Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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Πέμπτη 13 Ιουλίου 2017
New process for 3D printing of cellulose
Source:Materials Today
Author(s): Laurie Donaldson
http://ift.tt/2sWIHDo
Stereotactic Ablative Radiation Therapy in Renal Cell Carcinoma: from oligometastatic to localized disease
Publication date: Available online 13 July 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Filippo Alongi, Stefano Arcangeli, Luca Triggiani, Rosario Mazzola, Michela Buglione di Monale e Bastia, Sergio Fersino, Anna Baiguini, Barbara Alicja Jereczek-Fossa, Stefano Maria Magrini
Renal Cell Carcinoma (RCC) has historically been considered a radioresistant cancer, and radiotherapy was usually delivered with a palliative goal. Stereotactic ablative radiotherapy (SABR) allows the delivery of high doses on small treatment volumes in a safe and effective way, thus opening the doors to new applicationsof radiotherapy both in the treatment of the primary and oligometastasic disease. Aim of the current review is to explore the state of art of SABR in the therapeutic approach to RCC.
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Validation, comparison, and combination of algorithms for automatic detection of pulmonary nodules in computed tomography images: the LUNA16 challenge
Publication date: Available online 13 July 2017
Source:Medical Image Analysis
Author(s): Arnaud Arindra Adiyoso Setio, Alberto Traverso, Thomas de Bel, Moira S.N. Berens, Cas van den Bogaard, Piergiorgio Cerello, Hao Chen, Qi Dou, Maria Evelina Fantacci, Bram Geurts, Robbert van der Gugten, Pheng Ann Heng, Bart Jansen, Michael M.J. de Kaste, Valentin Kotov, Jack Yu-Hung Lin, Jeroen T.M.C. Manders, Alexander Sóñora-Mengana, Juan Carlos García-Naranjo, Evgenia Papavasileiou, Mathias Prokop, Marco Saletta, Cornelia M Schaefer-Prokop, Ernst T. Scholten, Luuk Scholten, Miranda M. Snoeren, Ernesto Lopez Torres, Jef Vandemeulebroucke, Nicole Walasek, Guido C.A. Zuidhof, Bram van Ginneken, Colin Jacobs
Automatic detection of pulmonary nodules in thoracic computed tomography (CT) scans has been an active area of research for the last two decades. However, there have only been few studies that provide a comparative performance evaluation of different systems on a common database. We have therefore set up the LUNA16 challenge, an objective evaluation framework for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified. This paper describes the setup of LUNA16 and presents the results of the challenge so far. Moreover, the impact of combining individual systems on the detection performance was also investigated. It was observed that the leading solutions employed convolutional networks and used the provided set of nodule candidates. The combination of these solutions achieved an excellent sensitivity of over 95% at fewer than 1.0 false positives per scan. This highlights the potential of combining algorithms to improve the detection performance. Our observer study with four expert readers has shown that the best system detects nodules that were missed by expert readers who originally annotated the LIDC-IDRI data. We released this set of additional nodules for further development of CAD systems.
Graphical abstract
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Electrospun polymeric nanofibers: New horizons in drug delivery
Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Shreya Thakkar, Manju Misra
Nanofibers obtained using electrospinning technique are being used since ages especially in fields of textile industry, sensors, filters, protective clothing and tissue engineering. Their use as drug delivery system is an emerging platform in the field of pharmaceuticals and now-a-days formulation scientists are paying great attention to the technology due to several advantages prime being easy modulation of drug release profile depending upon the properties of polymer/polymeric blends/other materials used. Although there are several reports citing the use of antibiotics-loaded nanofibers as wound dressing materials and as antimicrobial therapy in periodontics; still there is a good scope of expanding the horizon for its application in newer ailments. This article reviews various aspects related to loading and release of drug as such or in nano-particulate form to polymeric nanofibers by taking critical process parameters (CPPs) for electrospinning and critical material attributes (CMAs) into account. Commercially available products and electrospinning technologies are described in brief along with some of the patents related to their use as drug delivery systems. The main focus of this review is applicability of drug/drug nanoparticle loaded nanofibers in the management of diseases/disorders related to the brain, eye, ear, cardiovascular system, lungs and oral cavity. Use in diseases with higher mortality rates like diabetes, Acquired immunodeficiency syndrome (AIDS) and cancer is also described in brief.
Graphical abstract
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Follicle-stimulating hormone encapsulation in the cholesterol-modified chitosan nanoparticles via molecular dynamics simulations and binding free energy calculations
Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Mohammad Yahyaei, Faramarz Mehrnejad, Hossein Naderi-manesh, Ali Hossein Rezayan
Follicle-stimulating hormone (FSH) is widely applied in the modern ovarian stimulation techniques. However, it must be administered daily because of its short half-life. Recently, the cholesterol (CS) modified chitosan (CTS) nanogels have attracted significant interest as promising controlled release protein delivery because of their ability to minimize the aggregation and irreversible denaturation of proteins. Herein, we report a molecular dynamics (MD) simulation investigation on the molecular mechanisms of FSH encapsulation in the CS-CTS nanogels. The MD simulations have been performed using the GROMACS software for up to 200ns simulation time. Furthermore, the binding free energy has been calculated by the molecular mechanics [MM] with Poisson-Boltzmann [PB] and surface area solvation (MM/PBSA) method by using the g_mmpbsa tool. Our findings suggest that the main driving force of the formation of the CS-CTS nanogels is the hydrophobic interactions between the CS–CS moieties in water. The results have also indicated that the CS-CTS nanogel formation can occur through the hydrogen bonding in addition to the hydrophobic interactions. The obtained data demonstrate that the FSH encapsulation into the CS-CTS nanogels is a gradual process driven by the hydrophobic interactions between the hydrophobic patch of FSH and the hydrophobic nanodomains of the nanogel. Our results also reveal that except in the hydrophobic patch region, the flexibility of FSH was reduced in the presence of the nanogel. This study provides the elucidation of the nanogel–FSH interactions at the molecular level and presents new perspective for the ideal design and applications of the CS-CTS nanogel in protein delivery.
Graphical abstract
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Mechanistic insights of the enhancement effect of sorbitan monooleate on olanzapine transdermal patch both in release and percutaneous absorption processes
Publication date: 30 September 2017
Source:European Journal of Pharmaceutical Sciences, Volume 107
Author(s): Ning Li, Peng Quan, XiaoCao Wan, Chao Liu, Xiaochang Liu, Liang Fang
In this paper, based on the optimized formulation of olanzapine (OLN) transdermal patch, the role of sorbitan monooleate (SP) in OLN release and percutaneous absorption processes was probed in vitro and in vivo. Rheological test, DSC, FT-IR and molecular modeling were conducted to elucidate the effect of SP on the release process of OLN from transdermal patch. Additionally, the action of SP on the percutaneous absorption process was probed using tape stripping transdermal experiment, confocal laser scanning microscopy (CLSM), ATR-FTIR and molecular docking. The results showed that the hydrogen bonding interaction between OLN and pressure sensitive adhesive (PSA) was weakened by SP, which resulted in a decrease in the cohesive interaction between polymer chains and an increase in the formation of free volume of PSA, thus, the release of OLN from patch was promoted. Meanwhile, the OH groups of SP interacted with the polar head groups of the ceramides, which increased the fluidity of the skin lipids, thereby improved the ability of OLN percutaneous absorption. In summary, this study demonstrated that not only the release but also the percutaneous absorption processes were promoted by SP. This study provided comprehensive molecular level understanding on the effect of penetration enhancer on transdermal patch and strategies for rationally selection of chemical enhancer for transdermal drug delivery systems.
Graphical abstract
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Stereotactic Ablative Radiation Therapy in Renal Cell Carcinoma: from oligometastatic to localized disease
Source:Critical Reviews in Oncology/Hematology
Author(s): Filippo Alongi, Stefano Arcangeli, Luca Triggiani, Rosario Mazzola, Michela Buglione di Monale e Bastia, Sergio Fersino, Anna Baiguini, Barbara Alicja Jereczek-Fossa, Stefano Maria Magrini
Renal Cell Carcinoma (RCC) has historically been considered a radioresistant cancer, and radiotherapy was usually delivered with a palliative goal. Stereotactic ablative radiotherapy (SABR) allows the delivery of high doses on small treatment volumes in a safe and effective way, thus opening the doors to new applicationsof radiotherapy both in the treatment of the primary and oligometastasic disease. Aim of the current review is to explore the state of art of SABR in the therapeutic approach to RCC.
http://ift.tt/2tPq2ME
Acute facial nerve paralysis in children,............................................................................................................................................ Bell's palsy in an adolescent girl - not always a neurologist's territory: A case report and review of literature by Latha M Sneha via CHRISMED Journal of Health and Research : 2014 - 1(4) Latha M Sneha, Raichel Priyanka, Shanthini Thanga Tamilselvan, Julius Xavier Scott CHRISMED Journal of Health and Research 2017 4(3):209-211 Infections, inflammatory, and autoimmune conditions are the well-recognized etiologies of acute facial nerve paralysis in children. Bell's palsy is idiopathic peripheral facial nerve palsy. Cranial neuropathies do occur in children due to the central nervous system involvement by malignancies but uncommon in pediatric acute lymphoblastic leukemias and even rarer in acute myeloid leukemias (AMLs). We report a case of a 13-year-old girl who presented with acute facial nerve palsy, wa
CASE REPORT | |
|
Bell's palsy in an adolescent girl - not always a neurologist's territory: A case report and review of literature
Latha M Sneha1, Raichel Priyanka2, Shanthini Thanga Tamilselvan2, Julius Xavier Scott3
1 Department of Pediatrics, Division of Pediatric Hemato Oncology, Sri Ramachandra University, Chennai, Tamil Nadu, India
2 Department of Pediatrics, Sri Ramachandra University, Chennai, Tamil Nadu, India
3 Division of Pediatric Hemato Oncology, Sri Ramachandra University, Chennai, Tamil Nadu, India
Date of Web Publication | 13-Jul-2017 |
Correspondence Address:
Latha M Sneha
Division of Pediatric Hemato Oncology, Sri Ramachandra University, No. 1, Ramachandra Nagar, Porur, Chennai - 600 116, Tamil Nadu
India
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/cjhr.cjhr_123_16
Abstract |
Infections, inflammatory, and autoimmune conditions are the well-recognized etiologies of acute facial nerve paralysis in children. Bell's palsy is idiopathic peripheral facial nerve palsy. Cranial neuropathies do occur in children due to the central nervous system involvement by malignancies but uncommon in pediatric acute lymphoblastic leukemias and even rarer in acute myeloid leukemias (AMLs). We report a case of a 13-year-old girl who presented with acute facial nerve palsy, was being treated as Bell's palsy elsewhere and was later diagnosed to have AML.
Keywords: Acute myeloid leukemia, Bell's palsy, child
How to cite this article: Sneha LM, Priyanka R, Tamilselvan ST, Scott JX. Bell's palsy in an adolescent girl - not always a neurologist's territory: A case report and review of literature. CHRISMED J Health Res 2017;4:209-11 |
How to cite this URL: Sneha LM, Priyanka R, Tamilselvan ST, Scott JX. Bell's palsy in an adolescent girl - not always a neurologist's territory: A case report and review of literature. CHRISMED J Health Res [serial online] 2017 [cited 2017 Jul 14];4:209-11. Available from: http://www.cjhr.org/text.asp?2017/4/3/209/210478 |
Introduction |
Acute, peripheral facial palsy can be presenting feature of infections, inflammatory, and autoimmune conditions and has a good prognosis in children. The incidence of facial paralysis in children <10 years of age is reported to be 2.7/100,000.[1] Majority of them are unilateral, idiopathic, and termed Bell's palsy. A diagnosis of exclusion, Bell's palsy accounts for 42%–85% of cases in children with facial nerve paralysis.[2] Although association of facial palsies in malignancies is well reported, facial paralysis is not a well-recognized presenting feature of leukemias in children, especially in acute myeloid leukemia (AML). The presence of Bell's palsy in children warrants a complete evaluation to rule out leptomeningeal diseases. We report a case of an adolescent girl who presented with acute facial nerve palsy, treated as Bell's palsy elsewhere and was later diagnosed to have AML.
Case Report |
A 13-year-old girl presented with acute onset of right-sided facial nerve palsy of 2 weeks duration. She was diagnosed to have idiopathic Bell's palsy elsewhere and was being treated symptomatically with physiotherapy and oral steroids with no improvement in symptoms. She had no constitutional symptoms of fever, anorexia or fatigue, bone pain, mucocutaneous, or skin bleeds. In view of persistent symptoms, she was referred to a higher center for further evaluation. Examination revealed a right-sided lower motor neuron facial nerve palsy [Figure 1], without hepatosplenomegaly or lymphadenopathy. Central nervous system examination and rest of the systemic examination were normal. Investigations revealed hemoglobin 5.9 g/dl, total leukocyte count 14,900/μL (polymorphs: 64.1%, lymphocytes 30.3%), and platelet count 83,000/μL. Peripheral smear revealed leukocytosis with increase in blasts (50%) with Auer rods More Details along with thrombocytopenia [Figure 2].
Figure 1: Right-sided lower motor neuron palsy Click here to view |
Figure 2: Peripheral smear showing blasts with Auer rods Click here to view |
Bone marrow aspiration showed hypercellular marrow with 58% blasts, promyelocytes - nil, myelocytes - 9, metamyelocytes - 9, neutrophil - 3, eosinophil - 2, band - 4, lymphocytes - 9, monocytes - nil, and plasma cells - 1 [Figure 3]. Cerebrospinal fluid (CSF) analysis was negative for malignant cells. Flow cytometry revealed blasts positive for CD33, cytoplasmic myeloperoxidase, and Human leukocyte antigen –D related (HLA-DR). Magnetic resonance imaging (MRI) brain, MRI angiogram, and venogram were normal. Cytogenetics was negative for t(8:21), inversion 16, t(9:11), and t(15:17). The girl was diagnosed as AML M0. She was started on chemotherapy and after the first cycle of chemotherapy, the bone marrow is in remission and she had partial resolution of facial nerve palsy.
Figure 3: Bone marrow aspirate showing hypercellular marrow with increased blasts 58% Click here to view |
Discussion |
The common etiology associated with acute facial nerve paralysis in children are otitis media, mastoiditis, viral infections such as herpes, varicella, mumps, HIV, meningitis, encephalitis, mycoplasma, Lyme disease, and inflammatory conditions such as vasculitis, Henoch–Schonlein purpura, Kawasaki syndrome, Gullain–Barre syndrome, and hypertension.[3]
Seventy percent of the children with acute lower motor neuron facial paralysis have a favorable prognosis and it resolves spontaneously within 3 months without any sequela. In 40%–75% of children, cause of unilateral facial paralysis is idiopathic, described as Bell's palsy and most of them have a positive history of viral illness 2–3 weeks preceding the neurological manifestations. The use of steroids to reduce the duration of paralysis and reduce the risk of long-term impairment was based on adult studies though the benefits of steroids in children is yet to be proven.[4] Due to the self-resolving nature of the idiopathic variety of the facial palsy seen in children, the neurological manifestations of leukemia as an etiology is never thought of. Steroids, when commonly prescribed in such cases causes a partial recovery thereby masking the primary pathology and adds to the diagnostic dilemma.
The frequency of symptomatic facial palsy has been found to be higher in the younger age group when compared to the idiopathic variety.[5]
AML accounts for 15% of all leukemia and presents with symptoms of prolonged fever, hepatosplenomegaly, and skin or mucocutaneous bleeds. When focal masses of immature myeloid cells from the granulocytic lineage infiltrate the soft tissues and bones, they are called granulocytic sarcomas or chloromas and occur in 5% of cases of AML. It is postulated that the granulocytic sarcomas traverse through the haversian canals from the bone marrow and gets deposited in the subperiosteum to form soft tissue masses.[6]
Granulocytic sarcomas may manifest concurrently with the disease or during remission or relapse. However, when sarcomas precede the disease in peripheral blood or marrow, it often poses a diagnostic challenge, more so, if cranial neuropathies are caused by unidentifiable chloromas as in our case. Facial paralysis resulting from leukemic infiltration, though rare, occurs during the relapse of the disease or as a complication primary disease, but it is not a well-recognized presenting symptom of childhood leukemia. Diagnostic delays of 1 month have been reported when facial nerve palsy was the isolated manifestation of AML in children.[7] Otomastoiditis due to the leukemic infiltration of the temporal bone has been attributed to the facial nerve paralysis. MRI with contrast of the facial nerve canal helps in identifying the facial nerve enhancement. However, the clinical findings of facial nerve paralysis were not always associated with radiological findings in most of the cases.[7]
Baek et al. have reported 11 children who had facial nerve paralysis as isolated feature of AML. Brain imaging studies showed mastoiditis in four of them and chloroma was identified in five of them. Six of them did not have blast in the CSF. Facial nerve palsy improved within a mean period of 1–6 months of chemotherapy.[7] Rohit et al. have reported a case of 13-year-old girl-AML with t(8:21) positivity who presented with bilateral proptosis and facial nerve palsy.[8]
When leukemic children presented with cranial neuropathies, the treatment included systemic and intrathecal chemotherapy with whole brain irradiation. However, Baek et al. recommend allogenic bone marrow transplant, avoiding whole brain irradiation in children to reduce the development of secondary malignancies and to prevent the long-term sequelae on cognitive and endocrine function.
Due to the self-resolving nature of the idiopathic variety of facial nerve palsy, when these children present to general physicians or neurologists, the diagnosis of leukemia is overlooked. Gradual progression of the paralysis beyond 3 weeks should warrant additional investigations to rule out the etiology.
Conclusion |
While managing young children with acute lower motor neuron facial nerve palsy, neurologists and general physicians should have an index of suspicion for the neurological manifestations of acute leukemia and hence complete blood counts, peripheral smear and a bone marrow study if needed should be a part of the work up for etiology in such cases. The routine use of steroids may result in partial remission and can cause diagnostic delays.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References |
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Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Concomitant Epstein-Barr Virus-associated smooth muscle tumor and granulomatous inflammation of the liver
Publication date: Available online 13 July 2017
Source:Pathology - Research and Practice
Author(s): Nhu Thuy Can, James Grenert, Poonam Vohra
Epstein-Barr Virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor typically seen in immunocompromised patients. Here, we report a case of EBV-SMT and associated granulomatous inflammation in the liver of a 32-year-old man with history of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). To our knowledge, an association of these two lesions has not been previously reported. We review the literature and discuss pathogenesis, differential diagnosis and immunohistochemical (IHC) stains helpful for the diagnosis of this rare entity. Finally, we consider possible explanations for the concomitant presence of these lesions.
http://ift.tt/2sWuI08
Anti-IL-21 monoclonal antibody combined with liraglutide effectively reverses established hyperglycemia in mouse models of type 1 diabetes
Source:Journal of Autoimmunity
Author(s): Anna K. Rydén, Nikole R. Perdue, Philippe P. Pagni, Claire B. Gibson, Sowbarnika S. Ratliff, Rikke K. Kirk, Travis J. Friesen, Claus Haase, Ken Coppieters, Matthias G. von Herrath, Tamar E. Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D. We report here that treatment with anti-IL-21 monoclonal antibody delays diabetes onset in the spontaneous non-obese diabetic (NOD) and NOD.scid adoptive transfer models, while its effect in reversing recent-onset hyperglycemia is limited. However, the combination of anti-IL-21 plus the GLP-1R agonist liraglutide is effective in reversing established disease compared to either monotherapy in both the NOD and rat insulin promotor-lymphocytic choriomeningitis virus glycoprotein (RIP-LCMV-GP) models of autoimmune diabetes. Enhanced efficacy is particularly evident in severely hyperglycemic mice, with return to normoglycemia remaining stable for the majority of mice even after therapy is withdrawn. Importantly, increased beta cell proliferation does not appear to be the predominant mechanism. In conclusion, combination therapy with anti-IL-21 and liraglutide is able to consistently reverse disease in mouse models of T1D. The observed effects rival the most effective experimental disease-modifying treatments tested in preclinical studies.
http://ift.tt/2tOXdQd
Novel therapeutic targets for inflammatory bowel disease
Source:Journal of Autoimmunity
Author(s): Marjorie Argollo, Gionata Fiorino, Pieter Hindryck, Laurent Peyrin-Biroulet, Silvio Danese
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy. The treat to target approach possibly correlates with minor risk for complications associated with IBD, specially surgery and cancer.The most studied inflammatory pathway in IBD, is described to be dependent of the pro-inflammatory cytokine tumor necrosis factor-alfa (TNF-α), and compose the first line studies for development of biological drugs, in this case, targeting specifically the action of TNF-α. Even though, the use of anti-TNFs drugs are associated with improvement of the inflammation in some patients, a great portion do not respond at first or lose response over time. These findings made clear about the possibility of other mechanisms involved in perpetuating the chronic inflammatory state.Many years of intensive research have led to the identification of different inflammatory pathways that form the basis of the intensive drug development that we are experiencing today. These novel drugs include agents that target leukocyte trafficking, Interleukin (IL) 23, Janus kinases (JAK), Sphingosine 1 phosphate (S1P) and Smad7, an inhibitor of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1). In this manuscript, we aim to review the most promising late-stage drug candidates for the treatment of IBD.
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Clinical Management of Potential Toxicities and Drug Interactions Related to Cyclin‐Dependent Kinase 4/6 Inhibitors in Breast Cancer: Practical Considerations and Recommendations
AbstractAberrations of the cell cycle are pervasive in cancer, and selective cell cycle inhibition of cancer cells is a target of choice for a number of novel cancer therapeutics. Cyclin‐dependent kinases (CDKs) are key regulatory enzymes that control cell cycle transitions and the commitment to cell division. Palbociclib and ribociclib are both orally active, highly selective reversible inhibitors of CDK4 and CDK6 that are approved by the U.S. Food and Drug Administration (FDA) for hormone receptor‐positive metastatic breast cancer in combination with specific endocrine therapies. A third oral CDK4/6 inhibitor, abemaciclib, received Breakthrough Therapy designation status from the FDA and is also being developed in breast cancer. The most common adverse events associated with palbociclib and ribociclib are hematologic, particularly neutropenia. However, the neutropenia associated with CDK4/6 inhibitors is distinct from chemotherapy‐induced neutropenia in that it is rapidly reversible, reflecting a cytostatic effect on neutrophil precursors in the bone marrow. Most hematologic abnormalities seen with CDK4/6 inhibitors are not complicated and are adequately managed with standard supportive care and dose adjustments when indicated. Cytopenias are less prevalent with abemaciclib, although fatigue and gastrointestinal toxicity is more common with this agent. This review focuses on the clinical management of potential toxicities and drug interactions seen with the use of CDK4/6 inhibitors in breast cancer, with a focus on palbociclib and ribociclib, and summarizes practical management strategies for an oncologist.Implications for Practice.The emergence of modern cyclin‐dependent kinase (CDK) inhibitors has changed the treatment paradigm for metastatic hormone receptor (HR)‐positive breast cancer. Palbociclib, ribociclib, and abemaciclib are highly selective reversible inhibitors of CDK4 and CDK6. Palbociclib is U.S. Food and Drug Administration (FDA)‐approved in the first‐ and second‐line settings in combination with endocrine therapy for HR‐positive metastatic breast cancer. Ribociclib is FDA‐approved in the first‐line setting. Abemaciclib has received FDA Breakthrough Therapy designation status. This review focuses on the clinical management of potential toxicities and drug interactions seen with the use of CDK4/6 inhibitors in breast cancer.
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Perceptions of Cancer Care and Clinical Trials in the Black Community: Implications for Care Coordination Between Oncology and Primary Care Teams
AbstractBackground.Despite efforts to ameliorate disparities in cancer care and clinical trials, barriers persist. As part of a multiphase community‐engaged assessment, an exploratory community‐engaged research partnership, forged between an academic hospital and a community‐based organization, set out to explore perceptions of cancer care and cancer clinical trials by black Bostonians.Materials and Methods.Key informant interviews with health care providers and patient advocates in community health centers (CHCs), organizers from grassroots coalitions focused on cancer, informed the development of a focus group protocol. Six focus groups were conducted with black residents in Boston, including groups of cancer survivors and family members. Transcripts were coded thematically and a code‐based report was generated and analyzed by community and academic stakeholders.Results.While some participants identified clinical trials as beneficial, overall perceptions conjured feelings of fear and exploitation. Participants describe barriers to clinical trial participation in the context of cancer care experiences, which included negative interactions with providers and mistrust. Primary care physicians (PCPs) reported being levied as a trusted resource for patients undergoing care, but lamented the absence of a mechanism by which to gain information about cancer care and clinical trials.Conclusions.Confusion about cancer care and clinical trials persists, even among individuals who have undergone treatment for cancer. Greater coordination between PCPs and CHC care teams and oncology care teams may improve patient experiences with cancer care, while also serving as a mechanism to disseminate information about treatment options and clinical trials.Implications for Practice.Inequities in cancer care and clinical trial participation persist. Our findings indicate that greater coordination with primary care physicians (PCPs) and community health center (CHC) providers may be an important step for both improving the quality of cancer care in communities and increasing awareness of clinical trials. However, PCPs and CHCs are often stretched to capacity with caring for their communities. This leaves the oncology community well positioned to create programs to bridge the communication gaps and provide resources necessary to support oncologic care along the cancer continuum, from prevention through survivorship.
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The growth and aflatoxin production of Aspergillus flavus strains on a cheese model system are influenced by physicochemical factors
Source:Journal of Dairy Science
Author(s): Rocío Casquete, María José Benito, María de Guía Córdoba, Santiago Ruiz-Moyano, Alberto Martín
Traditional cheeses may be contaminated by aflatoxin-producing Aspergillus flavus during the ripening process, which has not been sufficiently taken into account. The objectives of this study were to evaluate the influence of water activity (aw), pH, and temperature on the lag phases, growth, and aflatoxin production of 3 A. flavus strains (CQ7, CQ8, and CG103) on a cheese-based medium. The results showed that the behavior of A. flavus strains was influenced by pH, aw, and temperature conditions. The CQ7 strain showed the maximum growth at pH 5.5, 0.99 aw, and 25°C, whereas for CQ8 and CQ103 strains, no differences were obtained at pH 5.5 and 6.0. In general, low pH, aw, and temperature values increased the latency times and decreased the growth rate and colony diameter, although aw and temperature were the most limiting factors. Maximum aflatoxin production on the cheese-based medium occurred at pH 5.0, 0.95 aw, and 25 or 30°C, depending on the strain. This study shows the effect of pH, aw, and temperature factors on growth and aflatoxin production of 3 aflatoxigenic A. flavus strains on a cheese-based medium. The findings may help to design control strategies during the cheesemaking process and storage, to prevent and avoid aflatoxin contamination by aflatoxigenic molds.
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Genetic correlations between the cumulative pseudo-survival rate, milk yield, and somatic cell score during lactation in Holstein cattle in Japan using a random regression model
Source:Journal of Dairy Science
Author(s): O. Sasaki, M. Aihara, A. Nishiura, H. Takeda
Trends in genetic correlations between longevity, milk yield, and somatic cell score (SCS) during lactation in cows are difficult to trace. In this study, changes in the genetic correlations between milk yield, SCS, and cumulative pseudo-survival rate (PSR) during lactation were examined, and the effect of milk yield and SCS information on the reliability of estimated breeding value (EBV) of PSR were determined. Test day milk yield, SCS, and PSR records were obtained for Holstein cows in Japan from 2004 to 2013. A random subset of the data was used for the analysis (825 herds, 205,383 cows). This data set was randomly divided into 5 subsets (162–168 herds, 83,389–95,854 cows), and genetic parameters were estimated in each subset independently. Data were analyzed using multiple-trait random regression animal models including either the residual effect for the whole lactation period (H0), the residual effects for 5 lactation stages (H5), or both of these residual effects (HD). Milk yield heritability increased until 310 to 351 d in milk (DIM) and SCS heritability increased until 330 to 344 DIM. Heritability estimates for PSR increased with DIM from 0.00 to 0.05. The genetic correlation between milk yield and SCS increased negatively to under −0.60 at 455 DIM. The genetic correlation between milk yield and PSR increased until 342 to 355 DIM (0.53–0.57). The genetic correlation between the SCS and PSR was −0.82 to −0.83 at around 180 DIM, and decreased to −0.65 to −0.71 at 455 DIM. The reliability of EBV of PSR for sires with 30 or more recorded daughters was 0.17 to 0.45 when the effects of correlated traits were ignored. The maximum reliability of EBV was observed at 257 (H0) or 322 (HD) DIM. When the correlations of PSR with milk yield and SCS were considered, the reliabilities of PSR estimates increased to 0.31–0.76. The genetic parameter estimates of H5 were the same as those for HD. The rank correlation coefficients of the EBV of PSR between H0 and H5 or HD were greater than 0.9. Additionally, the reliabilities of EBV of PSR of H0 were similar to those for H5 and HD. Therefore, the genetic parameter estimates in H0 were not substantially different from those in H5 and HD. When milk yield and SCS, which were genetically correlated with PSR, were used, the reliability of PSR increased. Estimates of the genetic correlations between PSR and milk yield and between PSR and SCS are useful for management and breeding decisions to extend the herd life of cows.
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The effect of Mycobacterium avium subspecies paratuberculosis infection on clinical mastitis occurrence in dairy cows
Source:Journal of Dairy Science
Author(s): G. Rossi, Y.T. Grohn, Y.H. Schukken, R.L. Smith
Endemic diseases can be counted among the most serious sources of losses for livestock production. In dairy farms in particular, one of the most common diseases is Johne's disease, caused by Mycobacterium avium ssp. paratuberculosis (MAP). Infection with MAP causes direct costs because it affects milk production, but it has also been suspected to increase the risk of clinical mastitis (CM) among infected animals. This might contribute to further costs for farmers. We asked whether MAP infection represents a risk factor for CM and, in particular, whether CM occurrences were more common in MAP-infected animals. Our results, obtained by survival analysis, suggest that MAP-infected cows had an increased probability of experiencing CM during lactation. These results highlight the need to account for the interplay of infectious diseases and other health conditions in economic and epidemiological modeling. In this case, accounting for MAP-infected cows having an increased CM occurrence might have nonnegligible effects on the estimated benefit of MAP control.
http://ift.tt/2uftOzI
Short communication: Implementation of a breeding value for heat tolerance in Australian dairy cattle
Source:Journal of Dairy Science
Author(s): Thuy T.T. Nguyen, Phil J. Bowman, Mekonnen Haile-Mariam, Gert J. Nieuwhof, Benjamin J. Hayes, Jennie E. Pryce
Excessive ambient temperature and humidity can impair milk production and fertility of dairy cows. Selection for heat-tolerant animals is one possible option to mitigate the effects of heat stress. To enable selection for this trait, we describe the development of a heat tolerance breeding value for Australian dairy cattle. We estimated the direct genomic values of decline in milk, fat, and protein yield per unit increase of temperature-humidity index (THI) using 46,726 single nucleotide polymorphisms and a reference population of 2,236 sires and 11,853 cows for Holsteins and 506 sires and 4,268 cows for Jerseys. This new direct genomic value is the Australian genomic breeding value for heat tolerance (HT ABVg). The components of the HT ABVg are the decline in milk, fat, and protein per unit increase in THI when THI increases above the threshold of 60. These components are weighted by their respective economic values, assumed to be equivalent to the weights applied to milk, fat, and protein yield in the Australian selection indices. Within each breed, the HT ABVg is then standardized to have a mean of 100 and standard deviation (SD) of 5, which is consistent with the presentation of breeding values for many other traits in Australia. The HT ABVg ranged from −4 to +3 SD in Holsteins and −3 to +4 SD in Jerseys. The mean reliabilities of HT ABVg among validation sires, calculated from the prediction error variance and additive genetic variance, were 38% in both breeds. The range in ABVg and their reliability suggests that HT can be improved using genomic selection. There has been a deterioration in the genetic trend of HT, and to moderate the decline it is suggested that the HT ABVg should be included in a multitrait economic index with other traits that contribute to farm profit.
http://ift.tt/2sWqohm
A comparative study of the in vitro activity of iodopropynyl butylcarbamate and amphotericin B against Prototheca spp. isolates from European dairy herds
Source:Journal of Dairy Science
Author(s): T. Jagielski, Z. Bakuła, S. Di Mauro, C. Casciari, V. Cambiotti, H. Krukowski, B. Turchetti, M. Ricchi, E. Manuali, P. Buzzini
The objective of this study was to assess the in vitro effect of iodopropynyl butylcarbamate (IPBC) and amphotericin B (AMB) on Prototheca zopfii genotype 2 and Prototheca blaschkeae isolates recovered from dairy herds of Belgium, France, Italy, Germany, and Poland. The combination of IPBC with AMB on Prototheca isolates and toxicity of IPBC to the bovine mammary epithelial cells were also evaluated. The in vitro activity of IPBC and AMB against 96 isolates of P. zopfii genotype 2 and 42 isolates of P. blaschkeae was performed. Minimum inhibitory concentrations (MIC) and minimum algicidal concentrations (MAC) of IPBC and AMB were determined. To determine any synergistic, additive, or antagonistic effect of the combination of IPBC and AMB, 2-dimensional checkerboard combination tests were also performed to calculate fractional inhibitory concentrations. Cytotoxicity analysis of IPBC to the bovine mammary epithelial cell line was performed using a 3-(4,5-dimethyl-2-thiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The MIC for 50 and 90% of isolates (MIC50 and MIC90, respectively) for IPBC were 4 and 8 mg/L versus 0.5 and 1 mg/L for AMB, respectively. The MIC profiles differed between P. zopfii genotype 2 and P. blaschkeae, with the latter species being more susceptible to both compounds. The MIC50 and MIC90 of IPBC were 4 and 8 mg/L for P. zopfii genotype 2 and 1 and 2 mg/L for P. blaschkeae, respectively. The MIC50 and MIC90 of AMB were both 1 mg/L for P. zopfii genotype 2 and 0.25 and 1 mg/L for P. blaschkeae, respectively. Both IPBC and AMB exhibited the ability to kill Prototheca spp. The MAC for 90% of isolates of IPBC was twice the MIC90, whereas an 8-fold increase of the MIC90 was algicidal in the case of AMB. Overall, the combined use of IPBC and AMB exhibited an increased algicidal effect, albeit the fractional inhibitory concentration index showed synergistic activity only against 3 P. zopfii genotype 2 isolates. For all the remaining isolates (87.5%), this combination produced only an additive effect. The MTT assay results showed both IPBC and AMB, at the concentrations employed in the study, to be nontoxic to the epithelial mammary gland cells (cell viability >90%). Notably, only IPBC at the highest concentration (i.e., 8 mg/L) exerted a slight cytotoxic effect on the cell line tested (mean cell viability: 88.54 ± 3.88 and 90.66 ± 3.0, after 2 and 4 h of MTT treatment, respectively). The anti-Prototheca activity of IPBC was here demonstrated for the first time. In addition, the combined use of IPBC with AMB enhanced each other's effect, creating an additive rather than synergistic interaction. Both agents, used at concentrations corresponding to MIC values against Prototheca spp., showed no toxic effect for the mammary epithelial cells. In conclusion, IPBC, used either alone or in combination with AMB, can be considered a promising option in the treatment armamentarium for protothecal mastitis in dairy cows.
http://ift.tt/2uftOjc
Feeding a concentrate rich in rapeseed oil improves fatty acid composition and flavor in Norwegian goat milk
Source:Journal of Dairy Science
Author(s): R.A. Inglingstad, S. Skeie, G.E. Vegarud, T.G. Devold, Y. Chilliard, M. Eknæs
Impaired quality due to a high content of free fatty acids (FFA) and off-flavors has caused challenges in the development of Norwegian goat milk products. The present study aimed to examine the effect of lipid-supplemented concentrates on milk fat content, fatty acid composition, FFA, lipoprotein lipase activity, sensory properties, and size of milk fat globules of goat milk. Thirty goats assigned to 3 experimental groups were fed different concentrates from 60 d in milk (DIM) until late lactation (230 DIM). The diets were (1) control concentrate (no added fat); (2) control concentrate with 8% (added on air-dry basis) hydrogenated palm oil enriched with palmitic acid (POFA); and (3) control concentrate with 8% (added on air-dry basis) rapeseed oil (RSO). The POFA group produced milk with the highest fat content, and fat content was positively correlated with the mean size of milk fat globules. Goats in the RSO group had a higher content of long-chain and unsaturated fatty acids, whereas milk from goats in the POFA group had a higher content of palmitic and palmitoleic acids (C16:0 and C16:1 cis). The control group produced milk with a higher content of short-, medium-, odd-, and branched-chain fatty acids compared with the 2 other groups. The content of FFA in milk was low in early and late lactation and peaked in mid lactation (90 DIM). A high content of FFA was correlated with poor sensory properties (tart/rancid flavor). The RSO group produced milk with lower content of FFA and off-flavors in mid lactation and a higher proportion of unsaturated fatty acids. Therefore, replacement of palm oil with rapeseed oil as a lipid source in dairy goat feed would be favorable.
http://ift.tt/2sVVRRa
Strains of the Lactobacillus casei group show diverse abilities for the production of flavor compounds in 2 model systems
Source:Journal of Dairy Science
Author(s): Ewelina Stefanovic, Anne Thierry, Marie-Bernadette Maillard, Andrea Bertuzzi, Mary C. Rea, Gerald Fitzgerald, Olivia McAuliffe, Kieran N. Kilcawley
Cheese flavor development is directly connected with the metabolic activity of microorganisms used during its manufacture, and the selection of metabolically diverse strains represents a potential tool for the production of cheese with novel and distinct flavor characteristics. Strains of Lactobacillus have been proven to promote the development of important cheese flavor compounds. As cheese production and ripening are long-lasting and expensive, model systems have been developed with the purpose of rapidly screening lactic acid bacteria for their flavor potential. The biodiversity of 10 strains of the Lactobacillus casei group was evaluated in 2 model systems and their volatile profiles were determined by gas chromatography-mass spectrometry. In model system 1, which represented a mixture of free AA, inoculated cells did not grow. In total, 66 compounds considered as flavor contributors were successfully identified, most of which were aldehydes, acids, and alcohols produced via AA metabolism by selected strains. Three strains (DPC2071, DPC3990, and DPC4206) had the most diverse metabolic capacities in model system 1. In model system 2, which was based on processed cheese curd, inoculated cells increased in numbers over incubation time. A total of 47 compounds were identified, and they originated not only from proteolysis, but also from glycolytic and lipolytic processes. Tested strains produced ketones, acids, and esters. Although strains produced different abundances of volatiles, diversity was less evident in model system 2, and only one strain (DPC4206) was distinguished from the others. Strains identified as the most dissimilar in both of the model systems could be more useful for cheese flavor diversification.
http://ift.tt/2ufQS1z
Characterization and bioactivities of the exopolysaccharide from a probiotic strain of Lactobacillus plantarum WLPL04
Source:Journal of Dairy Science
Author(s): Zhengqi Liu, Zhihong Zhang, Liang Qiu, Fen Zhang, Xiongpeng Xu, Hua Wei, Xueying Tao
Exopolysaccharide (EPS) was extracted and purified from Lactobacillus plantarum WLPL04, which has been confirmed previously as a potential probiotic for its antagonistic and immune-modulating activity. It has a molecular weight of 6.61 × 104 Da, consisting of xylose, glucose, and galactose in an approximate molar ratio of 3.4: 1.8: 1. Microstructural studies demonstrated that the EPS appeared as a smooth sheet structure with many homogeneous rod-shaped lumps. The preliminary in vitro assays indicated that the EPS could significantly inhibit the adhesion of Escherichia coli O157:H7 to HT-29 cells in competition, replacement, and inhibition assays at a dose of 1.0 mg/mL, with an inhibition rate of 20.24 ± 2.23, 29.71 ± 1.21, and 30.57 ± 1.73%, respectively. Additionally, the EPS exhibited a strong inhibition against the biofilm forming of pathogenic bacteria, including Pseudomonas aeruginosa CMCC10104, E. coli O157:H7, Salmonella Typhimurium ATCC13311, and Staphylococcus aureus CMCC26003. Furthermore, the EPS showed good inhibitory activity for the proliferation of HT-29 cells. The characteristics and bioactivities of this EPS may provide a promising candidate in developing functional food.
http://ift.tt/2sVYEK5
Development of an isothermal amplification-based assay for the rapid visual detection of Salmonella bacteria
Source:Journal of Dairy Science
Author(s): Hai-bin Liu, Yu-Xuan Zang, Xin-jun Du, Ping Li, Shuo Wang
The efficient and timely detection of pathogens is a major concern worldwide. The aim of this study was to establish a rapid detection method for Salmonella bacteria in food samples to facilitate timely treatment. Widely used detection methods currently include culture-based methods and PCR-based methods. The former are time consuming, requiring 2 to 3 d, whereas the latter have higher accuracy but are typically complicated, requiring expertise and expensive instruments. In this study, a sensitive and rapid approach for the visual and point-of-use detection of Salmonella bacteria based on recombinase polymerase amplification (RPA) and a lateral-flow (LF) nucleic acid strip was established. We designed a pair of primers according to the invA gene of Salmonella bacteria: one was modified with digoxin, and the other was modified with biotin. In the presence of the biotin- and digoxin-modified primers and target DNA, the RPA produced a substantial amount of duplex DNA attached to biotin and digoxin. The products were detected using LF strips through immunoreaction: anti-digoxin antibodies on the gold nanoparticles, digoxin on the duplex, streptavidin on the LF test line, and biotin on the duplex. The developed RPA-LF assay allowed detection of Salmonella genomic DNA in less than 20 min with simple water bath equipment or portable thermal equipment. In addition, the RPA-LF assay was highly sensitive, with a detection limit as low as 20 fg of target DNA or 1.05 × 101 cfu of bacteria in pure culture, and highly specific, exhibiting no cross-reaction with Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, Shigella, Enterobacter aerogenes, or Campylobacter jejuni. Importantly, Salmonella could be detected in milk and chicken breast at concentrations as low as 1.05 × 100 cfu/mL or 1.05 × 100 cfu/g after enrichment for 2 h and in eggs at 1.05 × 100 cfu/g after enrichment for 4 h. Furthermore, RPA was more sensitive than PCR, which requires a thermal cycling device. In summary, this study describes a sensitive, simple, and point-of-use detection method for Salmonella bacteria.
http://ift.tt/2ufA4HL
Genetic analysis for quality of frozen embryos produced by Holstein cattle donors in Canada
Source:Journal of Dairy Science
Author(s): C. Jaton, F.S. Schenkel, F. Malchiodi, M. Sargolzaei, C.A. Price, C. Baes, F. Miglior
The number of embryos produced by Holstein donors has been shown to be heritable, so it could be possible to genetically select for this trait to improve the efficiency of the assisted reproductive technology (ART) in dairy cattle. Another important parameter to consider for achieving good results from ART is embryo quality because embryos of good quality have more chance of producing live offspring. The possibility of using genetic selection for increasing the quality of embryo produced from ART has yet to be assessed. The objective of this study was, therefore, to perform a genetic analysis of embryo quality of Holstein donors in Canada using data recorded by Holstein Canada. The data set used was missing quality score data for embryos transferred fresh into a recipient, so the analyses were only performed for frozen embryos. With most traits in the Canadian dairy industry being evaluated with linear models, embryo quality was also evaluated with this class of models. However, considering the categorical nature of embryo quality, a threshold model was also evaluated. Embryo quality data were analyzed with either a univariate linear animal model or a univariate binomial threshold animal model. Genetic parameters estimated from the different models were comparable. A low heritability was found for the donor (0.04 ± <0.01) and the service sire (0.02 ± <0.01), but the repeatability estimate for the donor was higher (0.17), indicating that it was worthwhile to use a repeated records model. Overall, considering the low genetic parameters estimated, slow genetic progress is expected for the quality of frozen embryos produced by Canadian Holstein donors. Rank correlations were calculated between breeding values estimated from different models. High correlations were found between all models, indicating that no substantial re-ranking of the animals is expected from the different models. So, even though a threshold model is better suited for the analysis of categorical data, a linear model could be used for the analysis of embryo quality because it is less computationally demanding.
http://ift.tt/2sVVSoc
Association of candidate gene polymorphisms with milk technological traits, yield, composition, and somatic cell score in Italian Holstein-Friesian sires
Source:Journal of Dairy Science
Author(s): E. Viale, F. Tiezzi, F. Maretto, M. De Marchi, M. Penasa, M. Cassandro
Advances in DNA-based marker technology have enabled the identification of genomic regions underlying complex phenotypic traits in livestock species. The incorporation of detected quantitative trait loci into genetic evaluation provides great potential to enhance selection accuracies, hence expediting the genetic improvement of economically important traits. The objective of the present study was to investigate 96 single nucleotide polymorphisms (SNP) located in 53 candidate genes previously reported to have effects on milk production and quality traits in a population of highly selected Holstein-Friesian bulls. A total of 423 semen samples were used to genotype the bulls through a custom oligo pool assay. Forty-five SNP in 32 genes were found to be associated with at least 1 of the tested traits. Most significant and favorable SNP trait associations were observed for polymorphisms located in CCL3 and AGPAT6 genes for fat yield (0.037 and 0.033 kg/d, respectively), DGKG gene for milk yield (0.698 kg/d), PPARGC1A, CSN1S1, and AGPAT6 genes for fat percentage (0.127, 0.113, and 0.093%, respectively), GHR gene for protein (0.064%) and casein percentage (0.053%), and TLR4 gene for fat (0.090%), protein (0.066%), and casein percentage (0.050%). Somatic cell score was favorably affected by GHR (−0.095) and POU1F1 (−0.137), and interesting SNP-trait associations were observed for polymorphisms located in CSN2, POU1F1, and AGPAT6 genes for rennet coagulation time (−0.592, −0.558, and −0.462 min, respectively), and GHR and CSN2 genes for curd firmness 30 min after rennet addition (1.264 and 1.183 mm, respectively). In addition to the influence of individual SNP, the effects of composite genotypes constructed by grouping SNP according to their individual effects on traits considered in the analysis were also examined. Favorable and significant effects on milk traits were observed for 2 composite genotypes, one including 10 SNP and the other 4 SNP. The former was associated with an increase of milk (0.075 kg/d), fat (0.097 kg/d), protein (0.083 kg/d), and casein yields (0.065 kg/d), and the latter was associated with an increase of fat (0.244%), protein (0.071%), and casein percentage (0.047%). Although further research is required to validate the identified SNP loci in other populations and breeds, our results can be considered as a preliminary foundation for further replication studies on gene-assisted selection programs.
http://ift.tt/2ufvMjR
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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