Biomechanical evaluation of the impact of collared cementless total hip arthroplasty stems on implant subsidence: a cadaveric study in German Shepherd.

Background: With the increasing use of cementless total hip arthroplasty (THA), stem subsidence has emerged as one of the primary complications. Although electron beam melting (EBM)-manufactured stems have been demonstrated to prevent subsidence, there has been limited investigation into the comparative biomechanical impact of collarless and collared EBM cementless stems on stem subsidence in veterinary medicine. Aims: This study aimed to compare the stem implant resistance and failure mechanical properties between collarless and collared EBM-manufactured stems. Methods: Seven pairs of femurs were harvested from canine cadavers. In each pair of femurs, the left femur was implanted with a collarless, and the right femur with a same-sized collared cementless stem. Specimen constructs were mounted to the loading frame of a testing machine and load was transferred to the femoral stem parallel to the longitudinal axis of the femur until the stem subsided 5 mm. Load and stem displacement data acquired during the tests were used to generate load-displacement curves and obtain stiffness, yield, and failure data for each specimen construct. Yield and failure energies were calculated as the areas under the load-displacement curves to the respective points. The effects of implant type and load during subsidence were analyzed using paired t-tests. Results: The yield and failure loads for the collared stems were approximately 40% greater than for the collarless stems (156.39 ± 43.63 kgf vs. 112.01 ± 59.83 kgf, P<0.05). Conclusion: This study supported the advantages of collared EBM stems, including subsidence prevention and better initial stability for early osteointegration.

What is the degree of variability in formal training for pediatric orthopedic surgeons performing scoliosis surgery?

INTRODUCTION: although pediatric orthopedic surgeons worldwide perform scoliosis surgery, the training received is variable and poorly understood. By surveying the European Pediatric Orthopedic Society (EPOS) and the Sociedad Latinoamericana de Ortopedia (SLAOTI), we aim to characterize this variability. MATERIAL AND METHODS: in 2021, we distributed an anonymous online questionnaire to EPOS and SLAOTI. RESULTS: 43% EPOS and 22% SLAOTI perform scoliosis procedures (p < 0.05). 18% EPOS and 2% SLAOTI performed > 35 procedures annually (p < 0.05). 70% EPOS and 27% SLAOTI received formal training in spinal deformity surgery (p < 0.005). CONCLUSIONS: results show significant differences in training and performance of scoliosis procedures between societies.

INTRODUCCIÓN: aunque muchos cirujanos ortopédicos pediátricos alrededor del mundo realizan cirugías para la escoliosis, el entrenamiento es variable y poco conocido. A través de encuestar a la Sociedad Europea de Ortopedia Pediátrica (EPOS) y a la Sociedad Latinoamericana de Ortopedia (SLAOTI) queremos caracterizar esta variabilidad. MATERIAL Y MÉTODOS: distribuimos un cuestionario anónimo en 2021 a los miembros de EPOS y SLAOTI. RESULTADOS: realizan las cirugías de escoliosis 43% de EPOS, en comparación con 22% de SLAOTI (p < 0.05); 18% de EPOS realizó > 35 cirugías al año, en comparación con 2% de SLAOTI (p < 0.05); 70% de EPOS y 27% de SLAOTI recibieron capacitación formal en cirugía de deformidades de la columna (p < 0.005). CONCLUSIONES: los resultados de este estudio subrayan las diferencias en el entrenamiento de las cirugías de escoliosis entre diferentes sociedades.

Long-term performance of the IGRA to predict and prevent active tuberculosis development in HIV-infected patients.

To estimate the long-term performance of the interferon-gamma release assay (IGRA) in predicting active tuberculosis (ATB) development among human immunodeficiency virus (HIV) infected patients in an intermediate TB burden country. A retrospective cohort study was conducted. HIV-infected patients with 1 IGRA result but no current or previous ATB who had been retained in care for 1 year were enrolled and observed for ATB development from 2006 to 2016. Sixty-two IGRA-positive and 354 IGRA-negative patients were observed for a median period of 4.03 years. ATB incidence in IGRA-positive vs. negative patients was respectively 15.24/1000 person-years (py) (95%CI 4.15-39.02) vs. 0.67/1000 py (95%CI 0.01-3.68) (P = 0.001). The sensitivity, specificity and positive and negative predictive values of the IGRA were respectively 80.0% (28.4-99.5%), 85.9% (82.1-89.1%), 6.5% (4.0-10.2%) and 99.7% (98.4-99.9%). Among the 62 IGRA-positive patients, 25 were treated for latent tuberculous infection (LTBI) and 37 were not. Patients with LTBI treatment did not develop ATB, while four cases of ATB occurred among patients without LTBI treatment. Among the 257 IGRA-negative patients who received a follow-up IGRA, 34 (12.9%) patients converted to positive. No ATB developed in IGRA converters. Screening for LTBI using IGRAs and LTBI treatment can be useful to prevent ATB in an intermediate TB burden country. .

In vivo skin reactions from pulsed-type, bipolar, alternating current radiofrequency treatment using invasive noninsulated electrodes.

BACKGROUND: Bipolar, alternating current radiofrequency (RF) conduction using invasive noninsulated electrodes consecutively generates independent tissue coagulation around each electrode and then, the converged coagulation columns. METHODS: Two pulsed-type RF models at the on-time pulse width/pulse pack of 30 and 40 milliseconds were designed to amplify the early stage of RF-induced tissue reaction using hairless mouse skin in vivo. Then, structural and ultrastructural changes were evaluated in hairless mouse skin samples at baseline and immediately 1 day, 3 days, 7 days, and 14 days after treatment. RESULTS: Immediately after pulsed-RF treatment, a few chrysanthemum-like zones of electrothermal coagulation and hypereosinophilic collagen fibers were found in the dermis and dermo-subcutaneous fat junction. Histochemical staining for periodic acid-Schiff and immunohistochemical staining for type IV collagen revealed marked thickening of basement membranes. Transmission electron microscopy demonstrated that pulsed-RF treatment resulted in higher electron-dense and remarkably thicker lamina densa, as well as increases in anchoring fibrils, compared with untreated control specimens. Furthermore, CD31-positive blood vessels were smaller in size with a slit-like luminal appearance, without excessive damage to endothelial cells. CONCLUSION: Our data indicated that pulse-type, bipolar RF energy induces structural and ultrastructural changes in basement membranes and vascular components in hairless mouse skin.

Periorbital melasma: Hierarchical cluster analysis of clinical features in Asian patients.

BACKGROUND: Studies have shown melasma lesions to be distributed across the face in centrofacial, malar, and mandibular patterns. Meanwhile, however, melasma lesions of the periorbital area have yet to be thoroughly described. METHODS: We analyzed normal and ultraviolet light-exposed photographs of patients with melasma. The periorbital melasma lesions were measured according to anatomical reference points and a hierarchical cluster analysis was performed. RESULTS: The periorbital melasma lesions showed clinical features of fine and homogenous melasma pigmentation, involving both the upper and lower eyelids that extended to other anatomical sites with a darker and coarser appearance. The hierarchical cluster analysis indicated that patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face. Significant differences between cluster 1 and cluster 2 were found in lateral distance and inferolateral distance, but not in medial distance and superior distance. Comparing the two clusters, patients in cluster 2 were found to be significantly older and more commonly accompanied by melasma lesions of the temple and medial cheek. CONCLUSION: Our hierarchical cluster analysis of periorbital melasma lesions demonstrated that Asian patients with periorbital melasma can be categorized into two clusters according to the surface anatomy of the face.

The 7 × 1 Fermi Surface Reconstruction in a Two-dimensional f -electron Charge Density Wave System: PrTe3.

The electronic structure of a charge density wave (CDW) system PrTe3 and its modulated structure in the CDW phase have been investigated by employing ARPES, XAS, Pr 4 f RPES, and first-principles band structure calculation. Pr ions are found to be nearly trivalent, supporting the CDW instability in the metallic Te sheets through partial filling. Finite Pr 4 f spectral weight is observed near the Fermi level, suggesting the non-negligible Pr 4 f contribution to the CDW formation through the Pr 4 f -Te 5p hybridization. The two-fold symmetric features in the measured Fermi surface (FS) of PrTe3 are explained by the calculated FS for the assumed 7 × 1 CDW supercell formation in Te sheets. The shadow bands and the corresponding very weak FSs are observed, which originate from both the band folding due to the 3D interaction of Te sheets with neighboring Pr-Te layers and that due to the CDW-induced FS reconstruction. The straight vertical FSs are observed along kz, demonstrating the nearly 2D character for the near-EF states. The observed linear dichroism reveals the in-plane orbital character of the near-EF Te 5p states.

Electronic Structure of YbB_{6}: Is it a Topological Insulator or Not?

To finally resolve the controversial issue of whether or not the electronic structure of YbB_{6} is nontrivially topological, we have made a combined study using angle-resolved photoemission spectroscopy (ARPES) of the nonpolar (110) surface and density functional theory (DFT). The flat-band conditions of the (110) ARPES avoid the strong band bending effects of the polar (001) surface and definitively show that YbB_{6} has a topologically trivial B 2p-Yb 5d semiconductor band gap of ∼0.3 eV. Accurate determination of the low energy band topology in DFT requires the use of a modified Becke-Johnson exchange potential incorporating spin-orbit coupling and an on-site Yb 4f Coulomb interaction U as large as 7 eV. The DFT result, confirmed by a more precise GW band calculation, is similar to that of a small gap non-Kondo nontopological semiconductor. Additionally, the pressure-dependent electronic structure of YbB_{6} is investigated theoretically and found to transform into a p-d overlap semimetal with small Yb mixed valency.

Cross-sectional area of the ulnar nerve after decompression at the cubital tunnel.

UNLABELLED: A total of 48 patients undergoing surgical decompression of the ulnar nerve at the cubital tunnel between February 2010 and May 2013 were retrospectively studied to determine changes in the cross-sectional area of the nerve by the technique of neurosonography. The mean follow-up was 46 months. Post-operative follow-up examination of the cross-sectional area of the ulnar nerve showed a slight reduction in the mean value from 13.8 mm(2) (pre-operative) to 12.9 mm(2) (post-operative). Of the 48 patients, 36 showed a reduction in the cross-sectional area. No correlation was detected between the clinical and sonographic outcomes. Ultrasound seems to be of limited value in the post-operative assessment of patients with entrapment neuropathy of the ulnar nerve. LEVEL OF EVIDENCE: IV.

Preperitoneal femoral hernioplasty: an "umbrella" technique.

INTRODUCTION: Tension-free inguinal mesh-plug hernioplasty is well established. However, femoral hernia repair remains challenging and controversial. We aimed to evaluate a preperitoneal approach of tension-free hernioplasty for femoral hernia upon the anatomy rationality. METHODS: A prospective study of 62 patients between October 1999 and June 2011 received femoral hernioplasty in our hospital. This repair method involved a preperitoneal approach accomplished under regional or local anesthesia with mesh and plug; the emphasis was put on fulfilling the abdominal defect, i.e., the myopectineal orifice, with the plug flattened like an "umbrella", above the femoral ring but not to fill the femoral ring. RESULTS: All cases receiving preperitoneal tension-free hernioplasty had a smooth recovery. There were no severe complications, and no recurrences were detected within a 0.5- to 4-year follow-up. No specific restrictions with regard to activity were placed on the patients after surgery. All cases were able to return to normal life, including work, within 2 weeks. CONCLUSIONS: The preperitoneal tension-free hernioplasty may be a more effective method of femoral hernia repair; meanwhile, we must re-understand the anatomy of femoral hernia correctly so as to restore the anatomic and physiologic functions at this region optimally.

White matter damage is related to ataxia severity in SCA3.

Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms.

An epidemiological study of androgenic alopecia in 3114 Korean patients.

BACKGROUND: Androgenetic alopecia (AGA) is the most common type of hair loss, and is characterized by the transformation of terminal scalp hair into vellus hair. The epidemiology of AGA is not fully understood. A strong genetic basis has long been identified, although little is known of its nongenetic causes. AIM: To evaluate the association of AGA with a number of environmental factors, including smoking, drinking and sleeping habit. METHODS: In total, 3114 Korean individuals with AGA who attended any one of 17 dermatology clinics in 6 cities in South Korea between March 2011 and February 2012 were enrolled in the study. Epidemiologic a data were collected using a standard questionnaire. RESULTS: No association was seen between eating or sleeping habits and severity of hair loss. However, drinking and smoking were associated with the severity of AGA in male patients. We also found that patients of both genders with a family history had more advanced types of hair loss, and the age of onset of AGA in male patients with a family history was earlier than that in male patients without a family history. CONCLUSIONS: Although the evidence for an environmental influence on AGA remains very weak, we did find an association between hair loss severity and certain environmental factors, such as smoking and drinking. Family history with more severe hair loss and an earlier age of onset.

The effect of CD34+ cell-containing autologous platelet-rich plasma injection on pattern hair loss: a preliminary study.

BACKGROUND: Mobilized CD34+ cells in peripheral blood have angiogenic potential, which is an important factor in active hair growth. In addition, activated autologous platelet-rich plasma (PRP) has been reported to induce the proliferation of dermal papilla cells. OBJECTIVES: To investigate the clinical efficacy of interfollicular injection of CD34+ cell-containing PRP preparation for pattern hair loss. PATIENTS AND METHODS: CD34+ cell-containing PRP preparation was injected on the scalps of 13 patients with pattern hair loss, and 13 patients were treated with interfollicular placental extract injection as a control. The numbers of platelets in PRP were microscopically counted and CD34+ cells were evaluated with flow cytometry. RESULTS: Three months after the first treatment, the patients presented clinical improvement in the mean number of hairs, 20.5 ± 17.0% (P < 0.0001), mean hair thickness, 31.3 ± 30.1% (P < 0.0001), and mean two-point score, 84.4 ± 51.7% (P < 0.0001) compared with baseline values. At 6 months, the patients presented clinical improvement in mean hair count, 29.2 ± 17.8% (P < 0.0001), mean hair thickness, 46.4 ± 37.5% (P < 0.0001), and mean two-point score, 121.3 ± 66.8% (P < 0.0001) compared with baseline. The MIXED procedure revealed that CD34+ cell-containing PRP treatment presented a higher degree of improvement than placental extract treatment in hair thickness (P = 0.027) and overall clinical improvement (P = 0.023). CONCLUSION: Our data suggest that the interfollicular injection of autologous CD34+ cell-containing PRP preparation has a positive therapeutic effect on male and female pattern hair loss without remarkable major side-effects.

A stable fixed-dose combination tablet of pseudoephedrine and KOB extracts for the extended release.

Allergic rhinitis (AR) is characterized by inflammation of the nasal mucosa with hypersensitivity resulting from seasonal or perennial responses to specific environmental allergens and by symptoms like nasal rubbing, sneezing, rhinorrhea, lacrimation, nasal congestion and obstruction, and less frequently cough. KOB extracts, which is a polyherbal medicine consisting of 5 different herbs (Atractylodes macrocephala, Astragalus membranaceus, Saposhnikovia divaricata, Ostericum koreanum and Scutellaria baicalensis) had commonly been used for the treatment of various allergic diseases showed an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis, recently. On the other hand, pseudoephedrine is a sympathomimetic amine commonly used to relieve congestion in patients with allergic rhinitis and common colds. Considering the KOB's therapeutic mechanism, the combination with pseudoephedrine would be suitable for allergic rhinitis. This study is to obtain an effective extended release formulation using pseudoephedrine and KOB extracts to reduce side effects of drug due to repeated dosing and improve the compliance of patients for treatment of rhinitis and nasal decongestion. So, the fixed-dose combination tablet of pseudoephedrine and KOB extracts was prepared by direct compression and characterized by drug content, flowing characteristics and dissolution test. The drug content of baicalin of KOB extracts was within the range of 95-105% except for T1 formulation. The hardness and friability values of all formulations ranged from 9 to 13 kp and less than 1%, respectively. Taken together, T4 or T8 could be a stable fixed-dose combination tablet for extended release of pseudoephedrine and KOB extracts for nasal rhinitis.

Inventory of Non-Ataxia Signs (INAS): validation of a new clinical assessment instrument.

Although ataxia is by definition the prominent symptom of ataxia disorders, there are various neurological signs that may accompany ataxia in affected patients. Reliable and quantitative assessment of these signs is important because they contribute to disability, but may also interfere with ataxia. Therefore we devised the Inventory of Non-Ataxia Signs (INAS), a list of neurological signs that allows determining the presence and severity of non-ataxia signs in a standardized way. INAS underwent a rigorous validation procedure that involved a trial of 140 patients with spinocerebellar ataxia (SCA) for testing of inter-rater reliability and another trial of 28 SCA patients to assess short-term intra-rater reliability. In addition, data of the ongoing EUROSCA natural history study were used to determine the reproducibility, responsiveness and validity of INAS. Inter-rater reliability and short-term test-retest reliability was high, both for the total count and for most of the items. However, measures of responsiveness, such as the smallest detectable change and the clinically important change were not satisfactory. In addition, INAS did not differentiate between subjects that were subjectively stable and those that worsened in the 2-year observation period. In summary, INAS and INAS count showed good reproducibility, but unsatisfactory responsiveness. The present analysis and published data from the EUROSCA natural history study suggest that INAS is a valid measure of extracerebellar involvement in progressive ataxia disorders. As such, it is useful as a supplement to the measures of ataxia, but not as a primary outcome measure in future interventional trials.

A human monoclonal antibody 264RAD targeting αvß6 integrin reduces tumour growth and metastasis, and modulates key biomarkers in vivo.

αvß6 integrin expression is upregulated on a wide range of epithelial tumours, and is thought to play a role in modulating tumour growth. Here we describe a human therapeutic antibody 264RAD, which binds and inhibits αvß6 integrin function. 264RAD cross-reacts with human, mouse and cynomolgus monkey αvß6, and inhibits binding to all ligands including the latency-associated peptide of TGF-ß. Screening across a range of integrins revealed that 264RAD also binds and inhibits the related integrin αvß8, but not the integrins α5ß1, αvß3, αvß5 and α4ß1. In vitro 264RAD inhibited invasion of VB6 and Detroit 562 cells in a Matrigel invasion assay and αvß6 mediated production of matrix metalloproteinase-9 in Calu-3 cells. It inhibited TGF-ß-mediated activation of dermal skin fibroblasts by preventing local activation of TGF-ß by NCI-H358 tumour cells in a tumour cell-fibroblast co-culture assay. In vivo 264RAD showed dose-dependent inhibition of Detroit 562 tumour growth, regressing established tumours when dosed at 20 mg/kg once weekly. The reduction in growth associated with 264RAD was related to a dose-dependent inhibition of Ki67 and phospho-ERK and a reduction of αvß6 expression in the tumour cells, coupled to a reduction in fibronectin and alpha smooth muscle actin expression in stromal fibroblasts. 264RAD also reduced the growth and metastasis of orthotopic 4T1 tumours. At 20 mg/kg growth of both the primary tumour and the number of metastatic deposits in lung were reduced. The data support the conclusion that 264RAD is a potent inhibitor of αvß6 integrin, with some activity against αvß8 integrin, that reduces both tumour growth and metastasis.

SVCT-2 in breast cancer acts as an indicator for L-ascorbate treatment.

L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.

The effects of humidity and serum on the surface microhardness and morphology of five retrograde filling materials.

The purpose of this study was to compare the surface morphology and surface hardness of five materials 24 h after filling, in conditions of 100% humidity, and fetal bovine serum. The five materials were ProRoot Mineral Trioxide Aggregate (MTA), Super-EBA, Intermediate Restorative Materials (IRM), Zinc Oxide Eugenol (ZOE), and Amalgam. The microhardness of these materials was evaluated by Vickers microhardness test, and their morphologies were compared by using scanning electron microscopy (SEM). To evaluate the microhardness, the mixed five materials were measured with Vickers microhardness test. Differences between the experimental groups were analyzed by two-way ANOVA and Duncan's multiple comparison tests. All analyses were performed using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL). For the microstructural morphological evaluation, the cross cut and root-end cavity prepared surfaces followed by retrograde filling with five different materials were observed under a Scanning Electron Microscope (Steroscan 440; Leica, Cambridge, England) at ×500. To summarize, Super EBA was less influenced by storage medium than the other materials, especially MTA. However, further long-term studies considering other factors, such as biocompatibility (i.e. cellular toxicity) and retention, are needed to be collaborated with these findings in the clinical context.

Sustainability of donor programs: evaluating and informing the transition of a large HIV prevention program in India to local ownership.

BACKGROUND: Sustainability is the holy grail of many development projects, yet there is limited evidence about strategies that effectively support transition of programs from donor funding to national governments. The first phase of Avahan, the India AIDS Initiative supported by the Bill and Melinda Gates Foundation (2003-2009), aimed to demonstrate an HIV/AIDS prevention program at scale, primarily targeted at high-risk groups. During the second phase (2009-2013), this large-scale program will be transitioned to its natural owners: the Government of India and local communities. This paper describes the evaluation design for the Avahan transition strategy. METHODS/DESIGN: A detailed logic model for the transition was developed. The Avahan transition strategy focuses on three activities: (1) enhancing capacities among communities, non-governmental organizations (NGOs), and government entities, in line with India's national AIDS control strategy; (2) aligning technical and managerial aspects of Avahan programs with government norms and standards; and (3) promoting and sustaining commitment to services for most-at-risk populations. It is anticipated that programs will then transfer smoothly to government and community ownership, become institutionalized within the government system, and support a sustained HIV/AIDS response.The research design evaluates the implementation and effectiveness of (1) activities undertaken by the program; (2) intermediate effects including the process of institutionalization and the extent to which key Avahan organizational procedures and behaviors are integrated into government systems; and (3) overarching effects namely the impact of the transition process on the sustained delivery of HIV/AIDS prevention services to high-risk groups. Both qualitative and quantitative research approaches are employed so that the evaluation will both assess outcomes and explain why they have occurred. CONCLUSIONS: It is unusual for donor-supported projects in low- and middle-income countries to carefully plan transition processes, and prospectively evaluate these. This evaluation is designed so as to both inform decision making throughout the transition process and answer larger questions about the transition and sustainability of donor programs.

Brief exposures of human body lice to sublethal amounts of ivermectin over-transcribes detoxification genes involved in tolerance.

Transcriptional profiling results, using our non-invasive induction assay {short exposure intervals (2-5 h) to sublethal amounts of insecticides [< lethal concentration 3% (LC(3)) at 24 h] administered by stress-reducing means (contact vs. immersion screen) and with induction assessed in a time frame when tolerance is still present [~lethal concentration 90% (LC(90)) in 2-4 h]}, showed that ivermectin-induced detoxification genes from body lice are identified by quantitative real-time PCR analyses. Of the cytochrome P450 monooxygenase and ATP binding cassette transporter genes induced by ivermectin, CYP6CJ1, CYP9AG1, CYP9AG2 and PhABCC4 were respectively most significantly over-expressed, had high basal expression levels and were most closely related to genes from other organisms that metabolized insecticides, including ivermectin. Injection of double-stranded RNAs (dsRNAs) against either CYP9AG2 or PhABCC4 into non-induced female lice reduced their respective transcript level and resulted in increased sensitivity to ivermectin, indicating that these two genes are involved in the xenobiotic metabolism of ivermectin and in the production of tolerance.