Virulence of Burkholderia pseudomallei ATS2021 Unintentionally Imported to United States in Aromatherapy Spray.

In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India. We established that ATS2021 represents a virulent strain of B. pseudomallei capable of robust formation of biofilm at physiologic temperatures that may contribute to virulence. By using mouse melioidosis models, we determined median lethal dose estimates and analyzed the bacteriologic and histopathologic characteristics of the organism, particularly the potential neurologic pathogenesis that is probably associated with the bimABm allele identified in B. pseudomallei strain ATS2021. Our data, combined with previous case reports and the identification of endemic B. pseudomallei strains in Mississippi, support the concept that melioidosis is emerging in the United States.

Anaplasma phagocytophilum Ats-1 enhances exosome secretion through Syntenin-1.

Anaplasma phagocytophilum is an intracellular obligate parasite that causes granulocytic anaplasmosis. Effector Ats-1 is an important virulence factor of A. phagocytophilum. Multiomics screening and validation has been used to determine that Ats-1 regulates host cell apoptosis and energy metabolism through the respiratory chain mPTP axis. In this study, a total of 19 potential binding proteins of Ats-1 in host cells were preliminarily screened using a yeast two-hybrid assay, and the interaction between syntenin-1 (SDCBP) and Ats-1 was identified through immunoprecipitation. Bioinformatics analysis showed that SDCBP interacted with SDC1, SDC2, and SDC4 and participated in the host exosome secretion pathway. Further studies confirmed that Ats-1 induced the expression of SDC1, SDC2, and SDC4 in HEK293T cells through SDCBP and increased the exosome secretion of these cells. This indicated that SDCBP played an important role in Ats-1 regulating the exosome secretion of the host cells. These findings expand our understanding of the intracellular regulatory mechanism of A. phagocytophilum, which may enhance its own infection and proliferation by regulating host exosome pathways.

European Society for Organ Transplantation (ESOT) Consensus Statement on Outcome Measures in Liver Transplantation According to Value-Based Health Care.

Liver transplantation is a highly complex, life-saving, treatment for many patients with advanced liver disease. Liver transplantation requires multidisciplinary teams, system-wide adaptations and significant investment, as well as being an expensive treatment. Several metrics have been proposed to monitor processes and outcomes, however these lack patient focus and do not capture all aspects of the process. Most of the reported outcomes do not capture those outcomes that matter to the patients. Adopting the principles of Value-Based Health Care (VBHC), may provide an opportunity to develop those metrics that matter to patients. In this article, we present a Consensus Statement on Outcome Measures in Liver Transplantation following the principles of VBHC, developed by a dedicated panel of experts under the auspices of the European Society of Organ Transplantation (ESOT) Guidelines' Taskforce. The overarching goal is to provide a framework to facilitate the development of outcome measures as an initial step to apply the VMC paradigm to liver transplantation.

The rising threat of illicit amphetamine-type stimulant use among methadone maintenance treatment patients in East Coast Malaysia: a retrospective observational study.

Background: In recent years, amphetamine-type-stimulants (ATS) have been extensively misused in South-East Asia, inducing major problems among methadone-maintenance-treatment (MMT) patients.Objective: We examine ATS-misuse prevalence and its determinants among MMT patients in East-Coast-Malaysia.Methods: A retrospective-observational study was conducted on government-subsidized medication for opioid-use-disorder (MOUD) treatment clinics involving 292 MMT-patients (98% males) who were selected using a multilevel-proportional-stratified random sampling technique. Information obtained during the mandatory monitoring procedure from January 1 to December 31 2019, was utilized to determine ATS misuse prevalence from consecutive random urine drug screening. The determinants associated with its use, namely sociodemographics, social networks, comorbidities, and pharmacological assessments were analyzed via a logistic model.Results: Overall, 52.2% of the MMT-patients (95% CI: 0.42-0.54) had misused ATS at least once during their methadone treatment. These misusing patients were active smokers, hepatitis B and C seronegative, concurrently misused opioids, and had received suboptimum prescribed doses of methadone. Multiple logistic regression analysis demonstrated that the odds of misusing ATS during methadone treatment were 37 times higher among those who concurrently misused opioids (AOR: 37.60, 95% CI: 14.03-100.74) and 12 times higher among those who received suboptimal methadone doses (<60 mg/day) (AOR: 12.24, 95% CI: 5.58-25.43).Conclusion: This study demonstrated the significant prevalence of ATS misuse among MMT-patients in East-Coast-Malaysia, especially among patients who were prescribed suboptimal doses of methadone and/or demonstrated concomitant opioid-misuse. Stringent urine-monitoring is crucial to prevent diversion to ATS misuse. Nonetheless, to avoid negligence and improve physician engagement, the relevant authorities should immediately plan a comprehensive national-standard training module comprising support activities for professional methadone-prescribers.

Toxicology Certification: The Need, the Value, and an Evolving Landscape.

Certification in toxicology remains a subject of interest to those in the field, as evidenced by the number of presentations at major meetings and publications in the past decade. In 2009, Brock and colleagues summarized the certifications available in the field of toxicology and provided an international perspective of the pros and cons of gaining certification. Though that article has been viewed thousands of times, the certification processes have evolved over the past decade. Therefore, the purpose of the article is to build upon the prior work and present current information for toxicologists seeking certification with the American Board of Toxicology (DABT), Academy of Toxicological Sciences (ATS), as a European Registered Toxicologist (ERT), as a Diplomate, Japanese Society of Toxicology (DJSOT), and as a Diplomate of the Chinese Society of Toxicology (DCST). In addition, other certifications are presented, but available details are limited.

Factors associated with drug use during pregnancy and breastfeeding among females who use drugs (FWUDs) in Malaysia.

Females who use drugs (FWUDs) are at risk of continuing illicit substance use during pregnancy and breastfeeding. We investigated the prevalence rates and factors associated with these practices in a sample of 200 FWUDs recruited from a publicly-run drug rehabilitation center. A semi-structured questionnaire was used to collect the data. The majority (86%) was Malay (n = 171/200), currently single (71%, n = 141/200), and 51% had nine years of education. The mean age of respondents was 32.2 years (SD = 8.61). Thirty-eight percent (n = 75/200) reported ever using illicit substances during pregnancy, while 15% (n = 30/200) had used them during breastfeeding. Higher odds of using drugs during pregnancy were associated with having an intimate male drug-using partner and with persons who reported abandoning an infant in the past. Lower odds were linked with women who used heroin with ATS (relative to those who used only ATS), and shorter-term ATS (≤3 years) relative to long term ATS users. At a lower level of significance (p = 0.054), being married also lowered the odds. Higher odds of drug use during breastfeeding were associated with having an intimate male drug-using partner, and previous methadone use history, while lower odds were associated with short-term ATS use and being employed. The findings highlight the need for timely and targeted interventions to inform, engage and promote the participation of FWUDs in pre- and post-natal care services.

Multiomics analyses reveals Anaplasma phagocytophilum Ats-1 induces anti-apoptosis and energy metabolism by upregulating the respiratory chain-mPTP axis in eukaryotic mitochondria.

BACKGROUND: Anaplasma translocated substrate 1 (Ats-1) is an effector of type 4 secretory systems (T4SS) and the main virulence factor of Anaplasma phagocytophilum. Ats-1 is involved in the regulation of host cell biological processes, but the specific molecular mechanism of its action is unclear. RESULTS: In this study, we identified Ats-1 as involved in mitochondrial respiratory regulation of HEK293T cells by multi-omics analysis. After intracellular expression of Ats-1, adenosine triphosphate levels and the proliferation of HEK293T cells were both up-regulated, while HEK293T cells apoptosis was inhibited. Ats-1 targeted translocation to the mitochondria where it up-regulated the expression of NDUFB5, NDUFB3, NDUFS7, COX6C, and SLC25A5, thereby enhancing energy production and inhibiting HEK293T cells apoptosis while enhancing HEK293T cells proliferation, and ultimately facilitating Anaplasma phagocytophilum replication in HEK293T cells. CONCLUSIONS: This study demonstrated that Anaplasma phagocytophilum Ats-1 induces anti-apoptosis and energy metabolism by upregulating the respiratory chain-mPTP axis in eukaryotic mitochondria. These results provide a better understanding of the pathogenic mechanism of Anaplasma phagocytophilum within host cells.

Clean gene technology to develop selectable marker-free pod borer-resistant transgenic pigeon pea events involving the constitutive expression of Cry1Ac.

The most crucial yield constraint of pigeon pea is susceptibility to the pod borer Helicoverpa armigera, which causes extensive damage and severe economic losses every year. The Agrobacterium-mediated plumular meristem transformation technique was applied for the development of cry1Ac transgenic pigeon pea. Bioactivity of the cry1Ac gene was compared based on integration and expression driven by two promoters, the constitutive CaMV35S promoter and the green-tissue-specific ats1A promoter, in those transgenic events. The transgenic events also contained the selectable marker gene nptII flanked by loxP sites. Independent transgenic events expressing the Cre recombinase gene along with a linked bar selection marker were also developed. Integration and expression patterns of both cry1Ac and cre were confirmed through Southern and western blot analysis of T1 events. The constitutive expression of the Cry1Ac protein was found to be more effective for conferring resistant activity against H. armigera larvae in comparison to green-tissue-specific expression. Constitutively expressing Cry1Ac T1 events were crossed with Cre recombinase expressing T1 events. The crossing-based Cre/lox-mediated marker gene elimination strategy was demonstrated to generate nptII-free Cry1Ac-expressing T2 events. These events were subsequently analyzed in the T3 generation for the segregation of cre and bar genes. Five Cry1Ac-expressing T3 transgenic pigeon pea events were devoid of the nptII marker as well as cre-bar genes. H. armigera larval mortality in those marker-free T3 events was found to be 80-100%. The development of such nptII selectable marker-free Cry1Ac-expressing pigeon pea transgenics for the first time would greatly support the sustainable biotechnological breeding program for pod borer resistance in pigeon pea. KEY POINTS: • Constitutive expression of Cry1Ac conferred complete resistance against Helicoverpa armigera • Green-tissue-specific expression of Cry1Ac conferred partial pest resistance • Cre/lox-mediated nptII elimination was successful in constitutively expressing Cry1Ac transgenic pigeon pea events.

Different phases of ATS use call for different interventions: a large qualitative study in Europe.

BACKGROUND: Amphetamine-type stimulants (ATS) are globally widely used. Scientific literature generally defines four phases of substance use (initiation, continuation, increase and decrease); however, there is limited understanding of what influences these different phases of ATS use. The ATTUNE study investigated which factors shape individual phases of use, or ATS use patterns. In this article, we report on these phases into and out of ATS use, and propose a set of recommendations for prevention, harm reduction and treatment of the different phases of ATS use. METHODS: Qualitative, semi-structured interviews (n = 237) were conducted in five different European countries with participants who had used ATS, varying from a few times in a lifetime to daily. RESULTS: Amphetamine and MDMA were the most commonly used ATS. Yet, types of ATS used differed between the countries. We found that people who use ATS have various motives for and dynamic patterns of ATS use with alternating phases of increase, continuation, decrease and sometimes dependence. Cessation was pursued in different ways and for diverse reasons, such as mental health problems and maturing out. Availability seemed not an issue, regardless of the type of ATS, phase or country. CONCLUSIONS: These findings demonstrate that tailor-made interventions are needed for the diverse types of people who use ATS and different phases or patterns of ATS use, to reduce possible harms of use. We recommended a set of interventions for the different ATS phases. These include drug checking services, peer-led information, self-management of ATS use, mental health support to help people cope with stressful life events and prevent uncontrolled use, and follow-up support after treatment.

Accuracy of 18F-FDG in Detecting Stage I Lung Adenocarcinomas According to IASLC/ATS/ERS Classification.

BACKGROUND: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. METHODS: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results. RESULTS: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005). CONCLUSIONS: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.

Substrate properties as controlling parameters in attached algal cultivation.

There is growing interest in attached algae cultivation systems because they could provide a more cost- and energy-efficient alternative to planktonic (suspended algae) cultivation systems for many applications. However, attached growth systems have been far less studied than planktonic systems and have largely emphasized algae strains of most interest for biofuels. New algal biorefinery pathways have assessed the commercial potentials of algal biomass beyond biofuel production and placed more emphasis on value-added products from that biomass. Therefore, algal strain selection criteria and biomass cultivation methods need to be updated to include additional strains for improved efficiency. One possible way of improving attached cultivation systems is through engineering substrate surface characteristics to boost algal adhesion and enable strain selective algal colonization and growth. This review explores the effect of substrate chemical and topographical characteristics on the cultivation of attached algae. It also highlights the importance of considering algal community structure and attachment mechanisms in investigating attached algae systems using the example of filamentous algae found in algal turf scrubber (ATS™) systems. KEY POINTS : • Attached algal cultivation is a promising alternative to planktonic cultivation. • Performance increase results from tuning surface qualities of attachment substrates. • Attachment adaptation of periphytic algae has innate potential for cultivation.

Brain-specific monoallelic expression of bovine UBE3A is associated with genomic position.

Genomic imprinting is a rare epigenetic process in mammalian cells that leads to monoallelic expression of a gene with a parent-specific pattern. The UBE3A (ubiquitin protein ligase E3A) gene is imprinted with maternal allelic expression in the brain but biallelically expressed in all other tissues in humans. The silencing of the paternal UBE3A allele is thought to be caused by the paternally expressed antisense RNA transcript of UBE3A-ATS. The aberrant imprinted expression of the UBE3A is associated with several neurodevelopmental syndromes and psychological disorders. Cattle are a valuable model species in determining the genetic etiology of sporadic human disorder, and maternal expression of UEB3A has been revealed by next-generation sequencing study in the bovine conceptus. In this study, we investigated the allelic expression of UBE3A and UBE3A-ATS in adult bovine somatic tissues. To confirm the splicing pattern of bovine UBE3A, five 5' alternative transcripts (MT210534-MT210538) were first obtained from bovine brain tissue by RT-PCR. Based on 10 SNP genotypes, we found that the brain-specific monoallelic expression of bovine UBE3A did not occur along the entire locus, and there was a shift from biallelic expression to monoallelic expression in exon 14 of the UBE3A gene. However, the brain-specific monoallelic expression of bovine UBE3A-ATS occurred in the entire gene. These observations demonstrated that the monoallelic expression did not occur along the bovine UBE3A entire locus and was associated with the genomic position.

Connective Tissue Disorders and Cardiovascular Complications: The Indomitable Role of Transforming Growth Factor-ß Signaling.

Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that segregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. With overwhelming evidence of the involvement of aberrant Transforming Growth Factor-beta (TGF-ß) signaling in MFS and LDS, this signaling pathway may represent the common link in the relationship between connective tissue disorders and their associated cardiovascular complications. To further explore this hypothetical link, this chapter will review the TGF-ß signaling pathway, the heritable connective tissue syndromes related to aberrant TGF-ß signaling, and will discuss the pathogenic contribution of TGF-ß to these syndromes with a primary focus on the cardiovascular system.

'We are not aware of notification of tuberculosis': A mixed-methods study among private practitioners from western India.

BACKGROUND: Implementing the Standards for tuberculosis care in India (STCI) guidelines in the private sector is vital. This study attempted to estimate the knowledge and practices regarding STCI guidelines among private practitioners and to explore the reasons and solutions for low tuberculosis (TB) notification rates. METHODS: We conducted a cross-sectional study for assessing the knowledge and practices of the STCI guidelines among 100 full-time allopathic private practitioners in Bhavnagar (in western part of India) from September 2018 to January 2019. Knowledge and practice were categorised as good or poor by assigning scores to the responses to a questionnaire based on the STCI guidelines. It was followed by two focus group discussions to explore the reasons and solutions for low notification rates of TB as perceived by private practitioners. RESULTS: Among the 100 private practitioners, 55% had good knowledge, and 41% had good practice regarding the STCI guidelines; 69% knew about the gazette notification of mandatory notification of TB, and 58% were notifying TB cases to the government. Lack of awareness about the process as well as incentives for notification, time constraints and infrequent visits by health workers were the main reasons perceived by private practitioners for not notifying TB cases to the government. The critical solutions suggested by them were creating awareness regarding the notification process as well as incentives, increasing health worker visits and use of social media for notification. CONCLUSION: Only about half of private practitioners follow the STCI guidelines for TB care, and the notification rates are low in our setting. Regular sensitisation programs need to be arranged for private practitioners to create awareness on TB notification.

Perceptions of sex offenders with intellectual disability: A comparison of forensic staff and the general public.

BACKGROUND: Existing literature suggests that individuals with intellectual disability are not always held accountable for their actions and forensic staff are unlikely to report their sexually harmful behaviour. METHOD: This research explores how categorization of an offender as having intellectual disability and the framing of an offence as planned or opportunistic, impacts upon ratings of risk, blame and intent by forensic staff and the general public. The impact of pre-existing attitudes towards sex offenders upon these ratings was also considered. RESULTS: Differences are identified between participants' ratings when the offender is categorized as having an intellectual disability. More positive attitudes are associated with lower ratings of several factors. CONCLUSIONS: Individuals with overly positive attitudes towards sex offenders could underestimate the risk posed by sex offenders with intellectual disability. These results are important to consider alongside the NHS Transforming Care Agenda.

Short-term response to phenytoin sodium in Andersen-Tawil syndrome-1 with a cardiac-dominant phenotype.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare familial periodic paralysis that typically also affects the heart and skeletal system. Ventricular arrhythmias (VAs) are profound and difficult to control, but minimally symptomatic. In this report, we describe an atypical phenotype of ATS in two related families. We also report our experience with phenytoin sodium for the control of resistant VAs in these patients. METHODS AND RESULTS: Between 2014 and 2018, seven siblings were diagnosed with ATS on the basis of cardiac arrhythmias and genetic evaluation. Heterozygous mutation with c.431G > C (p.G144A) in exon 2 of KCNJ2 gene was observed in all patients. Characteristic cardiac manifestations were noted in all patients but periodic paralysis or objective neurological involvement was distinctly absent. Phenytoin was considered for control of symptomatic VA in three patients. Intake of oral phenytoin (5 mg/kg/day) for 1 month completely suppressed VA (<1% in 24-h Holter monitoring) in two patients, and significantly in the third (8% per 24 h) patient. Phenytoin was well-tolerated in all three patients. CONCLUSIONS: We describe a cardiac-predominant phenotype in ATS. ATS should be suspected in patients with typical cardiac manifestations even in the absence of periodic paralysis. Our initial experience with short-term use of phenytoin for control of resistant VAs is encouraging.

Urine-derived podocytes-lineage cells: A promising tool for precision medicine in Alport Syndrome.

Alport Syndrome (ATS) is a rare genetic disorder caused by collagen IV genes mutations, leading to glomerular basement membrane damage up to end-stage renal disease. Podocytes, the main component of the glomerular structure, are the only cells able to produce all the three collagens IV alpha chains associated with ATS and thus, they are key players in ATS pathogenesis. However, podocytes-targeted therapeutic strategies have been hampered by the difficulty of non-invasively isolating them and transcripts-based diagnostic approaches are complicated by the inaccessibility of other COL4 chains-expressing cells. We firstly isolated podocyte-lineage cells from ATS patients' urine samples, in a non-invasive way. RT-PCR analysis revealed COL4A3, COL4A4, and COL4A5 expression. Transcripts analysis on RNA extracted from patient's urine derived podocyte-lineage cells allowed defining the pathogenic role of intronic variants, namely one mutation in COL4A3 (c.3882+5G>A), three mutations in COL4A4 (c.1623+2T>A, c.3699_3706+1del, c.2545+143T>A), and one mutation in COL4A5 (c.3454+2T>C). Therefore, our cellular model represents a novel tool, essential to unequivocally prove the effect of spliceogenic intronic variants on transcripts expressed exclusively at a glomerular level. This process is a key step for providing the patient with a definite molecular diagnosis and with a proper recurrence risk. The established system also opens up the possibility of testing personalized therapeutic approaches on disease-relevant cells.

HIV prevalence, related risk behaviors, and correlates of HIV infection among people who use drugs in Cambodia.

BACKGROUND: Although HIV prevalence in Cambodia has declined to 0.6% among the general population, the prevalence remains high among female sex workers (14.0%) and men who have sex with men (2.3%). Over the past 10 years, the number of people who use drugs (PWUDs) has increased considerably. PWUDs, especially people who inject drugs (PWIDs), who have multiple sex partners or unprotected sex contribute to a higher HIV prevalence. This paper aims to estimate the prevalence of HIV across PWUD groups and to identify factors associated with HIV infection. METHODS: Respondent-driven sampling (RDS) was used to recruit 1626 consenting PWUDs in 9 provinces in 2012. Questionnaires and blood specimens were collected. HIV prevalence estimates were calculated using RDSAT 7.1. Individual weightings for HIV were generated with RDSAT and used for a weighted analysis in STATA 13. Multivariate logistic regression was used to identify the independent factors associated with HIV prevalence. RESULTS: Most of the PWUDs were men (82.0%), and 7.3% were PWIDs. Non-PWIDs, especially users of amphetamine-type stimulants (ATS), represented the larger proportion of the participants (81.5%). The median age for of the PWUDs was 24.0 years (IQR: 20-29). The HIV prevalence among the PWUDs was 5.1% (95% CI: 4.1-6.2), 24.8%, among PWIDs and 4.0% among non-PWIDs. The HIV prevalence among female PWIDs was 37.5, and 22.5% among male PWIDs. Four factors were independently associated with HIV infection: female sex, with AOR = 7.8 (95% CI: 3.00-20.35); age groups 21-29 and older (AOR = 10.3, 95% CI: 1.2-20.4); and using drugs for ≥12 months (AOR = 4.0, 95% CI: 1.38-11.35). Finally, injecting drugs remained a strong predictor of HIV infection, with an AOR = 4.1 (95% CI: 1.53-10.96). CONCLUSION: HIV prevalence remains high among PWIDs. Harm reduction efforts, such as needle and syringe provision programs, must improve their coverage. Innovative strategies are needed to reach sub-groups of PWUDs, especially women who inject drugs. Furthermore, the large proportion of non-PWIDs, especially ATS users, should not be ignored. Therefore, combined HIV prevention and harm reduction programs should integrate ATS users.

Clinical Variability in Two Macedonian Families with Arterial Tortuosity Syndrome.

Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder caused by mutations in the solute carrier family 2 member 10 (SLC2A10) gene encoding a glucose/ascorbic acid transporter. The clinical features of ATS are mild-to-severe tortuosity of the large and medium arteries throughout the body, accompanied by dysmorphisms and joint laxity. Vascular changes in different parts of the body lead to stenosis and/or aneurysms requiring difficult surgical procedures. Here we present two new patients with ATS from two unrelated families. Patient 1 presented at 10 years of age with headache and typical physical appearance, delicate skeleton, large visible pulsation of the carotid arteries in the neck, and joint laxity. On computed tomography (CT) angiography she had severe tortuosity of the aortal branches and cerebral arteries, but no significant tortuosity of the pulmonary arteries. Two cousins of the girl carried the same homozygous c.254T>C, p.(Leu85Pro) mutation in SLC2A10, however, they additionally had a severe involvement of the pulmonary vessels. Patient 2 was a 9-year-old girl diagnosed with severe tortuosity and stenosis of the pulmonary arteries and progressive myocardiopathy. Her physical appearance was very similar to Patient 1, except that she also had growth retardation. After long-term follow-up by cardiologists, she underwent cardiac surgery abroad, with an unfavorable outcome. Homozygosity for the c.685C>T, p.(Arg229*) mutation in the SLC2A10 gene was detected. Consanguinity was disclosed within both families. Our findings confirm the intrafamilial phenotype variability of ATS. A novel finding is the severe tortuosity of cerebral arteries causing migraine that has not been described before in a child with ATS.

Validation of respiratory questionnaire for lung function assessment among an occupational group of textile workers in Pakistan.

OBJECTIVE: To determine the association of spirometric lung pattern with respiratory symptoms and to validate the American Thoracic Society respiratory questionnaire for lung function assessment among textile workers. METHODS: This cross-sectional survey was conducted from August to December 2009 among adult textile workers of Karachi. Data was collected through the American Thoracic Society Division of Lung Disease respiratory questionnaire and the lung function was assessed by using a spirometer. Results of three acceptable readings of spirogram were recorded and the best of the three readings was used for analysis. SPSS 19 was used for data analysis. RESULTS: There were 372 participants in the study with an overall mean age of 27±8.5 years. In linear regression analysis, forced expiratory volume in one second for workers who had chronic cough was -829.1 (confidence interval: -1273.1, -385.2), chronic wheeze -168.8 (confidence interval: -319.3, -18.2) and shortness of breath grade 2 -215.6 (confidence interval: -387.8, -43.4). In logistic regression model, after adjusting for covariates, odds of reduced percentage predicted forced expiratory volume in one second for workers who had chronic cough was 3.09 (confidence interval: 1.26, 7.56), chronic wheeze 1.98 (confidence interval: 1.05, 3.71) and shortness of breath grade 2 2.07 (confidence interval: 1.05, 4.07), while odds of reduced percentage predicted forced vital capacity for shortness of breath grade 2 was 2.35 (confidence interval: 1.05, 5.21). In logistic regression model 2, for assessing the effect of different combinations of chronic respiratory symptoms, the odds of reduced percentage predicted forced expiratory volume in one second for the combination of cough and wheeze was 2.08 (confidence interval: 1.05, 4.10), cough and shortness of breath grade 2 2.47 (confidence interval: 1.18, 5.18), phlegm and shortness of breath grade 2 2.59 (confidence interval: 1.23, 5.43), cough, wheeze and shortness of breath grade 2 4.64 (confidence interval: 1.97, 10.93)and cough, phlegm, wheeze and shortness of breath grade 2 4.18 (confidence interval: 1.68, 10.37). CONCLUSIONS: A combination of chronic respiratory symptoms was best associated with decrements in lung function.