Risk factors for HIV infection in injection drug users and evidence for onward transmission of HIV to their sexual partners in Chennai, India

OBJECTIVES: Determining HIV prevalence in injection drug users (IDUs) and their regular sex partners in Chennai, India. METHODS: A total of 226 IDUs and their regular sex partners were enrolled during April-July 2003. After informed consent was obtained, a semistructured questionnaire was administered and serum was tested for HIV antibody. RESULTS: The HIV seroprevalence was 30% (68/226) in IDUs and 5% in their regular sex partners (11/226). While in 25% of couples only the male partner was HIV positive, 5% of the couples were concordant for HIV infection and 70% were HIV negative. Fifty-seven percent of the HIV-positive IDUs and 45% of the HIV-infected women thought that they had "no chance" or "very little chance" of getting HIV, reflecting low HIV risk perception. More than 20% IDUs reported borrowing or lending of injection equipment. In univariate analyses "sex" and "condom use" with sex workers had no bearing but "more than twice a day injecting frequency," "history of incarceration," "tattoos," "recruitment from northern part of the city," and ever-injecting drugs in drug-selling places had significant association with HIV infection in IDUs. In an adjusted model, the odds of HIV infection were 2 times higher among IDUs who had ever injected drugs in drug-selling places and 6 times higher in those who were recruited from the northern part of central Chennai. CONCLUSION: Reducing sharing of injection equipment and unsafe tattooing through targeted and environmental interventions, increasing HIV risk perception, and promoting safer sex practices among IDUs and their sex partners are urgent program needs.     

On the use of EPID-based implanted marker tracking for 4D radiotherapy

Four-dimensional (4D) radiotherapy delivery to dynamically moving tumors requires a real-time signal of the tumor position as a function of time so that the radiation beam can continuously track the tumor during the respiration cycle. The aim of this study was to develop and evaluate an electronic portal imaging device (EPID)-based marker-tracking system that can be used for real-time tumor targeting, or 4D radiotherapy. Three gold cylinders, 3 mm in length and 1 mm in diameter, were implanted in a dynamic lung phantom. The phantom range of motion was 4 cm with a 3-s "breathing" period. EPID image acquisition parameters were modified, allowing image acquisition in 0.1 s. Images of the stationary and moving phantom were acquired. Software was developed to segment automatically the marker positions from the EPID images. Images acquired in 0.1 s displayed higher noise and a lower signal-noise ratio than those obtained using regular (> 1 s) acquisition settings. However, the markers were still clearly visible on the 0.1-s images. The motion of the phantom blurred the images of the markers and further reduced the signal-noise ratio, though they could still be successfully segmented from the images in 10-30 ms of computation time. The positions of gold markers placed in the lung phantom were detected successfully, even for phantom velocities substantially higher than those observed for typical lung tumors. This study shows that using EPID-based marker tracking for 4D radiotherapy is feasible, however, changes in linear accelerator technology and EPID-based image acquisition as well as patient studies are required before this method can be implemented clinically.     

The effect of dose calculation uncertainty on the evaluation of radiotherapy plans

Monte Carlo dose calculations will potentially reduce systematic errors that may be present in currently used dose calculation algorithms. However, Monte Carlo calculations inherently contain random errors, or statistical uncertainty, the level of which decreases inversely with the square root of computation time. Our purpose in this study was to determine the level of uncertainty at which a lung treatment plan is clinically acceptable. The evaluation methods to decide acceptability were visual examination of both isodose lines on CT scans and dose volume histograms (DVHs), and reviewing calculated biological indices. To study the effect of systematic and/or random errors on treatment plan evaluation, a simulated "error-free" reference plan was used as a benchmark. The relationship between Monte Carlo statistical uncertainty and dose was found to be approximately proportional to the square root of the dose. Random and systematic errors were applied to a calculated lung plan, creating dose distributions with statistical uncertainties of between 0% and 16% (1 s.d.) at the maximum dose point and also distributions with systematic errors of -16% to 16% at the maximum dose point. Critical structure DVHs and biological indices are less sensitive to calculation uncertainty than those of the target. Systematic errors affect plan evaluation accuracy significantly more than random errors, suggesting that Monte Carlo dose calculation will improve outcomes in radiotherapy. A statistical uncertainty of 2% or less does not significantly affect isodose lines, DVHs, or biological indices.     

Chaetogaster limnaei (Annelida: Oligochaeta) as a parasite of the zebra mussel Dreissena polymorpha,and the quagga mussel Dreissena bugensis (Mollusca: Bivalvia)

Dreissenid mussels, Dreissena polymorpha and D. bugensis, were found to be infected by the naidid oligochaete Chaetogaster limnaei at four sites in the St. Lawrence River. This is the first report of this species infecting dreissenids anywhere in the world. Most worms inhabited the mantle cavity, where they caused erosion of the mantle and gill epithelia as determined by histopathological examination. Others penetrated various tissues; one had invaded the ovary and was feeding on oocytes and ovarian tissues. Of 606 mussels examined, 166 (27.4%) harbored at least 1 C. limnaei. The prevalence varied between 1% and 80%, depending on the collection site and date. The worms were slightly but significantly more prevalent in D. bugensis than in D. polymorpha. The intensity ranged from 1 to 18 worms per infected host. Variations in prevalence and intensity were not related to the size or sex of the host, but the data did suggest some seasonality.     

Mutations selected in rotavirus enterotoxin NSP4 depend on the context of its expression

The rotavirus NSP4 protein is cytotoxic when transiently expressed in cells and is capable of inducing secretory diarrhea in neonatal mice. NSP4 consists of 175 amino acids, and sequences important for its toxic effects have been mapped to the carboxy-terminal half of the protein. In this report, we compared NSP4-encoding nucleotide sequences recovered from cell lines engineered to express NSP4 from human rotavirus strain Wa with NSP4 sequences recovered from cells persistently infected with either Wa or simian rotavirus strain SA11. In cells stably transfected with Wa NSP4, we found that proline(138) was changed to either serine or threonine. However, in cells persistently infected with SA11, we found that phenylalanine(33) was changed to leucine, and in cells persistently infected with Wa, no changes were observed in NSP4. Expression of Wa NSP4 in Caco-2 cells resulted in increased cell-doubling times and decreased cell viability in comparison to cells expressing NSP4-serine(138) or NSP4-threonine(138). This result suggests that sequence polymorphism at residue 138 in Wa NSP4 influences the cytotoxicity of the protein. Therefore, mutations in the carboxy-terminal half of NSP4 are selected when NSP4 is expressed in cells in the absence of other viral proteins, but not in the context of viral replication. These findings suggest that cytotoxic functions of NSP4 are not operant during natural rotavirus infection.     

A method for photon beam Monte Carlo multileaf collimator particle transport

Monte Carlo (MC) algorithms are recognized as the most accurate methodology for patient dose assessment. For intensity-modulated radiation therapy (IMRT) delivered with dynamic multileaf collimators (DMLCs), accurate dose calculation, even with MC, is challenging. Accurate IMRT MC dose calculations require inclusion of the moving MLC in the MC simulation. Due to its complex geometry, full transport through the MLC can be time consuming. The aim of this work was to develop an MLC model for photon beam MC IMRT dose computations. The basis of the MC MLC model is that the complex MLC geometry can be separated into simple geometric regions, each of which readily lends itself to simplified radiation transport. For photons, only attenuation and first Compton scatter interactions are considered. The amount of attenuation material an individual particle encounters while traversing the entire MLC is determined by adding the individual amounts from each of the simplified geometric regions. Compton scatter is sampled based upon the total thickness traversed. Pair production and electron interactions (scattering and bremsstrahlung) within the MLC are ignored. The MLC model was tested for 6 MV and 18 MV photon beams by comparing it with measurements and MC simulations that incorporate the full physics and geometry for fields blocked by the MLC and with measurements for fields with the maximum possible tongue-and-groove and tongue-or-groove effects, for static test cases and for sliding windows of various widths. The MLC model predicts the field size dependence of the MLC leakage radiation within 0.1% of the open-field dose. The entrance dose and beam hardening behind a closed MLC are predicted within +/- 1% or 1 mm. Dose undulations due to differences in inter- and intra-leaf leakage are also correctly predicted. The MC MLC model predicts leaf-edge tongue-and-groove dose effect within +/- 1% or 1 mm for 95% of the points compared at 6 MV and 88% of the points compared at 18 MV. The dose through a static leaf tip is also predicted generally within +/- 1% or 1 mm. Tests with sliding windows of various widths confirm the accuracy of the MLC model for dynamic delivery and indicate that accounting for a slight leaf position error (0.008 cm for our MLC) will improve the accuracy of the model. The MLC model developed is applicable to both dynamic MLC and segmental MLC IMRT beam delivery and will be useful for patient IMRT dose calculations, pre-treatment verification of IMRT delivery and IMRT portal dose transmission dosimetry.     

Quantifying the predictability of diaphragm motion during respiration with a noninvasive external marker

The aim of this work was to quantify the ability to predict intrafraction diaphragm motion from an external respiration signal during a course of radiotherapy. The data obtained included diaphragm motion traces from 63 fluoroscopic lung procedures for 5 patients, acquired simultaneously with respiratory motion signals (an infrared camera-based system was used to track abdominal wall motion). During these sessions, the patients were asked to breathe either (i) without instruction, (ii) with audio prompting, or (iii) using visual feedback. A statistical general linear model was formulated to describe the relationship between the respiration signal and diaphragm motion over all sessions and for all breathing training types. The model parameters derived from the first session for each patient were then used to predict the diaphragm motion for subsequent sessions based on the respiration signal. Quantification of the difference between the predicted and actual motion during each session determined our ability to predict diaphragm motion during a course of radiotherapy. This measure of diaphragm motion was also used to estimate clinical target volume (CTV) to planning target volume (PTV) margins for conventional, gated, and proposed four-dimensional (4D) radiotherapy. Results from statistical analysis indicated a strong linear relationship between the respiration signal and diaphragm motion (p<0.001) over all sessions, irrespective of session number (p=0.98) and breathing training type (p=0.19). Using model parameters obtained from the first session, diaphragm motion was predicted in subsequent sessions to within 0.1 cm (1 sigma) for gated and 4D radiotherapy. Assuming a 0.4 cm setup error, superior-inferior CTV-PTV margins of 1.1 cm for conventional radiotherapy could be reduced to 0.8 cm for gated and 4D radiotherapy. The diaphragm motion is strongly correlated with the respiration signal obtained from the abdominal wall. This correlation can be used to predict diaphragm motion, based on the respiration signal, to within 0.1 cm (1 sigma) over a course of radiotherapy.     

Trichothiodystrophy type 4 in an Indian family

Trichothiodystrophy, non‐photosensitive type 4 (TTD4), is a rare genetic disorder with an autosomal recessive mode of inheritance. It is characterized by coarse and brittle hair, anomalies of the tissues derived from the neuro‐ectoderm (skin, hair, and nails) and intellectual disability. We herein report two male siblings aged 13 and 16 years with TTD4 and a known homozygous pathogenic variant, c.229del [p.(Arg77Glyfs*76)] in exon 1 of MPLKIP (NM_138701.3). We herein highlight the clinical and molecular findings of the first reported case of TTD4 in probands of Indian ethnicity.     

Ambient temperature related sleep changes in rats neonatally treated with capsaicin

Ambient temperature related sleep changes in rats neonatally treated with capsaicin. PHYSIOL BEHAV 00(0) 000-000, 2004. The study was conducted on adult male Wistar rats, neonatally treated with capsaicin to destroy the peripheral warm receptors. The sleep-wakefulness was recorded for 5 h at an ambient temperature (T(amb)) of 18, 24, 30 and 33 degrees C on different days. The rectal temperatures (T(r)) of the rats were studied on exposure to 6 and 37 degrees C for 2 h to assess their thermoregulatory ability. The changes in the behavioral thermoregulation were assessed by noting the thermal preference of rats when they were placed in an environmental chamber with 3 interconnected compartments maintained at 24, 27 and 30 degrees C. Slow wave (SWS) and rapid eye movement (REM) sleep were decreased at 18 degrees C and increased at 30 degrees C, in control rats. There was a decrease in REM sleep and no change in SWS when T(amb) was raised from 30 to 33 degrees C. However, in neonatally capsaicin treated rats, sleep was increased even at 33 degrees C, though there was no significant change in sleep when T(amb) was increased from 18 to 24 degrees C. Capsaicin treated rats showed thermoregulatory deficiency at 37 degrees C but the thermal preference was unaltered in these rats. The results suggest that the central warm receptors can produce alteration in sleep at different T(amb), even in absence of peripheral warm receptors. The behavioral thermoregulation was unaffected in these rats, though their ability to defend the body temperature in warm environment was affected.     

Choriocarcinoma with negative urinary and serum beta human chorionic gonadotropin (betaHCG)--a case report

This was a rare case where a patient presented clinically as a case of post abortal sepsis and ultrasound showing the picture of an intramural degenerating fibroid. Her serum and urine both were negative for beta human chorionic gonadotropin (betaHCG). Patient succumbed to choriocarcinoma 1 month later. Failure to detect urinary and serum betaHCG lead to maternal mortality due to the choriocarcinoma. The failure to detect, certain degradation products of HCG which may predominate in gestational trophoblastic neoplasia, by many common HCG testing kits lead to the error of diagnosis. Only 3 of the 7 common commercial serum HCG tests appropriately detects nicked HCG and its free betaHCG, DPC immulite assay, being the most sensitive method. Though of rare occurrence, this awareness is important for diagnosis and follow-up of gestational trophoblastic neoplasia and could have been life saving in our case.