bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Progressive Renal Decline Precedes the Onset of Microalbuminuria and Its Progression to Macroalbuminuria
Authors: Krolewski Andrzej S. , Niewczas Monika A. , Skupien Jan , Gohda Tomhito , Smiles Adam , Eckfeldt Jon H. , Doria Alessandro , Warram James H. 
Published: August 2013

OBJECTIVE
Progressive decrease in the glomerular filtration rate (GFR), or renal decline, in type 1 diabetes (T1D) is observed in patients with macroalbuminuria. However, it is unknown whether this decline begins during microalbuminuria (MA) or normoalbuminuria (NA).

RESEARCH DESIGN AND METHODS
The study group (second Joslin Kidney Study) comprises patients with T1D and NA (n = 286) or MA (n = 248) who were followed for 4–10 years (median 8 years). Serial measurements (median 6, range 3–16) of serum creatinine and cystatin C were used jointly to estimate GFR (eGFRcr-cys) and assess its trajectories during follow-up.

RESULTS
Renal decline (progressive eGFRcr-cys loss of at least 3.3% per year) occurred in 10% of the NA and 35% of the MA (P &lt; 0.001). In both groups, the strongest determinants of renal decline were baseline serum concentrations of uric acid (P &lt; 0.001) and tumor necrosis factor receptor 1 or 2 (TNFR-1 or -2, P &lt; 0.001). Other significant risk factors included baseline HbA1c, age/diabetes duration, and systolic blood pressure. Relative impacts of these determinants were similar in NA and MA. Renal decline was not associated with sex or baseline serum concentration of TNF-α, IL-6, IL-8, IP-10, MCP-1, VCAM, ICAM, Fas, or FasL.

CONCLUSIONS
Renal decline in T1D begins during NA and it is determined by multiple factors, similar to MA. Thus, this early decline is the primary disease process leading to impaired renal function in T1D. Changes in albumin excretion rate, such as the onset of MA or its progression to macroalbuminuria, are either caused by or develop in parallel to the early renal decline.
Comparison Intra Articular Steroid vs. Hydraulic Distention for the Treatment of Frozen Shoulder
Authors: Singh GP 
Published: August 2013

Background Frozen shoulder is a chronic fibrosing condition of the capsule of the shoulder joint. OBJECTIVE The objective of the study was to compare the result of treatment of frozen shoulder by Hydraulic Distention under local anesthesia with steroid and intra articular steroid alone. Sample Size: 60 patients were taken in this study and were divided into two groups. Duration and Setting: The study was conducted in 2005-2006 treated in the department of orthopaedic, Janaki medical college Teaching Hospital, Janakpur. Materials and Methods: It was a prospective, observational, comparative and clinical study. Sixty patients were selected from Dhanusha District of Janakpur, Nepal. They were divided into two groups. Since January 2005 to January 2006 periods in the department of orthopedics surgery, Janaki Medical College & Teaching Hospital, Janakpur. The Group I was treated by hydraulic distention of glenohumeral joint with 50ml normal saline with steroid, oral medicines (analgesics and muscle relaxants) and exercises. Patients in group II were treated by intra-articular steroid followed by oral medicines (analgesics and muscle relaxants) and exercises. Results: The average age of patients in group I was 52 ± 2.16 years and 50 ± 2.03 in group II. There were 37 (63%) females and 23 (37%) males in our study. Female to male ratio was 1.7:1. All patients in group noted immediate pain relief with excellent return of range of motion (ROM) and resumption of normal sleep. At the end of 45 days of follow up all patients had returned to their normal daily activities. Most of them got excellent ROM and pain relief. All patients in group II noted immediate pain relief and resumption of almost normal sleep. At the end of 45 days of follow up most of the patient presented with good relief of pain but could not return to most of their normal activities because of less improvement in ROM. Conclusions: Hydraulic distension technique is quick, safe and gives early results, so it should be considered first for the treatment of frozen shoulder. DOI: http://dx.doi.org/10.3126/jucms.v1i1.8415 Journal of Universal College of Medical Sciences Vol.1(1) 2013: 3-9
C-Reactive Protein in Patients with NSTEMI Acute Coronary Syndrome
Authors: Dubey RK , Dhakal N , Das BKL , Pandey NK , Baral N , Lamsal M 
Published: August 2013

Background: C- reactive protein (CRP) is an acute phase inflammatory mediator that has been implicated as a risk factor for cardiovascular disease (CVD). The clinical presentation of acute coronary syndrome (ACS) ranges from unstable angina (UA) to non ST- segment elevation myocardial infarction (NSTEMI) and ST- segment elevation myocardial infarction (STEMI). Although, elevated levels of serum CRP have been reported in patients with CVD, the serum levels of CRP in patients with NSTEMI ACS is unknown. The purpose of the study was to determine whether the serum levels of CRP are higher in patients with NSTEMI ACS as compared to healthy controls. Methods: The study subjects consisted of two groups. Group I: (controls) twenty- five age-matched healthy men and Group II: Forty- five NSTEMI ACS patients. Fasting blood samples were collected and serum levels of CRP were measured by using highly sensitivity immunoassay rate method technology. Results: The serum levels of CRP in Group I and Group II were 3.2 ± 0.25 and 11.32 ± 2.1 mg/L, respectively and these values were significantly different from each other (p< 0.05). Group II showed a 253% higher level of CRP as compared to Group I subjects. Conclusion: The results demonstrate that the serum levels of CRP are higher in patients with NSTEMI ACS as compared to controls. Serum CRP levels are elevated in patients with NSTEMI ACS and may contribute to the inflammation and thrombosis associated with acute coronary syndrome. DOI: http://dx.doi.org/10.3126/jucms.v1i1.8416 Journal of Universal College of Medical Sciences Vol.1(1) 2013: 10-14
Study of Pathway to Care among Patients with Epilepsy
Authors: Subedi S , Shyangwa PM , Shakya R , Pandey AK 
Published: August 2013

Objective: To assess the pathway to care among patients with epilepsy up to the tertiary care centre Methods: It is a hospital based, cross-sectional descriptive study of 47 patients visiting BPKIHS psychiatry OPD. Written informed consent was taken from the patients and the primary caretaker. A semi structured Performa was used to record the basic sociodemographic details. Pathway Interview Schedule developed by WHO was used to collect the data. Results Majority (66.0%) of subjects were male. Generalized Seizures were most common (76.6%) type of seizure followed by complex-partial seizure (10.6%). More than half (51.1%) first contacted dhami-jhakri for treatment of their illness. About sixty two percent of patients had the first contact with the treatment provider less than 4 yrs ago. Thirty eight percent subjects sought treatment as per advice from the family members while only 2.1% sought treatment as per advice from the healthcare worker. The most common presenting complaints were sudden loss of consciousness in 89.4%of patients. In majority of patients (57.4%), problem arised ≤ 4yrs back. Significant high numbers of patients (51.1%) were prescribed alternative forms of treatment like herbal medications, talisman, offerings and sacrifices and jhadphook for their presenting problem. About eighty seven percent patients had to travel ≤12 hours for the treatment while 10.7% had to travel a distance of >24 hrs for treatment. The mean duration that one had to travel for seeking treatment was 7.95±14.58 hours. It was found that the mean duration that one patient spend before coming to a hospital for modern treatment was 5.64 months. Conclusions People suffering from epilepsy are still using the traditional healing practices leading to delay in the patient care. These findings call for a comprehensive educational program that can remove the misconcepts regarding the illness. DOI: http://dx.doi.org/10.3126/jucms.v1i1.8418 Journal of Universal College of Medical Sciences Vol.1(1) 2013: 20-25
Anaesthesia in Paediatric Bronchoscopy
Authors: Khadgaray RN 
Published: August 2013

General anaesthesia for emergency bronchoscopy is Frought with dangers especially in paediatric age group where inhalation of foreign bodies are common especially where respiratory obstruction is present and management becomes perilous. DOI: http://dx.doi.org/10.3126/jucms.v1i1.8419 Journal of Universal College of Medical Sciences Vol.1(1) 2013: 26-27
Palisaded Encapsulated Neuroma (PEN): A Case Report
Authors: Samdurkar A , Poudel S , Regmi S , Khurana S 
Published: August 2013

A growth or tumor of nerve is neuroma. Localised and circumscribed neuromas are termed as true neoplasm, as per James W. Patterson's quotation. Further, Palisaded encapsulated Neuroma (PEN) is a distinctive cutaneous nodular lesion often in the head, neck and face regions and are benign. They have schwannian and axonal components. A 30 year old male presented to surgical OPD with nodular enlargement in the scar behind the ear. Grossly these are usually pear shaped or bulb like dermal nodule. Microscopy showed peripheral circumscription for nodules of axonal and schwannian cells with predominance of fibroblastic component. Various references support above findings. And therefore, we arrived to a conclusion of this being PEN within scar tissue, as regards to clinical and histopathlogic peculiarities both gross and microscopic. DOI: http://dx.doi.org/10.3126/jucms.v1i1.8420 Journal of Universal College of Medical Sciences Vol.1(1) 2013: 28-32
Bacterial endophytes enhance competition by invasive plants
Authors: Rout Marnie E. , Chrzanowski Thomas H. , Westlie Tara K. , DeLuca Thomas H. , Callaway Ragan M. , Holben William E. 
Published: August 2013

• Premise of the study: Invasive plants can alter soil microbial communities and profoundly alter ecosystem processes. In the invasive grass Sorghum halepense, these disruptions are consequences of rhizome‐associated bacterial endophytes. We describe the effects of N2‐fixing bacterial strains from S. halepense (Rout and Chrzanowski, 2009) on plant growth and show that bacteria interact with the plant to alter soil nutrient cycles, enabling persistence of the invasive.• Methods: We assessed fluxes in soil nutrients for ∼4 yr across a site invaded by S. halepense. We assayed the N2‐fixing bacteria in vitro for phosphate solubilization, iron chelation, and production of the plant‐growth hormone indole‐3‐acetic acid (IAA). We assessed the plant's ability to recruit bacterial partners from substrates and vertically transmit endophytes to seeds and used an antibiotic approach to inhibit bacterial activity in planta and assess microbial contributions to plant growth.• Key results: We found persistent alterations to eight biogeochemical cycles (including nitrogen, phosphorus, and iron) in soils invaded by S. halepense. In this context, three bacterial isolates solubilized phosphate, and all produced iron siderophores and IAA in vitro. In growth chamber experiments, bacteria were transmitted vertically, and molecular analysis of bacterial community fingerprints from rhizomes indicated that endophytes are also horizontally recruited. Inhibiting bacterial activity with antibiotics resulted in significant declines in plant growth rate and biomass, with pronounced rhizome reductions.• Conclusions: This work suggests a major role of endophytes on growth and resource allocation of an invasive plant. Indeed, bacterial isolate physiology is correlated with invader effects on biogeochemical cycles of nitrogen, phosphate, and iron.
Genetic and morphological structure of a spruce hybrid (Picea sitchensis×P. glauca) zone along a climatic gradient
Authors: Hamilton Jill A. , Aitken Sally N. 
Published: August 2013

•Premise of the study:Historic colonization and contemporary evolutionary processes contribute to patterns of genetic variation and differentiation among populations. However, separating the respective influences of these processes remains a challenge, particularly for natural hybrid zones, where standing genetic variation may result from evolutionary processes both preceding and following contact, influencing the evolutionary trajectory of hybrid populations. Where adaptation to novel environments may be facilitated by interspecific hybridization, teasing apart these processes will have practical implications for forest management in changing environments.•Methods:We evaluated the neutral genetic architecture of thePicea sitchensis(Sitka spruce) ×P. glauca(white spruce) hybrid zone along the Nass and Skeena river valleys in northwestern British Columbia using chloroplast, mitochondrial, and nuclear microsatellite markers, in combination with cone morphological traits.•Key results:Sitka spruce mitotype “capture”, evidenced by this species dominating the maternal lineage, is consistent with earlier colonization of the region by Sitka spruce. This “capture” differs from the spatial distribution of chloroplast haplotypes, indicating pollen dispersal and its contribution to geographic structure. Genetic ancestry, based on nuclear markers, was strongly influenced by climate and geography. Highly parallel results for replicate transects along environmental gradients provide support for the bounded hybrid superiority model of hybrid zone maintenance.•Conclusions:This broad‐scale analysis of neutral genetic structure indicates the importance of historic and contemporary gene flow, environmental selection, and their interaction in shaping neutral genetic variation within this hybrid zone, informative to seed transfer development and reforestation for future climates.
CCR7 Plays No Appreciable Role in Trafficking of Central Memory CD4 T Cells to Lymph Nodes
Authors: Vander Lugt Bryan , Tubo Noah J. , Nizza Suzanne T. , Boes Marianne , Malissen Bernard , Fuhlbrigge Robert C. , Kupper Thomas S. , Campbell James J. 
Published: August 2013

Abstract
CCR7−/− mice exhibit profound anomalies in lymph node and spleen architecture, which complicates the study of CCR7-mediated T cell trafficking in vivo. To circumvent this problem, we established in vivo models in which wild-type and CCR7−/− populations coexist within mice possessing normal lymphoid organs and must compete for developmental niches within the tissues of these mice. Under the conditions we have created in vivo, we find the entry of memory CD4 T cells into lymph nodes from the blood to be independent of CCR7. Thus, the central memory CD4 T cells that traffic though lymph nodes, which are often defined by their expression of CCR7, do not appear to gain any competitive homing advantage by expressing this receptor. Furthermore, in contrast to cutaneous dendritic cell populations, we found that CCR7 deficiency had no appreciable effect on the exit of CD4 T cells from inflamed skin. Finally, we found that wild-type and CCR7−/− precursors were equally represented within the major thymic subpopulations, despite previous findings that CCR7 plays a role in seeding the thymus from bone marrow–derived T cell precursors.
CD8+ T Cells Produce the Chemokine CXCL10 in Response to CD27/CD70 Costimulation To Promote Generation of the CD8+ Effector T Cell Pool
Authors: Peperzak Victor , Veraar Elise A. M. , Xiao Yanling , Bąbała Nikolina , Thiadens Klaske , Brugmans Marieke , Borst Jannie 
Published: August 2013

AbstractVarious cell types can produce the chemokine CXCL10 in response to IFN-γ stimulation. CXCL10 is generally viewed as a proinflammatory chemokine that promotes recruitment of CD8+ and Th1-type CD4+ effector T cells to infected or inflamed nonlymphoid tissues. We show that CXCL10 plays a role during CD8+ T cell priming in the mouse. Genome-wide expression profiling revealed the Cxcl10 gene as a target of CD27/CD70 costimulation in newly activated CD8+ T cells. CD27/CD70 costimulation is known to promote activated T cell survival, but CXCL10 did not affect survival or proliferation of primed CD8+ T cells in vitro. Accordingly, CXCL10 could not fully rescue CD27 deficiency in mice infected with influenza virus. Rather, CXCL10 acted as chemoattractant for other activated CD8+ T cells. It signaled downstream of CD27 in a paracrine fashion to promote generation of the CD8+ effector T cell pool in the Ag-draining lymph nodes. Consistently, CD8+ T cells required expression of the CXCL10 receptor CXCR3 for their clonal expansion in a CD27/CD70-dependent peptide-immunization model. Our findings indicate that CXCL10, produced by primed CD8+ T cells in response to CD27/CD70 costimulation, signals to other primed CD8+ T cells in the lymph node microenvironment to facilitate their participation in the CD8+ effector T cell pool.
Death Receptor–Independent Activation-Induced Cell Death in Human Melanoma Antigen–Specific MHC Class I–Restricted TCR-Engineered CD4 T Cells
Authors: Chhabra Arvind , Mukherji Bijay 
Published: August 2013

AbstractEngaging CD4 T cells in antitumor immunity has been quite challenging, especially in an Ag-specific manner, because most human solid tumors usually do not express MHC class II molecules. We have recently shown that human CD4 T cells engineered to express a human melanoma–associated antigenic epitope, MART-127–35, specific MHC class I–restricted transgenic TCR function as polyfunctional effectors that can exhibit a helper as well as cytolytic effector function, in an epitope-specific and MHC class I–restricted manner (Chhabra et al. 2008. J. Immunol. 181: 1063–1070; Ray et al. 2010. Clin. Immunol. 136: 338–347). TCR-engineered (TCReng) CD4 T cells therefore have translational potential, and clinical trials with MHC class I TCReng CD4 T cells are under way. In this study, we show that although TCReng CD4 T cells could be useful in cancer immunotherapy, they are also susceptible to epitope-specific activation-induced cell death (AICD). We also show that the AICD in TCReng CD4 T cells is a death receptor–independent process and that JNK and p53 play critical roles in this process as pharmacological inhibitors targeting JNK activation and p-53–mediated transcription-independent mitochondria-centric death cascade rescued a significant fraction of TCReng CD4 T cells from undergoing AICD without affecting their effector function. Our data offer novel insights toward AICD in TCReng CD4 T cells and identify several potential targets to interfere with this process.
Type I IFNs Downregulate Myeloid Cell IFN-γ Receptor by Inducing Recruitment of an Early Growth Response 3/NGFI-A Binding Protein 1 Complex That Silences ifngr1 Transcription
Authors: Kearney Staci J. , Delgado Christine , Eshleman Emily M. , Hill Krista K. , O’Connor Brian P. , Lenz Laurel L. 
Published: August 2013

Abstract
The ability of type I IFNs to increase susceptibility to certain bacterial infections correlates with downregulation of myeloid cell surface IFNGR, the receptor for the type II IFN (IFN-γ), and reduced myeloid cell responsiveness to IFN-γ. In this study, we show that the rapid reductions in mouse and human myeloid cell surface IFNGR1 expression that occur in response to type I IFN treatment reflect a rapid silencing of new ifngr1 transcription by repressive transcriptional regulators. Treatment of macrophages with IFN-β reduced cellular abundance of ifngr1 transcripts as rapidly and effectively as actinomycin D treatment. IFN-β treatment also significantly reduced the amounts of activated RNA polymerase II (pol II) and acetylated histones H3 and H4 at the ifngr1 promoter and the activity of an IFNGR1-luc reporter construct in macrophages. The suppression of IFNGR1-luc activity required an intact early growth response factor (Egr) binding site in the proximal ifngr1 promoter. Three Egr proteins and two Egr/NGFI-A binding (Nab) proteins were found to be expressed in bone macrophages, but only Egr3 and Nab1 were recruited to the ifngr1 promoter upon IFN-β stimulation. Knockdown of Nab1 in a macrophage cell line prevented downregulation of IFNGR1 and prevented the loss of acetylated histones from the ifngr1 promoter. These data suggest that type I IFN stimulation induces a rapid recruitment of a repressive Egr3/Nab1 complex that silences transcription from the ifngr1 promoter. This mechanism of gene silencing may contribute to the anti-inflammatory effects of type I IFNs.
Alendronate Attenuates Eosinophilic Airway Inflammation Associated with Suppression of Th2 Cytokines, Th17 Cytokines, and Eotaxin-2
Authors: Sasaki Oh , Imamura Mitsuru , Yamazumi Yusuke , Harada Hiroaki , Matsumoto Taku , Okunishi Katsuhide , Nakagome Kazuyuki , Tanaka Ryoichi , Akiyama Tetsu , Yamamoto Kazuhiko , Dohi Makoto 
Published: August 2013

AbstractBisphosphonates (BPs) have been widely used to treat osteoporosis. They act by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. This resembles the action of statins, whose immune-modulating effect has recently been highlighted. In contrast, the effect of BPs on immune responses has not been elucidated well. In this study, we examined the effect of alendronate (ALN), a nitrogen-containing BP, on allergic airway inflammation in a mouse model. BALB/c mice were sensitized twice with OVA and challenged three times with nebulized OVA to induce eosinophilic airway inflammation. ALN was administered by an intragastric tube before each inhalation. ALN strongly suppressed airway eosinophilia and Th2, as well as Th17 cytokine production in the lung. ALN also attenuated eotaxin-2 production in the lung. Immunohistochemistry demonstrated that the major cell source of eotaxin-2 was peribronchial/perivascular macrophages, and flow cytometrical studies confirmed that ALN decreased eotaxin-2 expression in these macrophages. Furthermore, ALN attenuated eotaxin-2 production from mouse pleural macrophages and human monocyte/macrophage-like THP-1 cells in vitro. These results suggest that ALN suppressed Ag-induced airway responses in the mouse model. The suppression of eotaxin-2 production from macrophages appears to be one of ALN’s immunomodulatory effects, whereas the mechanism by which ALN suppressed Th2 and Th17 responses could not be fully elucidated in this study. Although a clinical study should be conducted, ALN could be a novel therapeutic option for asthma.
Induction of Functional Human Macrophages from Bone Marrow Promonocytes by M-CSF in Humanized Mice
Authors: Li Yan , Chen Qingfeng , Zheng Dahai , Yin Lu , Chionh Yok Hian , Wong Lan Hiong , Tan Shu Qi , Tan Thiam Chye , Chan Jerry K. Y. , Alonso Sylvie , Dedon Peter C. , Lim Bing , Chen Jianzhu 
Published: August 2013

Abstract
Engraftment of human CD34+ hematopoietic stem/progenitor cells into immunodeficient mice leads to robust reconstitution of human T and B cells but not monocytes and macrophages. To identify the cause underlying the poor monocyte and macrophage reconstitution, we analyzed human myeloid cell development in humanized mice and found that it was blocked at the promonocyte stage in the bone marrow. Expression of human M-CSF or GM-CSF by hydrodynamic injection of cytokine-encoding plasmid completely abolished the accumulation of promonocytes in the bone marrow. M-CSF promoted the development of mature monocytes and tissue-resident macrophages whereas GM-CSF did not. Moreover, correlating with an increased human macrophages at the sites of infection, M-CSF–treated humanized mice exhibited an enhanced protection against influenza virus and Mycobacterium infection. Our study identifies the precise stage at which human monocyte/macrophage development is blocked in humanized mice and reveals overlapping and distinct functions of M-CSF and GM-CSF in human monocyte and macrophage development. The improved reconstitution and functionality of monocytes/macrophages in the humanized mice following M-CSF expression provide a superior in vivo system to investigate the role of macrophages in physiological and pathological processes.