabolism, toxicity and endocrine disrupting effects of di-n-butyl phthalate were reviewed.


Quantitative genetic correlation between trait and preference supports a sexually selected sperm process.
Sperm show patterns of rapid and divergent evolution that are characteristic of sexual selection. Sperm competition has been proposed as an important selective agent in the evolution of sperm morphology. However, several comparative analyses have revealed evolutionary associations between sperm length and female reproductive tract morphology that suggest patterns of male-female coevolution. In the dung beetle Onthophagus taurus, males with short sperm have a fertilization advantage that depends on the size of the female's sperm storage organ, the spermatheca; large spermathecae select for short sperm. Sperm length is heritable and is genetically correlated with male condition. Here we report significant additive genetic variation and heritability for spermatheca size and genetic covariance between spermatheca size and sperm length predicted by both the "good-sperm" and "sexy-sperm" models of postcopulatory female preference. Our data thus provide quantitative genetic support for the role of a sexually selected sperm process in the evolutionary divergence of sperm morphology, in much the same manner as precopulatory female preferences drive the evolutionary divergence of male secondary sexual traits.


Dynamic Kinetic Resolution of Allylic Azides via Asymmetric Dihydroxylation.
The catalytic enantioselective preparation of densely functionalized amines is a fundamental synthetic challenge. To address this challenge, we report for the first time that the Winstein rearrangement can be enlisted as the racemization pathway in a dynamic kinetic resolution of allylic azides. Alkene functionalization by Sharpless dihydroxylation affords tertiary azides in excellent enantioselectivity (up to 99:1 er). This approach establishes the chirality of the tertiary azide, obviates the need to directly forge either a congested C-N or C-C bond at the new nitrogenous stereocenter, and establishes additional functionality. Several examples demonstrate further elaboration of this functionality.


[Anatomical basis and technique of thoracic paravertebral blockade].
This article presents in illustrations the classical technique of transdermal identification and anatomy of paravertebral space (PVS) comparing to other techniques. This have to be acknowledged by anaesthesiologists as well as by other specialists to perform thoracic paravertebral blockade (TPVB)--earlier elapsed but nowadays getting more popular--safely. In addition the article contains a short description of author's own modification of Eason's and Wyatt's technique.


Treatment of haemoptysis in pulmonary atresia with tranexamic acid.
We report the case of a young woman with continuing haemoptysis, pulmonary atresia, previous shunt surgery, and pulmonary hypertension. She was not suitable for further surgery or for therapeutic embolisation of bronchial vessels. Treatment with tranexamic acid resolved the haemoptysis.


Inflammatory process complicating giant hemangioma of the liver: report of three cases.
Three cases of giant hemangioma of the liver associated with clinical and laboratory signs of inflammatory process, including low-grade fever, weight loss, abdominal pain, accelerated erythrocyte sedimentation rate, anemia, thrombocytosis, and increased fibrinogen level with normal white blood cell count are described. One patient presented with slight cholestatic jaundice because of tumor-related bile duct compression, but the other two patients had normal liver function tests, except for a slight increase in gammaglutamyl transferase. Clinical and laboratory abnormalities disappeared after surgical excision. Inflammatory manifestations have rarely been reported during giant liver hemangioma. Intratumoral inflammation necrosis or bleeding could explain the symptoms but histological signs of inflammation were not detected in two of three surgical specimens. The release of immune mediators by liver endothelial cells lining the hemangioma is an alternative explanation. The incidence of inflammatory process complicating giant hemangioma is probably underestimated because our three cases were observed within a span of only 3 years.


Mastitis caused by Bacillus anthracis in a beef cow.
A mixed-breed beef cow was presented with swelling of the front and hind left quarters of the mammary gland and mild depression. Direct examination and culture of the serosanguinous-like milk samples collected from these quarters were consistent with Bacillus anthracis infection.


Gold(III)-Catalyzed Site-Selective and Divergent Synthesis of 2-Aminopyrroles and Quinoline-Based Polyazaheterocycles.
A facile, site-selective, and divergent approach to construct 2-aminopyrroles and quinoline-fused polyazaheterocycles enabled by a simple gold(III) catalyst from ynamides and anthranils under mild reaction conditions is described. This one-pot strategy uses readily available starting materials, proceeds in a highly step- and atom-economical manner, with broad substrate scope and scale-up potential. The key element for success in this tandem reaction is a catalyst-directed preferred quenching of the in situ generated gold carbene intermediates by a nucleophilic benzyl/2-furylmethyl moiety on the ynamides as an alternative to the known C-H annulation leading to indoles.


Mannose-coated gadolinium liposomes for improved magnetic resonance imaging in acute pancreatitis.
Acute pancreatitis (AP) is an acute inflammatory condition of the pancreas. The symptoms, treatment, and prognosis of mild and severe AP are different, and severe AP is a potentially life-threatening disease with a high incidence of complications and high mortality rate. Thus, it is urgent to develop an effective approach to reliably discriminate between mild and severe AP. We have developed novel gadolinium-diethylenetriaminepentaacetic (Gd-DTPA)-loaded mannosylated liposomes (named thereafter M-Gd-NL) that preferably target macrophages in AP. The targeting ability of M-Gd-NL toward macrophages in AP and its ability to discriminate between mild and severe AP were evaluated. The liposomes were of desired particle size (~100 nm), Gd-DTPA encapsulation efficiency (~85%), and stability. M-Gd-NL and non-targeted Gd-DTPA-loaded liposomes (Gd-NL) exhibited increased relaxivity compared with Gd-DTPA. Compared with Gd-NL and Gd-DTPA, M-Gd-NL showed increased uptake in macrophages, resulting in increased T1 imaging ability both in vitro (macrophage cell line) and in vivo (severe AP model). Importantly, M-Gd-NL had the ability to discriminate between mild and severe AP, as reflected by a significantly higher T1 magnetic resonance imaging signal in severe AP than in mild AP. M-Gd-NL did not show severe organ toxicity in rats. Our data suggest that M-Gd-NL had enhanced magnetic resonance imaging ability by targeting macrophages in AP and good ability to discriminate between mild and severe AP. We believe that M-Gd-NL could shed new light on the diagnosis of AP in the near future.


pH sensing in bacterial chemotaxis.
Bacteria are able to sense a broad range of chemical and energetic stimuli and modulate their swimming behaviour to migrate to more favourable environments. Signal transduction in bacterial chemotaxis is mediated by a two-component system composed of a protein histidine kinase, CheA, and a response regulator, CheY. The phosphorylated response regulator, P approximately CheY, binds to a protein at the flagellar motor, FliM, to cause reversals in flagellar motor rotation. The level of P approximately CheY is controlled by the activity of the kinase CheA, which is in turn regulated by membrane receptors at the cell surface. Membrane receptors such as the aspartate receptor, Tar, are composed of two distinct regions: an extracellular sensing domain that binds stimulatory ligands, aspartate in the case of Tar; and an intracellular signalling domain that forms a complex with the protein kinase CheA. What is the mechanism of transmembrane signalling? How does aspartate binding to the sensing domain at the outside surface of the membrane translate into a change in kinase activity at the membrane cytosol interface? Recent results suggest that the mechanism depends on perturbations in lateral packing within an extensive array of receptors localized to patches at the cell poles. Receptor patching appears to depend on higher-order associations with the kinase CheA as well as an adaptor protein, CheW. It is difficult to assess the locus of pH effects within the context of even a simple signal transduction system like that involved in bacterial chemotaxis. Previous results with mutant strains have indicated that the serine receptor, Tsr, is critical for pH sensing, but in vitro results do not support such a straightforward interpretation of the genetic data.


Collagen types VIII and X, two non-fibrillar, short-chain collagens. Structure homologies, functions and involvement in pathology.
Collagens can be divided into two groups, i.e., fibrillar and non-fibrillar collagens. Short-chain collagens, a subgroup of non-fibrillar collagens, comprises collagen type VIII and type X. These two collagen types show several similarities in structure and possibly also in function. Type VIII collagen appears to be secreted by rapidly proliferating cells. It can be found in basement membranes and may serve as a molecular bridge between different types of matrix molecules. In different tissues this collagen type may serve different functions. Stabilization of membranes, angiogenesis, and interactions with other extracellular matrix molecules. Since collagen type X is produced by hypertrophic chondrocytes, this collagen type can only be found in matrix of the hypertrophic zone of the epiphyseal growth plate cartilage. Collagen type X is probably involved in the process of mineralization, endochondral ossification, and is also proposed to play a role in angiogenesis. Collagen types VII and X may be involved in matrix and bone disorders. Their structure, function, and involvement in pathology are discussed in this review.


Acute Heart Failure Triggered by Coronary Spasm With Transient Left Ventricular Dysfunction.
Coronary spasm is abnormal contraction of an epicardial coronary artery resulting in myocardial ischemia. Coronary spasm induces not only depressed myocardial contractility, but also incomplete myocardial relaxation, which leads to elevated ventricular filling pressure. We herein report the case of a 55-year-old woman who had repeated acute heart failure caused by coronary spasm. Acetylcholine provocation test with simultaneous right heart catheterization was useful for the diagnosis of elevated ventricular filling pressure as well as coronary artery spasm. We should add coronary spasm to a differential diagnosis for repeated acute heart failure.


Altered enzyme function and premature sequestration of erythrocytes in aged individuals.
Experimentation performed to determine the parameters of the life-span of the erythrocyte in hosts of various ages have determined that, in aged individuals, the rate of turnover of cells is considerably increased over that observed in young individuals. These observations are based on studies in humans, rats, mice, and rabbits in which either in situ 59Fe labelling or age-density gradient separation were used. The mechanisms for the recognition of the effete red cell in the aged host and the nature of the membrane alterations that bring about the premature sequestration are not fully understood. However, it has been consistently observed that the red cells of aged individuals have higher levels of IgG bound to their membranes than do young cells, with the most dense cells having the highest levels of immunoglobulin. Studies of most enzymes, particularly those involved in protection against oxidative damage have shown reduced activity as a function of both cell and donor age. Evidence of enzyme damage has been observed even in the youngest circulating red blood cells of old individuals. This fact leads us to hypothesize that the erythrocyte of the aged individual as it differentiates and is released from the bone marrow is less functional and partially damaged. The erythrocytes of both old and young individuals age in the circulation, accumulating subtle alterations that are recognized by the immune and/or reticuloendothelial systems and lead to sequestration. The cells of the elderly individual accumulate a greater degree of damage due to their initially reduced capacity to protect themselves from environmental stress. These alterations eventually bring them to their early sequestration.


Various clinical aspects of alcohol consumption in trauma patients.
The aim of the study was the evaluation of alcohol consumption pattern, clinical outcome of alcohol misuse patients admitted to traumatology ward as well as estimation of usage of brief intervention strategy. The analyzed group consisted of 137 patients (49 females and 88 males) aged from 17 to 95 (mean 47.8 +/- 21.3) years hospitalized in 2004. All the patients were asked to complete the AUDIT and CAGE tests and were divided into groups according to alcohol consumption. There were analyzed alcohol consumption patterns, patient's medical history and also diagnosis of alcohol misuse. Almost half of the men (45.5%) hospitalized in the traumatology ward had been drinking in hazardous pattern in comparison with 4.1% of women. The most numerous population in this cohort were patients < 35-year-old (38.1%). Both, the group of patients with hazardous alcohol consumption (HAC) (>7 pts. according to AUDIT) and the group of alcohol addicted patients (>1 pts according to CAGE) were mainly represented by males. The anamnesis concerning the alcohol consumption was conducted by the surgeons in only 1 (0.7%) case, but without using any tests. Brief intervention was not used even among those patients who were drunk on admission. There were 45.5% of hazardous drinking males and 4.1% of females among patients admitted to the traumatology ward. None of the surgeons used the screening test to evaluate the drinking misuse of the patients. The brief intervention was not used by the medical staff despite its low cost and high effectiveness.


[Neu-Laxova syndrome: Three case reports and a review of the literature].
The Neu-Laxova syndrome (NLS) is a rare autosomal recessive and early lethal disorder. It is characterized by severe intra-uterine growth retardation, abnormal facial features, ichthyotic skin lesions and severe central nervous system malformations, especially microlissencephaly. Others characteristic features associated with fetal hypokinesia sequence, including arthrogryposis, subcutaneous edema and pulmonary hypoplasia, are frequently reported in NLS. The clinicopathological characteristics of NLS are described in three cases with striking prenatal diagnostic findings and detailed post-mortem examinations. A review of the literature is undertaken with a focus on molecular basis. We present three new patients with NLS: one stillbirth male and two female newborns, delivered at 29, 35 and 40 weeks of gestational age, respectively. Characteristic ultrasound findings included hydramnios, severe intra-uterine growth restriction, craniofacial and cental nervous system anomalies. The cytogenetic study, performed in one case, was normal. The post-mortem examination revealed characteristic abnormalities in all three cases, that allowed to make a prompt diagnosis of the NLS. Data from these patients suggest that the NLS represents a heterogeneous phenotype. This feature has been highlighted in the literature. The SNL is a lethal developmental disorder characterized by phenotypic heterogeneity with striking neurological defects. It is underpinned by genetic heterogeneity. It can be caused by mutations in all three genes involved in de novo L-serine biosynthesis: PHGDH, PSAT1 and PSPH. Hence, the NLS constitutes the most severe end of already known human disease, i.e. serine-deficiency disorder.


In vivo expression analysis of the P97 and P102 paralog families of Mycoplasma hyopneumoniae.
The P97 adhesin and P102 genes of Mycoplasma hyopneumoniae each have six paralogs in the genome. We tested whether these genes were expressed during infection. P102 is associated with the mycoplasma and with swine cilia. Further, most of the paralogs were transcribed in vivo in two gene transcriptional units.


Swiss roll operation for giant fibroadenoma.
Fibroadenoma 5 cm or more is called giant fibroadenoma. Giant fibroadenoma can distort the shape of breast and causes asymmetry, so it should be excised. There are several techniques for excision of giant fibroadenoma. In our technique we remove them through cosmetically acceptable circumareolar incision to maintain the shape and symmetry of breast. The objectives were to assess the cosmetic results of Swiss roll operation for giant fibroadenoma. The study was conducted for six years from January, 2002 to December, 2007. Seventy patients of giant fibroadenoma were included in this study. They were diagnosed on history and clinical examination supported by ultrasound and postoperative histopathological examination. Data were collected from outpatient department and operation theatre. Swiss roll operation was performed under general anaesthesia. Mean tumor size was 6.38 cm. Three cm and 4 cm incisions were used for tumour < or = 6 cm and > 6 cm in size respectively. Skin closed with Vicryl 3/0 subcuticular stitches. Sixteen out of 70 patients had no scar while others hadminimal scar. All patients had normal shape and symmetry of breast. On histopathology fibroadenoma was confirmed. Giant fibroadenoma should be removed through cosmetically acceptable cicumareolar incision especially in unmarried young females who have small breast. Swiss-roll operation is superior in maintaining the shape and symmetry of breast. No major complication was found in our series except seroma formation in 10 patients.


Subclinical hypothyroidism: to treat or not to treat, that is the question! A systematic review with meta-analysis on lipid profile.
Previous studies suggested that subclinical hypothyroidism has a detrimental effect on cardiovascular risk factors, and that its effective treatment may have a beneficial impact on overall health. The main purpose of this review and meta-analysis was to assess whether subclinical hypothyroidism treatment is of clinical relevance, based on cardiovascular risk parameters correction. A systemic research of the literature using MEDLINE tool was performed to identify the relevant studies. Only placebo-controlled randomized control trials were included. A quantitative analysis was also performed. This systematic review and meta-analysis of randomized placebo-controlled trials assess the different impact of levothyroxine vs placebo treatment. A significant decrease in serum thyroid-stimulating hormone and total and low-density lipoprotein cholesterol was obtained with levothyroxine therapy (66, 9 and 14%, respectively) and, although modest, this could be significant in terms of reduction of the incidence of coronary artery disease. Other significant results of lipid parameters were not obtained. This systematic review provides a strong evidence-based data in favour of specific changes and beneficial effects of levothyroxine treatment.


Amino acid substitutions in the Candida albicans sterol Δ5,6-desaturase (Erg3p) confer azole resistance: characterization of two novel mutants with impaired virulence.
To determine the mechanisms responsible for fluconazole resistance in two Candida albicans isolates (CAAL2 and CAAL76) recovered from two hospitalized patients after fluconazole prophylaxis. MICs of fluconazole and voriconazole were determined by the broth microdilution method (CLSI M27-A3), and by Etest(®) for amphotericin B. RNA expression levels of CDR1, MDR1 and ERG11 were determined by RT-PCR. Mutations in ERG11 and ERG3 were investigated by amplification and sequencing. Sterol membrane profiles were determined by gas chromatography-mass spectrometry (GC-MS). In vivo virulence was determined in a murine model of invasive candidiasis. Both isolates displayed azole cross-resistance and reduced susceptibility to amphotericin B, and are novel Δ(5,6)-desaturase (Erg3p) mutants. CAAL2 harbours a new amino acid substitution (L193R), whereas a 13 bp deletion leading to a truncated Erg3p (Δ366-378) was found in CAAL76. Both genetic alterations impaired Erg3p function as shown by GC-MS in these isolates (ergosterol content below 10%, and accumulation of ergosta-7,22-dienol above 40%). In vivo, in a murine model of invasive candidiasis, both CAAL2 and CAAL76 exhibited a significant trend toward reduced virulence, which seems to be linked to a reduced capacity for hyphal growth. These findings demonstrate the critical role of residue 193 in Erg3p function and azole resistance. We suggest that this attenuated in vivo virulence phenotype could be linked to lower potential for hyphal growth. Taken together, our findings highlight the fact that erg3 mutants must be considered in future studies aiming at investigating azole antifungal drug resistance.


A new model of hepatitis B virus reinfection: liver transplantation in the woodchuck1.
Reinfection of liver grafts with hepatitis B virus (HBV) is a pertinent problem in clinical liver transplantation, requiring the development of new treatment strategies. However, no animal model is currently available to study the course and mechanism of hepatitis B reinfection. This was the reason to establish the technique of liver transplantation in the woodchuck, which is a widely used animal model for HBV infection. For the reinfection study, woodchuck hepatitis virus (WHV)-negative animals were selected as donors, whereas chronic carriers served as recipients (n=3). Immunosuppression consisted of cyclosporine in a daily dose of 5 mg/kg. Blood and liver samples were obtained before and 8 hr, 3 weeks, and 10 weeks after transplantation. Virological markers included serological testing for WHV DNA, WHV surface antigen (WHsAg), core antigen (WHcAg), and their antibodies (anti-WHs and anti-WHc). WHV DNA replication intermediates and viral RNA were detected by Southern blot hybridization and Northern blot, respectively. Viral proteins in the liver were visualized by immunohistochemistry for WHsAg and WHcAg. Early after transplantation membranous but no intracytoplasmic staining for WHsAg was detected in the liver graft, which was negative for WHcAg as well as WHV-DNA and RNA. Nearly all hepatocytes in the liver grafts of animals killed at 3 weeks and 10 weeks posttransplant showed strong membranous (WHsAg) and intracytoplasmic (WHsAg and WHcAg) staining, which was higher in frequency and intensity than in carriers before transplantation. The apparently reduced level of WHV replication intermediates and viral RNA in the reinfected liver grafts compared with the carrier animals was caused by the severe morphological changes leading to a replacement of hepatocytes by extended portal infiltrates. The woodchuck proved to be a suitable model to study WHV reinfection after liver transplantation, because the operative procedure was well tolerated. The first sign of viral presence in the graft was WHsAg detected exclusively in the sinusoids. Reinfection was proven by heavy intracytoplasmic staining for WHsAg and WHcAg in the majority of hepatocytes and detection of viral DNA and RNA in the graft.