UK families with children with rare chromosome disorders: Changing experiences of diagnosis and counselling (2003-2013).

The latest United Kingdom (UK) strategy for rare diseases emphasises the need to empower affected populations to improve diagnosis, intervention, and coordination of care. Families who have a child with a rare chromosome disorder (RCD) are a challenging group to include. We report the findings of 2 large-scale surveys, undertaken by the UK RCD Support Group Unique, of these families' experiences over a 10-year period. Seven stages of the patient journey were examined. From pre-testing, through diagnosis, genetics consultation, clinical follow-up and peer support. Overall, 1158 families replied; 36.4% response rate (2003) and 53.6% (2013). Analysis of responses identifies significant differences (P < .001) over time with a decrease in results reported face to face (76%-62%), doubling by telephone (12%-22%), improved explanation of chromosome disorder (57%-75%), and increased signposting to peer support group (34%-62%). However, conduct of the consultation raises a number of important questions. Overall, 28 aspects of the patient journey are recognised as requiring improvement; only 12/28 are currently incorporated in UK service specifications. Involvement of RCD families has identified key service improvements. This approach can empower those affected by such extremely rare disorders, and also enable professionals to design improved services in partnership with "expert families." Further surveys are planned.

The Association between Distress Tolerance and Alcohol Related Problems: The Pathway of Drinking to Cope.

Binge drinking (BD) and alcohol related problems (ARP) are highly prevalent among college students. However, current models examining ARP suggest drinking quantity only accounts for a portion of the variance, suggesting other variables contribute to ARP. Distress tolerance (DT), or the ability to withstand negative affect, is associated with alcohol misuse and may be an important mechanism related to ARP. However, studies have reported inconsistent findings on this association, which may be due to the use of only global scores to measure DT rather than specific DT components. Furthermore, the mechanisms underlying this association remain unknown. Drinking to cope with negative affect has been associated with both DT and ARP, suggesting it may be a mechanism explaining the relationship between DT and ARP. The current study examined the association between specific proposed DT components (i.e., tolerance, absorption, appraisal, and regulation) and drinking to cope and ARP in 147 college students who BD. A hierarchical linear regression was performed in order to examine which DT component best predicted ARP. Four follow-up mediation models were then tested to examine whether drinking to cope mediated the relationship between each DT component and ARP. Appraisal of DT was the only DT component that significantly predicted ARP, in the model controlling for drinking quantity and sex differences. Drinking to cope mediated the relationship between ARP and tolerance, absorption, and regulation, but not appraisal of DT. Implications for furthering our understanding of DT and treatment of BD as it relates to DT are explored.

Sugar before bed: a simple dietary risk factor for caries experience.

Clinical care pathways have placed renewed emphasis on caries risk assessment and the ability to predict and prevent further disease. With diet considered a key factor in the development of caries, the level of caries risk posed by dietary habits, such as the frequency of intake and timing of free sugars is questioned. OBJECTIVE: To identify reliable and simple dietary risk factors for caries experience. RESEARCH DESIGN: A cross-sectional observational study of a convenience sample with data gained from clinical examinations, questionnaire and a 24 hour dietary-recall interview. PARTICIPANTS: 128 subjects aged 11-12 from comprehensive schools in Greater Manchester and Newcastle upon-Tyne, UK. OUTCOME MEASURES: free sugars consumed between meals, before bed and total % of total free sugars consumed were assessed from dietary assessments led by a dietitian. D4-6MFT was generated with a caries threshold of ICDAS stage 4 from clinical examinations. RESULTS: Analysis revealed no significant differences in caries experience when looking specifically at caries into dentine, referred to as the cavity group (split at D4-6MFT), between high and low deprivation, consumption of free sugars between meals and free sugars (%). The consumption of free sugars within the hour before bed revealed a statistically significant difference between the cavity/no cavity groups (p=0.002). Logistic regression analysis on the cavity/no cavity groups revealed an odds ratio of 2.4 (95%CI 1.3,4.4) for free sugars consumption before bedtime. CONCLUSIONS: The study suggests that the consumption of free sugars before bedtime may be an important risk factor for adolescent caries into dentine experience.

Association of interleukin-10 polymorphisms with chronic hepatitis C virus infection in a case-control study and its effect on the response to combined pegylated interferon/ribavirin therapy.

We conducted a case-control study involving 150 genotype 3 chronic hepatitis C virus (HCV) patients and 150 healthy controls to investigate the association of polymorphisms in the interleukin-10 (IL-10) gene with chronic HCV infection and the association of these polymorphic variants with the combination of pegylated interferon (Peg-IFN) and ribavirin therapy response. Our data revealed that the GG genotype of IL-10 -1082A/G exhibited significant association with genotype 3 chronic HCV infection compared to controls. Treatment response data also showed a significant increase in risk for the GG genotype of IL-10 -1082A/G in response-relapse patients or non-responder patients compared to sustained virological response patients. Further, a significant increase in risk was also revealed for the CC genotype of IL-10 -592A/C in response-relapse patients or non-responder patients compared to sustained virological response patients, suggesting a role of the GG genotype of IL-10 -1082A/G and CC genotype of IL-10 -592A/C in the treatment outcome of combined Peg-IFN/ribavirin therapy.

Basal subtype, as approximated by triple-negative phenotype, is associated with locoregional recurrence in a case-control study of women with 0-3 positive lymph nodes after mastectomy.

PURPOSE: Basal subtype, as approximated by the triple-negative phenotype (ER-PR-Her2-), has correlated with higher LRR in recent studies. Indications for postmastectomy RT (PMRT) in women with 0-3 positive lymph nodes remain unclear. We evaluated the importance of biologic subtype in a cohort of women with LRR after mastectomy. METHODS: We identified 22 women with 0-3 positive lymph nodes at our institution who were initially treated with mastectomy (without post-mastectomy radiation), suffered LRRs, and had paraffin-embedded tissue blocks from the primary mastectomy specimen available for staining. None of these women received PMRT. We case-control matched these to 29 women with 0-3 positive nodes who had mastectomy (no PMRT) and remained without evidence of disease at last follow-up and had available primary specimens for processing. We matched controls for age (±3 years) and follow-up duration (<5 year vs. more). Paraffin-embedded specimens were used to construct a triple-redundant tissue microarray. We used conditional logistic regressions to study the association between each predictor and LRR. Results were summarized based on odds ratio (OR). RESULTS: On univariate analysis, ER+, PR+, or the combination was strongly associated with lower odds of LRR. Basal subtype, as approximated by ER-PR-Her2- (TN), was associated with higher LRR (OR 8.5, p = 0.048). Use of chemotherapy also was associated with lower LRR (OR 0.126, p = 0.0073). CONCLUSIONS: Our data are concordant with reports from others demonstrating that TN phenotype is associated with higher LRR and can be considered along with other predictors of LRR when selecting women for PMRT.

Identification of Chili leaf curl virus Causing Leaf Curl Disease of Petunia in Oman.

Petunias (Petunia × hybrida) are the most important ornamental plants in Oman. In 2012, petunias were observed in public parks and airport landscape in Dhofar region with symptoms of upward leaf curling, yellowing and vein clearing, and size reduction in leaves. Almost all plants in the surveyed landscape showed high infestation of Bemisia tabaci and symptoms that suggested infection with a begomovirus. Six symptomatic samples were collected from three different sites. All symptomatic samples were found PCR-positive with diagnostic primers for begomovirus (3) when DNA extracted from infected leaves was used as template. Nucleic acids extracted from the symptomatic leaves were used to amplify circular DNA molecules by rolling circle amplification method. The amplified concatameric products were digested with restriction enzyme PstI, which yielded a product ∼2.8 kb in size. The putative begomovirus fragment was cloned and sequenced in both orientations. Partial sequences of six clones were 99 to 100% similar and thus only two clones, PT-2 and PT-3, were fully sequenced. The whole genomes of both clones were 2,761 bp, and both were deposited in GenBank under accession numbers HF968755 and HF968756 for the isolates PT-2 and PT-3, respectively. Both sequences had six open reading frames; Rep, TrAP, REn, and C4 genes in complementary sense; and CP and V2 genes in virion-sense, typical of the begomovirus genome organization. Upon alignment, the two sequences showed 99.4% nucleotide identity with each other, thus representing isolates of a single begomovirus species. BlastN comparison showed PT-2 and PT-3 from petunia were 94 to 95% identical to the sequences of ChCLV from Oman (JN604490 to JN604500), which were obtained from other hosts. ClustalV multiple sequence alignment showed that isolates PT-2 and PT-3 shared maximum sequence identity of 93.3 and 92.8%, respectively, with an isolate of ChLCV-OM (JN604495). According to ICTV rules for begomoviruses, PT-3 should be considered to be a new strain of ChLCV-OM and PT-2 a variant of the already existing ChLCV-OM strain. We propose the name for this new strain as the "Petunia strain" of Chili leaf curl virus (ChLCV-Pet). Two infectious clones were constructed from the PT-2 and PT-3 sequences, clones as 1.75-genome sequences in a binary vector, suitable for agroinfection to confirm their infectivity. Both clones, PT-2 and PT-3, produced typical leaf curl disease symptoms upon inoculation on petunia 18 days post inoculation. The presence of the same virus in symptomatic field infected and inoculated petunia was confirmed by Southern blot using 650 bp DIG labeled probe prepared from CP region of PT-3 isolate. ChLCV-OM, a monopartite begomovirus, is widely associated with leaf curl disease of tomato and pepper in Oman, with its origin traced to the Indian subcontinent (2). Identification of a new strain of ChLCV from petunia provides evidence of an ongoing rapid evolution of begomoviruses in this region. Although petunia has been tested as an experimental host for some begomoviruses (1,4), this is the first report of petunia as natural host for ChLCV, a begomovirus previously reported in tomato and pepper in Oman. References: (1) Cui et al. J. Virol. 78:13966, 2004. (2) Khan et al. Virus Res. 177:87, 2013. (3) Khan et al. Plant Dis. 97:1396, 2013. (4) Urbino et al. Arch. Virol. 149:417, 2003.

A Distinct Strain of Chickpea chlorotic dwarf virus Infecting Pepper in Oman.

During a field survey in 2011, pepper (Capsicum annum) plants showing symptoms suggestive of geminivirus infection were observed in three fields in the Al-Sharqiya region of Oman. Symptoms observed included upward leaf curling leading to cupping and stunting with 15 to 25% disease incidence in surveyed fields. Total DNA was extracted from the leaves of seven symptomatic plants and subjected to rolling circle amplification (RCA). The RCA product was digested with several restriction endonucleases to obtain unit length of ~2.6 to 2.8, typical of geminivirus. Out of seven samples, only four yielded a product of ~2.6 kb in size by KpnI digestion. The fragments were cloned in pUC19 and sequenced. The partial sequences of four isolates were >95% identical to each other at the nucleotide (nt) level and thus only one isolate (P-25) was fully sequenced, determined to be 2,572 nt in length, and its sequence deposited in GenBank (KF111683). The P-25 sequence showed a genome organization typical of a mastrevirus, with four open reading frames (ORFs), two in virion-sense and two in complementary-sense. The virion and complementary-sense ORFs were separated by a long intergenic region, containing a predicted hairpin structure with the nonanucleotide sequence (TAATATTAC) in the loop, and a short intergenic region. An initial comparison to all sequences in the NCBI database using BlastN showed the isolate to have the highest level of sequence identity with isolates of the dicot-infecting mastrevirus Chickpea chlorotic dwarf virus (CpCDV). Subsequent alignments of all available CpCDV isolates using the species demarcation tool (2) showed the isolate P-25 to share between 83.6 and 90.3% identity to isolates of CpCDV available in databases, with the highest (90.3%) to CpCDV strain A originating from Syria (FR687959) (3). Amino acid sequence comparison showed that the predicted proteins encoded by the four ORFs of P-25 (coat protein [CP], movement protein [MP], replication associated protein A [RepA], and RepB) share 91.5, 88.2, 89.1, and 90.8% amino acid sequence identity, respectively, with the homologous proteins of the CpCDV isolate from Syria. Based on the recently revised mastreviruses species and strain demarcation criteria (78 and 94% whole genome nt identity, respectively) proposed by Muhire et al. (2), the results indicate that isolate P-25 represents a newly identified strain (strain F) of CpCDV. The presence of CpCDV in symptomatic pepper plants was further confirmed by Southern blot hybridization technique using digoxygenin (DIG) labeled probe prepared from CpCDV isolate P-25. The genus Mastrevirus consists of geminiviruses with single component genomes that are transmitted by leafhoppers. Mastreviruses have so far only been identified in the Old World and infect either monocotyledonous or dicotyledonous plants (1). To our knowledge, this is the first report of a mastrevirus on the Arabian Peninsula and the first record of pepper as host of CpCDV. Recently, several begomoviruses of diverse geographic origins have been found infecting vegetable crops in Oman. The propensity of geminiviruses to evolve through recombination may lead to evolution of recombinant CpCDV with new host adaptability. Due to extensive agricultural/travel links of Oman with rest of the world, there exists high probability for the spread of this virus. References: (1) M. I. Boulton. Physiol. Mol. Plant Pathol. 60:243, 2002. (2) B. Muhire et al. Arch. Virol. 158:1411, 2013 (3) H. Mumtaz et al. Virus Genes 42:422, 2011.

A social enterprise model for TB detection and treatment through the private sector in Pakistan.

BACKGROUND: Existing models to increase TB case notifications from the private sector in Pakistan are financially unsustainable and have achieved modest success due to limited coverage. OBJECTIVE: To evaluate the impact of a social enterprise model (SEM) intervention on TB case detection in Karachi, Pakistan, and to assess its financial sustainability. METHODS: Purpose-built centres were established within the private sector that integrated TB screening, diagnostics and treatment and operated 12 hours per day with convenient locations to improve access. TB services were offered free of cost, and revenue generation took place through user fees from other diagnostics. Private providers with a focus on the informal sector were engaged through community workers to generate screening referrals. RESULTS: Overall 171,488 people were screened and 18,683 cases were notified, including 197 individuals with drug-resistant TB. Annual TB notifications in Karachi increased from 18,105 in 2014 to a maximum of 25,840 (40% increase). The proportion of cases in Karachi notified by the centres grew to 27% in 2020. Commercial revenue reached USD288,065 and enabled operating cost recovery of 15%. Average cost per TB case notified was USD203. CONCLUSION: The SEM intervention contributed a large proportion of notifications in Karachi and achieved modest cost recovery.

CONTEXTE: Les modèles existants visant à augmenter les notifications de cas de TB par le secteur privé au Pakistan ne sont pas viables financièrement et n'ont obtenu qu'un succès modeste en raison d'une couverture limitée. OBJECTIF: Évaluer l'impact d'un modèle déntreprise sociale (SEM, pour l'anglais « social entreprise model ¼) sur la détection des cas de TB à Karachi, au Pakistan, et évaluer sa viabilité financière. MÉTHODES: Des centres spécialisés ont été créés dans le secteur privé. Ils intègrent le dépistage, le diagnostic et le traitement de la TB et fonctionnent 12 heures par jour dans des lieux adaptés afin dén faciliter l'accès. Les services de lutte contre la TB étaient gratuits et les recettes provenaient des frais d'utilisation des autres diagnostics. Des prestataires privés, axés sur le secteur informel, ont été engagés par l'intermédiaire d'agents communautaires pour orienter les patients vers les services de dépistage. RÉSULTATS: Au total, 171 488 personnes ont été dépistées et 18 683 cas ont été notifiés, dont 197 personnes atteintes de TB résistante aux médicaments. Les notifications annuelles de TB à Karachi sont passées de 18 105 en 2014 à un maximum de 25 840 (augmentation de 40%). La proportion de cas à Karachi notifiés par les centres est passée à 27% en 2020. Les recettes commerciales ont atteint 288 065 USD et ont permis un recouvrement des coûts déxploitation de 15%. Le coût moyen par cas de TB notifié était de 203 USD. CONCLUSION: L'intervention SEM a contribué à une grande proportion de notifications à Karachi et a permis un modeste recouvrement des coûts.

Dosimetric feasibility and acute toxicity in a prospective trial of ultrashort-course accelerated partial breast irradiation (APBI) using a multi-lumen balloon brachytherapy device.

BACKGROUND: Shorter courses of APBI, including single-fraction intraoperative therapy, are under active investigation. We designed a prospective trial to identify and address the potential radiobiological and logistical shortcomings of single-fraction APBI. METHODS: We designed a single-arm, multi-institutional, prospective phase II trial that sequentially treats 3 cohorts of women (each n = 30) with 3 progressively hypofractionated schedules. Eligible women were age ≥50 years with unifocal invasive or in situ tumors ≤3.0 cm, excised with negative margins, and with negative lymph nodes and positive hormone receptors. We defined strict dosimetric criteria for appropriateness. RESULTS: A total of 30 patients were enrolled at the 7 Gy × 4 fractions dose-level and followed for 6 months. The median skin dose as a percent of prescription dose (PD) was 84 % (40-100), and the median rib dose was 71 % (16-119). Also, 95 % of the PTV_eval received a median of 95 % of PD (range 85-103). The V150 (range 14-48 cc) and V200 (range 0-29 cc) criteria were met in all cases. One breast infection occurred and was treated; 2 cases of symptomatic fat necrosis and 2 cases of symptomatic seromas occurred. CONCLUSION: Short-course APBI is dosimetrically feasible using the Contura MLB and appears to be tolerable in terms of acute toxicities. Our approach is based on well-defined radiobiological parameters and allows for an abbreviated course of treatment that is guided by full pathological review and the ability to objectively achieve and validate acceptable dosimetric criteria in each case. We have opened enrollment to the next schedule of 8.25 Gy for 3 fractions.

Persisting role of healthcare settings in hepatitis C transmission in Pakistan: cause for concern.

Transmission of hepatitis C (HCV) in Pakistan is a continuing public health problem; 15 years ago it was linked to the practice of reusing therapeutic instruments in healthcare settings. We sought to examine current risk factors for HCV transmission in a hospital population in Karachi, Pakistan. We enrolled 300 laboratory-confirmed HCV-positive participants and 300 laboratory confirmed HCV-negative participants from clinics at Indus Hospital. Independent and significant risk factors for both men and women were: receiving o12 injections in the past year, blood transfusions, having had dental work performed, and delivery in hospital or transfusion for women. Interestingly, being of Mohajir origin or born in Sindh province were protective.Encouragingly, a strong protective effect was observed for those that reported bringing their own needle for injections (59%). The widespread reuse of therapeutic needles in healthcare settings in Karachi remains a major driver of the HCV epidemic.

A Distinct Strain of Tomato leaf curl Sudan virus Causes Tomato Leaf Curl Disease in Oman.

Tomato leaf curl disease (ToLCD) is a significant constraint for tomato production in the Sultanate of Oman. The disease in the north of the country has previously been shown to be caused by the monopartite begomoviruses (family Geminiviridae) Tomato yellow leaf curl virus and Tomato leaf curl Oman virus. Many tomato plants infected with these two viruses were also found to harbor a symptom enhancing betasatellite. Here an analysis of a virus isolated from tomato exhibiting ToLCD symptoms originating from south and central Oman is reported. Three clones of a monopartite begomovirus were obtained. One of the clones was shown to be infectious to tomato and Nicotiana benthamiana and to induce symptoms typical of ToLCD. Analysis of the cloned sequences show them to correspond to isolates of Tomato leaf curl Sudan virus (ToLCSDV), a virus that occurs in Sudan and Yemen. However, the sequences showed less than 93% nucleotide sequence identity to previously characterized ToLCSDV isolates, indicating that the viruses represent a distinct strain of the species, for which we propose the name "Oman" strain (ToLCSDV-OM). Closer analysis of the sequences showed them to differ from their closest relative, the "Tobacco" strain of ToLCSDV originating from Yemen, in three regions of the genome. This suggests that the divergence of the "Oman" and "Tobacco" strains has occurred due to recombination. Surprisingly, ToLCSDV-OM was not found to be associated with a betasatellite, even though the isolates of the other ToLCSDV strains have been shown to be. The significance of these findings and the possible reasons for the distinct geographic distributions of the tomato-infecting begomoviruses within Oman are discussed.

Six-year analysis of treatment-related toxicities in patients treated with accelerated partial breast irradiation on the American Society of Breast Surgeons MammoSite Breast Brachytherapy registry trial.

BACKGROUND: The American Society of Breast Surgeons (ASBrS) enrolled women in a registry trial to prospectively study patients treated with the MammoSite RTS device. This report presents 6-year data on treatment-related toxicities from the trial. METHODS: A total of 1449 primary early-stage breast cancers were treated with accelerated partial breast irradiation (APBI) using the MammoSite device (34 Gy in 10 fractions) in 1440 women. Of these, 1255 case (87%) had invasive breast cancer (IBC) (median size = 10 mm) and 194 cases (13%) had ductal carcinoma in situ (DCIS) (median size = 8 mm). Median follow-up was 59 months. Fisher exact test was performed to correlate categorical covariates with toxicity. RESULTS: Breast seromas were reported in 28% of cases (35.5% with open cavity and 21.7% with closed cavity placement). Also, 13% of all treated breasts developed symptomatic seromas, and 77% of these seromas developed during the 1st year after treatment. There were 172 cases (11.9%) that required drainage to correct. Use of chemotherapy and balloon fill >50 cc were associated with the development of symptomatic seromas. Also, 2.3% of patients developed fat necrosis (FN). The incidence of FN during years 1 and 2 were 0.9% and 0.8%, respectively. Seroma formation, use of hormonal therapy, breast infection, and A/B cup size were associated with fat necrosis. There were 138 infections (9.5%) recorded; 98% occurred during the 1st year after treatment. Chemotherapy and seroma formation were associated with the development of infections. CONCLUSIONS: Treatment-related toxicities 6 years after treatment with APBI using the MammoSite device are similar to those reported with other forms of APBI with similar follow-up.

Identification of Cotton leaf curl Gezira virus in Papaya in Oman.

Papaya is an important fruit crop in Oman covering some 130 ha with an annual production of 20 tonnes. In 2011, during surveys of farms in the Quriyat region of Oman, papaya plants were found severely affected by leaf curl disease. Leaves with severe curling, vein darkening, and vein thickening were collected for study. Disease incidence ranged from 30 to 50%, particularly in fields with young papaya. A begomovirus (family Geminiviridae) was suspected as the causal agent based on symptoms (1) and the presence of whiteflies in the field. Samples (four to five) were collected from three farms. Total nucleic acids extracted from symptomatic leaves using the CTAB method were used as templates to amplify circular DNAs using Φ29 DNA polymerase and products were digested with restriction enzymes to identify fragments of 2.6 to 2.8 kb typical of geminiviruses. PstI yielded a fragment of ~1.8 kb when the digested product was analyzed by electrophoresis on a 1% agarose gel. The fragment was cloned and sequenced using primer walking strategy in both directions. The sequencing confirmed the exact size (1,764 bp) and the sequence was deposited in GenBank (HE800524). The viral sequence from Oman (isolate Pap-2) showed four open reading frames (ORFs) in the complementary sense (replication associated protein [Rep] gene, the C2 gene, the replication enhancer protein [REn] gene, and the C4 gene) and the virion-sense ORFs (V1 and V2) were missing in the sequence. An initial comparison to NCBI database sequences using BLAST showed the clone from Oman had the highest level of sequence identity to Cotton leaf curl Gezira virus (CLCuGeV) (FJ868828) cloned from okra in Sudan. Subsequent pair wise sequence comparison was done using ClustalV algorithm. Full length sequences of CLCuGeV from database were trimmed according to the size and genomic coordinates of Pap-2 isolate. The Pap-2 isolate sequence was found to have 83.3 to 95.1% sequence identity to CLCuGeV sequences with maximum value to the Sudan isolate. Amino acid sequence comparison showed that the four predicted proteins (Rep, C2, REn, and C4) encoded by the Pap-2 isolate shared 95.3%, 97.8%, 97.7%, and 87.6% sequence identity, respectively, with the homologous proteins of CLCuGeV-SD (FJ868828). The absence of virion-sense protein sequences indicated it to be a subgenomic molecule of CLCuGeV. According to the recommendations of International Committee on Taxonomy of Viruses, these results indicate that the virus identified in association with papaya leaf curl disease in Oman is a variant of CLCuGeV. CLCuGeV is a begomovirus of African origin which is distinct from the begomoviruses of the Middle East and Asia. To our knowledge, this is the first report of CLCuGeV, or any other cotton infecting begomovirus, from papaya in Oman. The presence of a recombinant fragment of CLCuGeV in a Tomato yellow leaf curl virus isolate from Iran (2), and the association of CLCuGeV with cotton in Pakistan (3) and hollyhock in Jordan (GU945265) suggests this virus has moved into the Middle East and Asia from Africa. The identification of CLCuGeV in Oman shows the widespread occurrence of this virus species. This discovery is important since Oman, and other countries in the area, are a hub of international trade and travel, particularly by air and sea, meaning that the virus could spread further. References: (1) R. W. Briddon and P. G. Markham. Virus Res. 71:151, 2000. (2) P. Lefeuvre et al. PLoS Pathog. 6:e1001164, 2010. (3) M. N. Tahir et al. PLoS ONE 6:e20366, 2011.

An unusual alphasatellite associated with monopartite begomoviruses attenuates symptoms and reduces betasatellite accumulation.

The Oman strain of Tomato yellow leaf curl virus (TYLCV-OM) and its associated betasatellite, an isolate of Tomato leaf curl betasatellite (ToLCB), were previously reported from Oman. Here we report the isolation of a second, previously undescribed, begomovirus [Tomato leaf curl Oman virus (ToLCOMV)] and an alphasatellite from that same plant sample. This alphasatellite is closely related (90 % shared nucleotide identity) to an unusual DNA-2-type Ageratum yellow vein Singapore alphasatellite (AYVSGA), thus far identified only in Singapore. ToLCOMV was found to have a recombinant genome comprising sequences derived from two extant parents, TYLCV-OM, which is indigenous to Oman, and Papaya leaf curl virus from the Indian subcontinent. All possible combinations of ToLCOMV, TYLCV-OM, ToLCB and AYVSGA were used to agro-inoculate tomato and Nicotiana benthamiana. Infection with ToLCOMV yielded mild leaf-curl symptoms in both hosts; however, plants inoculated with TYLCV-OM developed more severe symptoms. Plants infected with ToLCB in the presence of either helper begomovirus resulted in more severe symptoms. Surprisingly, symptoms in N. benthamiana infected with the alphasatellite together with either of the helper viruses and the betasatellite were attenuated and betasatellite DNA accumulation was substantially reduced. However, in the latter plants no concomitant reduction in the accumulation of helper virus DNA was observed. This is the first example of an attenuation of begomovirus-betasatellite symptoms by this unusual class of alphasatellites. This observation suggests that some DNA-2 alphasatellites encode a pathogenicity determinant that may modulate begomovirus-betasatellite infection by reducing betasatellite DNA accumulation.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

First Report of a Group 16SrII Phytoplasma Associated with Witches'-Broom of Eggplant in Oman.

Eggplant (Solanum melongena L.) belongs to the family Solanaceae and is an important vegetable cash crop grown in most parts of Oman. In February 2010, plants showing phyllody symptoms and proliferation of shoots resembling those caused by phytoplasma infection were observed at Khasab, 500 km north of Muscat. Total genomic DNA was extracted from healthy and two symptomatic plants with a modified (CTAB) buffer method (2) and analyzed by direct and nested PCR with universal phytoplasma 16S rDNA primers P1/P7 and R16F2n/ R16R2, respectively. PCR amplifications from all infected plants yielded an expected product of 1.8 kb with P1/P7 primers and a 1.2-kb fragment with nested PCR, while no products were evident with DNA from healthy plants. Restriction fragment length polymorphism (RFLP) profiles of the 1.2-kb nested PCR products of two eggplant phyllody phytoplasma and five phytoplasma control strains belonging to different groups used as positive control were generated with the restriction endonucleases RsaI, AluI, Tru9I, T-HB8I, and HpaII. The eggplant phytoplasma DNA yielded patterns similar to alfalfa witches'-broom phytoplasma (GenBank Accession No. AF438413) belonging to subgroup 16SrII-D, which has been recorded in Oman (1). The DNA sequence of the 1.8-kb direct PCR product was deposited in GenBank (Accession No. HQ423156). Sequence homology results using BLAST revealed that the eggplant phyllody phytoplasma shared >99% sequence identity with Scaevola witches'-broom phytoplasma (Accession No. AB257291.1), eggplant phyllody phytoplasma (Accession No. FN257482.1), and alfalfa witches'-broom phytoplasma (Accession No. AY169323). The RFLP and BLAST results of 16S rRNA gene sequences confirm that eggplant phyllody phytoplasma is similar to the alfalfa phytoplasma belonging to subgroup 16SrII-D. To our knowledge, this is the first report of a phytoplasma of the 16SrII-D group causing witches'-broom disease on eggplant in Oman. References: (1) A. J. Khan et al. Phytopathology 92:1038, 2002. (2) M. A. Saghai-Maroof et al. Proc. Natl. Acad. Sci. USA, 81:8014, 1984.

Expressive suppression and cognitive reappraisal in veterans with PTSD: Results from the mind your heart study.

OBJECTIVE: This study examined whether expressive suppression (ES), a maladaptive regulation strategy, was more strongly associated with PTSD diagnosis and symptom clusters in veterans than cognitive reappraisal (CR), an adaptive regulation strategy. METHOD: In a cohort study, 746 participants recruited from VHA facilities completed Clinician Administered PTSD Scale-IV, Emotion Regulation Questionnaire, and Patient Health Questionnaire. Participants were categorized into groups: Current, Remitted/Lifetime, and Never PTSD. RESULTS: One-way ANOVA revealed significant differences between Current PTSD and both Remitted and Never PTSD for ES, but not CR. The Remitted and Never PTSD groups did not vary significantly from each other and were collapsed into one group for regressions. Adjusting for sex, race, employment, and comorbid depression, binary logistic regression showed ES, but not CR, was associated with increased likelihood of Current PTSD (p < .001, OR: 1.43). ES was also significantly associated with increased odds of meeting criteria for all symptom clusters (ps < 0.001). CR was not significantly associated with meeting criteria for Current PTSD or any symptom cluster. LIMITATIONS: Cross-sectional design and use of self-report limit causality inferences that can be drawn. CONCLUSIONS: ES is associated with increased odds of Current PTSD diagnosis and symptom clusters. Veterans in the Remitted and Never PTSD groups did not differ significantly. Greater suppression of emotional expression is more strongly linked with PTSD criteria in veterans than decreased cognitive reappraisal.

COVID-19 related moral injury: Associations with pandemic-related perceived threat and risky and protective behaviors.

BACKGROUND: The coronavirus-2019 (COVID-19) pandemic is associated with increased potential for morally injurious events, during which individuals may experience, witness, or learn about situations that violate deeply held moral beliefs. However, it is unknown how pandemic risk and resilience factors are associated with COVID-related moral injury. METHODS: Individuals residing in the U.S. (N = 839; Mage = 37.09, SD = 11.06; 78% women; 63% White; 33% PTSD) participating in an online survey reported on COVID-19 related moral injury (modified Moral Injury Events Scale), perceived current and future threat of pandemic on life domains (social, financial, health), and COVID-19 risky and protective behaviors. Multivariate linear regressions examined associations of perceived threat and risky and protective behaviors on type of COVID-19 related moral injury (betrayal, transgression by others, self). RESULTS: Participants endorsed MI betrayal (57%, N = 482), transgression by other (59%, N = 497), and by self 17% (N = 145). Adjusting for sociodemographics, only future threat of COVID-19 to health was significantly associated with betrayal (B = 0.21, p = .001) and transgression by other (B = 0.16, p = .01), but not by self. In contrast, high frequency of risky behaviors was associated with transgressions by self (B = 0.23, p < .001). Sensitivity analyses showed PTSD did not moderate the observed effects. CONCLUSIONS: Betrayal and transgression by others was associated with greater perceived future threat of COVID-19 to health, but not financial or social domains. Stronger endorsement of transgression by self was associated with more frequently engaging in risky behaviors for contracting COVID-19. These findings may suggest the need for individual, community, and system level interventions to address COVID-19 related moral injury.

Suppression, but not reappraisal, is associated with inflammation in trauma-exposed veterans.

BACKGROUND: Emotion dysregulation can elicit inflammatory activity. The current study examined whether specific maladaptive and adaptive emotion regulation strategies were associated with inflammatory markers in trauma-exposed veterans, above and beyond PTSD. METHODS: In a cohort study, 606 participants exposed to a Criterion A trauma and recruited from Veteran Health Administration facilities completed fasting blood draws, the Emotion Regulation Questionnaire, and the Clinician Administered PTSD Scale-IV. Inflammation was assessed with high sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen levels. An inflammation index was created by summing standardized log-transformed levels of the three biomarkers. Our primary linear regression models were adjusted for sex, age, race, education, income, creatinine, and PTSD. RESULTS: Suppression, but not cognitive reappraisal, was significantly associated with higher levels of the inflammatory index (ß = 0.14, p = 0.001). Parallel analyses for the individual inflammatory markers also showed suppression, but not reappraisal, was significantly associated with higher hsCRP (ß = 0.11, p = 0.01), WBC (ß = 0.11, p = 0.01), and fibrinogen (ß = 0.10, p = 0.02). CONCLUSIONS: Emotional suppression is related to elevated systemic inflammation independent of PTSD. Cognitive reappraisal is unrelated to inflammation. Findings suggest over-utilization of maladaptive, rather than under-utilization of adaptive, emotion regulation strategies may be associated with systemic inflammation in trauma-exposed veterans.

How do gender and military sexual trauma impact PTSD symptoms in cognitive processing therapy and prolonged exposure?

OBJECTIVE: Effectiveness of evidence-based psychotherapy (EBP) for PTSD can vary based on gender and trauma type, with poorer outcomes for men and sexual traumas. Among veterans receiving EBPs for PTSD, the effects of the interaction between gender and military sexual trauma (MST) on treatment outcome are unclear. This study examined how gender and MST impact PTSD symptoms following cognitive processing therapy (CPT) and prolonged exposure (PE). METHOD: We conducted a national, retrospective cohort study of all post 9/11 veterans who had a PTSD diagnosis from 10/2001-9/2017 at VHA facilities and >1 psychotherapy visit. Inclusion criteria included completion of ≥8 CPT/PE sessions and pre- and post-treatment PCL (N = 9711). Mixed-effects linear regression models were conducted, separately by treatment, to examine associations between changes in PTSD symptoms and gender, MST, and their interactions with time. RESULTS: For both treatments, there were no significant differences in pre-treatment PCL by gender or MST, and PCL decreased significantly over time. In adjusted models, only the gender by time interaction on pre-to-post-CPT change was significant (p < .001); the decrease in women's PCL was 2.67 points greater, compared to men. CONCLUSIONS: Women veterans demonstrated greater reductions in PTSD symptoms from CPT. There were no differences by gender for PE, suggesting men and women veterans benefit similarly. Results suggest outcomes may be impacted by gender socialization when utilizing certain cognitive behavioral techniques. MST, regardless of gender, did not impact PTSD outcomes for either treatment. Both CPT and PE may thus be effective for veterans irrespective of MST history.