Primary lateral sclerosis-like picture in a patient with a remote history of anti-N-methyl-D- aspartate receptor (anti-NMDAR) antibody encephalitis

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a well-recognised disorder, first fully characterised in 2007. The long-term sequelae reported thus far include relapses with typical, as well as partial aspects of the well-defined neuropsychiatric syndrome. Rarely, isolated atypical symptoms (diplopia, ataxia and tremor) have been reported as relapse phenomenon. We report a case of a patient with a remote history of likely anti-NMDAR encephalitis with the longest follow-up reported in the literature to date (22 years). The relapse presentation was of a purely upper motor neuron syndrome with a primary lateral sclerosis-like picture.

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Raised intracranial pressure with bilateral anterior uveitis

We report the rare case of a 5-year-old boy with an infective cause of papilloedema and bilateral uveitis secondary to Mycoplasma pneumoniae. The patient presented with generalised headache and malaise. MRI showed signs of raised intracranial pressure and lumbar puncture opening pressure was 43 cmH₂O.

Lumbar puncture did not reveal any infective organisms. Blood tests showed raised inflammatory markers. The patient was started on prednisolone, acetazolamide and intravenous cefotaxime. Following an improvement, the patient was discharged.

However, the patient re-presented 2 weeks later with bilateral anterior uveitis. With the combination of papilloedema and bilateral uveitis, M. pneumoniae infection was suspected. Tests confirmed recent mycoplasma infection. Topical dexamethasone and oral azithromycin were given and symptoms improved.

Vision remained normal throughout. At 1-year follow-up, the patient remains well. The authors would like to highlight a rare infectious cause of papilloedema in young children.

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Acute hepatitis E superinfection leading to chronic hepatitis B reactivation

Reactivation of chronic hepatitis B (CHB) can be associated with significant morbidity and mortality. There are many different causes of hepatitis B reactivation. This case describes an Asian woman with stable CHB presenting with significant hepatitis flare with markedly elevated serum aminotransferases and hepatitis B virus DNA level. The clinical symptoms were subtle with fatigue and vague right upper quadrant tenderness. We ruled out drug-associated hepatotoxicity and screened for common causes of acute hepatitis. Interestingly, she was noted to have reactive anti-hepatitis E virus (HEV) IgM at initial presentation followed by anti-HEV IgG positivity a month later. The serological pattern confirmed the diagnosis of acute hepatitis E. The combination of antiviral therapy for hepatitis B and resolution of acute hepatitis E resulted in normalisation of serum aminotransferases. This case illustrates the importance of taking a careful history and having a high index of suspicion for various aetiologies when evaluating patients with reactivation of CHB.

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Common anaesthetic agent causing an uncommon side effect

Description

A 30-year-old man was brought to our trauma centre with a history of road traffic accident 1 hour back. He had sustained a right both bone forearm fracture and surgery in the form of open reduction internal fixation with plating was planned. The preoperative routine haematological and biochemical investigations revealed normal values and the patient was posted for surgery after achieving preanaesthetic fitness. General anaesthesia was induced with fentanyl and propofol 100 mg and maintained with nitrous oxide and vecuronium. Intraoperative period was uneventful with the fractures being treated with a 7-hole dynamic compression plate (DCP) for radius and a 6-hole DCP for ulna. Glycopyrrolate and neostigmine were used for the reversal of neuromuscular blockade. The patient was extubated successfully and transferred to the postoperative ward. Two to 3 hours postsurgery, the nursing staff noticed green-coloured urine, thereby alarming them and the other medical personnel (figure 1). Urinary tract infection (UTI) was suspected. After a thorough re-evaluation of the patient and...

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Bimanual joint action: correlated timing or “bimanual” movements accomplished by two people

Abstract

A crew of two rowing together in perfect synchrony is an example of a task that requires each performer to maintain meticulous timing when coordinating their movements with the other. At the individual level, temporal coordination of the limbs has been observed in bimanual pointing movements even when made to targets of different distance. Timing of the arms is not independent; rather there is a natural temporal coupling. The aim of this experiment was to investigate whether the temporal characteristics of pointing movements can be observed under joint conditions. Sixteen pairs of participants made short and long, unimanual and bimanual pointing movements. In the unimanual and bimanual solo conditions, participants made the movements alone. In the joint condition, each participant contributed one arm to the joint "bimanual" movements. Absolute temporal coupling at movement initiation and termination was measured by the differences in reaction time and total response time. Relative temporal coupling at movement initiation and termination was measured by correlating reaction time and total response time of the left and right limbs. Pointing movements had synchronous movement termination in the bimanual solo conditions and asynchronous termination in the unimanual solo and bimanual joint conditions. The initiation and termination of the arms were not correlated in the unimanual solo condition (initiation r = 0.01, termination r = 0.03). Small-to-medium correlations (r = 0.19, r = 0.24) were observed in the bimanual joint condition, and they were larger than the unimanual solo condition (p = 0.022, p = 0.063). As expected, there were large correlations in the bimanual solo conditions (r = 0.91, r = 0.81). Our findings suggest that absolute temporal coupling does not occur between individuals, but there is evidence for relative temporal coupling in the bimanual joint condition.

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Oncolytic Tanapoxvirus Expressing Interleukin-2 is Capable of Inducing the Regression of Human Melanoma Tumors in the Absence of T Cells

Background: Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-2 (IL-2), a T-cell growth factor, plays a critical role in activating T cells, natural killer (NK) cells and macrophages in both the innate and adaptive immune system.

Objective: We aimed to develop a recombinant TANV expressing mouse IL-2 (TANVΔ66R/mIL- 2), replacing the viral thymidine kinase (TK) gene (66R) with the mouse (m) mIL-2 transgene resulting in TANVΔ66R/mIL-2.

Methods: Human melanoma tumors were induced in female athymic nude mice by injecting SKMEL- 3 cells subcutaneously. Mice were treated with an intratumoral injection of viruses when the tumor volumes reached 45 ± 4.5 mm3.

Results: In cell culture, expression of IL-2 attenuated virus replication of not only TANVΔ66R/ mIL-2, but also TANVGFP. It was demonstrated that IL-2 inhibited virus replication through intracellular components and without activating the interferon-signaling pathway. Introduction of mIL-2 into TANV remarkably increased its anti-tumor activity, resulting in a more significant regression than with wild-type (wt) TANV and TANVΔ66R. Histopathological studies showed that extensive cell degeneration with a significantly increased peri-tumor accumulation of mononuclear cells in the tumors treated with TANVΔ66R/mIL-2, compared to wtTANV or TANVΔ66R.

Conclusion: We conclude that TANVΔ66R/mIL-2 is potentially therapeutic for human melanomas

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Meet Our Editorial Board Member

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Tunneling Nanotubes: A Versatile Target for Cancer Therapy

Currently Cancer is the leading cause of death worldwide. Malignancy or cancer is a class of diseases characterized by uncontrolled cell growth that eventually invade other tissues and develop secondary malignant growth at other sites by metastasis. Intercellular communication plays a major role in cancer, particularly in the process of cell proliferation and coordination which in turn leads to tumor invasion, metastasis and development of resistance to therapy. Cells communicate among themselves in a variety of ways, namely: i) via gap junctions with adjacent cells; ii) via exosomes with nearby cells; and iii) via chemical messengers with distant cells. Besides, cell - cell connection by tunneling nanotubes (TnTs) is recently gaining importance where intercellular components are transferred between cells. In general cell organelles like Golgi vesicle and mitochondria; and biomolecules like nucleic acids and proteins are transferred through these TnTs. These TnTs are long cytoplasmic extensions made up of actin that function as intercellular bridge and connect a wide variety of cell types. Malignant cells form TnTs with either other malignant cells or cells of the surrounding tumor matrix. These TnTs help in the process of initiation of tumor formation, its organization and propagation. The current review focuses on the role of TnTs mediated cell – cell signaling in cancer micro-environment. Drugs that inhibit TnT-formation such as metformin and everolimus can be targeted towards TnTs in the management of cancer growth, proliferation, tumor invasion and metastasis.

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Redox Biotransformation and Delivery of Anthracycline Anticancer Antibiotics: How Interpretable Structure-activity Relationships of Lethality Using Electrophilicity and the London Formula for Dispersion Interaction Work

Background: Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of either insufficient accuracy, huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out, even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted.

Objective: In order to make a breakthrough of QSAR, mechanistically interpretable molecular descriptors were used to correlate with biological activity to establish structure-activity plots. The biological activity is the lethality of anthracycline anticancer antibiotics denoted as log LD50. The mechanistically interpretable molecular descriptors include electrophilicity and the mathematical function in the London formula for dispersion interaction.

Method: The descriptors were calculated using quantum chemical methods.

Results: The plots for electrophilicity, which is interpreted as redox reactivity of anthracyclines, can describe oxidative degradation for detoxification and reductive bioactivation for toxicity induction. The plots for the dispersion interaction function, which represents the attraction between anthracyclines and biomolecules, can describe efflux from and influx into the target cells of toxicity. The plots can also identify three structural scaffolds of anthracyclines that have different metabolic pathways, resulting in their different toxicity behavior.

Conclusion: This structure-dependent toxicity behavior revealed in the plots can provide perspectives on drug design and drug metabolism study.

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Towards Prevention of Ovarian Cancer

Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal antiinflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and antiinflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges.

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Fertility Drugs and Ovarian Cancer

The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer have also been highlighted.

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Oxidative Stress and Cancer: The Role of Nrf2

Oxidative stress due to imbalance between ROS production and detoxification plays a pivotal role in determining cell fate. In response to the excessive ROS, apoptotic signaling pathway is activated to promote normal cell death. However, through deregulation of biomolecules, high amount of ROS promotes carcinogenesis in cells with defective signaling factors. In this line, NRF2 appears to be as a master regulator, which protects cells from oxidative and electrophilic stress. Nrf2 is an intracellular transcription factor that regulates the expression of a number of genes to encode anti-oxidative enzymes, detoxifying factors, anti-apoptotic proteins and drug transporters. Under normal condition, Nrf2 is commonly degraded in cytoplasm by interaction with Keap1 inhibitor as an adaptor for ubiquitination factors. However, high amount of ROS activates tyrosine kinases to dissociate Nrf2: Keap1 complex, nuclear import of Nrf2 and coordinated activation of cytoprotective gene expression. Nevertheless, deregulation of Nrf2 and/or Keap1 due to mutation and activated upstream oncogenes is associated with nuclear accumulation and constitutive activation of Nrf2 to protect cells from apoptosis and induce proliferation, metastasis and chemoresistance. Owning to the interplay of ROS and Nrf2 signaling pathways with carcinogenesis, Nrf2 modulation seems to be important in the personalization of cancer therapy.

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Diallyl Disulfide Inhibits Breast Cancer Stem Cell Progression and Glucose Metabolism by Targeting CD44/PKM2/AMPK Signaling

Background: It has been reported that diallyl disulfide (DADS) has anti-proliferative activity in many cancers.

Objective: The purpose of this study was to investigate the functions of DADS and the underlying mechanisms of its effect in breast cancer stem cells (BCSCs).

Method: Mammosphere formation assay, glucose consumption assay, lactate production assay and mouse xenograft experiments were performed to explore the functions of DADS in BCSCs. ATPase activity assay, western blotting and immunohistochemistry (IHC) assay were conduct to explore the mechanisms underlying the effects of DADS in BCSCs.

Results: The results showed that DADS suppressed cell stemness and glucose metabolism in BCSCs. In vivo mouse xenograft experiments showed that DADS inhibited the proliferation and metastasis of BCSCs. Then, we continued to explore the mechanisms underlying the effects of DADS in BCSCs and found that DADS acts by targeting CD44, Pyruvate kinase M2 (PKM2) and AMP-activated protein kinase (AMPK) signaling pathways. IHC analysis of 125 breast cancer patients' tissues demonstrated that CD44, PKM2 and AMPK expression levels were positively correlated. In addition, positive CD44, PKM2 and AMPK expression was associated with poor patient overall survival (OS) and disease-free survival (DFS).

Conclusion: In summary, DADS suppresses cell stemness, proliferation, metastasis and glucose metabolism in BCSCs partly through the inhibition of CD44/PKM2/AMPK. DADS may be used as a potential therapy for breast cancer treatment.

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Role of Glioma-associated GLI1 Oncogene in Carcinogenesis and Cancertargeted Therapy

Glioma-associated oncogenes (GLIs) are zinc finger protein family members and downstream regulatory factors of the classic Hedgehog (Hh) signaling pathway. GLI proteins influence the growth and development of organisms and aid in tissue repair. However, aberrant expression of the GLI family member GLI1 promotes carcinogenesis by inducing epithelial–mesenchymal transition (EMT), angiogenesis, and other signaling pathways. Overexpression of GLI1 is thought to be an indicator of poor prognosis as well as a potential therapeutic target for cancers. GLI inhibitors such as zerumbone, GANT61, resveratrol, and cyclopamine depress the Hh pathway in vitro and in vivo cancer research, and other non-canonical pathways may also activate expression of GLI1. Here, we summarize GLI function in carcinogenesis and cancer-targeted therapy.

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CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death

Background: Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and promotes a "non-oncogene addiction" phenotype. Whether this kinase regulates BCR signaling, being a suitable pharmacological target in DLBCL, is unknown.

Objective: The objective was to establish if CK2 controls DLBCL cell survival and the BCR signaling, to check if the combination of CK2 inhibitor CX-4945 and BCR blockers Ibrutinib and Fostamatinib is more effectively cytotoxic for DLBCL cells than the single agents and to survey the changes in signaling molecules downstream BCR upon CK2 inhibition.

Method: A panel of GC and ABC DLBCL cells was treated with CX-4945 and Fostamatinib or Ibrutinib. BCR signaling was assayed by intracellular Ca++ measurement and looking at the phosphorylation of signaling molecules. The effects on cell survival were assessed by flow cytometry, western blot and MTT assays.

Results: CK2 inhibition with CX-4945 causes DLBCL cell death. CX-4945 impaired AKT phosphorylation and intracellular Ca++ mobilization upon BCR engagement. The CK2 inhibitor acted synergistically with either the SYK inhibitor Fostamatinib or the BTK inhibitor Ibrutinib in inducing DLBCL cell death. CX-4945 was equally effective in GC and ABC DLBCL subtypes as well as in "double hit" DLBCL cell lines.

Conclusion: These findings suggest a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in the DLBCL.

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Treating synchronous bilateral ocular adnexal marginal zone lymphoma: the consortium for improving survival of lymphoma study

Abstract

Both-side synchronous involvement has been reported to account for 7–24% of ocular adnexal marginal zone lymphoma (OAML). We conducted a retrospective analysis to identify the clinical features and treatment outcomes of synchronous bilateral OAML (SB-OAML) by treatment modality. We analyzed patients with a histologic diagnosis of SB-OAML, excluding metachronous bilateral involved OAML. We enrolled a total of 95 patients for this analysis, 36 males and 59 females; the median patient age was 42 years (range 16–77 years). Eleven (11.6%) patients had been treated with chemotherapy or chemo-immunotherapy (eight R-CVP, two CVP, and one R-CHOP). The median number of treatments was 6 (range 6–8); there were 9 complete responses (CRs; 81.8%) and 2 partial responses (PRs; 18.2%). Nearly all patients (88.4%) received radiotherapy in both eyes, and the median radiation dose was 27 Gy (range 20–40 Gy) to each eye; 68 CRs (80.9%) and 14 PRs (16.7%) were achieved. Ten-year progression-free survival (PFS) and overall survival (OS) rates were 79.8 and 91.1%, respectively. Radiotherapy continued to be an independent prognostic marker, with the hazard of progression (P = 0.036). Eleven patients (13.1%) had surgery for cataract treatment during follow-up, and patients who received low-dose radiation (< 30.3 Gy) experienced fewer cataract operations. SB-OAML was predominantly observed in young females, and they had good response and prognosis regardless of treatment modalities. Low-dose radiotherapy to both eyes showed a tendency of longer PFS than did chemotherapy and could decrease cataract operations.

https://ift.tt/2JwMaAB

Cancers, Vol. 10, Pages 192: Recombinant TSR1 of ADAMTS5 Suppresses Melanoma Growth in Mice via an Anti-angiogenic Mechanism

Cancers, Vol. 10, Pages 192: Recombinant TSR1 of ADAMTS5 Suppresses Melanoma Growth in Mice via an Anti-angiogenic Mechanism

Cancers doi: 10.3390/cancers10060192

Authors: Bhuvanasundar Renganathan Vinoth Durairaj Dogan Can Kirman Paa Kow A. Esubonteng Swee Kim Ang Ruowen Ge

Inhibiting tumor angiogenesis is a well-established approach for anticancer therapeutic development. A Disintegrin-like and Metalloproteinase with ThromboSpondin Motifs 5 (ADAMTS5) is a secreted matrix metalloproteinase in the ADAMTS family that also functions as an anti-angiogenic/anti-tumorigenic molecule. Its anti-angiogenic/anti-tumorigenic function is independent from its proteinase activity, but requires its first thrombospondin type 1 repeat (TSR1). However, it is not known if recombinant TSR1 (rTSR1) can function as an anticancer therapeutic. In this report, we expressed and purified a 75-residue recombinant TSR1 polypeptide from E. coli and investigated its ability to function as an anticancer therapeutic in mice. We demonstrate that rTSR1 is present in the blood circulation as well as in the tumor tissue at 15 min post intraperitoneal injection. Intraperitoneal delivery of rTSR1 potently suppressed subcutaneous B16F10 melanoma growth as a single agent, accompanied by diminished tumor angiogenesis, increased apoptosis, and reduced cell proliferation in the tumor tissue. Consistently, rTSR1 dose-dependently induced the apoptosis of cultured human umbilical vein endothelial cells (HUVECs) in a caspase-dependent manner. This work indicates that rTSR1 of ADAMTS5 can function as a potent anticancer therapy in mice. It thus has the potential to be further developed into an anticancer drug.

https://ift.tt/2sYg5uJ

Deep venous thrombosis, pulmonary embolism and long-distance flights

Abstract

Deep vein thrombosis resulting in lethal pulmonary thromboembolism is not-infrequently encountered in forensic cases. Predisposing factors include immobility, recent surgery, previous deep venous thromboses/pulmonary thromboembolism, indwelling central venous lines, major trauma, the oral contraceptive pill, pregnancy, congenital cardiac disease, sepsis, malignancy, systemic lupus erythematosus, renal failure and certain inherited thrombophilias. Venous thrombosis associated with air travel was reported in the early 1950's and called the "economy class syndrome", although it is now recognized that reduced movement on long distance flights is more significant than seating class. Long-distance flights of eight hours or more are associated with a two to fourfold increase in the risk of deep venous thrombosis, but only in those individuals who have underlying risk factors. With increasing numbers of flights of more than 16 h duration forensic pathologists are well placed to monitor the potential impact of extended flying on the incidence of lethal pulmonary thromboembolism.

https://ift.tt/2HCZdyP

Myosin 5a regulates tumor migration and epithelial-mesenchymal transition in esophageal squamous cell carcinoma: utility as a prognostic factor

Esophageal squamous cell carcinoma (ESCC) is highly malignant. Recently, the expression of myosin 5a, a member of the myosin superfamily, was reported to be associated with increased invasiveness and metastasis in many tumor types. Moreover, myosin 5a is upregulated by Snail and activated by Akt2, both of which are epithelial-mesenchymal transition (EMT) markers. In this study, we confirmed the expression of myosin 5a in ESCC surgical specimens and cell lines, revealing its correlation with tumor invasion, migration, patient prognosis, and expression of EMT-related proteins.

https://ift.tt/2JqNYiW

FOXP3-positive T-cell lymphomas in non-HTLV1 carriers include ALK-negative anaplastic large cell lymphoma: expanding the Spectrum of T-cell lymphomas with regulatory phenotype

Forkhead box P3 (FOXP3) is a specific marker for regulatory T-cells (Tregs). We report 6 cases of T-cell lymphomas with Treg phenotype based on diffuse positivity for FOXP3 in tumor cells. The patients showed a median age of 56years with a male predominance. Sites of disease included lymph nodes (4), skin (2), subcutaneous tissue (1) and bone marrow (1). All cases showed monomorphic large cells, some with Hodgkin-like or anaplastic cells. All cases expressed pan T cell markers and lacked cytotoxic markers; one case showed diffuse PD1 staining.

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Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency

We present a protocol for efficient, bulk, and rapid chemical reversion of conventional lineage-primed human pluripotent stem cells (hPSC) into an epigenomically-stable naïve preimplantation epiblast-like pluripotent state. This method results in decreased lineage-primed gene expression and marked improvement in directed multilineage differentiation across a broad repertoire of conventional hPSC lines.

https://ift.tt/2sNVM3G

Collecting Hair Samples for Hair Cortisol Analysis in African Americans

Hair cortisol concentration analysis provides an alternative to traditional measures of cortisol; however, to collect hair samples from African Americans, scientists need to be culturally informed and competent. The purpose of this protocol is to demonstrate a culturally informed technique to collect hair samples for cortisol analysis from African Americans.

https://ift.tt/2y1H9Pi

Characterization of Synthetic Polymers via Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) Mass Spectrometry

A protocol for the matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) characterization of synthetic polymers is described including the optimization of sample preparation, spectral acquisition, and data analysis.

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CD30 Is Highly Expressed in Chronic Obstructive Pulmonary Disease and Induces the Pulmonary Vascular Remodeling

Chronic obstructive pulmonary disease (COPD) is one of the common and underdiagnosed diseases with the highest morbidity and mortality in the world. The development of COPD can lead to pulmonary vascular remodeling and pulmonary hypertension, further causing the occurrence of pulmonary heart disease. Therefore, attenuation of pulmonary vascular remodeling and pulmonary hypertension caused by COPD can significantly delay cardiovascular complications. In the study, we firstly found that the expression of CD30 and CD30L was increased in COPD. Importantly, the serum CD30L levels were significantly higher in patients with stable COPD relative to those with acute exacerbation of COPD (AECOPD). This suggested that CD30 might be related to the development of COPD. In addition, we found that the expression of CD30 in the COPD rat model was significantly increased compared with control group. And treatment with the anti-CD30 antibody reduced the serum concentration and tissue expression of CD30 in rat. Importantly, anti-CD30 antibody alleviated pulmonary vascular remodeling in COPD model rats. This suggested that CD30 played an important role in the course of COPD. Finally, we found that, in the HPASMC and HPAEC cell lines, CD30 can affect the cell viability and cell migration and inhibited hypoxia-induced cell apoptosis in a concentration-dependent manner. We also found CD30 induced extracellular matrix formation through decreasing the expression of MMP-2, thus promoting the pulmonary vascular remodeling. The study indicated that CD30 and CD30L were involved in pulmonary vascular remodeling and inflammatory response in COPD. Altogether, CD30 might be a marker for the early diagnosis and progression of COPD.

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Rhodiola rosea Improves Lifespan, Locomotion, and Neurodegeneration in a Drosophila melanogaster Model of Huntington’s Disease

Huntington's disease (HD) is a dominant, late-onset disease characterized by choreiform movements, cognitive decline, and personality disturbance. It is caused by a polyglutamine repeat expansion in the Huntington's disease gene encoding for the Huntingtin protein (Htt) which functions as a scaffold for selective macroautophagy. Mutant Htt (mHtt) disrupts vesicle trafficking and prevents autophagosome fusion with lysosomes, thus deregulating autophagy in neuronal cells, leading to cell death. Autophagy has been described as a therapeutic target for HD, owing to the key role Htt plays in the cellular process. Rhodiola rosea, a plant extract used in traditional medicine in Europe and Asia, has been shown to attenuate aging in the fly and other model species. It has also been shown to inhibit the mTOR pathway and induce autophagy in bladder cancer cell lines. We hypothesized that R. rosea, by inducing autophagy, may improve the phenotype of a Huntington's disease model of the fly. Flies expressing HttQ93 which exhibit decreased lifespan, impaired locomotion, and increased neurodegeneration were supplemented with R. rosea extract, and assays testing lifespan, locomotion, and pseudopupil degeneration provided quantitative measures of improvement. Based on our observations, R. rosea may be further evaluated as a potential therapy for Huntington's disease.

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Significance of Methylation of FBP1 Gene in Non-Small Cell Lung Cancer

Because NSCLC has poor overall prognosis and is frequently diagnosed at later stage, we aimed to seek novel diagnosis biomarkers or therapy target of the disease in this study. Fructose-1,6-bisphosphatase 1 (FBP1) is a rate-limiting enzyme in gluconeogenesis, which was usually lost in NSCLC due to abnormal methylation in promoter DNA sequence. The clinical data indicated that the methylation rate in FBP1 gene promoter was negatively related to the overall survival of the NSCLC patients. DNA methylation transferase inhibitor 5-aza treatment could significantly increase both expression levels of mRNA and protein in A549 cell line. On the other hand, silence of FBP1 in H460 cell line by using specific siRNA against FBP1 dramatically improved the cell proliferation and cell migration according to the date of FACS and transwell assays. All these findings implied the important roles of FBP1 expression in lung cancer development and progression and the potential use of the methylation status detected in FBP1 promoter region as a novel predictor for prognosis and therapeutic target for NSCLC patients.

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Cytotoxicity of Air Pollutant 9,10-Phenanthrenequinone: Role of Reactive Oxygen Species and Redox Signaling

Atmospheric pollution has been a principal topic recently in the scientific and political community due to its role and impact on human and ecological health. 9,10-phenanthrenequinone (9,10-PQ) is a quinone molecule found in air pollution abundantly in the diesel exhaust particles (DEP). This compound has studied extensively and has been shown to develop cytotoxic effects both in vitro and in vivo. 9, 10-PQ has been proposed to play a critical role in the development of cytotoxicity via generation of reactive oxygen species (ROS) through redox cycling. This compound also reduces expression of glutathione (GSH), which is critical in Phase II detoxification reactions. Understanding the underlying cellular mechanisms involved in cytotoxicity can allow for the development of therapeutics designed to target specific molecules significantly involved in the 9,10-PQ-induced ROS toxicity. This review highlights the developments in the understanding of the cytotoxic effects of 9, 10-PQ with special emphasis on the possible mechanisms involved.

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The effectiveness of a standard drill connected to a core biopsy needle: how to obtain specimens in very strong bone tumors

Publication date: Available online 9 June 2018
Source:Injury
Author(s): J. Baldi, D. Attala, A. Scotto di Uccio, V. Laquintana, R. Biagini, C. Zoccali
IntroductionCore biopsy is today recognized as the gold standard for the diagnosis of bone lesions; unfortunately, when the bone is too solid it can be very difficult to penetrate it; in case of failure, open biopsy is indicated but it is associated with greater contamination and complications. A possible solution is to connect a common orthopedic drill to the core biopsy needle.The aim of the presenting study was to present a technique useful for performing biopsies in case of very strong bone lesions and to evaluate the adequacy and quality of the obtained specimen.Materials and methodsA standard bone biopsy set was connected to a commercial drill to perform bone biopsies. Data was collected over a 2-year period (2015-2016). Information regarding technical success, diagnostic data and complication rates was all collated to assess the technical feasibility of this technique.ResultsOut of 357 bone biopsies, 34 patients underwent the procedure using a common orthopedic drill connected to a core biopsy needle. Diagnostic material was obtained in each patient and the artifacts were considered irrelevant. No major complications occurred in any patient.DiscussionThe use of a core biopsy needle connected to a common orthopedic drill facilitates the penetration of thick cortical bone by simply applying continuous speed and pressure; nevertheless, the biopsy needle we use is not designed for a drilling procedure and for this reason it can be damaged, but if the biopsy is performed with particular attention, the mechanical failure can be avoidedConclusionsBone biopsy using a commercial hand drill has a technically high success rate with minimal complications. Further studies with more cases are necessary to verify our results.



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A Double-Blind, Randomized Controlled Trial of Gabapentin vs. Placebo for Acute Pain Management in Critically Ill Patients with Rib Fractures

Publication date: Available online 9 June 2018
Source:Injury
Author(s): Eliza E. Moskowitz, Lucin Garabedian, Kimberly Harden, Emily Perkins-Pride, Menilik Asfaw, Candice Preslaski, Kiara N. Liasia, Ryan Lawless, Clay Cothren Burlew, Fredric Pieracci
IntroductionAchieving adequate pain control for rib fractures remains challenging; prescription of alternatives to narcotics is imperative to curtail the current opioid epidemic. Although gabapentin has shown promise following elective thoracic procedures, its efficacy in patients with rib fractures remains unstudied. We hypothesized that gabapentin, as compared to placebo, would both improve acute pain control and decrease narcotic use among critically ill patients with rib fractures.Materials and MethodsAdult patients admitted to the trauma surgery service from November 2016 – November 2017 at an urban, Level I trauma center with one or more rib fractures were randomized to either gabapentin 300 mg thrice daily or placebo for one month following their injury. Daily numeric pain scores, opioid consumption, oxygen requirement, respiratory rate, and incentive spirometry recordings during the index admission, as well as and one-month quality of life survey data were abstracted.ResultsForty patients were randomized. The groups were well matched with respect to age, gender, prior narcotic use, tobacco use, and prior respiratory disease. Although the median RibScore did not differ between groups, the gabapentin group had a higher median number of ribs fractured as compared to the placebo group (7 vs. 5, respectively). Degree of pulmonary contusion and injury severity score were similar between groups. Use of loco-regional anesthetic modalities did not differ between groups. Daily numeric pain scores, opioid consumption, oxygen requirement, respiratory rate, and incentive spirometry recordings were similar between both groups. No benefit was observed when adding gabapentin to a multi-modal analgesic regimen for rib fractures. There were no instances of pneumonia, respiratory failure, or mortality in either group. Hospital and intensive care unit length of stay were similar between groups. Both overall and chest-specific quality of life was equivalent between groups at one month follow-up.ConclusionsIn this group of critically ill patients with rib fractures, gabapentin did not improve acute outcomes for up to one month of treatment.



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Cephalic region war injuries in children: Experience in French NATO hospital in Kabul AFGHANISTAN

Publication date: Available online 9 June 2018
Source:Injury
Author(s): Hussam El Chehab, Emilie Agard, Corinne Dot
BackgroundsThe NATO KAIA Hospital (Kabul International Airport), under French command, provided medical support for NATO forces in the Kabul region from 2009 to 2014. Medical assistance to civilians was an additional mission which included support for children who were war injured. The objective of this study was to analyze characteristics of cephalic injuries in children victims of war trauma.MethodsA retrospective study was conducted and commenced with the hospital opening (July 2009) to March 2012 on all children (<15years) with war trauma. We distinguished cephalic lesions in cranial (neuro-surgical), ophthalmological and neck regions. We analyzed mechanism, region, severity score, surgeries and resuscitation efforts.Results217 children were operated on with 81 war traumas (mean age 10.2years).36 children (44.4%) had a cephalic injury.52.9% of the injured had an ophthalmological injury, 38.2% a cranial region injury and 29.4% a neck lesion. Mortality rate was 5.6% (1 hemorrhagic shock and 1 cerebral wound) in this cephalic lesion group.Ophthalmic injuries were the most common of cephalic injuries; 19 children of which 7 had a bilateral injury (26 eyes). In this group, fragmentary injuries were the most frequent (64% of eyes).In cerebral lesion group, the lesions were linked to a bullet or a shrapnel in 9 of 13 children. This mechanism systematically caused a crania-cerebral wound.Explosion (fragmentary and shrapnel) was the most important in the neck lesions (7 children of 10).ConclusionsThe cephalic lesions were the second most common region in children during our experience in Afghanistan. Lack of protection (helmet) in children may explain the frequency of cephalic wounds.



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Cement-augmented sacroiliac screw fixation with cannulated versus perforated screws – a biomechanical study in an osteoporotic hemipelvis model

Publication date: Available online 9 June 2018
Source:Injury
Author(s): J. Hack, A. Krüger, A. Masaeli, R. Aigner, S. Ruchholtz, L. Oberkircher
IntroductionCement-augmentation is a well-established way to improve the stability of sacroiliac screw fixation in osteoporosis-associated fragility fractures of the posterior pelvic ring. However, to date little is known about the influence of different techniques of cement augmentation on construct stability. The aim of this study was to evaluate the primary stability of cement-augmented sacroiliac screw fixation with cannulated versus perforated screws under cyclic loading.Materials and MethodsA total of eight fresh-frozen human cadaveric hemipelvis specimens with osteoporosis were used. After generating ventral osteotomies on both sides of the sacrum, each specimen was treated using a cement-augmented cannulated screw on one side and a cement-augmented perforated screw on the other side. Afterwards, axial cyclic loading was performed.ResultsNo statistically significant difference was found between cannulated and perforated screws concerning maximum load (356.25 N versus 368.75 N, p = 0.749), plastic deformation (1.95 mm versus 1.43 mm, p = 0.798) and stiffness (27.04 N/mm versus 40.40 N/mm, p = 0.645).ConclusionsConsidering the at least equivalent results for perforated screws, cement augmentation via perforated screws might be an interesting option in clinical practice because of potential advantages, e.g. radiological control before cement application, reduced risk of cement displacement and time saving.



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Effect of Polyvalence on the Antibacterial Activity of a Synthetic Peptide Derived from Bovine Lactoferricin against Healthcare-Associated Infectious Pathogens

Antimicrobial peptides (AMPs) are gaining interest as potential therapeutic agents. Peptides derived from bovine lactoferricin B (LfcinB) have been reported to exhibit antimicrobial activity, and the LfcinB RRWQWR sequence is the smallest known motif that exhibits antibacterial and cytotoxic activity. Our goal was to examine the effect of multicopy arrangements of the RRWQWR motif, on its antibacterial activity against healthcare-associated infections (HCAIs). Linear and branched peptides containing the RRWQWR motif were generated using solid phase peptide synthesis-Fmoc/tBu methodology, purified, and characterized using reverse phase-high performance liquid chromatography and matrix-assisted laser desorption/ionization time of flight mass spectrometry. For each peptide, the antibacterial activity against Staphylococcus aureus (ATCC 25923 and 33591 strains) and Klebsiella pneumoniae (ATCC 13883 and 700603 strains) was assessed by measuring the minimum inhibitory and the minimum bactericidal concentrations, in the exponential phase. Cells were observed by scanning electron microscopy, and the hemolytic activity of the peptides was assessed. The overall results demonstrate that, compared to linear analogues, polyvalent presentation of the RRWQWR motif enhances its antibacterial activity against both Gram-negative and Gram-positive bacteria even on resistant strain.

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Evaluation of Lsa46 and Lsa77 Leptospiral Proteins for Their Immunoprotective Activities in Hamster Model of Leptospirosis

Leptospirosis is a neglected tropical disease caused by pathogenic Leptospira spp. The lack of an effective vaccine favors the increase of the disease. Currently, surface-exposed proteins are the main targets for the search of vaccine candidates. In this study, we examined whether the surface Lsa46 and Lsa77 proteins, previously identified as laminin and plasminogen binding proteins, have the capacity of inducing protection and sterilizing immunity against challenge with virulent Leptospira in hamster model. Animals were subcutaneously immunized with Lsa46, Lsa77, or a combination of both in Alum adjuvant and challenged intraperitoneally with L. interrogans serovar Kennewicki strain Pomona Fromm. Hamster immunization with Lsa46 or Lsa77 or both promoted a strong IgG response. Th2- and Th1-biased immune responses were observed when Lsa46 and Lsa77 were individually administered, respectively, as detected by the IgG1/IgG2/3 ratio. Immunized hamsters with the combined proteins induced a Th1-biased immune response. Although the immunization with Lsa46 and Lsa77 stimulated protective immunity with reduction of bacterial burden, when compared to animals individually immunized with the proteins, the data was not statistically significant. Thus, although promising, more studies are needed before the role of these proteins in stimulating sterilizing immunity in mammals is conclusively determined.

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Genetic Analysis with Random Amplified Polymorphic DNA of the Multiple Enterocin-Producing Enterococcus lactis 4CP3 Strain and Its Efficient Role in the Growth of Listeria monocytogenes in Raw Beef Meat

In this manuscript, a multiple enterocin-producing Enterococcus lactis strain named 4CP3 was used to control the proliferation of Listeria monocytogenes in refrigerated raw beef meat model. Also, the intraspecific genetic differentiation of 4CP3 strain was assessed by Random Amplified Polymorphic DNA Polymerase Chain Reaction (RAPD-PCR) analysis. E. lactis 4CP3 strain was found to produce the enterocins A, B, and P. It displayed activity against L. monocytogenes EGDe 107776 by agar-well diffusion method. The application of E. lactis 4CP3 culture at 107 CFU/g in raw beef meat was evaluated using both ANOVA and ANCOVA linear models in order to examine its effect on the growth of the pathogen L. monocytogenes during refrigerated storage. Hence, a very interesting result in decreasing (P

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Intentional Undercorrection by Implantation of Posterior Chamber Phakic Intraocular Lens With A Central Hole (Hole ICL) For Early Presbyopia

Purpose. To assess visual performance at near to far distances in early presbyopic patients with undercorrection by implantation of an ICL with a central hole (hole ICL). Methods. This prospective study evaluated forty-two eyes of 21 early presbyopic patients (age, 40 to 53 years) with spherical equivalents of -7.37 ± 3.18 D [mean ± standard deviation] who underwent hole ICL implantation and whose targeted refraction was set at slight myopia (-0.61 ± 0.28 D) for both eyes. We assessed the safety, efficacy at near to far distances, predictability, and adverse events of the surgery, during the 6-month observation period. Results. Corrected distance visual acuity did not improve significantly, from -0.17 ± 0.07 preoperatively to -0.19 ± 0.08 logMAR postoperatively (p=0.066, Wilcoxon signed-rank test). Uncorrected distance visual acuity was significantly improved from 1.30 ± 0.24 preoperatively to -0.03 ± 0.20 logMAR postoperatively (p

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Aging-Induced Biological Changes and Cardiovascular Diseases

Aging is characterized by functional decline in homeostatic regulation and vital cellular events. This process can be linked with the development of cardiovascular diseases (CVDs). In this review, we discussed aging-induced biological alterations that are associated with CVDs through the following aspects: (i) structural, biochemical, and functional modifications; (ii) autonomic nervous system (ANS) dysregulation; (iii) epigenetic alterations; and (iv) atherosclerosis and stroke development. Aging-mediated structural and biochemical modifications coupled with gradual loss of ANS regulation, vascular stiffening, and deposition of collagen and calcium often disrupt cardiovascular system homeostasis. The structural and biochemical adjustments have been consistently implicated in the progressive increase in mechanical burden and functional breakdown of the heart and vessels. In addition, cardiomyocyte loss in this process often reduces adaptive capacity and cardiovascular function. The accumulation of epigenetic changes also plays important roles in the development of CVDs. In summary, the understanding of the aging-mediated changes remains promising towards effective diagnosis, discovery of new drug targets, and development of new therapies for the treatment of CVDs.

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Postoperative Cognitive Dysfunction and Noncardiac Surgery

Postoperative cognitive dysfunction (POCD) is an objectively measured decline in cognition postoperatively compared with preoperative function. POCD has been considered in the anesthetic and surgical literature in isolation of cognitive decline which is common in the elderly within the community and where it is labeled as mild cognitive impairment, neurocognitive disorder, or dementia. This narrative review seeks to place POCD in the broad context of cognitive decline in the general population. Cognitive change after anesthesia and surgery was described over 100 years ago, initially as delirium and dementia. The term POCD was applied in the 1980s to refer to cognitive decline assessed purely on the basis of a change in neuropsychological test results, but the construct has been the subject of great heterogeneity. The cause of POCD remains unknown. Increasing age, baseline cognitive impairment, and fewer years of education are consistently associated with POCD. In geriatric medicine, cognitive disorders defined and classified as mild cognitive impairment, neurocognitive disorder, and dementia have definitive clinical features. To identify the clinical impact of cognitive impairment associated with the perioperative period, POCD has recently been redefined in terms of these geriatric medicine constructs so that the short-, medium-, and long-term clinical and functional impact can be elucidated. As the aging population present in ever increasing numbers for surgery, many individuals with overt or subclinical dementia require anesthesia. Anesthesiologists must be equipped to understand and manage these patients. Accepted for publication May 3, 2018. Funding: Institutional and/or departmental. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Lisbeth A. Evered, PhD, Department of Anaesthesia and Acute Pain Medicine, St Vincent's Hospital, PO Box 2900 Fitzroy, Victoria 3065, Australia. Address e-mail to lis.evered@svha.org.au. © 2018 International Anesthesia Research Society

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A Prospective Observational Study of Anesthesia-Related Adverse Events and Postoperative Complications Occurring During a Surgical Mission in Madagascar

BACKGROUND: Two-thirds of the world's population lack access to safe anesthesia and surgical care. Nongovernmental organizations (NGOs) play an important role in bridging the gap, but surgical outcomes vary. After complex surgeries, up to 20-fold higher postoperative complication rates are reported and the reasons for poor outcomes are undefined. Little is known concerning the incidence of anesthesia complications. Mercy Ships uses fully trained staff, and infrastructure and equipment resources similar to that of high-income countries, allowing the influence of these factors to be disentangled from patient factors when evaluating anesthesia and surgical outcomes after NGO sponsored surgery. We aimed to estimate the incidence of anesthesia-related and postoperative complications during a 2-year surgical mission in Madagascar. METHODS: As part of quality assurance and participation in a new American Society of Anesthesiologists Anesthesia Quality Institute sponsored NGO Outcomes registry, Mercy Ships prospectively recorded anesthesia-related adverse events. Adverse events were grouped into 6 categories: airway, cardiac, medication, regional, neurological, and equipment. Postoperative complications were predefined as 16 adverse events and graded for patient impact using the Dindo-Clavien classification. RESULTS: Data were evaluated for 2037 episodes of surgical care. The overall anesthesia adverse event rate was 2.0% (confidence interval [CI], 1.4–2.6). The majority (85% CI, 74–96) of adverse events occurred intraoperatively with 15% (CI, 3–26) occurring in postanesthesia care unit. The most common intraoperative adverse event, occurring 7 times, was failed regional (spinal) anesthesia that was due to unexpectedly long surgery in 6 cases; bronchospasm and arrhythmias were the second most common, occurring 5 times each. There were 217 postoperative complications in 191 patients giving an overall complication rate of 10.7% (CI, 9.3–12.0) per surgery and 9.4% (CI, 8.1–10.7) per patient. The most common postoperative complication was unexpected return to the operating room and the second most common was surgical site infection (39.2%; CI, 37.0–41.3 and 33.2%; CI, 31.1–35.3 of all complications, respectively). The most common (42.9%; CI, 40.7–45.1) grade of complication was grade II. There was 1 death. CONCLUSIONS: This study adds to the scarce literature on anesthesia outcomes after mission surgery in low- and middle-income countries. We join others in calling for an international NGO anesthesia and surgical outcome registry and for all surgical NGOs to adopt international standards for the safe practice of anesthesia. Accepted for publication April 30, 2018. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website. Reprints will not be available from the authors. Address correspondence to Michelle C. White, MBChB, Department of Anesthesia, Great Ormond Street Hospital for Children, London WC1N 3JH, UK. Address e-mail to doctormcw@gmail.com. © 2018 International Anesthesia Research Society

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Adjusting the Ventilator? Not Only Size Matters!

No abstract available

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Miller’s Anesthesia Review

No abstract available

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Evidence Review Conducted for the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery: Focus on Anesthesiology for Total Knee Arthroplasty

Enhanced recovery after surgery (ERAS) has rapidly gained popularity in a variety of surgical subspecialities. A large body of literature suggests that ERAS leads to superior outcomes, improved patient satisfaction, reduced length of hospital stay, and cost benefits, without affecting rates of readmission after surgery. These patterns have been described for patients undergoing elective total knee arthroplasty (TKA); however, adoption of ERAS to orthopedic surgery has lagged behind other surgical disciplines. The Agency for Healthcare Research and Quality, in partnership with the American College of Surgeons and the Johns Hopkins Medicine Armstrong Institute (AI) for Patient Safety and Quality, has developed the Safety Program for Improving Surgical Care and Recovery. The program comprises a national effort to incorporate best practice in perioperative care and improve patient safety, for over 750 hospitals and multiple procedures over the next 5 years, including orthopedic surgery. We have conducted a full evidence review of anesthetic interventions to derive anesthesiology-related components of an evidence-based ERAS pathway for TKA. A PubMed search was performed for each protocol component, focusing on the highest levels of evidence in the literature. Search findings are summarized in narrative format. Anesthesiology components of care were identified and evaluated across the pre-, intra-, and postoperative phases. A summary of the best available evidence, together with recommendations for inclusion in ERAS protocols for TKA, is provided. There is extensive evidence in the literature, and from society guidelines to support the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery goals for TKA. Accepted for publication March 22, 2018. Funding: This project was funded under contract number HHSP233201500020I from the Agency for Healthcare Research and Quality and the US Department of Health and Human Services. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website. The opinions expressed in this document are those of the authors and do not reflect the official position of Agency for Healthcare Research and Quality or the US Department of Health and Human Services. Reprints will not be available from the authors. Address correspondence to Christopher L. Wu, MD, Department of Anesthesiology, Hospital for Special Surgery/Weill Cornell Medical College, 535 E 70th St, New York, NY 10021. Address e-mail to wuch@hss.edu. © 2018 International Anesthesia Research Society

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In Response

No abstract available

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In Response

No abstract available

https://ift.tt/2HAnjdH

Perioperative Care of the Elderly Patient

No abstract available

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The Future of Activated Clotting Time?

No abstract available

https://ift.tt/2LEoI5m

Inhibitory Effects of Compounds and Extracts from Ampelopsis brevipedunculata on IL-6-Induced STAT3 Activation

Ampelopsis brevipedunculata (Maxim.) Trautv. (AB), a traditional East Asian medicine, exhibits protective effects against several inflammatory diseases. Our search for an inhibitor of IL-6-induced JAK2/STAT3 activation revealed that AB ethanolic extract (ABE) had a significant inhibitory effect on IL-6-induced STAT3 expression in Hep3B cells. The isolation and purification of an EtOAc-soluble fraction of ABE (ABEA) using reversed-phase high-performance liquid chromatography (RP-HPLC) afforded 17 compounds. The structures of these compounds (1-17) were elucidated based on 1H and 13C nuclear magnetic resonance (NMR) spectroscopy as well as electrospray-ionization mass spectrometry (ESI-MS) data. ABE and ABEA were screened by a luciferase assay using Hep3B cells transfected with the STAT3 reporter gene. ABEA exhibited potent inhibitory effects on IL-6-induced STAT3 expression; moreover, these effects arose from the inhibition of the phosphorylation of the STAT3, JAK2, and ERK proteins in U266 cells. In addition, the compounds isolated from ABEA were measured for their inhibitory effects on IL-6-stimulated STAT3 expression. Of the compounds isolated, betulin showed the greatest inhibitory effects on IL-6-induced STAT3 activation in the luciferase assay (IC50 value: 3.12 μM). Because of its potential for inhibiting STAT3 activation, A. brevipedunculata could be considered a source of compounds of pharmaceutical interest.

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An Investigation into the High Prevalence of Hepatitis B in a Rural Area of Kerala State, India: Hypothesis on Chrysops sp. (Diptera: Tabanidae) Transmission

Objective. Since 2005 there have been several reports of hepatitis B outbreak in the state of Kerala in southern India. Objective of this study was to analyze such outbreaks and to explore hypothesis pertaining the transmission mode. Methods. Retrospective observational study involving cases of acute hepatitis B acquired between 1 January 2015 and 31 December 2015 and their family members residing in Mazhuvanoor village in Ernakulam district of Kerala State in southern India. Results. 59 houses were included in the survey. The number of patients diagnosed to have acute viral hepatitis B was 59. Majority (66.10%) were over 50 years old. There were no cases below the age of 15 years. All 59 patients claimed to have been bitten frequently by a fly which was identified as "deer fly" belonging to the genus Chrysops. Conclusion. Given the current understanding of mechanical transmission of pathogens in both humans and animals by insects belonging to the Tabanidae family which also includes Chrysops, it is plausible that the same mechanism may hold true for hepatitis B also. However this needs to be proven in further studies both at the laboratory level and at field studies.

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Long-Lasting Alterations in Gene Expression of Postsynaptic Density 95 and Inotropic Glutamatergic Receptor Subunit in the Mesocorticolimbic System of Rat Offspring Born to Morphine-Addicted Mothers

Prenatal exposure to morphine causes altered glutamatergic neurotransmission, which plays an important pathophysiological role for neurobiological basis of opiate-mediated behaviors in such offspring. However, it is still not clear whether such alteration involves gene expression of ionotropic glutamate receptor subunits. In this study, we further studied whether prenatal morphine exposure resulted in long-term changes in the gene expression of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, -methyl--aspartate (NMDA) receptor, and postsynaptic density 95 in the mesocorticolimbic area (an essential integration circuitry for drug craving behavior), nucleus accumbens (NAc), ventral tegmental area (VTA), and prefrontal cortex (PFC), of rat offspring from morphine-addicted mothers. Experimental results showed that prenatal morphine exposure led to a persistent downregulation of gene expression in the AMPA and NMDA receptor subunit, with a differential manner of decreased magnitudes, at the age of postnatal days 14 (P14) and P30. However, in PFC, the gene expression of the AMPA receptor subunit was not synchronized in observed rat offspring subjected to prenatal morphine exposure. An upregulation of gene expression in the AMPA receptor subunit 3 (GluR3) was persistently observed at P14 and P30. Furthermore, the gene expressions of PSD-95 in NAc, VTA, and PFC were all decreased concurrently. Collectively, the results suggest that prenatal exposure to morphine may initiate molecular mechanisms leading to a long-lasting, differential alteration in gene expression of the inotropic glutamate receptor subunit and PSD-95 in the mesocorticolimbic circuitry in rat offspring. This study raises a possibility in which differential changes in gene expression with a long-lasting manner may play a role for the development of nearly permanent changes in opiate-mediated behaviors, at least in part for the neurobiological pathogenesis in offspring.

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Prevalence and Factors Associated with Contraceptive Use among HIV-Infected Women of Reproductive Age Attending Infectious Disease Clinic at Gulu Regional Referral Hospital, Northern Uganda

Background. Reproductive planning by HIV-infected women is essential, as it helps to prevent transmission of HIV to their unborn babies. Integrating contraceptive services to routine HIV care significantly increases the use of modern contraceptive methods, thus reducing vertical transmission of HIV. Objectives. To determine the prevalence and factors associated with contraceptive use among HIV-infected women attending Infectious Disease Clinic (IDC) at Gulu Regional Referral Hospital (GRRH) in Northern Uganda. Methodology. A hospital-based cross-sectional study was performed. We used simple random sampling to recruit HIV-infected women receiving routine care from IDC, GRRH, into our study. Sample size was estimated using modified Kish-Leslie formula and semistructured questionnaire was used for data collection. Data was entered into EpiData version 3.1 and analysed using Stata v11.0. We used logistic regression model to assess the associations and any factor with p≤0.05 was considered statistically significant. Results. The prevalence of contraceptive use was found to be 36% (95% CI 31 – 40%). Factors which promoted contraceptive use were as follows: being married (aOR=2.68, 95% CI 1.54-4.65, p

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Modernization of Traditional Oriental Medicine: New Dosage Forms and Medical Instruments

https://ift.tt/2sJvTSE

A case of severe Pembrolizumab-induced neutropenia

Immune checkpoint inhibitors have revolutionized cancer therapy. Given their mechanism of action, immune-related adverse events have been associated with their use. We present the first documented case of pembrolizumab-induced grade IV neutropenia. A 73-year-old women known for myositis, Crohn's disease, and hypothyroidism and diagnosed with PD-L1 positive stage IV pulmonary adenocarcinoma is treated with Pembrolizumab. She develops grade IV neutropenia 2 weeks after her second infusion. She is therefore hospitalized and treated initially with corticosteroids, granulocyte colony-stimulating factor, and intravenous immunoglobulins. Given the persistent neutropenia, cyclosporine was added, but quickly stopped owing to fever. The patient recovered her neutrophils 6.5 weeks after her initial Pembrolizumab infusion and 12 days after admission. She has been subsequently successfully tapered off steroids with no recurrence after 3 months of follow-up. This is the first case of grade IV neutropenia secondary to Pembrolizumab. This case is of particular interest given the patient's pre-existing autoimmune history. Treatment of severe neutropenia due to other PD1 inhibitors has generally consisted of steroids, granulocyte colony-stimulating factor, intravenous immunoglobulins, mycophenolate mofetil, cyclosporine A, and anti-thymocyte globulins – though the benefits of immunosuppression are not clear and may be harmful given the infectious risks. Large studies are required to clarify the spectrum and optimal management of immune-related adverse events and overall risk/benefits of immune checkpoint inhibitors in patients with pre-existing autoimmunity. Correspondence to Peter G. Maliha, MD, Department of Nuclear Medicine, McGill University Health Centre, 1001 Decarie Blvd, Quebec, QC, H4A 3J1, Montreal, Canada E-mail: peter.maliha@mail.mcgill.ca Received February 25, 2018 Accepted May 21, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Comparative Analysis of ADR on China’s National Essential Medicines List (2015 Edition) and WHO Model List of Essential Medicines (19th Edition)

Objective. To explore the safety of the essential medicines recorded in China's list through the comparison of the list of essential medicines of China and the World Health Organization (WHO), as well as the analysis of the basic situation and characteristics of adverse drug reactions (ADRs) on the two essential medicines recorded in China's and WHO lists in order to provide a reference for the improvement of China's list. Methods. A retrospective descriptive study was conducted, based on the database in Jiangsu Province ADR Monitoring Center from 2013 to 2015. A total of 266869 cases reports were collected within this period, comparing the differences between the two essential medicines recorded in China's and WHO lists, considering number of ADRs, type of report, and modes of administration. Compare the differences between the two groups of drugs in the presence of new, severe, and new severe adverse events using chi square test. Results. Comparing the two essential medicines list, they have the same 117 species. When comparing ADRs in the two groups, most are antimicrobial, electrolytes, and acid-base balance drugs, regulate water, and are higher in China. In addition, with respect to the number of ADR types in the two groups, there is statistical significance (p

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Neuropeptide B and Vaspin as New Biomarkers in Anorexia Nervosa

Introduction. The aim of the study was to assess the correlation between the levels of neuropeptide B (NPB), neuropeptide W (NPW), vaspin (VAS), and the total antioxidant status (TAS) in the blood, as well as nutritional status of patients with anorexia nervosa (AN). Materials and Methods. The study covered a cohort of 76 female teenagers, including 46 females with extreme AN and 30 healthy peers (CONTR) aged 12-17. Results. AN persons were characterized by higher (in comparison to CONTR) NPB and VAS concentrations and lower values of TAS levels, body weight, and anthropometric values. Positive correlations between NPB and VAS levels were noted in the AN group (R=0.33; p

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Effects of Cyclic Tensile Strain on Oxidative Stress and the Function of Schwann Cells

Schwann cells (SCs) are significant due to the way in which they sustain and myelinate axons within the peripheral nervous system (PNS). This study has investigated the effect of cyclic tensile strain (CTS) on the oxidative stress and function of SCs derived from the sciatic nerves of an infant rat population. A group of 20 6-day-old Wistar rats was selected, and SCs were separated from the sciatic nerve. The SCs then underwent a 6-hour period of cyclical straining, and ElectroForce 3200 in combination with the BioDynamic chamber was employed to apply 0% and 5% strains at a 0.25 Hz frequency. The results showed that the control group suffered higher oxidative stress than that in 5% strains group (P

https://ift.tt/2xWcjHK

Aryl Hydrocarbon Receptor: A New Player of Pathogenesis and Therapy in Cardiovascular Diseases

The aryl hydrocarbon receptor (AhR) is a DNA binding protein that acts as a nuclear receptor mediating xenobiotic metabolism and environmental responses. Owing to the evolutionary conservation of this gene and its widespread expression in the immune and circulatory systems, AhR has for many years been almost exclusively studied by the pharmacological/toxicological field for its role in contaminant toxicity. More recently, the functions of AhR in environmental adaption have been examined in the context of the occurrence, development, and therapy of cardiovascular diseases. Increasing evidence suggests that AhR is involved in maintaining homeostasis or in triggering pathogenesis by modulating the biological responses of critical cell types in the cardiovascular system. Here, we describe the structure, distribution, and ligands of AhR and the AhR signaling pathway and review the impact of AhR on cardiovascular physiology. We also discuss the potential contribution of AhR as a new potential factor in the targeted treatment of cardiovascular diseases.

https://ift.tt/2JtXTA5

Curcumin as Treatment for Bladder Cancer: A Preclinical Study of Cyclodextrin-Curcumin Complex and BCG as Intravesical Treatment in an Orthotopic Bladder Cancer Rat Model

Objective. To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. Methods. Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. Results. CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. Conclusions. Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.

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A Case of Herpes Simplex Virus-1 Encephalitis from a Medicolegal Point of View

We present a case of herpes simplex virus-1 encephalitis (HSVE) and discuss the difficulty of early diagnosis and the possibility of a wrong or delayed diagnosis and treatment of this encephalitis. We show the importance of considering HSVE to pursue every case of suspicious medical liability.

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Intracardiac Teratoma in an Infant: Report of a New Case and Literature Review

Primitive intracardiac tumours are rare, especially in childhood, and are often discovered on autopsy. The intracardiac teratoma is the rarest intracardiac tumours of childhood. Herein, we report the case of an 11-month-old infant, which featured recurrent bronchoalveolitis since the age of 3 months, with a thoracic deformation. Physical examination did found discrete respiratory distress signs. Chest radiography showed large mediastinal enlargement. The computed tomography showed a solid cystic-cloisonned mass with fat and central calcification highly suggestive of an intracardiac teratoma. A radical surgical excision was made and the histological examination found a well circumscribed tumour containing elements of the three germ layers confirming the diagnosis of mature well-differentiated teratoma, with no need of immunohistochemical support.

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