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Chest pain/discomfort (CP) is a common symptom and can be a diagnostic dilemma for many clinicians. The misdiagnosis of an acute or progressive chronic cardiac etiology may carry a significant risk of morbidity and mortality. This review summarizes the different options and modalities for establishing the diagnosis and severity of coronary artery disease. An effective test selection algorithm should be individually tailored to each patient to maximize diagnostic accuracy in a timely fashion, determine short- and long-term prognosis, and permit implementation of evidence-based treatments in a cost-effective manner. Through collaboration, a decision algorithm was developed (www.chowmd.ca/cadtesting) that could be adopted widely into clinical practice., (© 2023 The Authors.)

Competing Interests: Dr Hsiao serves in a volunteer capacity on the Medical Registry Advisory Board of the International Fibrodysplasia Ossificans Progressiva Association and on the Fibrous Dysplasia Foundation Medical Advisory Board, is a member of the International Clinical Council on FOP, and receives clinical trials support from Clementia Pharmaceuticals, an Ipsen Company; and Ultragenyx, Inc. Dr Haemel is a consultant to Guidepoint LLC and to CSL Behring. Author Kazmi and Drs Zhang, Gross, Grouse, Link, Tetzlaff, and Theodosopoulos have no conflicts of interest to declare.

Herein, we present a patient with a lipidized fibrous histiocytoma, an underrecognized variant of dermatofibroma (cutaneous fibrous histiocytoma). Our patient presented with a nodule on the ankle that showed foamy histiocytes and hyalinized collagen bundles on histology. This case highlights a classic presentation and features of lipidized fibrous histiocytoma, raising further awareness of this distinctive variant of dermatofibroma that should be distinguished from xanthoma and xanthogranuloma.

Background: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in the pediatric population and can represent a medical emergency. However, many features of JDM remain poorly understood, disease presentation is highly variable, and predictors of disease course have yet to be identified., Methods: This retrospective chart review included 47 JDM patients seen at a tertiary care center over a 20-year period. Characteristics such as demographics, clinical signs and symptoms, antibody positivity, dermatopathology features, and treatments were recorded., Results: All patients had evidence of cutaneous involvement, whereas 88.4% experienced muscle weakness. Constitutional symptoms and dysphagia were commonly present. The most frequent cutaneous findings were Gottron papules, heliotrope rash, and nailfold changes. Anti-TIF1? was the most prevalent myositis-specific autoantibody. Management involved systemic corticosteroids in nearly all cases. Strikingly, the dermatology department was only involved in the care of four in every ten (19/47) patients., Conclusions: Prompt recognition of the strikingly reproducible skin findings present in JDM can improve disease outcomes in this population. This study highlights the need for increased education of such pathognomonic findings as well as more multidisciplinary care. In particular, a dermatologist should be involved in the care of patients presenting with muscle weakness and skin changes.

Abstract: Tattoo reactions have become more common as tattoos gain visibility and popularity worldwide. A variety of inflammatory patterns have been described in association with tattoos- more commonly fibrosing, granulomatous, lichenoid, pseudolymphomatous, and spongiotic patterns. To date, there has been one case report of a Wells syndrome-like inflammatory pattern associated with a temporary Henna tattoo. Here we present the first case of a permanent tattoo with resulting flame figures, histologically resembling Wells syndrome. We believe this uncommon histologic pattern might be of interest for pathologists to be aware of., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The synthesis and bioactivity of neurotrophic banglenes and derivatives is described, establishing a structure-activity relationship which enables future mechanistic studies. Neuritogenesis assays indicate that (-) trans -banglene is the active enantiomer. Assays performed with and without NGF protein suggest that neurotrophic activity and potentiation of NGF activity by (-) trans -banglene might be distinct unassociated processes. Interestingly, (-) trans -banglene potentiation of NGF-induced neuritogenesis is unaffected by the presence of Erk1/2, Akt and Pkc inhibitors.

Organ transplants have been a life-saving form of treatment for many patients who are facing end stage organ failure due to conditions such as diabetes, hypertension, various congenital diseases, idiopathic diseases, traumas, and other end-organ failure. While organ transplants have been monumental in treatment for these conditions, the ten year survival and long-term outcome for these patients is poor. After receiving the transplant, patients receive a multi-drug regimen of immunosuppressants. These drugs include cyclosporine, mTOR inhibitors, corticosteroids, and antibodies. Polyclonal antibodies, which inhibit the recipient's B lymphocytes, and antibodies targeting host cytokine inhibitors which prevent activation of B cells by T cells. Use of these drugs suppresses the immune system and increases the risk of opportunistic pathogen infections, tumors, and further damage to the transplanted organs and vasculature. Many regulatory mechanisms are present in organs to prevent the development of autoimmune disease, and Tregs are central to these mechanisms. Tregs secrete suppressive cytokines such as IL-10, TGF-B, and IL-35 to suppress T cells. Additionally, Tregs can bind to target cells to induce cell cycle arrest and apoptosis and can inhibit induction of IL-2 mRNA in target T cells. Tregs also interact with CTLA-4 and CD80/CD86 on antigen presenting cells (APCs) to prevent their binding to CD28 present on T cells. Due to their various immunosuppressive capabilities, Tregs are being examined as a possible treatment for patients that receive organ transplants to minimize rejection and prevent the negative outcomes. Several studies in which participants were given Tregs after undergoing organ transplantations were reviewed to determine the efficacy and safety of using Tregs in solid organ transplantation to prevent adverse outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Juneja, Kazmi, Mellace and Saidi.)

Background Non-alcoholic fatty liver disease (NAFLD) is prevalent in almost 25% of the Western population and is predicted to become one of the leading causes of end-stage liver disease. There is increasing evidence that NAFLD is a risk factor for cardiovascular disease, specifically for coronary artery disease, via disruption of the metabolism of glucose and lipids in the body, leading to a state of systemic inflammation that promotes atherosclerosis. This study aims to explore outcomes in patients who underwent percutaneous coronary intervention (PCI) with or without placement of drug-eluting stents (DES) to determine whether the concurrent diagnosis of NAFLD led to worse in-hospital outcomes. Methods We used the National Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality 2016 to conduct a cross-sectional study that included all adult patients who underwent PCI with or without placement of DES during hospital admission. Patients with NAFLD were identified and compared to patients without NAFLD. Patients were selected by using ICD-10-CM and ICD-10-PCS codes. Outcomes included mortality, length of stay and total hospital charges, and major adverse cardiac events (MACE). Data on patient demographics, inpatient statistics, and comorbidities were obtained and analyzed using cross-tabulation, Pearson χ 2 test, and independent samples t -test. Data were adjusted for confounders using logistic and linear regression. Results Among 429,855 patients who underwent PCI with or without placement of DES, 2,560 patients (0.6%) had a diagnosis of NAFLD. There was no significant difference with regard to mortality and MACE. The NAFLD group had a higher proportion of females, a longer average length of hospital stay, and patients presented at a younger average age. Regarding comorbidities, more patients in the NAFLD group had diabetes mellitus type II, obesity, obstructive sleep apnea (OSA), chronic kidney disease (CKD), and peripheral vascular disease (PVD). Conclusion NAFLD is emerging as a risk factor for cardiovascular disease. Increasing evidence suggests that the disease contributes to systemic atherosclerosis and thus coronary artery disease. We found that among patients who underwent PCI in 2016, those with NAFLD had a longer length of stay, were admitted at a younger age, and had significantly more cardiovascular comorbidities than those without NAFLD. Increasing evidence has shown that advanced liver disease due to NAFLD will continue to place a significant burden on the healthcare system and is, therefore, an area that the medical community should continue to focus on, especially, regarding preventative and therapeutic efforts., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ali et al.)

It is now widely recognized that COVID-19 illness can be associated with significant intermediate and potentially longer-term physical limitations. The term, "long COVID-19" is used to define any patient with persistent symptoms after acute COVID-19 infection (ie, after 4 weeks). It is postulated that cardiac injury might be linked to symptoms that persist after resolution of acute infection, as part of this syndrome. The Canadian Cardiovascular Society Rapid Response Team has generated this document to provide guidance to health care providers on the optimal management of patients with suspected cardiac complications of long COVID-19., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: This project aimed to implement a rigorous evaluation of influenza vaccine education as a learning tool for influenza and medical knowledge and clinical proficiency., Methods: Among 280 Stony Brook University first-year medical students, 80 were randomly selected to participate in the Stony Brook influenza vaccine education program. Participants completed an anonymous pre-survey assessing participants': (1) experience and attitudes towards flu vaccines, (2) knowledge base of the flu virus and vaccine, (3) self-rated knowledge of the flu virus and vaccine, and (4) self-rated proficiency of clinical skills relevant to administering flu vaccines. Students then completed an educational module and vaccinated either employee healthcare workers or patients at a student-run free health clinic. Following the vaccination experience, participants completed a post-survey including questions identical to those on the pre-survey and questions regarding their evaluation of the flu vaccine education program. The pre- and post-survey data were paired, established through matching surrogate study identification codes, and differences between survey responses were analyzed using paired t-tests., Results: Eighty first-year medical students participated in the pre-survey, while 55 participated in the post-survey. Compared to the pre-survey, participants significantly improved their knowledge base related to the flu virus and vaccine as well as their self-rated knowledge and clinical skills, in the post-survey., Conclusions: The Stony Brook influenza vaccination program succeeded in establishing medical student training and practice with service learning. Our study is the first to provide quantitative evidence of influenza vaccine education programs improving medical student knowledge and clinical skills., Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-021-01355-2., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© International Association of Medical Science Educators 2021.)

Boron-containing heterocycles are important in a variety of applications from drug discovery to materials science; therefore a clear understanding of their structure and reactivity is desirable to optimize these functions. Although the boranol (B-OH) unit of boronic acids behaves as a Lewis acid to form a tetravalent trihydroxyborate conjugate base, it has been proposed that pseudoaromatic hemiboronic acids may possess sufficient aromatic character to act as Brønsted acids and form a boron oxy conjugate base, thereby avoiding the disruption of ring aromaticity that would occur with a tetravalent boronate anion. Until now no firm evidence existed to ascertain the structure of the conjugate base and the aromatic character of the boron-containing ring of hemiboronic "naphthoid" isosteres. Here, these questions are addressed with a combination of experimental, spectroscopic, X-ray crystallographic, and computational studies of a series of model benzoxazaborine and benzodiazaborine naphthoids. Although these hemiboronic heterocycles are unambiguously shown to behave as Lewis acids in aqueous solutions, boraza derivatives possess partial aromaticity provided their nitrogen lone electron pair is sufficiently available to participate in extended delocalization. As demonstrated by dynamic exchange and crossover experiments, these heterocycles are stable in neutral aqueous medium, and their measured p K a values are consistent with the ability of the endocyclic heteroatom substituent to stabilize a partial negative charge in the conjugate base. Altogether, this study corrects previous inaccuracies and provides conclusions regarding the properties of these compounds that are important toward the methodical application of hemiboronic and other boron heterocycles in catalysis, bioconjugation, and medicinal chemistry.

Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an "endemic" phase and therefore an ongoing risk within a "new normality". These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.

Purpose: Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive function is a major issue and its effects in young males are largely neglected by novel research. To improve clinician awareness, we systematically reviewed side effects of chemotherapy for Hodgkin lymphoma (HL) in young males., Methods: The review was prospectively registered (PROSPERO N. CRD42019122868). Three databases (Medline via PUBMED, SCOPUS, and Cochrane Library) were searched for studies featuring males aged 13-51-years who underwent chemotherapy for HL using ABVD (Adriamycin® (doxorubicin), bleomycin, vinblastine, and dacarbazine) or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) regimens. These chemotherapy regimens were compared against each other using sperm characteristics, FSH, and inhibin B levels to measure fertility levels., Results: Data were extracted from five studies featuring 1344 patients. 6 months post-ABVD saw marked deterioration in sperm count, further reduced by more cycles (P = 0.05). Patients treated with BEACOPP rather than ABVD were more prone to oligospermia. Receiving fewer cycles of both regimens increased the likelihood of sperm production recovering. Patients treated with 6-8 cycles of BEACOPP did not recover spermiogenesis., Conclusions: ABVD and BEACOPP regimens significantly reduce fertility function to varying effects depending on treatment duration. ABVD temporarily causes significant reductions in male fertility, whereas BEACOPP's effects are more permanent. Therefore, clinicians should discuss fertility preservation with male patients receiving infertility-inducing gonadotoxic therapy. Further high-quality studies are required to more adequality describe the risk to fertility by chemotherapy.

Hospitals and ambulatory facilities significantly reduced cardiac care delivery in response to the first wave of the COVID-19 pandemic. The deferral of elective cardiovascular procedures led to a marked reduction in health care delivery with a significant impact on optimal cardiovascular care. International and Canadian data have reported dramatically increased wait times for diagnostic tests and cardiovascular procedures, as well as associated increased cardiovascular morbidity and mortality. In the wake of the demonstrated ability to rapidly create critical care and hospital ward capacity, we advocate a different approach during the second and possible subsequent COVID-19 pandemic waves. We suggest an approach, informed by local data and experience, that balances the need for an expected rise in demand for health care resources to ensure appropriate COVID-19 surge capacity with continued delivery of essential cardiovascular care. Incorporating cardiovascular care leaders into pandemic planning and operations will help health care systems minimise cardiac care delivery disruptions while maintaining critical care and hospital ward surge capacity and continuing measures to reduce transmission risk in health care settings. Specific recommendations targeting the main pillars of cardiovascular care are presented: ambulatory, inpatient, procedural, diagnostic, surgical, and rehabilitation., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Keratoconus is a progressive, noninflammatory, bilateral ectatic corneal disease, characterized by paraxial stromal thinning and weakening that leads to corneal surface distortion. The objective of this research was to determine the effectiveness and safety of collagen crosslinking in progressive keratoconus, with keratometry (Kmax) value of 50 diopters or above. It was a retrospective study, conducted at Bodla Eye Care (BEC) and Multan Medical and Dental College, Multan (MMDC) from May 2018 to November 2019., Methods: In this research 52 eyes were studied. The best-corrected visual acuity, uncorrected visual acuity, maximum keratometry, mean keratometry value, and thinnest corneal thickness before surgery and 12 months after Cross-linking were observed. A Galeili G6 by Zeimer ophthalmic system was used to measure the clinical parameters. Dresden protocol was followed in this study. A written ethical approval was obtained and research was conducted under the light of declaration of Helsinki., Results: The average logarithm of the minimum angle of resolution (logMAR) of the uncorrected visual acuity decreased from 0.66±0.41 D to 0.49±0.40 D (p=0.012), while the mean thinnest point thickness of the cornea decreased from 435.31 37.91 μm to 419.41±70.12 μm (p=0.004) after 12 months. The decreases in the mean logMAR of the BCVA, Kmax and Kmean values were not analytically important (p>0.05) at the 12-month follow-up 94.2% positive results were obtained., Conclusion: Collagen cross-linking treatment was safe and maintained both the visual acuity and tomographic parameters at the one-year follow-up in eyes.

The Micra™ Transcatheter Pacing System (Medtronic, Minneapolis, MN, USA) is a fairly novel leadless intracardiac pacemaker implanted in the right ventricle via a femoral-vein transcatheter approach. Due to the less-invasive nature of the implantation procedure and its smaller size, patients receiving the Micra™ device tend to experience fewer complications, hospitalizations, and revisions when compared with those with transvenous pacemakers. Certain arrhythmias and conduction abnormalities, such as high-degree atrioventricular blocks, require urgent and timely pacemaker insertion-a necessity that has persisted even during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present a case series of 10 patients with various conduction disease abnormalities who required right ventricle pacemaker implantation during the months of March to May 2020, which was the initial peak of the COVID-19 pandemic in New Jersey, including the enhanced precautions taken to avoid viral spread., Competing Interests: The authors report no conflicts of interest for the published content., (Copyright: © 2021 Innovations in Cardiac Rhythm Management.)

Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly used to treat people with multiple sclerosis (MS). Supported by an evolving evidence base, AHSCT can suppress active inflammation in the central nervous system and induce long-term changes in immune cell populations, thereby stabilizing, and, in some cases, reversing disability in carefully selected MS patients. However, AHSCT is an intensive chemotherapy-based procedure associated with intrinsic risks, including profound cytopenia, infection, and organ toxicity, accompanied by an on-going degree of immuno-compromise and general deconditioning, which can be associated with a transient increase in functional impairment in the early stages after transplantation. Although international guidelines and recommendations have been published for clinical and technical aspects of AHSCT in MS, there has been no detailed appraisal of the rehabilitation needed following treatment nor any specific guidelines as to how this is best delivered by hospital and community-based therapists and wider multidisciplinary teams in order to maximize functional recovery and quality of life. These expert consensus guidelines aim to address this unmet need by summarizing the evidence-base for AHSCT in MS and providing recommendations for current rehabilitation practice along with identifying areas for future research and development., Competing Interests: FR and HH work for Hobbs Rehabilitation, JS declares honoraria for speaking at educational meetings from Sanofi, Jazz, Janssen, Gilead, and Mallinckrodt, BV declares honoraria for speaking at educational meetings and consultancy from Janssen, Takeda, and Amgen. PM reports travel support and speaker honoraria from unrestricted educational activities organized by Novartis, Bayer HealthCare, Bayer Pharma, Biogen Idec, Merck-Serono, and Sanofi Aventis. He also discloses consulting to Magenta Therapeutics and Jasper Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer EP declared a shared affiliation, with no collaboration, with two of the authors RS and CB to the handling Editor. The Handling Editor declared a past co-authorship with one of the authors GM., (Copyright © 2020 Roberts, Hobbs, Jessop, Bozzolini, Burman, Greco, Ismail, Kazmi, Kirgizov, Mancardi, Mawson, Muraro, Puyade, Saccardi, Withers, Verhoeven, Sharrack and Snowden.)

Seasonal influenza continues to impose a substantial healthcare and economic burden in the United States each year. This study assessed influenza vaccination rates among the uninsured population, determined the need for free flu vaccines, and analyzed associations of vaccination status with access, beliefs, and sociodemographic factors. Stony Brook Outreach and Medical Education (SB HOME) free clinic offers free flu vaccinations to uninsured patients over the age of 18 living in Suffolk County, New York. All patients visiting SB HOME between October 2018 and February 2019 were offered a 10-min anonymous survey assessing demographic characteristics, self-evaluation of health status, vaccination status during the 2017-2018 and 2018-2019 flu seasons, willingness to obtain a free flu vaccine, and beliefs and barriers surrounding flu vaccines. Analysis consisted of descriptive statistics, paired t tests, and χ 2 tests using a significance threshold of p < 0.05. A total of 102 participants were surveyed, 80% of whom identified as Hispanic/Latino. The majority of participants expressed positive attitudes towards the influenza vaccine. Despite these positive attitudes, 72% reported not receiving the influenza vaccination during the 2017-2018 flu season, the commonly cited reasons being fear of getting sick from the flu vaccine, high cost, and not knowing where to get the vaccine. During the 2018-2019 flu season 60% of participants elected to receive a free flu shot at SB HOME, and participants with positive attitudes towards flu vaccines were more likely to accept the vaccine when offered at no cost. Fear of getting sick from the flu vaccine remained the most common reason for participants declining a free flu vaccine. Only 17% of participants would seek vaccination at the market price of $30, compared to the 76% who would if the vaccine was offered for free. Our study highlights the need for convenient and affordable access to the flu vaccine among uninsured populations, who despite recognizing the benefits of receiving the flu vaccine are unable to overcome certain barriers. Elucidating and targeting barriers specific to uninsured populations at the local community level may improve public health strategies centered on increasing vaccination rates.

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials.

The inhibition of urease enzyme is very important as it plays a key role in the treatment of several urinary and gastrointestinal tract infections. This enzyme provides a suitable environment for Helicobacter pylori at the low pH of the stomach, a causative agent of gastric and peptic ulcer that may lead to cancer. In agriculture, the high urease content causes environmental and economic problems. In this pursuit, given the well-established importance of integrated pharmacophores in medicinal chemistry and to explore new inhibitors of urease featuring two distinct heterocyclic functionalities, we herein report a facile synthesis of carbazole-triazine hybrids (3a-j). These new propeller-shaped chemical scaffolds were evaluated for their urease inhibitory potential in order to identify suitable leads. The initial structure-activity survey work guided through in vitro bioactivity results recognized 3e and 3f as new starting point hits incorporating bulky iodo (3e) and strong electron-withdrawing nitro (3f) groups at the para-position of aryl amine component. The potent compounds (3e &3f) exhibited the highest activity with IC 50 values of 5.6 and 6.7 µM, respectively. In the molecular docking analysis, these compounds depicted excellent binding interactions with the active site residues. The key interactions observed include hydrogen bonding, π-π interactions, π-cation and nickel atom coordination to the triazine nitrogen of both inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although a diverse range of chemical entities offering striking therapeutic potential against urease enzyme has been reported, the key challenges (toxicity and safety) associated with these inhibitors create a large unmet medical need to unveil new, potent and safe inhibitors of urease enzyme. In this pursuit, the present study demonstrates the successful synthesis of carbazole-chalcone hybrids (4a-n) in good yields. The evaluation of the preliminary in vitro biological results showed that selected members of the investigated library of hybrid compounds possess excellent urease inhibitory efficacy. In particular, compounds 4c and 4k were the most potent inhibitors with lowest IC 50 values of 8.93 ± 0.21 and 6.88 ± 0.42 μM, respectively. Molecular docking analysis of the most potent inhibitor 4k suggests that the compound is fitted neatly at the active site interface and mediates interaction with both nickel atoms present in the active site. Several other obvious interactions including metal-carbonyl contact, hydrogen bonding and hydrophobic interactions were also observed, playing a crucial part in the stabilization of 4k in the active site of urease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Carbon dioxide storage in petroleum and other geological reservoirs is an economical option for long-term separation of this gas from the atmosphere. Other options include applications through conversion to valuable chemicals. Microalgae and plants perform direct fixation of carbon dioxide to biomass, which is then used as raw material for further microbial transformation (MT). The approach by microbial transformation can achieve reduction of carbon dioxide and production of biofuels. This review addresses the research and technological processes related to direct MT of carbon dioxide, factors affecting their efficiency in operation and the review of economic feasibility. Additionally, some commercial plants making utilization of CO 2 around the globe are also summarized along with different value-added chemicals (methane, acetate, fatty acids and alcohols) as reported in literature. Further information is also provided for a better understanding of direct CO 2 MT and its future prospects leading to a sustainable and clean environment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Over the last 20 years, haematopoietic stem cell transplantation (HSCT) has been used to treat patients with severe autoimmune and inflammatory diseases whose response to standard treatment options has been limited, resulting in a poor long-term prognosis in terms of survival or disability. The vast majority of patients have received autologous HSCT where an increasing evidence-base supports its use in a wide range of autoimmune diseases, particularly relapsing remitting MS, systemic sclerosis and Crohn's disease. Compared with standard treatments for autoimmune diseases, HSCT is associated with greater short-term risks, including a risk of treatment-related mortality and long-term complications. There is a need for a careful appraisal of potential benefits and risks by disease and transplant specialists working closely together with patients and carers to determine individual suitability for HSCT. HSCT should be conducted in accredited transplant centres with robust arrangements for long-term follow-up with both disease and transplant specialists. The aim of this open-access position statement is to provide plainly worded guidance for patients and non-specialist clinicians considering HSCT for an autoimmune disease, especially when treatment abroad is being considered. Recent technical publications in the field have been referenced to support the statement and provide more detail for clinicians advising patients.

Background: Consensus guidelines are not available for the use of immunoglobulin replacement therapy (IGRT) in patients developing iatrogenic secondary antibody deficiency following B-cell targeted therapy (BCTT) in autoimmune rheumatic disease., Objectives: To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD)., Methods: Using an agreed search string we performed a systematic literature search on Medline with Pubmed as vendor. We limited the search to English language papers with abstracts published over the last 10 years. Abstracts were screened for original data regarding hypogammaglobulinemia following BCTT and the use of IGRT for hypogammaglobulinemia following BCTT. We also searched current recommendations from national/international organisations including British Society for Rheumatology, UK Department of Health, American College of Rheumatology, and American Academy of Asthma, Allergy and Immunology., Results: 222 abstracts were identified. Eight papers had original relevant data that met our search criteria. These studies were largely retrospective cohort studies with small patient numbers receiving IGRT. The literature highlights the induction of a sustained antibody deficiency, risk factors for hypogammaglobulinemia after BCTT including low baseline serum IgG levels, how to monitor patients for the development of hypogammaglobulinemia and the limited evidence available on intervention thresholds for commencing IGRT., Conclusion: The benefit of BCTT needs to be balanced against the risk of inducing a sustained secondary antibody deficiency. Consensus guidelines would be useful to enable appropriate assessment prior to and following BCTT in preventing and diagnosing hypogammaglobulinemia. Definitions for symptomatic hypogammaglobulinemia, intervention thresholds and treatment targets for IGRT, and its cost-effectiveness are required., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Background: Whole body magnetic resonance imaging (WBMRI) is currently recommended by guidelines for the assessment of myeloma. This will inevitably result in incidental findings. We aimed to assess the frequency of extraskeletal incidental findings and the added value of contrast-enhanced (CE) T1-weighted (T1-W) and diffusion-weighted (DWI) sequences for their characterization in a single WBMRI examination., Patients and Methods: We performed 1.5 T WBMRI in 100 patients (53 female; median age, 65 years) with plasma-cell disorders from January 2014 to July 2017. T2-weighted sequences were reviewed initially for incidental findings, followed by sequential review of T1-W, CE T1-W, and DWI sequences for lesion characterization. Descriptive statistics were undertaken., Results: A total of 348 incidental findings were detected in 97 (97%) of 100 patients; only 38 (10.9%) of 348 findings were indeterminate. T1-W sequences increased diagnostic confidence in the characterization of 12 (31.6%) of 38; CE T1-W sequences in the characterization of 16 (50%) of 32; and DWI increased diagnostic confidence in 21 (55.3%) of 38 compared to the T2-weighted sequence alone., Conclusion: Incidental findings are common, but the majority are of no clinical consequence. No additional cancers were noted in our series. DWI and CE T1-W sequences increased diagnostic confidence in 50% of indeterminate findings and may reduce the need for further investigation., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective:: Cross-sectional imaging is now recommended by the National Institute for Health and Care Excellence (NICE) for patients with suspected and newly diagnosed myeloma instead of skeletal survey. The objectives of this study were: (1) To evaluate compliance of current UK imaging practice with reference to National Institute for Health and Care Excellence best-practice clinical guidelines for plasma cell malignancies. (2) To identify factors which may influence diagnostic imaging choices., Methods:: We conducted a national online survey to assess compliance with guidelines and to identify challenges to implementation (endorsed by Myeloma UK, UK Myeloma Forum and the British Society of Skeletal Radiologists)., Results:: Responses were received from 31 district general and 28 teaching hospitals. For suspected and confirmed myeloma, skeletal survey remained the most frequent first-line imaging test (suspected myeloma 44.3%, confirmed myeloma 37.7%). Only 9.8 % of responders offered first-line whole body MRI., Conclusion:: Significant challenges remain to standardisation of imaging practice in accordance with national best-practice guidelines., Advances in Knowledge:: This is the first publication to date evaluating current UK imaging practice for assessing myeloma since the publication of new guidelines recommending use of advanced cross-sectional imaging techniques. Skeletal survey remains the most commonly performed first-line imaging test in patients with suspected or confirmed myeloma and this is largely due to resource limitations within radiology departments.

Background and Aims: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for patients with severe, treatment-refractory Crohn's disease [CD]. The evidence base for AHSCT for CD is limited, with one randomised trial [ASTIC] suggesting benefit. The aim of this study was to evaluate safety and efficacy for patients undergoing AHSCT for CD in Europe, outside the ASTIC trial., Methods: We identified 99 patients in the European Society for Blood and Marrow Transplantation [EBMT] registry, who were eligible for inclusion. Transplant and clinical outcomes were obtained for 82 patients from 19 centres in seven countries., Results: Median patient age was 30 years [range 20-65]. Patients had failed or been intolerant to a median of six lines of drug therapy; 61/82 [74%] had had surgery. Following AHSCT, 53/78 [68%] experienced complete remission or significant improvement in symptoms at a median follow-up of 41 months [range 6-174]; 22/82 [27%] required no medical therapy at any point post-AHSCT. In patients who had re-started medical therapy at latest follow-up, 57% [24/42] achieved remission or significant symptomatic improvement with therapies to which they had previously lost response or been non-responsive. Treatment-free survival at 1 year was 54%. On multivariate analysis, perianal disease was associated with adverse treatment-free survival (hazard ratio 2.34, 95% confidence interval [CI] 1.14-4.83, p = 0.02). One patient died due to infectious complications [cytomegalovirus disease] at Day +56., Conclusions: In this multicentre retrospective analysis of European centres, AHSCT was relatively safe and appeared to be effective in controlling otherwise treatment-resistant Crohn's disease. Further prospective randomised controlled trials against standard of care are warranted., (© The Author(s) 2018. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Autologous haematopoietic stem cell transplantation (aHSCT) is commonly used for the treatment of haematological cancers, but is increasingly used in the treatment of patients severely affected by autoimmune diseases (ADs). In fact, ADs have become the fastest growing indication for aHSCT. A wide range of diseases have been treated, but the field has focused on three areas: multiple sclerosis, diffuse cutaneous systemic sclerosis and Crohn's disease, where there are populations of patients for whom disease control remains unsatisfactory despite the advent of biological and targeted small molecule therapies. Scientific studies of immune reconstitution have provided support for a 'rebooting' of the immune system through a re-diversification of naive and regulatory immune effector cells. In addition, there may be health economic benefits from a single one-off procedure. Even so, the treatment with aHSCT is intensive with a range of toxicities and risks which, despite being routine to transplant haematologists, are less familiar to disease specialists. Close collaboration between transplant haematologists and relevant disease specialists in patient selection, clinical management and follow-up is mandatory. Ideally, patients should be treated on a clinical trial if available., (© Royal College of Physicians 2018. All rights reserved.)

Diabetes mellitus (DM), a chronic multifarious metabolic disorder resulting from impaired glucose homeostasis has become one of the most challenging diseases with severe life threat to public health. The inhibition of α-glucosidase, a key carbohydrate hydrolyzing enzyme, could serve as one of the effective methodology in both preventing and treating diabetes through controlling the postprandial glucose levels and suppressing postprandial hyperglycemia. In this context, three series of diamine-bridged bis-coumarinyl oxadiazole conjugates were designed and synthesized by one-pot multi-component methodology. The synthesized conjugates (4a-j, 5a-j, 6a-j) were evaluated as potential inhibitors of glucosidases. Compound 6f containing 4,4'-oxydianiline linker was identified as the lead and selective inhibitor of α-glucosidase enzyme with an IC 50 value of 0.07 ± 0.001 μM (acarbose: IC 50  = 38.2 ± 0.12 μM). This inhibition efficacy was ∼545-fold higher compared to the standard drug. Compound 6f was also emerged as the lead molecule against intestinal maltase-glucoamylase with good inhibition strength (IC 50  = 0.04 ± 0.02 μM) compared to acarbose (IC 50  = 0.06 ± 0.01 μM). Against β-glucosidase enzyme, compound 6 g was noted as the lead inhibitor with IC 50 value of 0.08 ± 0.002 μM. Michaelis-Menten kinetic experiments were performed to explore the mechanism of inhibition. Molecular docking studies of the synthesized library of hybrid structures against glucosidase enzyme were performed to describe ligand-protein interactions at molecular level that provided an insight into the biological properties of the analyzed compounds. The results suggested that the inhibitors could be stabilized in the active site through the formation of multiple interactions with catalytic residues in a cooperative fashion. In addition, strong binding interactions of the compounds with the amino acid residues were effective for the successful identification of α-glucosidase inhibitors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Despite the major recent progress in the treatment of Crohn's disease [CD], there is a subset of patients in whom the disease runs an aggressive course with progressive tissue damage requiring early and repeated surgical management. Increasing evidence supports sustained and profound improvement in gastrointestinal parameters and quality of life following high-dose immunosuppressive therapy and autologous haematopoietic stem cell transplantation [AHSCT] compared to standard therapy in this context. In addition, international transplant registry data reflect the use of AHSCT in CD outside of trials in selected patients. However, AHSCT may be associated with significant treatment-related complications with risk of transplant-related mortality. In a joint initiative, the European Crohn's and Colitis Organisation [ECCO] and the European Society for Blood and Marrow Transplantation [EBMT] have produced a state-of-the-art review of the rationale, evaluation, patient selection, stem cell mobilization and transplant procedures and long-term follow up. Given the unique spectrum of issues, we recommend that AHSCT should only be performed in experienced centres with expertise in both haematological and gastroenterological aspects of the procedure. Where possible, patients should be enrolled on clinical trials and data registered centrally. Future development should be coordinated at both national and international levels.

Hematopoietic stem cell transplantation (HSCT) has evolved for >20 years as a specific treatment of patients with autoimmune disease (AD). Using European Society for Blood and Marrow Transplantation registry data, we summarized trends and identified factors influencing activity and outcomes in patients with AD undergoing first autologous HSCT (n = 1951; median age, 37 years [3-76]) and allogeneic HSCT (n = 105; median age, 12 years [<1-62]) in 247 centers in 40 countries from 1994 to 2015. Predominant countries of activity were Italy, Germany, Sweden, the United Kingdom, The Netherlands, Spain, France, and Australia. National activity correlated with the Human Development Index ( P = .006). For autologous HSCT, outcomes varied significantly between diseases. There was chronological improvement in progression-free survival (PFS, P < 10 -5 ), relapse/progression ( P < 10 -5 ), and nonrelapse mortality ( P = .01). Health care expenditure was associated with improved outcomes in systemic sclerosis and multiple sclerosis (MS). On multivariate analysis selecting adults for MS, systemic sclerosis, and Crohn disease, better PFS was associated with experience (≥23 transplants for AD, P = .001), learning (time from first HSCT for AD ≥6 years, P = .01), and Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation accreditation status ( P = .02). Despite improved survival over time ( P = .02), allogeneic HSCT use remained low and largely restricted to pediatric practice. Autologous HSCT has evolved into a treatment modality to be considered alongside other modern therapies in severe AD. Center experience, accreditation, interspecialty networking, and national socioeconomic factors are relevant for health service delivery of HSCT in AD., Competing Interests: Conflict-of-interest disclosure: J.A.S. has received honoraria from Sanofi and Jazz for speaking at educational events. J.B. has received travel support and/or lecture honoraria from Almirall, Biogen, Genzyme a Sanofi Company, Hospira, and Merck Serono, and unconditional research grants from Biogen and Merck Serono. The remaining authors declare no competing financial interests.

A series of iminothiazolines (4a-j) featuring 2,4,5-trichlorophenyl moiety and aroyl/heteroaroyl substituents has been prepared from readily accessible thioureas. In-vitro screening against glucosidase enzymes showed highly specific inhibition of α-glucosidase with a marked dependence of the potency upon the nature of the aroyl/heteroaroyl substituents. The most potent representatives, bearing ortho-tolyl and bulky naphthyl groups displayed the highest inhibitory potential with IC 50 value of 0.15±0.01µM compared to standard drug acarbose (IC 50 =38.2±0.12µM). Several other derivatives (4c, 4d, 4i and 4j) were also significantly powerful and selective inhibitors of α-glucosidase. Binding interactions of potent compounds 4b, 4c, 4h and 4i with α-glucosidase were explored by molecular docking simulation. These results clearly identified a new class of structural leads which can be further investigated for the development of promising α-glucosidase inhibitors for the prevention of diabetes mellitus., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The role of imaging in myeloma has gained increasing importance over the past few years. The recently revised definition of myeloma from the International Myeloma Working Group (IMWG) includes cross sectional imaging as a method to define bone disease and also incorporates its use in the disease definition for patients with suspected smouldering myeloma. The National Institute for Health and Care Excellence myeloma guidelines also recommend cross sectional imaging for patients with suspected myeloma. There is also increasing use of imaging in disease assessments and the International Myeloma Working Group has recently incorporated imaging in defining new response categories of minimal residual disease negativity, with or without imaging-based evidence of disease. Plain X-rays have previously been the standard imaging modality included in a myeloma work up at presentation but evidence is mounting for use of cross-sectional modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and 18 fluoro-deoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT. Funding and therefore availability of newer imaging techniques remains a barrier. Here, we propose an evidence-based approach to the use and technical application of the latest imaging modalities at diagnosis and in the follow-up of patients with myeloma and plasmacytoma., (© 2017 John Wiley & Sons Ltd.)

Introduction: A substantial proportion of patients with multiple sclerosis (MS) do not respond to pharmacological treatments and no currently approved therapy has been convincingly demonstrated to prevent or stop disease progression. With MS widely believed to be an auto-immune disease, immunoablative therapy followed by autologous haematopoietic stem cell transplantation (I/AHSCT) is being investigated as an alternative therapeutic option. Areas covered: With the results of phase III comparative trials only a few years away, this article reviews animal and clinical trials of I/AHSCT in the treatment of MS and discusses possible immunological mechanisms behind its action. Expert commentary: I/AHSCT can induce long-term suppression of inflammatory disease activity and can halt or reverse neurological deterioration even in progressive stages of the disease, altering the fundamental disease course. However, toxicity of the therapy remains a problem and longer term follow up is required. Immunological investigations of the reconstituting immune system have discovered that qualitative changes take place at the cellular and molecular levels, which support the hypothesis of a 'resetting' of the immune system towards a tolerant and anti-inflammatory state.

Pulmonary embolism can present in various ways, though seizure activity has been rarely reported. We report a 38 years old male who had met a road traffic accident, underwent surgery, presented a month later with seizures, chest pain, shortness of breath and low blood pressure. Massive pulmonary embolism was diagnosed on CTPA, with classical features on ECG and echocardiogram and the patient was successfully managed with thrombolysis. Massive pulmonary embolism (MPE) should be kept in mind in patients who present with seizures, chest pain and haemodynamic instability.

A wide range of image processing applications deploys two dimensional (2D)-filters for performing diversified tasks such as image enhancement, edge detection, noise suppression, multi scale decomposition and compression etc. All of these tasks require multiple type of 2D-filters simultaneously to acquire the desired results. The resource hungry conventional approach is not a viable option for implementing these computationally intensive 2D-filters especially in a resource constraint environment. Thus it calls for optimized solutions. Mostly the optimization of these filters are based on exploiting structural properties. A common shortcoming of all previously reported optimized approaches is their restricted applicability only for a specific filter type. These narrow scoped solutions completely disregard the versatility attribute of advanced image processing applications and in turn offset their effectiveness while implementing a complete application. This paper presents an efficient framework which exploits the structural properties of 2D-filters for effectually reducing its computational cost along with an added advantage of versatility for supporting diverse filter types. A composite symmetric filter structure is introduced which exploits the identities of quadrant and circular T-symmetries in two distinct filter regions simultaneously. These T-symmetries effectually reduce the number of filter coefficients and consequently its multipliers count. The proposed framework at the same time empowers this composite filter structure with additional capabilities of realizing all of its Ψ-symmetry based subtypes and also its special asymmetric filters case. The two-fold optimized framework thus reduces filter computational cost up to 75% as compared to the conventional approach as well as its versatility attribute not only supports diverse filter types but also offers further cost reduction via resource sharing for sequential implementation of diversified image processing applications especially in a constraint environment., Competing Interests: The authors have declared that no competing interests exist.

Over the past 15 years, SCT has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs). Mechanistic studies recently provided the proof-of-concept that restoration of immunological tolerance can be achieved by haematopoietic SCT in chronic autoimmunity through eradication of the pathologic, immunologic memory and profound reconfiguration of the immune system, that is, immune 'resetting'. Nevertheless, a number of areas remain unresolved and warrant further investigation to refine our understanding of the underlying mechanisms of action and to optimize clinical SCT protocols. Due to the low number of patients transplanted in each centre, it is essential to adequately collect and analyse biological samples in a larger cohort of patients under standardized conditions. The European society for blood and marrow transplantation Autoimmune Diseases and Immunobiology Working Parties have, therefore, undertaken a joint initiative to develop and implement guidelines for 'good laboratory practice' in relation to procurement, processing, storage and analysis of biological specimens for immune reconstitution studies in AD patients before, during and after SCT. The aim of this document is to provide practical recommendations for biobanking of samples and laboratory immune monitoring in patients with ADs undergoing SCT, both for routine supportive care purposes and investigational studies.

Background: Although autologous stem cell transplantation (ASCT) may achieve disease control in severe treatment-resistant Crohn's disease (CD), relapse is frequent, and there is little information regarding long-term outcomes in terms of response to subsequent treatments and complications of ASCT., Design: Retrospective evaluation of UK patients treated on a compassionate basis from three UK tertiary centres., Methods: We summarize long-term outcomes of six previously unreported patients with severe treatment-resistant CD treated with ASCT according to international guidelines between 2003 and 2009. Median duration of CD before ASCT was 14 (7-22) years. Following stem cell mobilization, patients were treated with high-dose cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (7.5 mg/kg) followed by ASCT., Results: All patients tolerated ASCT with routine toxicities and no treatment-related mortality and are alive at 50-123 months post-ASCT. Clinical and endoscopic remissions of CD were confirmed at 3 months post-ASCT in five patients, although median time to next treatment for inflammatory disease was 10 months (range: 3-16 months). Subsequently, disease control was achieved with previously ineffective and newer treatments, with surgery performed predominantly for pre-existing fibrotic strictures. Two patients became independent of home total parenteral nutrition (TPN). Reported late complications of ASCT included hypothyroidism and ovarian failure., Conclusion: Long-term follow-up supports the safety and feasibility of ASCT as a means of achieving short-term control of severe CD whilst potentially re-sensitizing the disease to medical therapy and reducing requirements for surgery and TPN. Given the inevitability of relapse, pre-emptive salvage and/or maintenance treatments post-ASCT should be the focus of future trials., (© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To evaluate the clinical course and outcomes in patients with acute severe asthma in a tertiary care setting., Methods: The retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of patients of age 16 and above who were admitted with a diagnosis of acute severe asthma from January 2000 to December 2013. These patients had undergone clinical evaluation to assess the severity of illness as well as the complications and eventual outcomes. SPSS 16 was used for statistical analysis., Results: Of the 50 patients in the study, 41 (82%) were females. The overall mean age was 53.1±20.3 years. Ventilator support was required by 37(74%) patients. Presence of acidaemia was associated with the need for invasive ventilation (p<0.033) which in turn was associated with increased hospital stay (p<0.043). Complications were observed in 37(74%) patients, the most common being respiratory failure in 35(70%) and arrhythmias in 8(16%). Use of both non-invasive and invasive ventilation was found to be significantly associated with development of complications (p<0.001 and p<0.009). A total of 4(8%) patients died. Presence of acidaemia was found to be significantly associated with mortality (p<0.032)., Conclusion: Overt acidaemia at initial presentation in patients with acute severe asthma was significantly associated with higher rates of invasive ventilation leading to increased hospital stay, complications and higher mortality rate.

Aim: To describe the state of development of bachelor's-to-doctoral-degree nursing programs and provide baseline data for future research exploring program outcomes., Background: BS-PhD programs were developed to address a shortage of nurse scientists and educators by decreasing the time from initial baccalaureate degree to PhD credentialing., Method: A random sample of BS-PhD program directors was selected. Interviews were conducted by phone using a semistructured questionnaire designed to capture both quantitative and qualitative data., Results: BS-PhD programs varied as to a number of characteristics, but several common themes emerged: their as-yet small impact, questions of innovation, unequal resource availability, and hope for the future and future challenges., Conclusion: BS-PhD programs have the potential to increase the number of nurse researchers and educators. However, the programs reviewed in this study varied in their ability to provide all the recognized components of PhD education.

In a multicenter collaboration, we carried out T cell-replete, peripheral blood stem cell (PBSC) transplantations from related, HLA-haploidentical donors with reduced-intensity conditioning (RIC) and post-transplantation cyclophosphamide (Cy) as graft-versus-host disease (GVHD) prophylaxis in 55 patients with high-risk hematologic disorders. Patients received 2 doses of Cy 50 mg/kg i.v. on days 3 and 4 after infusion of PBSC (mean, 6.4 × 10(6)/kg CD34(+) cells; mean, 2.0 × 10(8)/kg CD3(+) cells). The median times to neutrophil (500/μL) and platelet (>20,000/μL) recovery were 17 and 21 days respectively. All but 2 of the patients achieved full engraftment. The 1-year cumulative incidences of grade II and grade III acute GVHD were 53% and 8%, respectively. There were no cases of grade IV GVHD. The 2-year cumulative incidence of chronic GHVD was 18%. With a median follow-up of 509 days, overall survival and event-free survival at 2 years were 48% and 51%, respectively. The 2-year cumulative incidences of nonrelapse mortality and relapse were 23% and 28%, respectively. Our results suggest that PBSC can be substituted safely and effectively for bone marrow as the graft source for haploidentical transplantation after RIC., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

s-BuLi-induced α-lithiation-elimination of LiOMe from N-Boc-3-methoxyazetidine and further in situ α-lithiation generates N-Boc-2-lithio-2-azetine which can be trapped with electrophiles, either directly (carbonyl or heteroatom electrophiles) or after transmetalation to copper (allowing allylations and propargylations), providing a concise access to 2-substituted 2-azetines.

Rapid and accurate identification of bacterial pathogens is a fundamental goal of clinical microbiology. The diagnosis and surveillance of diseases is dependent, to a great extent, on laboratory services, which cannot function without effective reliable reagents and diagnostics. Despite the advancement in microbiology diagnosis globally, resourcelimited countries still struggle to provide an acceptable diagnosis quality which helps in clinical disease management and improve their mortality and morbidity data. During this study an indigenous product, Quick Test Strip (QTS) NE, was developed for the rapid identification of biochemically slower group of Gram-negative oxidase-positive bacilli that covers 19 different bacterial genera. Some of the members belonging to these groups are well-established human pathogens, e.g. various species of Vibrio, Pseudomonas, Burkholderia, Aeromonas, Achromobacter and Stenotrophomonas. This study also evaluates the performance of QTS-NE by comparing with genotypic characterization methods. A total of 232 clinical and reference bacterial isolates were tested by three different methods. QTSNE provides 100 percent concordant results with other rapid identification and molecular characterization methods and confirms the potential to be used in clinical diagnosis.