A Rare Presentation: Bilateral Necrotizing Scleritis in Primary Sjögren's Syndrome.

PURPOSE: We report a rare and challenging case of bilateral necrotizing scleritis in primary Sjögren's syndrome (pSS). METHODS: Retrospective case report. RESULTS: A 72-year-old diabetic, hypertensive female patient presented with sudden onset of painful red left eye and was noted to have a corneal ulcer with severe thinning. She was managed with topical fortified antibiotics and tissue glue and bandage contact lens. During subsequent follow-ups, she developed necrotizing scleral melts in both eyes. On investigations, antinuclear antibodies were positive in a dilution of 1:160 with 2+ speckled pattern, with antinuclear antibody line immunoassay showing anti SS-A/ Ro52 positive. In view of rapidly developing scleral thinning and impending perforation, she was started on intravenous methylprednisolone 1 g/day for 3 days, along with steroid-sparing immunomodulatory therapy (mycophenolate mofetil 500 mg twice a day). She showed a rapid response to therapy and is currently stable on tapering oral steroids and mycophenolate mofetil. CONCLUSION: This case underscores the unique presentation of pSS, characterized by bilateral necrotizing scleritis. The favorable outcome was attained through prompt immunosuppressive intervention and a collaborative, multidisciplinary approach. Further, this case report addresses a gap in the existing literature concerning pSS-related scleritis. It also emphasizes the crucial role of a rheumatologist in the comprehensive management of this condition.

Case report: Sustained complete remission with all-oral MEPED therapy in a patient with Hodgkin's disease developing resistance to pembrolizumab.

Targeted chemotherapy and immune checkpoint inhibitors (ICPi) have expanded the spectrum of therapies for patients with relapsed/refractory (r/r) Hodgkin's disease and significantly improved the proportion of patients with long-term disease control. However, there is no standardized therapeutic option in case of further progression. Recently, we demonstrated that therapy with MEPED (metronomic chemotherapy, everolimus, pioglitazone, etoricoxib, dexamethasone) is highly effective in patients with r/r Hodgkin's disease. The benefit after pre-treatment with ICPi has not been studied, yet. Here, we report a patient with progressive Hodgkin's disease on Pembrolizumab for the first time who achieved sustained complete remission (CR) after initiation of MEPED therapy. A 57-year-old patient was pre-treated with brentuximab vedotin for relapsed advanced Hodgkin's disease and had received Pembrolizumab for progression from November 2020 to July 2022. Due to further progression, MEPED therapy was started in August 2022 and continued until May 2023. It consisted of a strictly oral daily (28-day cycle) application of low-dose treosulfan 250 mg, everolimus 15 mg, pioglitazone 45 mg, etoricoxib 60 mg, and dexamethasone 0.5 mg. Treatment response was evaluated by F-18 FDG-PET/CT (PET/CT). CR was defined by a negative Deauville score (DS) of 1-3. Already 3 months after starting MEPED, a CR (DS: 3) was confirmed by PET/CT in November 2022. The next follow-up in May 2023 continued to show CR (DS: 3). The therapy was very well tolerated. No hematological or other organ toxicity was observed. However, in May 2023 the patient presented with leg edema and weight gain, most likely due to pioglitazone and the PET/CT revealed suspected everolimus-induced pneumonitis, so MEPED was discontinued and diuretic therapy and treatment with prednisolone was started with gradual dose reduction. This resulted in a rapid complete resolution of the symptoms. The next PET-CT in July 2023 continued to show CR (DS: 3) without evidence of pneumonitis. Currently, therapy with MEPED has not been resumed. In conclusion, we demonstrate for the first time that MEPED therapy is highly effective in a patient with Hodgkin's disease who has been refractory to ICPi. Sustained CR was achieved over 11 months after initiation of MEPED therapy. Further studies on a larger patient cohort should be performed.

Designing Calcium Silicate Cements with On-Demand Properties for Precision Endodontics.

Calcium silicate (C3S) cements are available in kits that do not account for patients' specific needs or clinicians' preferences regarding setting time, radiopacity, mechanical, and handling properties. Moreover, slight variations in powder components and liquid content affect cement's properties and bioactivity. Unfortunately, it is virtually impossible to optimize several cement properties simultaneously via the traditional "one variable at a time" strategy, as inputs often induce trade-offs in properties (e.g., a higher water-to-powder ratio [W/P] increases flowability but decreases mechanical properties). Herein, we used Taguchi's methods and genetic algorithms (GAs) to simultaneously analyze the effect of multiple inputs (e.g., powder composition, radiopacifier concentration, and W/P) on setting time, pH, flowability, diametral tensile strength, and radiopacity, as well as prescribe recipes to produce cements with predicted properties. The properties of cements designed with GAs were experimentally tested, and the results matched the predictions. Finally, we show that the cements increased the genetic expression of odonto/osteogenic genes, alkaline phosphatase activity, and mineralization potential of dental pulp stem cells. Hence, GAs can produce cements with tailor-made properties and differentiation potential for personalized endodontic treatment.

Comparative therapeutic efficacy of oral administration of gluconeogenic precursors with nicotinamide and intravenous hypertonic dextrose solution for management of subclinical ketosis in Chilika buffaloes.

Ketosis in dairy animals originates from negative energy status, associated increased absorption, and production of ketone bodies exceeding their use by the ruminants as an energy source. The present therapeutic experiment was carried out in 29 herds of Chilika buffaloes in 16 villages of three adjoining districts of Chilika Lake, Puri, Khurda, and Ganjam. Twenty Chilika buffaloes, detected positive for subclinical ketosis, were randomly selected for the study and divided into 2 groups, groups II and III, and were treated with hypertonic dextrose solution intravenously or gluconeogenic precursors along with nicotinamide orally, along with other supportive drugs in both the groups. Ten lactating Chilika buffaloes with no signs of ketosis and detected negative on Rothera test were included in the study as healthy controls (group I). Blood and milk samples were collected from all the 30 recruited buffaloes on days 0 (pre-treatment), 7, 14, and 28 for haematological and biochemical analysis. The subclinical ketosis in Chilika buffaloes did not have overt clinical signs. However, close examination revealed gradual drop in milk yield (100%), inappetence (59%), debility (46%), and uncoordinated gait (10%) without excitatory nervous signs. On day 7 following treatment, blood glucose concentration increased significantly. The mean serum triglyceride concentration of group III, treated with gluconeogenic precursors with nicotinamide, continued to decline significantly on subsequent observations. The serum enzyme activity, indicating status of liver function, declined following treatment in both the therapeutic groups. The intravenous administration of hypertonic dextrose solution compared to use of oral gluconeogenic precursors along with nicotinamide efficiently restored recovery from the subclinical ketosis in Chilika buffaloes.

Significantly longer time to deterioration of quality of life due to CANKADO PRO-React eHealth support in HR+ HER2- metastatic breast cancer patients receiving palbociclib and endocrine therapy: primary outcome analysis of the multicenter randomized AGO-B WSG PreCycle trial.

BACKGROUND: The multicenter, randomized, phase IV, intergroup AGO-B WSG PreCycle trial (NCT03220178) evaluated the impact of CANKADO-based electronic patient-reported outcome (ePRO) assessment on quality of life (QoL) in hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer (MBC) patients receiving palbociclib and an aromatase inhibitor or palbociclib + fulvestrant. CANKADO PRO-React, a European Union-registered medical device, is an interactive autonomous application reacting to patient self-reported observations. PATIENTS AND METHODS: Between 2017 and 2021, 499 patients (median age 59 years) from 71 centers were randomized (2 : 1, stratified by therapy line) between an active version of CANKADO PRO-React (CANKADO-active arm) and a version with limited functionality (CANKADO-inform arm). A total of 412 patients (271 CANKADO-active; 141 CANKADO-inform) were available for analysis of the primary endpoint, time to deterioration (TTD) of QoL [10-point drop on the Functional Assessment of Cancer Therapy-General (FACT-G) score], using an Aalen-Johansen estimator for cumulative incidence function of TTD DQoL (QoL deterioration) with 95% pointwise confidence intervals (CIs). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and DQoL. RESULTS: In all patients [intention-to-treat (ITT)-ePRO], cumulative incidence of DQoL was significantly more favorable (lower) in the CANKADO-active arm (hazard ratio 0.698, 95% CI 0.506-0.963). Among first-line patients (n = 295), the corresponding hazard ratio was 0.716 (0.484-1.060; P = 0.09), and in second-line patients (n = 117) it was 0.661 (0.374-1.168; P = 0.2). Absolute patient numbers declined in later visits; FACT-G completion rates were 80% and higher until about visit 30. Mean FACT-G scores showed a steady decline from baseline and an offset in favor of CANKADO-active. No significant differences in clinical outcome were observed between arms: median PFS (ITT population) was 21.4 (95% CI 19.4-23.7) (CANKADO-active) and 18.7 (15.1-23.5) months (CANKADO-inform); median OS was not reached (CANKADO-active) and 42.6 months (CANKADO-inform). CONCLUSIONS: PreCycle is the first multicenter randomized eHealth trial demonstrating a significant benefit for MBC patients receiving oral tumor therapy when using an interactive autonomous patient empowerment application.

Mass: The Conundrum in Spine.

Introduction: Immunoglobulin (Ig)G4-related disease belongs to a rare compilation of conditions in rheumatology and may involve a multitude of organs. Amidst the central nervous system (CNS) presentation, involvement of spinal cord is rarer still. Case Report: Case 1: A 50-year-old male came with chief complaints of tingling sensation over both soles since 2 months associated with lower back ache and gait disturbance in the form of spastic gait. X-rays of spine were suggestive of a growth at the level of D10-D12 compressing the spinal cord with no focal sclerotic/lytic lesions, and MRI dorsolumbar spine showed dural tail sign. The patient underwent excision of dural mass, and histopathology revealed majority of plasma cells positive for IgG4. Case 2: A 65-year-old female came with complaints of cough, shortness of breath, and fever on and off since 2 months. No history of hemoptysis, purulent sputum, weight loss. On examination: There were bilateral rhonchi in the left upper zone. MRI spine showed focal erosion with soft-tissue thickening at the right paravertebral region extending from D5-9. The patient underwent surgery (fusion D6-8 and ostectomy D7 posterior rib resection D7 right side) with the right pleural biopsy and transpendicular intracorporal biopsy D7. Histopathology was compatible with findings of IgG4 disease. Conclusion: IgG4 tumors presenting in CNS itself is rare and rarer in spinal cord. Histopathological examination is central to diagnose and prognosticate the disease further as IgG4-related disease manifestations may recur without proper treatment.

Elucidation of the population structure and genetic diversity of Bipolaris oryzae associated with rice brown spot disease using SSR markers.

Brown spot disease, caused by Bipolaris oryzae, is one of the several disastrous diseases affecting rice. The brown spot fungus illustrates substantial pathogenic and genetic variability. To the best of our knowledge, extensive analysis utilizing specific SSR primers for B. oryzae genome is quite inadequate for the population structure and genetic diversity of Indian B. oryzae isolates. A total of 84 brown spot isolates were collected from rice-cultivating areas across southern and eastern Indian states, viz., Tamil Nadu, Andhra Pradesh, Odisha and Chhattisgarh. The pathogenicity and virulence characteristics of these isolates were assessed with the susceptible cultivar CR Dhan 201. Twelve genome-specific SSR markers of B. oryzae warranted the investigation of the population structure and genetic diversity among the isolates. These isolates were categorized based on their disease grade as highly virulent isolates (4 nos.), virulent isolates (8 nos.), moderately virulent isolates (47 nos.) and less virulent isolates (25 nos.). PCR amplification and DNA sequencing confirmed the isolates to be B. oryzae. PCR amplification and DNA sequencing confirmed the isolates to be B. oryzae. The SSR markers produced a total of 35 alleles with 1 to 4 alleles per locus with a gene diversity ranging between 0.00 and 0.687 and a major allele frequency variation of 0.425-0.975. The PIC value ranged from 0.00 to 0.638 having a mean value of 0.34. Cluster analysis technique was applied to group the brown spot isolates into four distinct clusters. Principal coordinate and structure analysis identified two genetic clusters of B. oryzae isolates for individual states with some degree of distinctness complying with their virulence. Analysis of molecular variance revealed more genetic variation within populations and less among populations. The study outcome would expedite the comprehension of genetic diversity of B. oryzae across the southern and eastern states of India. Furthermore, we anticipate its guidance in the development of more effective disease management strategies as well as in the generation of novel resistant varieties through marker-assisted breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03347-4.

Expert Opinion on P2Y12 Inhibitors Use in Management of Acute Coronary Syndromes: Focus on Ticagrelor.

Ticagrelor is a potent, oral P2Y12 inhibitor used as a part of dual antiplatelet therapy (DAPT) in acute coronary syndromes (ACS). New evidence has emerged for its use in ACS, which may be crucial for the Indian context. This brought together nearly 150 experts in ACS management across the country who reviewed the current evidence and discussed the same through a series of 10 meetings on an online platform. With all experts' agreement, the key expert opinions for the P2Y12 inhibitors use in ACS management were finalized. These include the following. In ACS patients aged <75 years, with diabetes, a history of stroke/transient ischemic attack, and chronic kidney disease, ticagrelor may be preferred over other P2Y12 inhibitors. It may also be preferred in the elderly above 75 years with clopidogrel is a suitable alternative in patients at high-risk of bleeding. Rates of stent thrombosis are lower with ticagrelor than clopidogrel. In patients managed with fibrinolysis, use ticagrelor after 48 hours if streptokinase was the fibrinolytic agent or it can be used after 12 to 24 hours if fibrin-specific fibrinolytic was used. Rates of major bleeding in patients treated with fibrinolysis are similar to clopidogrel. Prehospital administration may be preferred over in-hospital administration with expected bleeding rates similar to clopidogrel. Switching among P2Y12 inhibitors should be done with due consideration of their pharmacodynamics. At present, DAPT should be continued for 12 months with discontinuation after three to six months in patients with high bleeding risk. The use of low dose ticagrelor may be considered in cases with high-bleeding risk. DAPT or ticagrelor continuation beyond one year should be individualized considering ischemic and bleeding risks. Dyspnea is a common, mild, and transient and does not necessitate ticagrelor discontinuation. Severe dyspnea should be investigated thoroughly. In conclusion, ticagrelor (180 mg, 90 mg, and 60 mg doses), a potent antiplatelet is expected to reshape the antiplatelet use in the management of ACS.

A Non-Fourier Bioheat Transfer Model for Cryosurgery of Tumor Tissue with Minimum Collateral Damage.

BACKGROUND AND OBJECTIVES: Incorporation of non-Fourier heat conduction while studying heat transfer phenomena in biological materials has emerged has an important approach as it predicts better and more realistic results than Fourier based models. In this article we have proposed a non-Fourier computational model and applied the same to simulate cryosurgery of lung tumor and attempted minimization of freezing damage of healthy lung tissue using pulsed laser irradiation. METHODS: A non-Fourier bioheat transfer model for phase change in biological tissues is solved via a Fourier heat conduction based solution approach. A unified model is proposed combining all variants of bioheat models: Fourier's heat conduction based Pennes' bioheat model, hyperbolic heat conduction model and dual phase lag model. The proposed model takes into account the different thermophysical properties of frozen and unfrozen regions. In order to mimic the actual biotransport process, the blood perfusion and metabolic heat generation are switched off in the frozen region. Implicit source based enthalpy method is used to model phase change process. A new iterative enthalpy update equation is developed for capturing evolution of freezing front implicitly. Finite Volume based numerical discretization technique is used to discretize the governing PDE. The resulting discrete algebraic equation set is solved implicitly by Tri-diagonal Matrix Algorithm. The proposed model is verified with existing results from the literature. RESULTS: For Fourier heat conduction, freezing time of 99.99% of tumor is 1247s, which increases to 1267s for τq= 5s (τT= 0s) and again reduces to 1255s for τq= 5s and τT= 3s. τq and τT are phase lag parameters for non-Fourier heat conduction. For τq= 5s and τT= 0.05s, the freezing damage of healthy tissue decreases by 23.76% when pulsed laser irradiation (Io = 106 W/m2) is used to warm the neighboring healthy tissue. CONCLUSIONS: So non-Fourier bioheat transport models are better and more accurate in predicting temperature history, freezing time and freezing front propagation as compared to Fourier based models. Pulsed laser irradiation can prove to be a very efficient technique in minimizing collateral damage during cryosurgery.

Role of climate change variables (standing water and rainfall) on dissipation of chlorantraniliprole from a simulated rice ecosystem.

Chlorantraniliprole (CAP) is extensively used for rice pest management. Lack of information on the role of standing water and amount and timing of rainfall on CAP dissipation in rice ecosystem could hamper its prospective use. Present study was performed to investigate the effects of different water regimes (saturated, 5 and 10 cm standing water) and simulated rainfall (40 and 100 mm occurred at 4, 8 and 24 h after CAP application) on leaching, surface runoff and dissipation of CAP into components of rice ecosystem. The results showed highest concentration of CAP residues in soil and plant under saturated condition followed by 5 and 10 cm standing water conditions. Whereas, the highest concentration of CAP in leachates was detected under 10 cm standing water (12.19 ng mL-1). The results revealed large amount of leaching (21.99 ng mL-1) and surface runoff (42.25 ng mL-1) losses of CAP when 100 mm rainfall occurred at 4 h after pesticide application. The total quantity of CAP residues in soil and plant was highest when rainfall occurred at 24 h after pesticide application under both the rainfall amounts. Water stagnation and high intensity rainfall occurred shortly after pesticide application will contribute to pesticide loss to non-target sites through surface run-off and leaching. There will be less pesticide available in soil for plant uptake which may not be sufficient to kill the target organisms.

Indigenous biobed to limit point source pollution of imidacloprid in tropical countries.

Point pollution of pesticides originating from the washing of spraying machines could be controlled by biobed system and it is in use in temperate countries. The biobed system is yet to be established in tropical countries. An indigenous biobed system was prepared using local resources like rice straw, farm yard manures (FYM) and paddy field soil to suit the tropical climate. Lowermost 3 cm layer of the biobed system was filled with rice husk biochar to prevent leaching of pesticides from the system. This model system was tested with high doses of imidacloprid (178 mg/column), a commonly used pesticide against number of insect-pests in different crops, for its degradation. The bio-mix trapped a major part of the imidacloprid on the top most layer of the biobed column and only a very small part of imidacloprid recovered from the leachate. The biobed system could degrade 70.13% of applied imidacloprid within 15 days of the experiment and only 5.27% of the total pesticide recovered 90 days after incubation. Addition of biochar layer adsorbed imidacloprid from the outgoing leachate from the biobed column. Biomixture boosted microbial activity more particularly fungal population, which might be responsible for imidacloprid degradation. Microbial biomass carbon, and soil enzymes indicated faster dissipation of imidacloprid from the top layer of the biobed. This simple but efficient biobed system using local resources can fulfill the need of the small and marginal farmers of Asian countries for pesticide decontamination.

Similar biologics in India: A story of access or potential for compromise?

Biosimilars or similar biotherapeutic products are the biological products approved by regulatory agencies based on the demonstration of similarity in quality, safety and efficacy with reference biologics (or original biologics). Though biosimilars could be considered as interchangeable therapeutic alternatives over original biologics, there are concerns regarding their similarity in effectiveness and safety with reference product along with the level of evidence of similarity required for approval. The biosimilars, particularly, monoclonal antibodies that are developed based on the complex manufacturing processes, require stringent comparative evaluations. The Indian Regulatory Authorities in July 2012 developed the first guidelines for approval of similar biologics, which comprised requirements for the manufacturing process, quality evaluation, preclinical and clinical studies, as well as post-marketing studies. The 2016 guidelines, an update to previous guidelines, were released with the intent to provide a well-defined pathway at par with international regulations for the approval of similar biologics in India. This article highlights the key attributes of the 2016 Regulatory Guidelines and also describes the aspects such as interchangeability, nomenclature and labelling of similar biologics in India. Rigorous consideration is imperative for highly complex similar biologics of monoclonal antibodies on a case-to-case basis.

Performance of the AsperGenius® PCR assay for detecting azole resistant Aspergillus fumigatus in BAL fluids from allogeneic HSCT recipients: A prospective cohort study from Essen, West Germany.

In this study a commercially available multiplex real-time PCR (AsperGenius®) was evaluated for its efficacy in detecting Aspergillus fumigatus and azole resistance markers in comparison with conventional culture methods and galactomannan (GM) testing from BAL fluids in allogeneic HSCT recipients. Between January 2015 and May 2017 100 allogeneic HSCT recipients with pulmonary infiltrates and suspicion of invasive fungal infection were recruited to the study from a tertiary care center in Germany. BAL fluid was routinely assessed using the following diagnostic tests: AsperGenius® PCR assay, GM testing (cut-off: 1.0) and conventional culture. Susceptibility testing of azoles was performed by using Etest and, in case presenting elevated MICs, PCR for mutations in the cyp51A gene was carried out. Criteria of EORTC/MSG were used to classify the patients for invasive fungal disease. According to the EORTC/MSG criteria 23 patients presented with probable invasive aspergillosis (IA). Aspergillus PCR showed a sensitivity of 65% for probable IA cases. A combination of PCR and GM results in BAL displayed a sensitivity of 96% (22/23) and 100% specificity. Mutations in the cyp51A gene were detected by PCR in three cases (3/23; 13%) which were also found resistant with the culture method. In one case a Y121F/T289A mutation and in two cases a L98H were found. The combination of a commercial Aspergillus PCR assay and GM testing from BAL demonstrated a high sensitivity and specificity for diagnosing IA in allogeneic HSCT recipients. The Aspergillus PCR assay was not superior in detecting azole resistant A. fumigatus compared to culture.

Candidate screening of blast resistance donors for rice breeding.

Rice blast is one of the most serious diseases in the world. The use of resistant cultivars is the most preferred means to control this disease. Resistance often breaks down due to emergence of new races; hence identification of novel resistance donors is indispensable. In this study, a panel of 80 released varieties from National Rice Research Institute, Cuttack was genotyped with 36 molecular markers that were linked to 36 different blast resistance genes, to investigate the varietal genetic diversity and molecular marker-trait association with blast resistance. The polymorphism information content of 36 loci varied from 0.11 to 0.37 with an average of 0.34. The cluster analysis and population structure categorized the 80 National Rice Research Institute released varieties (NRVs) into three major genetic groups. The principal co-ordinate analysis displays the distribution of resistant and moderately resistant NRVs into different groups. Analysis of molecular variance result demonstrated maximum (97%) diversity within populations and minimum (3%) diversity between populations. Among tested markers, two markers (RM7364 and pi21_79-3) corresponding to the blast resistance genes (Pi56(t) and pi21) were significantly associated and explained a phenotypic variance of 4.9 to 5.1% with the blast resistance. These associated genes could be introgressed through marker-assisted to develop durable blast resistant rice varieties. The selected resistant NRVs could be good donors for the blast resistance in rice crop improvement research.

In-vitro activity of active ingredients of disinfectants against drug-resistant fungi.

The biocidal activities of peracetic acid and ethanol were tested against nine clinical fungal isolates and four reference strains. Ethanol was active (≥4.0 log10 reduction) against yeasts at a concentration of 50% v/v and against moulds at 80% v/v. Exposure times in both cases were 1 min. Peracetic acid was active as a 0.25% solution against yeasts and as a 0.5% solution against moulds; exposure times in both cases were 5 min. Compared with the reference strains, clinical isolates, including multi-drug-resistant strains, showed similar or higher sensitivity to the active ingredients of disinfectants in vitro.

Dissipation of chlorantraniliprole in contrasting soils and its effect on soil microbes and enzymes.

An experiment was set up to determine the rate of dissipation of chlorantraniliprole (CTP) from two soils with contrasting properties. The other objective of the study was to find out the effect of CTP on soil microorganisms (population, microbial biomass carbon and soil enzymes) under controlled environment. CTP residues when applied at recommended dose ((RD) (at 40 g a.i./ha)) could not be recovered either from alluvial soil or red soil at 60 days post application of CTP in a microcosm study. Higher clay content led to higher half-life in alluvial soil compared to red soil. CTP could not be recovered from RD treatment at 30 days after pesticide application under controlled environment. Faster dissipation of CTP was observed in rice rhizosphere soil with 23.89 and 34.65 days dissipation half-lives for RD and double the recommended dose (DRD) treatments, respectively. Different doses of chlorantraniliprole did not have considerable negative effect on actinomycetes, fungi, biological nitrogen fixers and phospahte solubilising bacteria except the bacteria population. Among the treatments, DRD recorded the lowest activity of dehyrodeganse, fluoresein diacetate hydrolase, acid and alkaline phosphatases followed by RD treatment. Microbial biomass carbon, ß -glycosidase and urease did not vary significantly among the different doses of CTP. In general, RD did not have negative effcts on soil microbes. Hence, CTP can be recommeded in rice pest managment maintaining existing soil microbes and soil enzymes activity.

Correction: Blast resistance in Indian rice landraces: Genetic dissection by gene specific markers.

[This corrects the article DOI: 10.1371/journal.pone.0211061.].

Blast resistance in Indian rice landraces: Genetic dissection by gene specific markers.

Understanding of genetic diversity is important to explore existing gene in any crop breeding program. Most of the diversity preserved in the landraces which are well-known reservoirs of important traits for biotic and abiotic stresses. In the present study, the genetic diversity at twenty-four most significant blast resistance gene loci using twenty-eight gene specific markers were investigated in landraces originated from nine diverse rice ecologies of India. Based on phenotypic evaluation, landraces were classified into three distinct groups: highly resistant (21), moderately resistant (70) and susceptible (70). The landraces harbour a range of five to nineteen genes representing blast resistance allele with the frequency varied from 4.96% to 100%. The cluster analysis grouped entire 161 landraces into two major groups. Population structure along with other parameters was also analyzed to understand the evolution of blast resistance gene in rice. The population structure analysis and principal coordinate analysis classified the landraces into two sub-populations. Analysis of molecular variance showed maximum (93%) diversity within the population and least (7%) between populations. Five markers viz; K3957, Pikh, Pi2-i, RM212and RM302 were strongly associated with blast disease with the phenotypic variance of 1.4% to 7.6%. These resistant landraces will serve as a valuable genetic resource for future genomic studies, host-pathogen interaction, identification of novel R genes and rice improvement strategies.

Detection of invasive pulmonary aspergillosis in critically ill patients by combined use of conventional culture, galactomannan, 1-3-beta-D-glucan and Aspergillus specific nested polymerase chain reaction in a prospective pilot study.

Invasive pulmonary aspergillosis (IPA) is an emerging and life-threatening infectious disease in patients admitted to the intensive care unit (ICU). Most diagnostic studies are conducted in hematological patients and results cannot readily be transferred to ICU patients lacking classical host factors. In a multicenter, prospective clinical trial including 44 ICU patients, hematological (n = 14) and non-hematological patients (n = 30), concurrent serum and bronchoalveolar lavage (BAL) samples were analyzed by conventional culture, galactomannan (GM), 1-3-beta-D-glucan (BDG) as well as an Aspergillus specific nested polymerase chain reaction (PCR). Nine patients (20%) had putative IPA according to AspICU classification. GM and PCR showed superior performance in BAL with sensitivity/specificity of 56%/94% and 44%/94% compared to 33%/97% and 11%/94% in serum. Despite better sensitivity of 89%, BDG showed poor specificity of only 31% (BAL) and 26% (serum). Combination of GM and PCR (BAL) with BDG (serum) resulted in 100% sensitivity, but also reduced specificity to 23%. Whereas mean GM levels were significantly higher in hematological patients BDG and PCR did not differ between hematological and non-hematological patients. Under present clinical conditions test combinations integrating both BAL and blood samples are advantageous. BDG might best serve as possible indicator for ruling out IPA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01695499. First posted: September 28, 2012, last update posted: May 8, 2017.

Airborne Aspergillus fumigatus spore concentration during demolition of a building on a hospital site, and patient risk determination for invasive aspergillosis including azole resistance.

BACKGROUND: Invasive aspergillosis (IA) in immunocompromised patients has been associated with demolition in or adjacent to hospitals. In recent years, azole-resistant clinical isolates of Aspergillus fumigatus, the most common agent of IA, have emerged in Western Europe and are spreading globally. AIM: To determine the potential risk of IA, including azole resistance, in patients caused by demolition of a hospital building. METHODS: Air sampling before, during and after demolition, screening for azole resistance, genotyping of non-susceptible isolates, and comparing those with strains from patients with azole-resistant IA during demolition. FINDINGS: Mean concentrations of A. fumigatus spores did not differ significantly between the three periods before [17.5 colony-forming units (cfu)/m³], during (20.8 cfu/m³) (P=0.26) and after (17.7 cfu/m³) demolition (P=0.33). No significant difference in IA cases documented by clinicians was found when comparing the timeframe of demolition with the previous year (44 vs 42 cases). Thirty of 200 A. fumigatus isolates (15%) showed azole resistance. Genotyping by microsatellite polymerase chain reaction of the azole-resistant environmental and clinical isolates showed a polyclonal distribution. CONCLUSIONS: The results suggest that with implemented preventive measures, there is no increased risk for IA, including azole resistance, in immunocompromised patients during outdoor demolition work. Further prospective studies are needed to confirm these findings.