Active monitoring versus an abduction device for treatment of infants with centered dysplastic hips: study protocol for a randomized controlled trial (TReatment with Active Monitoring (TRAM)-Trial).

BACKGROUND: Developmental Dysplasia of the Hip (DDH) is one of the most common pediatric orthopedic disorders, affecting 1-3% of all newborns. The optimal treatment of centered DDH is currently under debate. This randomized controlled trial aims to study the (cost-)effectiveness of active monitoring versus abduction treatment for infants with centered DDH. METHODS: This is a multicenter, parallel-group, open-label, non-inferiority randomized controlled trial studying the (cost-)effectiveness of active monitoring versus abduction treatment for infants with centered DDH in fourteen hospitals in the Netherlands. In total, 800 infants with centered DDH (Graf IIa-/IIb/IIc), aged 10-16 weeks, will be randomly allocated to the active monitoring or abduction treatment group. Infants will be followed up until the age of 24 months. The primary outcome is the rate of normal hips, defined as an acetabular index lower than 25 degrees on an antero-posterior radiograph, at the age of 12 months. Secondary outcomes are the rate of normal hips at the age of 24 months, complications, time to hip normalization, the relation between baseline patient characteristics and the rate of normal hips, compliance, costs, cost-effectiveness, budget impact, health-related quality of life (HRQoL) of the infant, HRQoL of the parents/caregivers, and parent/caregiver satisfaction with the treatment protocol. DISCUSSION: The outcomes of this randomized controlled trial will contribute to improving current care-as-usual for infants with centered DDH. TRIAL REGISTRATION: Dutch Trial Register, NL9714, registered September 6, 2021. https://clinicaltrialregister.nl/en/trial/29596.

Treatment of decentered developmental dysplasia of the hip under the age of 1 year: an evidence-based clinical practice guideline - Part 2.

Background and purpose: Diagnostics and treatment of developmental dysplasia of the hip (DDH) are highly variable in clinical practice. To obtain more uniform and evidence-based treatment pathways, we developed the 'Dutch guideline for DDH in children < 1 year'. This study describes recommendations for unstable and decentered hips. Materials and methods: The Appraisal of Guidelines for Research and Evaluation criteria (AGREE II) were applied. A systematic literature review was performed for six predefined guideline questions. Recommendations were developed, based on literature findings, as well as harms/benefits, patient/parent preferences, and costs (GRADE). Results: The systematic literature search resulted in 843 articles and 11 were included. Final guideline recommendations are (i) Pavlik harness is the preferred first step in the treatment of (sub) luxated hips; (ii) follow-up with ultrasound at 3-4 and 6-8 weeks; (iii) if no centered and stable hip after 6-8 weeks is present, closed reduction is indicated; (iv) if reduction is restricted by limited hip abduction, adductor tenotomy is indicated; (v) in case of open reduction, the anterior, anterolateral, or medial approach is advised, with the choice based on surgical preference and experience; (vi) after reduction (closed/open), a spica cast is advised for 12 weeks, followed by an abduction device in case of residual dysplasia. Interpretation: This study presents recommendations on the treatment of decentered DDH, based on the available literature and expert consensus, as Part 2 of the first official and national evidence-based 'Guideline for DDH in children < 1 year'. Part 1 describes the guideline sections on centered DDH in a separate article.

Treatment of centered developmental dysplasia of the hip under the age of 1 year: an evidence-based clinical practice guideline - Part 1.

Despite the high incidence of developmental dysplasia of the hip (DDH), treatment is very diverse. Therefore, the Dutch Orthopedic Society developed a clinical practice guideline with recommendations for optimal and uniform treatment of DDH. This article summarizes the guideline on centered DDH (i.e. Graf types 2A-C). The guideline development followed the criteria of Appraisal of Guidelines for Research and Evaluation II. A systematic literature review was performed to identify randomized controlled trials and comparative cohort studies including children <1 year with centered DDH. Articles were included that compared (1) treatment with observation, (2) different abduction devices, (3) follow-up frequencies, and (4) discontinuation methods. Recommendations were based on Grading Recommendations Assessment, Development, and Evaluation, which included the literature, clinical experience and consensus, patient and parent comfort, and costs. Out of 430 potentially relevant articles, 5 comparative studies were included. Final guideline recommendations were (1) initially observe 3-month-old patients with centered DDH, start abduction treatment if the hip does not normalize after 6-12 weeks; (2) prescribe a Pavlik harness to children <6 months with persisting DDH on repeated ultrasonography, consider alternative abduction devices for children >6 months; (3) assess patients every 6 weeks; and (4) discontinue the abduction device when the hip has normalized or when the child is 12 months. This paper presents a summary of part 1 of the first evidence-based guideline for treatment of centered DDH in children <1 year. Part 2 presents the guideline on decentered DDH in a separate article.

HLA-Restriction of Human Treg Cells Is Not Required for Therapeutic Efficacy of Low-Dose IL-2 in Humanized Mice.

Regulatory T (Treg) cells are essential to maintain immune homeostasis in the intestine and Treg cell dysfunction is associated with several inflammatory and autoimmune disorders including inflammatory bowel disease (IBD). Efforts using low-dose (LD) interleukin-2 (IL-2) to expand autologous Treg cells show therapeutic efficacy for several inflammatory conditions. Whether LD IL-2 is an effective strategy for treating patients with IBD is unknown. Recently, we demonstrated that LD IL-2 was protective against experimental colitis in immune humanized mice in which human CD4+ T cells were restricted to human leukocyte antigen (HLA). Whether HLA restriction is required for human Treg cells to ameliorate colitis following LD IL-2 therapy has not been demonstrated. Here, we show that treatment with LD IL-2 reduced 2,4,6-trinitrobenzensulfonic acid (TNBS) colitis severity in NOD.PrkdcscidIl2rg-/- (NSG) mice reconstituted with human CD34+ hematopoietic stem cells. These data demonstrate the utility of standard immune humanized NSG mice as a pre-clinical model system to evaluate therapeutics targeting human Treg cells to treat IBD.

Perceptions of non-Western immigrant women on having breast cancer and their experiences with treatment-related changes in body weight and lifestyle: A qualitative study.

BACKGROUND: The number of non-Western immigrants with breast cancer in the Netherlands has increased over the past decades and is expected to triple by 2030. Due to insufficient representation in clinical studies, it is unclear what the specific experiences and needs of these women are. Understanding how culture and religion affect these women's experience of breast cancer and how they deal with chemotherapy and treatment-related changes in body weight and lifestyle is crucial for health care professionals to be able to provide effective support. METHODS: A qualitative study was conducted using semi-structured interviews with 28 immigrant women with a history of breast cancer treated with chemotherapy. RESULTS: Women often associated breast cancer with taboo, death or bad luck. Religion offered these women guidance, strength and meaning to the disease, but also limited the women to openly talk about their disease. Women perceived lifestyle factors to have little influence on the development and treatment of cancer. After treatment, however, their thinking changed and these lifestyle factors became of paramount importance to them. They realised that they missed out on information about managing their own diet, exercise and body weight and were eager to share their experiences with other women in their culture with newly diagnosed breast cancer. CONCLUSION: Women became aware during and after breast cancer treatment that it was difficult for them to actively deal with their illness under the influence of their culture and religion. Based on their own experiences and acquired knowledge, they would like to give advice to newly diagnosed women on how to deal with breast cancer within their own culture and religion. Their recommendations could be used by mosques, churches, support groups and health care professionals, to ensure interventions during breast cancer treatment meet their religious and cultural needs and thus improve their quality of life.

Detection of scales and its thickness determination in industrial pipes using Compton backscattering system.

The ability to detect and quantify scales in pipes has been an important yardstick for efficient transfer of fluids in domestic as well as in application related industries. Knowledge of different kinds of scales formed has become a precondition for trouble-shooting in operational lines. In this paper, collimated Compton backscattered gamma rays from a radioactive source have been used to inspect the scales by automatic scanning in steps along the axial direction of different pipes. The methodology has been extended for the quantification of scales that prevails in the real functionality of extensive usage of fluids. To aid for descaling processes, the desideratum is the density determination of scales and this parameter is quantified non-destructively and is also validated with the standard density. The described non-intrusive gamma ray densitometry is quite promising, efficient and has highly reliable results for scale detection with the squared correlation coefficient of 0.98. The proposed technique shows a better linearity than the gammatography technique.

Level of awareness and uptake of the female condom in women aged 18 to 49 years in Bindura district, Mashonaland Central province, Zimbabwe.

Zimbabwe introduced the female condom in 1997, but acceptance was slow. A study was conducted to determine its level of awareness and uptake in women aged 18 to 49 years at Bindura Provincial Hospital, and at Chipadze and Chiwaridzo council clinics. A descriptive cross-sectional study design was used. A total of 242 eligible consenting respondents were selected using simple random sampling. Data were processed using the Statistical Package for Social Sciences (SPSS) software version 16. Data revealed that 81.4% of the respondents had heard about the method. Most respondents 88 (36.4%) had heard about female condoms from nurses. However, 53.3% had not received health education on the method from healthcare providers. Knowledge of the female condom was low at 36.3% and most respondents (83.5%) had not used it. The major reasons cited for failure to use the method were unavailability (19.8%) and partner refusal (17.8%). Of the 16.5% who used the female condom only 4.1% used it consistently. Female condom uptake was very low at 16.1%. Knowledge of the method was associated with its uptake (χ(2) = 86, p < 0.05). Pearson's correlation was used to examine the relationship between awareness and uptake of the method. It indicated a weak positive linear relationship (r = 0.309, p < 0.01). A regression coefficient (R(2) = 0.095, p < 0.05) showed that female condom awareness accounts for 9.5% of the variance in uptake. This study revealed that women with increased level of awareness on the method are likely to use it. Therefore, healthcare providers need to strengthen health education on female condoms and make them readily available.

Level of Awareness and Uptake of the Female Condom in Women Aged 18 to 49 Years in Bindura District; Mashonaland Central Province; Zimbabwe

Zimbabwe introduced the female condom in 1997; but acceptance was slow. A study was conducted to determine its level of awareness and uptake in women aged 18 to 49 years at Bindura Provincial Hospital; and at Chipadze and Chiwaridzo council clinics. A descriptive cross-sectional study design was used. A total of 242 eligible consenting respondents were selected using simple random sampling. Data were processed using the Statistical Package for Social Sciences (SPSS) software version 16. Data revealed that 81.4 of the respondents had heard about the method. Most respondents 88 (36.4) had heard about female condoms from nurses. However; 53.3 had not received health education on the method from healthcare providers. Knowledge of the female condom was low at 36.3 and most respondents (83.5) had not used it. The major reasons cited for failure to use the method were unavailability (19.8) and partner refusal (17.8). Of the 16.5 who used the female condom only 4.1 used it consistently. Female condom uptake was very low at 16.1. Knowledge of the method was associated with its uptake (?2 = 86; p 0.05). Pearson's correlation was used to examine the relationship between awareness and uptake of the method. It indicated a weak positive linear relationship (r

Mitochondrial disease in childhood: mtDNA encoded.

Since the first description of a mitochondrial DNA (mtDNA)-associated disease in the late 1980s, there have been more than 275 mutations within the mtDNA genome described causing human disease. The phenotypic expression of these disorders is vast, as disturbances of the unique physiology of mitochondria can create a wide range of clinical heterogeneity. Features of heteroplasmy, threshold effect, genetic bottleneck, mtDNA depletion, mitotic segregation, and maternal inheritance have been identified and described as a result of novel biochemical and genetic controls of mitochondrial function. We hope that as we unfold this fascinating part of clinical medicine, the reader will see how alterations in the tapestry of mitochondrial biochemistry and genetics can give rise to human illness.

Intercomparison of gamma ray scattering and transmission techniques for fluid-fluid and fluid-air interface levels detection and density measurements.

This paper focuses on the fluid-fluid, fluid-air interface level detection and density determination by gamma scattering method and intercomparison with transmission (gammatography) technique. The Monte Carlo (MC) numerical simulation of the scattering phenomena is done using the MCNP code. The obtained accuracies and resolution of the level detections and density measurements are higher in case of gamma scattering method compared to transmission method.

Peroxide solvation by a toroidal lithium inverse crown ether complex assembled by multidentate polyimido sulfonates.

In this communication we present the synthesis of the inverse crown ether complex [Li(2)O(2)·Li(4){CH(2)(N(Me)CH(2)S(NtBu)(2))(2)}(2)] (1) which is able to accommodate peroxide in a torus of lithium ions.

Novel multidentate sulfur-nitrogen ligands with enhanced complexation properties.

Di(tert-butyl)sulfur diimide and bis(trimethylsilyl)sulfur diimide were reacted with different metalated amines to form versatile novel multidentate ligand systems with side-arm donation. Their complexation properties in terms of ligand design, denticity and the cation size are discussed. We report herein the synthesis and structure elucidation of [(tBuN)(2)S{LiMe(2)N(C(6)H(4))S(NtBu)(2)}(2)] (1), [(Li{Me(2)N(C(6)H(4))S(NSiMe(3))(2)})(2)] (2), [(Li(thf){Me(2)N(C(6)H(4))S(NSiMe(3))(2)})(2)] (3), [(Li{2-PicS(NSiMe(3))(2)})(2)] (4), [(Li{Me(2)N(CH(2))(2)N(Me)S(NSiMe(3))(2)})(2)] (5), [(Na{Me(2)N(CH(2))(2)N(Me)S(NSiMe(3))(2)})(2)] (6) and [(K{Me(2)N(C(6)H(4))S(NSiMe(3))(2)})(2)] (7).

Intercomparison of gamma scattering, gammatography, and radiography techniques for mild steel nonuniform corrosion detection.

This paper focuses on the mild steel (MS) corrosion detection and intercomparison of results obtained by gamma scattering, gammatography, and radiography techniques. The gamma scattering non-destructive evaluation (NDE) method utilizes scattered gamma radiation for the detection of corrosion, and the scattering experimental setup is an indigenously designed automated personal computer (PC) controlled scanning system consisting of computerized numerical control (CNC) controlled six-axis source detector system and four-axis job positioning system. The system has been successfully used to quantify the magnitude of corrosion and the thickness profile of a MS plate with nonuniform corrosion, and the results are correlated with those obtained from the conventional gammatography and radiography imaging measurements. A simple and straightforward reconstruction algorithm to reconstruct the densities of the objects under investigation and an unambiguous interpretation of the signal as a function of material density at any point of the thick object being inspected is described. In this simple and straightforward method the density of the target need not be known and only the knowledge of the target material's mass attenuation coefficients (composition) for the incident and scattered energies is enough to reconstruct the density of the each voxel of the specimen being studied. The Monte Carlo (MC) numerical simulation of the phenomena is done using the Monte Carlo N-Particle Transport Code (MCNP) and the quantitative estimates of the values of signal-to-noise ratio for different percentages of MS corrosion derived from these simulations are presented and the spectra are compared with the experimental data. The gammatography experiments are carried out using the same PC controlled scanning system in a narrow beam, good geometry setup, and the thickness loss is estimated from the measured transmitted intensity. Radiography of the MS plates is carried out using 160 kV x-ray machine. The digitized radiographs with a resolution of 50 µm are processed for the detection of corrosion damage in five different locations. The thickness losses due to the corrosion of the MS plate obtained by gamma scattering method are compared with those values obtained by gammatography and radiography techniques. The percentage thickness loss estimated at different positions of the corroded MS plate varies from 17.78 to 27.0, from 18.9 to 24.28, and from 18.9 to 24.28 by gamma scattering, gammatography, and radiography techniques, respectively. Overall, these results are consistent and in line with each other.

Access to new Janus head ligands: linking sulfur diimides and phosphanes for hemilabile tripodal scorpionates.

Reactions of lithium dialkyl/phenyl phosphanylmethylides, RR'PCH(X)Li (R, R' = Me, Et, Ph and R = Me, R' = Ph; X = H or Me), with sulfur diimides S(NR'')2 (R'' = (t)Bu or SiMe3) in an equimolar ratio yielded Janus head complexes with the structural motif [Li{RR'PCH(X)S(NR'')2}]2 (R'' = (t)Bu, SiMe3). The basic core of these dimeric complexes is composed of a (LiN)(2) four-membered ring containing two four-coordinated lithium atoms. A lithium complex of the new Janus head ligand with another structural motif [TMEDA·Li{Ph(2)PCH(2)S(NSiMe3)2}] (6) could be isolated from the reaction of [Ph2PCH2Li·TMEDA] with S(NSiMe3)2. Two monomeric complexes [Mg{Me2PCH2S(NR'')2}2] (7, 8) were synthesised by a straightforward reaction of [Li{Me2PCH2S(NR'')2}2] with MgCl2 in pentane. The magnesium atom is chelated by one phosphorus atom and two nitrogen atoms of each unit of the hemilabile ligand in a tripodal manner, leading to octahedral geometry around the magnesium cation. A complete analysis of [Ph2PCH2(SNSiMe3)(HNSiMe3)] (9) is also described in which one nitrogen atom of the imido moiety is protonated.

A single-tube screen for Salmonella and Shigella.

Salmonella and Shigella species are routinely sought in stool specimens submitted for culture. It is a common practice to screen lactose-negative colonies by using triple sugar iron agar, lysine iron agar, and Christensen urea agar to determine if further identification is necessary. We designed and evaluated a novel combination of media, which are layered in a single tube, for screening isolates suspected to possibly represent Salmonella or Shigella. We tested this media combination with 106 Salmonella, 56 Shigella, and 56 other gram-negative bacilli. All Salmonella and Shigella isolates tested were appropriately characterized as possible Salmonella or Shigella by using an algorithm developed for use with this media combination. Similarly, 53 (95%) of 56 other gram-negative bacilli were appropriately screened as non -Salmonella and non -Shigella isolates. This unique media combination provides the most important biochemical reactions needed to screen for Salmonella and Shigella in a single-tube format, which decreases labor by two thirds (ie, 1 tube is inoculated vs 3).

Adeno-associated virus (AAV)-mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation.

We explored whether exposure of mammalian germ line stem cells to adeno-associated virus (AAV), a gene therapy vector, would lead to stable transduction and transgene transmission. Mouse germ cells harvested from experimentally induced cryptorchid donor testes were exposed in vitro to AAV vectors carrying a GFP transgene and transplanted to germ cell-depleted syngeneic recipient testes, resulting in colonization of the recipient testes by transgenic donor cells. Mating of recipient males to wild-type females yielded 10% transgenic offspring. To broaden the approach to nonrodent species, AAV-transduced germ cells from goats were transplanted to recipient males in which endogenous germ cells had been depleted by fractionated testicular irradiation. Transgenic germ cells colonized recipient testes and produced transgenic sperm. When semen was used for in vitro fertilization (IVF), 10% of embryos were transgenic. Here, we report for the first time that AAV-mediated transduction of mammalian germ cells leads to transmission of the transgene through the male germ line. Equally important, this is also the first report of transgenesis via germ cell transplantation in a nonrodent species, a promising approach to generate transgenic large animal models for biomedical research.

Spontaneous myocarditis mimicking human disease occurs in the presence of an appropriate MHC and non-MHC background in transgenic mice.

Most individuals have viral infections at some point in their life, however, only few develop autoreactivity to cardiac myosin following infection resulting in myocarditis suggesting a genetic predisposition. Most mouse models of myocarditis are induced by viral infection or by immunization with cardiac myosin. We generated HLA-DR3.Abetao and HLA-DQ8.Abetao transgenic mice in NOD and HLA-DQ8.Abetao in B10 background to study spontaneous autoimmunity. A high mortality was observed in NOD.DQ8 female mice 16 weeks or older. Echocardiography showed marked systolic dysfunction. Histopathology of various organs revealed an enlarged heart with mononuclear infiltrate consisting of CD4 and Mac-1+ cells and myocyte necrosis. The autoimmunity was associated with the presence of spontaneous autoreactive T cells and antibodies to cardiac myosin. Serologically, mice were negative for all known mouse viruses. NOD.DR3.Abetao, the transgene negative littermates, NOD, and B10.DQ8 Abetao mice had no gross or microscopic cardiac pathology. Spontaneous cellular and humoral response to cardiac myosin suggests that NOD.DQ8 may harbor autoreactive cells that can lead to spontaneous myocarditis and dilated cardiomyopathy. HLA-DQ8 is required for the predisposition to the spontaneous autoreactivity while NOD background influences onset and progression of disease. This model of myocarditis occurs predominantly in female mice and may provide insight into the pathogenesis of heart disease in women.

Adapting to aging losses: do resources facilitate strategies of selection, compensation, and optimization in everyday functioning?

Previous cross-sectional research has shown that older people who are rich in sensorimotor-cognitive and social-personality resources are better functioning in everyday life and exhibit fewer negative age differences than resource-poor adults. Longitudinal data from the Berlin Aging Study was used to examine these findings across a 4-year time interval and to compare cross-sectional indicators of adaptive everyday functioning among survivors and nonsurvivors. Apart from their higher survival rate, resource-rich older people (a) invest more social time with their family members, (b) reduce the diversity of activities within the most salient leisure domain, (c) sleep more often and longer during daytime, and (d) increase the variability of time investments across activities after 4 years. Overall, findings suggest a greater use of selection, compensation, and optimization strategies in everyday functioning among resource-rich older adults as compared with resource-poor older adults.

A comparative study of two psychometric approaches to detect risk status for dementia.

This study results from an effort to examine the relationship between the diagnostic potentials for detecting risk status for dementia of a cognitive plasticity approach and a traditional status-oriented procedure (test battery) by Storandt et al. [Arch Neurol 1984;41:497-499]. The aim is to compare prediction accuracy for risk for developing dementia with these two approaches. A sample of 106 community-dwelling elderly adults were tested with both procedures, and their scores on the Structured Interview for the Diagnosis of Dementia used as external criterion for predicting risk status. The findings show that figural relations pretest and training gains account for a considerable amount of individual differences in mental status similar to that explained by the traditional test battery. In addition, the accuracy of discrimination between healthy and at-risk participants appears slightly higher when using the figural pretest and training gains. These results suggest the conclusion that use of figural relations tests and the cognitive plasticity approach represents a viable alternative to the traditional, status-oriented test battery as a means of early diagnosis of dementia in nonclinical populations.