Novel quinoxaline compound against extended-spectrum beta-lactamases producing bacteria.

OBJECTIVE: Extended-spectrum beta-lactamases (ESBLs) targeting beta-lactam antibiotics pose a major healthcare challenge. Carbapenems are known to be less impacted. However, the emergence of carbapenem-resistant strains can add further complexity to this existing challenge. With slow drug discovery and rapid resistance, repurposing existing drugs is crucial. This research study aims to provide insight into the antimicrobial effectiveness of 3-hydrazinoquinoxaline-2-thiol against diverse clinical ESBL-producing isolates. MATERIALS AND METHODS: The broth microdilution assay was conducted on a total of sixty-nine clinical ESBL-producing isolates to assess the minimum inhibitory concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol. The assay was conducted in triplicate, and the average MIC values were calculated. RESULTS: The most repeatedly observed MIC was 64 µg/ml (37.7%), followed by 256 µg/ml (23.2%) and 128 µg/ml (17.4%). Other MICs: 32 µg/ml (11.6%), 16 µg/ml (7.2%), 4-8 µg/ml (1.4%). CONCLUSIONS: This study demonstrated an effect of 3-hydrazinoquinoxaline-2-thiol on various ESBL-producing strains in vitro, indicating its promising therapeutic potential. To comprehensively understand the drug, rigorous testing, including pharmacokinetics, resistance assays, safety assessments, and exploration of potential synergies with other antibiotics against ESBL-producing organisms, is crucial.

COVID-19 Testing Trend: A Retrospective Analysis of the Three Major Pandemic Waves in Punjab, Pakistan.

BACKGROUND/OBJECTIVES: There is some evidence in the literature of under-testing of COVID-19 cases in Pakistan. This study aims to explore COVID-19 testing trends and the factors affecting them in a lower middle-income country for future infectious disease policy-making and intervention strategies. METHODOLOGY: The study was conducted as a serial cross-sectional study during the three major peaks from March 2020 to June 2021 on 1616 participants in Punjab, Pakistan. This is the first study to explore COVID-19 testing trends in association with flu-like symptoms (FLS) and the factors affecting all three major waves in Pakistan. RESULTS: The results show that in all three waves, only 18.8% reported COVID-19 tested despite that 86.7% thought they had already had COVID-19, with 51.3% reporting having FLS and 35.6% with exposure to FLS from their families and 19.8% of positive testing rate among their family members. Out of the survey participants, 66% received vaccination, and over 80% had their eligible family members immunized. Fear of contracting COVID-19 was 69.7% in all three waves. Factors positively associated with the uptake of testing were the age group of 31-40 years with an adjusted odds ratio of 3.27 (95% confidence interval (CI): 2.09-5.12) for the second wave and an adjusted odds ratio of 13.75 (95% CI: 9.43-20.01) for the third wave and traveling abroad with odds of 3.08 times when the reference was inland traveling. The adjusted odds ratio to test for FLS was 1.62 (95% CI: 1.21-2.16). CONCLUSION: In this study, there is convincing evidence of COVID-19 under-testing and thus under-reporting. This study also suggests that fear-based interventions may be counterproductive; however, economic factors such as education, employment, and traveling are significant in guiding the behavior for infectious disease prevention and management.

Mitigating risks and maximizing sustainability of treated wastewater reuse for irrigation.

Scarcity of freshwater for agriculture has led to increased utilization of treated wastewater (TWW), establishing it as a significant and reliable source of irrigation water. However, years of research indicate that if not managed adequately, TWW may deleteriously affect soil functioning and plant productivity, and pose a hazard to human and environmental health. This review leverages the experience of researchers, stakeholders, and policymakers from Israel, the United-States, and Europe to present a holistic, multidisciplinary perspective on maximizing the benefits from municipal TWW use for irrigation. We specifically draw on the extensive knowledge gained in Israel, a world leader in agricultural TWW implementation. The first two sections of the work set the foundation for understanding current challenges involved with the use of TWW, detailing known and emerging agronomic and environmental issues (such as salinity and phytotoxicity) and public health risks (such as contaminants of emerging concern and pathogens). The work then presents solutions to address these challenges, including technological and agronomic management-based solutions as well as source control policies. The concluding section presents suggestions for the path forward, emphasizing the importance of improving links between research and policy, and better outreach to the public and agricultural practitioners. We use this platform as a call for action, to form a global harmonized data system that will centralize scientific findings on agronomic, environmental and public health effects of TWW irrigation. Insights from such global collaboration will help to mitigate risks, and facilitate more sustainable use of TWW for food production in the future.

A novel potentiometric sensor based on ZnO decorated polyaniline/coal nanocomposite for diltiazem determination.

Diltiazem (DTZ) is one of the most effective medications for treating cardiovascular diseases. It has been widely used for the treatment of angina pectoris, hypertension and some types of arrhythmia. The development and application of a modified carbon paste sensor with improved detection limits for the potentiometric determination of diltiazem are the main goals of the current study. Sensitivity, long-term stability, reproducibility and improving the electrochemical performance are among the characteristics that have undergone careful examination. A modified carbon paste sensor based on ß-cyclodextrin (ß-CD) as ionophore, a lipophilic anionic additive (NaTPB) and a ZnO-decorated polyaniline/coal nanocomposite (ZnO@PANI/C) dissolved in dibutyl phthalate plasticizer, exhibited the best performance and Nernstian slope. The ZnO@PANI/C based sensor succeeded in lowering the detection limit to 5.0 × 10-7 through the linear range 1.0 × 10-6 to 1.0 × 10-2 mol L-1 with fast response time ≤ 10.0 s. The prepared nanomaterial was characterized using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). The surface properties of the proposed sensor were characterized by electrochemical impedance spectroscopy (EIS). The selectivity behavior of the investigated sensor was tested against a drug with similar chemical structure and biologically important blood electrolytes (Na+, K+, Mg2+, and Ca2+). The proposed analytical method was applied for DTZ analysis in pure drug, pharmaceutical products and industrial water samples with excellent recovery data.

Treatment of Acetabulum Anterior Wall Fractures Using the Modified Stoppa Approach.

Introduction The objective of this study was to describe the modified Stoppa approach for anterior wall fracture fixation and to present our radiological and functional results of this approach. Materials and methods Between April 2013 and December 2019, 256 acetabular fractures operated with the modified Stoppa approach in our clinic were retrospectively reviewed, and 11 patients who were operated for anterior acetabular wall fractures with at least two years of follow-up were included in the study. Results The median amount of bleeding during surgery was found to be 450 ml (200-800), and the median operation time was 120 minutes (90-180). The modified Merle d'Aubigné and Postel Hip Score (MDS), modified Harris Hip Score (HHS), Matta's Reduction Criteria (MRC), and Kellgren-Lawrence Classification (KLC) outcomes are similar to the anterior surgical approach. Conclusion We suggest that the modified Stoppa approach can be safely used in the surgical treatment of isolated anterior acetabular fractures due to its short operative duration, low amount of bleeding, low complication rate, and favorable radiological and clinical results. The modified Stoppa procedure is a considerable alternative to the ilioinguinal approach in anterior acetabular fractures.

TGF-ß Type I Receptor Signaling in Melanoma Liver Metastases Increases Metastatic Outgrowth.

Despite advances in treatment for metastatic melanoma patients, patients with liver metastasis have an unfavorable prognosis. A better understanding of the development of liver metastasis is needed. The multifunctional cytokine Transforming Growth Factor ß (TGF-ß) plays various roles in melanoma tumors and metastasis, affecting both tumor cells and cells from the surrounding tumor microenvironment. To study the role of TGF-ß in melanoma liver metastasis, we created a model to activate or repress the TGF-ß receptor pathway in vitro and in vivo in an inducible manner. For this, we engineered B16F10 melanoma cells to have inducible ectopic expression of a constitutively active (ca) or kinase-inactive (ki) TGF-ß receptor I, also termed activin receptor-like kinase (ALK5). In vitro, stimulation with TGF-ß signaling and ectopic caALK5 expression reduced B16F10 cell proliferation and migration. Contrasting results were found in vivo; sustained caALK5 expression in B16F10 cells in vivo increased the metastatic outgrowth in liver. Blocking microenvironmental TGF-ß did not affect metastatic liver outgrowth of both control and caALK5 expressing B16F10 cells. Upon characterizing the tumor microenvironment of control and caALk5 expressing B16F10 tumors, we observed reduced (cytotoxic) T cell presence and infiltration, as well as an increase in bone marrow-derived macrophages in caALK5 expressing B16F10 tumors. This suggests that caALK5 expression in B16F10 cells induces changes in the tumor microenvironment. A comparison of newly synthesized secreted proteins upon caALK5 expression by B16F10 cells revealed increased secretion of matrix remodeling proteins. Our results show that TGF-ß receptor activation in B16F10 melanoma cells can increase metastatic outgrowth in liver in vivo, possibly through remodeling of the tumor microenvironment leading to altered infiltration of immune cells. These results provide insights in the role of TGF-ß signaling in B16F10 liver metastasis and could have implications regarding the use of TGF-ß inhibitors for the treatment of melanoma patients with liver metastasis.

Indeterminate Pulmonary Nodules in Osteosarcoma Are Associated With Increased Risk of Pulmonary Metastasis.

Osteosarcoma is the most common primary malignant bone tumor in children. In addition to pulmonary metastasis, computed tomography frequently detects indeterminate pulmonary nodules (IPN). We conducted this study to determine the clinical significance of IPN in terms of progression to pulmonary metastasis and its impact on survival. It was a retrospective cohort study of pediatric nonmetastatic osteosarcoma patients treated from January 2005 to December 2018. Baseline computed tomography scans were reviewed for the presence of IPN (defined as a single nodule of <10 mm or ≥3 nodules of <5 mm). Subsequent scans were reviewed for the development of pulmonary metastasis. Of 155 patients, 31.6% (n=49) had IPN at baseline. A total of 43% (n=21) of those with IPN subsequently progressed to pulmonary metastasis compared with only 26% (n=28) of those without IPN (P<0.001) with a relative risk of 1.6 (1.03 to 2.5) in the IPN group. Patients with ≥3 IPN at baseline were at significantly greater risk of pulmonary metastasis as compared with <3 IPN (P=0.013). Overall and event-free survival in patients with and without IPN was 58% and 35%, and 72% and 46%, respectively. Our results suggest that patients with IPN may be at greater risk for progressing to pulmonary metastasis.

68-months progression-free survival with crizotinib treatment in a patient with metastatic ALK positive lung adenocarcinoma and sarcoidosis: A case report.

INTRODUCTION: Lung cancer still ranks first among the most common and most lethal cancers today. The most common subtype is non-small cell lung cancer, and in this group, adenocarcinoma has the worst prognosis. EGFR, ROS1 and ALK-EML4 gene fusion mutations are common in non-small cell lung cancer. CASE REPORT: A 62-year-old non-smoker patient applied in February 2014 for purulent sputum and pain in the chest. Computed tomography revealed a 39x33 mm mass in the right hilum, multiple parenchymal nodules in the bilateral lung and mediastinal multiple enlarged lymph nodes. The patient was admitted to the lung adenocarcinoma as a result of a biopsy from the mass in the hilum, and sarcoidosis was diagnosed by mediastinal lymph node biopsy. MANAGEMENT & OUTCOME: After 4 cycles of carboplatin-pemetrexed for the first line treatment, progression was detected. The patient did not have EGFR and ROS1 mutations. The patient with positive ALK fusion mutation started crizotinib treatment in July 2014. The patient's last response assessment was in March 2020, with 68-progression-free disease with crizotinib. No toxicity was observed except for Grade 1 weakness. No dose changes were made. The patient is still being followed up without brain metastasis under the treatment of crizotinib. DISCUSSION: In this article, we wanted to share our experience of crizotinib in a 68-months progression-free survival in a 62-years old non-smoking female patient with metastatic lung adenocarcinoma who is also diagnosed with sarcoidosis.

COVID-19 in third trimester may not be as scary as you think, it can be innocent: Evaluating vertical transmission from a COVID-19 positive asymptomatic pregnant woman with early membrane rupture.

In the literature, many cases of coronavirus disease 2019 (COVID-19) positive pregnancies have been observed, mostly with mild findings, but there is limited evidence about perinatal transition and early COVID-19 positive newborns. In this case, severe acute respiratory syndrome coronavirus 2 reverse transcription-polymerase chain reaction results were studied from samples obtained from the placenta, amniotic fluid, cord blood and postoperative breast milk - that were obtained while avoiding contamination and preserved appropriately - of a cesarean section performed under anesthesia on a woman with previous cesarean section and gestational diabetes mellitus history. This patient who presented to our emergency gynecology clinic with membrane rupture was infected with severe acute respiratory syndrome coronavirus 2 two weeks before delivery but was not treated as the disease was asymptomatic. In addition, literature data in line with this topic were evaluated to demonstrate that there was generally no perinatal transmission over 34 weeks of gestation.

Coronavirus Disease 2019 (COVID-19): Forecast of an Emerging Urgency in Pakistan.

Background/Aims Novel coronavirus disease 2019 (COVID-19) is a global challenge due to little available knowledge and treatment protocols. Thus, there is a great need for collecting data related to COVID-19 from all around the world. Hence, we conducted this study, collecting daily data on COVID-19, to map the epidemiology outbreak and forecast its trajectory for May 2020. Methodology The data was collected from the officially released reports of the National Institute of Health (NIH), Pakistan, and the World Health Organization (WHO). The analysis was done using Statistical Package for the Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY), and forecasting was done using a simple moving average in time series modeler/expert modeler. Results The purpose of this study is to draw the attention of international, as well as national, governing bodies to the rapidly rising number of COVID-19 cases in Pakistan, and the urgency of evaluating the efficacy of the currently implemented strategy against COVID-19. According to this study, there is now an alarming increase in the number of COVID-19 patients in Pakistan, despite a contained spread in the beginning. The predicted number of COVID-19 cases can go over 35,000 by the end of May 2020. Conclusion It is crucial for governing bodies, administrators, and researchers to re-evaluate the current situation, designed policies, and implemented strategies.

Outcome of inadvertent high dose BCG administration in newborns at a tertiary care hospital, Karachi- Case series.

Bacillus Calmette-Guérin (BCG) vaccine is given to newborns soon after birth. BCG vaccine overdose has been rarely reported. Here we report the outcome of newborns who accidently received high dose BCG at a tertiary care hospital, Karachi. We reviewed records of 26 newborns, who accidentally received intradermal high dose BCG, used for the treatment of urinary bladder cancers and 80 times higher dose than the BCG used for routine vaccination. The incident happened from 14-16th April, 2016 at Aga Khan University Hospital, Karachi. Analysis was carried out using SPSS. A total of 23/26(88.5%) newborns were followed for atleast 3 months and 11/26 (42.3%) were followed for atleast one year. 13/26 (50%) were male. All 26 patients were prescribed isoniazid and rifampicin for 3 months. 3/26 (11.5%) were lost to follow-up before completion of anti-tuberculous drugs (ATT). Lesions at the BCG site were observed in 16/26 (61.5%) infants, of which 15 (93.8%) had a papule, 3 (18.8%) developed a pustule, 3 (18.8%) had skin induration and 2 (12.5%) had skin erythema. Axillary lymphadenopathy was observed in 1/26 (3.8%) patient. Coagulation was deranged in 3/26 (11.5%) of babies. Intracranial bleeding was observed in 1/26 (3.8%) case. Localized skin lesions were the most common adverse events. None of them developed clinical tuberculosis. Chemoprophylaxis for inadvertent high dose BCG administration should be given for atleast 3 months. Furthermore, vigilant follow-up, transparency and disclosure are the vital steps in the management of any medical error.

Unilateral Thalamic Venous Infarction in an Infant: A Rare Presentation of Bilateral Deep Cerebral Venous Thrombosis.

Cerebral venous thrombosis (CVT) may manifest as superficial cerebral venous thrombosis (SCVT) or deep cerebral venous thrombosis (DCVT). Of the two patterns, DCVT is less commonly observed, although it often results in greater morbidity and mortality due to involvement of the deep gray nuclei. It can present at any age and typically results in edema of the bilateral thalami, with occasional extension into the basal ganglia. Unilateral thalamic infarct is rare and results in an ambiguous imaging pattern. We present the clinical and neuroimaging profile of an acute unilateral thalamic venous infarct in an infant secondary to bilateral DCVT. Early recognition of this atypical pattern will facilitate accurate diagnosis and treatment, and obviate the need for unnecessary interventions.

Comparison of Knowledge, Attitudes, and Practices of Educated and Uneducated Adults Regarding Human Immunodeficiency Virus in Karachi, Pakistan.

BACKGROUND: Despite the high prevalence of human immunodeficiency virus (HIV) in Pakistan, no prior work has been done to specifically highlight the importance of education as a social vaccine against HIV. Therefore, our study focuses on differences in knowledge and practices regarding HIV and acquired immunodeficiency syndrome (AIDS) among educated and uneducated adults. METHODOLOGY: A cross-sectional study was carried out in which data was collected from all over Karachi. An individual was designated as educated if he had received education above primary school level. Individuals who had studied till primary school or less were considered uneducated. The questionnaire was split into four sections that assessed respondents' demographics, knowledge, attitudes, and practices regarding HIV/AIDS. Chi square test was used as the primary statistical test. RESULTS: Out of the 446 adult participants, 235 (52.7%) were educated and 211 (47.3%) were uneducated. Educated participants were significantly more likely to have heard about HIV (183 vs. 39, p < 0.001) and had better knowledge about the symptoms of HIV/AIDS (p < 0.001). Among the participants who knew about AIDS, a greater percentage of uneducated (n = 28, 53%) than educated individuals (n = 68, 37%) believed that people suffering from AIDS should be isolated (p = o.o16) and that HIV can spread through water (40% vs 20% respectively, p < 0.001). Both educated (n = 49, 27%) and uneducated (n = 46, 89%) adults believed that awareness would help prevent the spread of HIV (p = 0.978) and were willing to educate their children about it (p = 0.696). CONCLUSION: Our study revealed a gap in the knowledge about HIV/AIDS between educated and uneducated adults. There is an urgent need for awareness programs that especially reach out to the uneducated masses that are otherwise uninformed about HIV and are under high risk of acquiring HIV.

Drivers of Microbial Risk for Direct Potable Reuse and de Facto Reuse Treatment Schemes: The Impacts of Source Water Quality and Blending.

Although reclaimed water for potable applications has many potential benefits, it poses concerns for chemical and microbial risks to consumers. We present a quantitative microbial risk assessment (QMRA) Monte Carlo framework to compare a de facto water reuse scenario (treated wastewater-impacted surface water) with four hypothetical Direct Potable Reuse (DPR) scenarios for Norovirus, Cryptosporidium, and Salmonella. Consumer microbial risks of surface source water quality (impacted by 0-100% treated wastewater effluent) were assessed. Additionally, we assessed risks for different blending ratios (0-100% surface water blended into advanced-treated DPR water) when source surface water consisted of 50% wastewater effluent. De facto reuse risks exceeded the yearly 10-4 infections risk benchmark while all modeled DPR risks were significantly lower. Contamination with 1% or more wastewater effluent in the source water, and blending 1% or more wastewater-impacted surface water into the advanced-treated DPR water drove the risk closer to the 10-4 benchmark. We demonstrate that de facto reuse by itself, or as an input into DPR, drives microbial risks more so than the advanced-treated DPR water. When applied using location-specific inputs, this framework can contribute to project design and public awareness campaigns to build legitimacy for DPR.

Impact of virus surface characteristics on removal mechanisms within membrane bioreactors.

In this study we investigated the removal of viruses with similar size and shape but with different external surface capsid proteins by a bench-scale membrane bioreactor (MBR). The goal was to determine which virus removal mechanisms (retention by clean backwashed membrane, retention by cake layer, attachment to biomass, and inactivation) were most impacted by differences in the virus surface properties. Seven bench-scale MBR experiments were performed using mixed liquor wastewater sludge that was seeded with three lab-cultured bacteriophages with icosahedral capsids of ∼30 nm diameter (MS2, phiX174, and fr). The operating conditions were designed to simulate those at a reference, full-scale MBR facility. The virus removal mechanism most affected by virus type was attachment to biomass (removals of 0.2 log for MS2, 1.2 log for phiX174, and 3 log for fr). These differences in removal could not be explained by electrostatic interactions, as the three viruses had similar net negative charge when suspended in MBR permeate. Removals by the clean backwashed membrane (less than 1 log) and cake layer (∼0.6 log) were similar for the three viruses. A comparison between the clean membrane removals seen at the bench-scale using a virgin membrane (∼1 log), and the full-scale using 10-year old membranes (∼2-3 logs) suggests that irreversible fouling, accumulated on the membrane over years of operation that cannot be removed by cleaning, also contributes towards virus removal. This study enhances the current mechanistic understanding of virus removal in MBRs and will contribute to more reliable treatment for water reuse applications.

Mechanisms of pathogenic virus removal in a full-scale membrane bioreactor.

Four pathogenic virus removal mechanisms were investigated in a full-scale membrane bioreactor (MBR; nominal pore size 0.04 µm): (i) attachment of virus to mixed liquor solids; (ii) virus retention by a just backwashed membrane; (iii) virus retention by the membrane cake layer; and (iv) inactivation. We quantified adenovirus, norovirus genogroup II (GII), and F+ coliphage in the influent wastewater, the solid and liquid fractions of the mixed liquor, return flow, and permeate using quantitative PCR (adenovirus and norovirus GII) and infectivity assays (F+ coliphage). Permeate samples were collected 4-5 days, 1 day, 3 h, and immediately after chlorine enhanced backwashes. The MBR achieved high log removals for adenovirus (3.9 to 5.5), norovirus GII (4.6 to 5.7), and F+ coliphage (5.4 to 7.1). The greatest contribution to total removal was provided by the backwashed membrane, followed by inactivation, the cake layer, and attachment to solids. Increases in turbidity and particle counts after backwashes indicated potential breakthrough of particles, but virus removal following backwashes was still high. This study demonstrates the ability of the MBR process to provide over 4 logs of removal for adenovirus and norovirus GII, even after a partial loss of the cake layer, and provides evidence for assigning virus disinfection credit to similar MBRs used to reclaim wastewater for reuse.

Tests and estimates (transmission disequilibrium test) for allelic association of CCR5delta32 with asthma in high-risk families.

OBJECTIVE: To examine the possible associations between CCR5delta32 and asthma and related phenotypes in high-risk families. METHODS: A total of 154 families (453 individuals), with at least two affected children with physician-diagnosed asthma (PDA) and atopy defined as one or more skin prick test to common inhaled allergen (SPT wheal > or = 3 mm), were studied. Samples were genotyped using PCR assay and tested for possible associations by TDT and PDT and case control analyses. RESULTS: Overall allelic frequency for CCR5delta32 was 26.1%, and both TDT and PDT demonstrated similar nonsignificant associations (p=0.123) and (p=0.088). Analysis by the clinical categories of non atopic and atopic asthma and presence or absence of atopy without asthma failed to identify any significant associations. However there were strong associations of the mutant allele with the phenotypes of negative SPT, PC 20 less than 8 mg/ml, baseline FEV1 greater than the population median (83.5% predicted) and serum IgE less than 100 IU/l for child probands but only for negative SPT in unrelated parents. CONCLUSION: Non-significant association was seen with family based association tests (FBATs). The strong associations with the asthma related phenotypes in child probands support previous observations that CCR5 is in linkage disequilibrium with CCR2 or CCR3.

Investigation of adult-sera for the presence of anti-Cryptosporidium antibodies.

Cryptosporidiosis is an acute diarrhoeal disease caused by Cryptosporidium spp for both human and animals. Typically, the duration of diarrhoeal illness and ultimate outcome of intestinal cryptosporidiosis depend on the immune status of the patient. Random serology-based studies in humans and animals have suggested that infection with this organism is common during a life time. 130 serum samples of adults, (18-30 years) from two main public hospitals at Jeddah City, Saudi Arabia were recruited to participate in the study. The aim was to identify the sero-prevalence of cryptosporidiosis infection and determine factors associated with increased risk of the infection. Western Blot analysis (WB) with two different Cryptosporidium antigen markers; the 15-17 KDa and the 27 KDa, were used. Among participants, 8.5 % had antibodies to the 15 KDa, 23.8 % had antibodies to the 27 kDa, 34.6 % were sero-positive to both antigens, and 33.1 % were sero-negative to both antigens. Source of drinking water with a strong association with drinking tap water was the only factor significantly associated with seropositivity to cryptosporidiosis infection (OR= 37.33, P< 0.001).

The -17 T/C chemokine receptor 3 genetic polymorphism is associated asthma but not atopy: transmission and association studies.

We genotyped and identified the asthma and atopic status and related phenotypes of 154 nuclear families (453 individuals) each containing at least two affected children with physician-diagnosed asthma (PDA) in order to confirm or refute the possible relevance of known single nucleotide polymorphisms (SNPs) in the gene coding for the CCR3 receptor. Allelic quantification for each SNP by DNA pooling identified -17/TC as the only allele with a clinically relevant frequency in this population with a frequencies of 0.142 in cases of PDA and 0.035 in asymptomatic controls. The whole population frequency of the -17/TC polymorphism was 13.9% and the functional binding site analyses by MatInd and MatInspector programs found that it belonged to the same family as activating transcription factor 6 (ATF-6). The pedigree disequilibrium test (PDT) was applied in 34 informative families and the mutant allele was preferentially transmitted with PDA (P = 0.0001) with methacholine bronchial hyperresponsiveness (BHR) (0.002) but not with markers of atopy as assessed by allergen skin prick tests (SPT) or elevated serum IgE. Case-control analyses in 303 unrelated parents (34-61y [median 43y]) revealed a significant association with both atopic and non atopic asthma (P = 0.001), and in 150 unrelated child probands for non-atopic asthma (P = 0.001). The mutant allele was associated with BHR, with baseline Forced Expiratory Volume in the first second (FEV1) below the population median value but not with atopy defined SPT or elevated serum IgE (>100 IU/ml). The T17C chemokine receptor 3 polymorphism appears to be associated with asthma BHR and disease severity but not with atopy.

Bulk phonon scattering in perturbed quasi-3D multichannel crystallographic waveguide.

In the present paper, we concentrate on the influence of local defects on scattering properties of elastic waves in perturbed crystalline quasi-three-dimensional nanostructures in the harmonic approximation. Our model consists of three infinite atomic planes, assimilated into a perfect waveguide in which different distributions of scatterers (or defects) are inserted in the bulk. We have investigated phonon transmission and conductance for three bulk defect configurations. The numerical treatment of the problem, based on the Landauer approach, resorts to the matching method initially employed for the study of surface localized phonons and resonances. We present a detailed study of the defect-induced fluctuations in the transmission spectra. These fluctuations can be related to Fano resonances and Fabry-Pérot oscillations. The first is due to the coupling between localized defect states and the perfect waveguide propagating modes whereas the latter results from the interference between incidental and reflected waves. Numerical results reveal the intimate relation between transmission spectra and localized impurity states and provide a basis for the understanding of conductance spectroscopy experiments in disordered mesoscopic systems.