bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycogen synthase kinase-3β inhibition induces nuclear factor-κB-mediated apoptosis in pediatric acute lymphocyte leukemia cells
Authors: Hu Yanni , Gu Xiaoyan , Li Ruiyan , Luo Qing , Xu Youhua 
Published: January 2011

Abstract

Background
Molecular therapies that target genetic abnormalities in leukemic cells and their affected signaling pathways have been emerging in pediatric acute lymphoblastic leukemia (ALL). Glycogen synthase kinase-3β (GSK-3β) has recently been found to positively regulate the activity of nuclear factor-κB (NF-κB). Here, we investigated the relationship between GSK-3β inhibition and NF-κB in apoptosis of pediatric primary leukemia cells obtained from 39 newly diagnosed ALL children in China.

Methods
Bone marrow mononuclear cells (BMMC) were isolated by density gradient centrifugation from the heparinized aspirates of children with ALL. We used immunofluorescence staining to detect nuclear GSK-3β in these cells. After treatment with chemically distinct GSK-3β inhibitors in vitro, NF-κB transcriptional activity was identified by means of western blotting and electrophoretic mobility shift assay (EMSA). NF-κB-mediated apoptosis was detected by Annexin V-PE/7-AAD double-staining flow cytometry. The expression level of the survivin gene was detected by reverse-transcriptase polymerase chain reaction (RT-PCR).

Results
GSK-3β significantly accumulates in the nuclei of ALL cells than in the nuclei of control cells. Cell death induced by GSK-3β inhibition in ALL cells was mediated by a downregulation of NF-κB p65 transcriptional activity. GSK-3β inhibition significantly decreased the expression of the NF-κB target gene survivin.

Conclusions
These results indicate that inhibition of GSK-3β downregulates the NF-κB activation pathway, leading to suppression of the expression of an NF-κB-regulated gene and promotion of apoptosis in ALL cells in vitro. Furthermore, our findings suggest that GSK-3β or NF-κB is a potential therapeutic target in the treatment of pediatric ALL.
XAF1 expression and regulatory effects of somatostatin on XAF1 in prostate cancer cells
Authors: Xing Zhaoquan , Zhou Zunlin , Yu Rong , Li Shuling , Li Chunde , Nilsson Sten , Liu Zhaoxu 
Published: January 2011

Abstract

Background
Somatostatin prevents cell proliferation by inducing apoptosis. Downregulation of the XAF1 transcript may occur during the development of prostate cancer. It is interesting to evaluate the potential regulatory effects of somatostatin on XAF1 expression during the development of prostate cancer cells.

Methods

XAF1 mRNA and protein expression in human prostate epithelial cells RWPE-1, androgen dependent prostate cancer LNCaP, and androgen independent DU145 and PC3 cells were evaluated using RT-PCR and Western blot. The regulation of XAF1 mRNA and protein expression by somatostatin and its analogue Octreotide was evaluated.

Results
Substantial levels of XAF1 mRNA and proteins were detected in RWPE-1 cells, whereas prostate cancer cells LNCaP, DU145 and PC3 exhibited lower XAF1 expression. Somatostatin and Octreotide up-regulated XAF1 mRNA and protein expression in all prostate cancer cell lines.

Conclusions

XAF1 down-regulation may contribute to the prostate cancer development. The enhanced XAF1 expression by somatostatin indicates a promising strategy for prostate cancer therapy.
Split tendon transfers for the correction of spastic varus foot deformity: a case series study
Authors: Vlachou Maria , Dimitriadis Dimitris 
Published: January 2011

AbstractBackgroundOveractivity of anterior and/or posterior tibial tendon may be a causative factor of spastic varus foot deformity. The prevalence of their dysfunction has been reported with not well defined results. Although gait analysis and dynamic electromyography provide useful information for the assessment of the patients, they are not available in every hospital. The purpose of the current study is to identify the causative muscle producing the deformity and apply the most suitable technique for its correction.MethodsWe retrospectively evaluated 48 consecutive ambulant patients (52 feet) with spastic paralysis due to cerebral palsy. The average age at the time of the operation was 12,4 yrs (9‐18) and the mean follow‐up 7,8 yrs (4‐14). Eigtheen feet presented equinus hind foot deformity due to gastrocnemius and soleus shortening. According to the deformity, the feet were divided in two groups (Group I with forefoot and midfoot inversion and Group II with hindfoot varus). The deformities were flexible in all cases in both groups. Split anterior tibial tendon transfer (SPLATT) was performed in Group I (11 feet), while split posterior tibial tendon transfer (SPOTT) was performed in Group II (38 feet). In 3 feet both procedures were performed. Achilles tendon sliding lengthening (Hoke procedure) was done in 18 feet either preoperatively or concomitantly with the index procedure.ResultsThe results in Group I, were rated according to Hoffer's clinical criteria as excellent in 8 feet and satisfactory in 3, while in Group II according to Kling's clinical criteria were rated as excellent in 20 feet, good in 14 and poor in 4. The feet with poor results presented residual varus deformity due to intraoperative technical errors.ConclusionOveractivity of the anterior tibial tendon produces inversion most prominent in the forefoot and midfoot and similarly overactivity of the posterior tibial tendon produces hindfoot varus. The deformity can be clinically unidentifiable in some cases when Achilles shortening co‐exists producing foot equinus. By identifying the muscle causing the deformity and performing the appropriate technique, very satisfying results were achieved in the majority of our cases. In three feet both muscles contributed to a combined deformity and simultaneous SPLATT and SPOTT were considered necessary. For complex foot deformities where the component of cavus co‐exists, supplementary procedures are required along with the index operation to obtain the best result.
Recovering mitochondrial DNA lineages of extinct Amerindian nations in extant homopatric Brazilian populations
Authors: Gonçalves Vanessa F , Parra Flavia C , Gonçalves-Dornelas Higgor , Rodrigues-Carvalho Claudia , Silva Hilton P , Pena Sergio DJ 
Published: January 2011

AbstractBackgroundBrazilian Amerindians have experienced a drastic population decrease in the past 500 years. Indeed, many native groups from eastern Brazil have vanished. However, their mitochondrial mtDNA haplotypes, still persist in Brazilians, at least 50 million of whom carry Amerindian mitochondrial lineages. Our objective was to test whether, by analyzing extant rural populations from regions anciently occupied by specific Amerindian groups, we could identify potentially authentic mitochondrial lineages, a strategy we have named 'homopatric targeting'.ResultsWe studied 173 individuals from Queixadinha, a small village located in a territory previously occupied by the now extinct Botocudo Amerindian nation. Pedigree analysis revealed 74 unrelated matrilineages, which were screened for Amerindian mtDNA lineages by restriction fragment length polymorphism. A cosmopolitan control group was composed of 100 individuals from surrounding cities. All Amerindian lineages identified had their hypervariable segment HVSI sequenced, yielding 13 Amerindian haplotypes in Queixadinha, nine of which were not present in available databanks or in the literature. Among these haplotypes, there was a significant excess of haplogroup C (70%) and absence of haplogroup A lineages, which were the most common in the control group. The novelty of the haplotypes and the excess of the C haplogroup suggested that we might indeed have identified Botocudo lineages. To validate our strategy, we studied teeth extracted from 14 ancient skulls of Botocudo Amerindians from the collection of the National Museum of Rio de Janeiro. We recovered mtDNA sequences from all the teeth, identifying only six different haplotypes (a low haplotypic diversity of 0.8352 ± 0.0617), one of which was present among the lineages observed in the extant individuals studied.ConclusionsThese findings validate the technique of homopatric targeting as a useful new strategy to study the peopling and colonization of the New World, especially when direct analysis of genetic material is not possible.
Hydrogen peroxide induced genomic instability in nucleotide excision repair-deficient lymphoblastoid cells
Authors: Gopalakrishnan Kalpana , Low Grace Kah Mun , Ting Aloysius Poh Leong , Srikanth Prarthana , Slijepcevic Predrag , Hande M Prakash 
Published: January 2011

Background
The Nucleotide Excision Repair (NER) pathway specialises in UV-induced DNA damage repair. Inherited defects in the NER can predispose individuals to Xeroderma Pigmentosum (XP). UV-induced DNA damage cannot account for the manifestation of XP in organ systems not directly exposed to sunlight. While the NER has recently been implicated in the repair of oxidative DNA lesions, it is not well characterised. Therefore we sought to investigate the role of NER factors Xeroderma Pigmentosum A (XPA), XPB and XPD in oxidative DNA damage-repair by subjecting lymphoblastoid cells from patients suffering from XP-A, XP-D and XP-B with Cockayne Syndrome to hydrogen peroxide (H2O2).

Results
Loss of functional XPB or XPD but not XPA led to enhanced sensitivity towards H2O2-induced cell death. XP-deficient lymphoblastoid cells exhibited increased susceptibility to H2O2-induced DNA damage with XPD showing the highest susceptibility and lowest repair capacity. Furthermore, XPB- and XPD-deficient lymphoblastoid cells displayed enhanced DNA damage at the telomeres. XPA- and XPB-deficient lymphoblastoid cells also showed differential regulation of XPD following H2O2 treatment.

Conclusions
Taken together, our data implicate a role for the NER in H2O2-induced oxidative stress management and further corroborates that oxidative stress is a significant contributing factor in XP symptoms. Resistance of XPA-deficient lymphoblastoid cells to H2O2-induced cell death while harbouring DNA damage poses a potential cancer risk factor for XPA patients. Our data implicate XPB and XPD in the protection against oxidative stress-induced DNA damage and telomere shortening, and thus premature senescence.
De-escalation as part of a global strategy of empiric antibiotherapy management. A retrospective study in a medico-surgical intensive care unit
Authors: Morel Jérôme , Casoetto Julie , Jospé Richard , Aubert Gérald , Terrana Raphael , Dumont Alain , Molliex Serge , Auboyer Christian 
Published: January 2011

Abstract
Introduction
Most data on de-escalation of empirical antimicrobial therapy has focused on ventilator-associated pneumonia. In this retrospective monocentric study, we evaluated de-escalation as part of a global strategy of empiric antibiotherapy management irrespective of the location and the severity of the infection. The goal of this trial was to assess the application of a de-escalation strategy and the impact in terms of re-escalation, recurrent infection and to identify variables associated with de-escalation.

Methods
All consecutive patients treated with empiric antibiotic therapy and hospitalized in the intensive care unit for at least 72 hours within a period of 16 months were included. We compared the characteristics and outcome of patients who have experienced de-escalation therapy with those who have not.

Results
A total of 116 patients were studied corresponding to 133 infections. Antibiotic therapy was de-escalated in 60 cases (45%). De-escalation, primarily accomplished by a reduction in the number of antibiotics used, was observed in 52% of severe sepsis or septic shock patients. Adequate empiric antibiotic and use of aminoglycoside were independently linked with de-escalation. De-escalation therapy was associated with a significant reduction of recurrent infection (19% vs 5% P = 0.01). Mortality was not changed by de-escalation.

Conclusions
As part of a global management of empiric antibiotherapy in an intensive care unit, de-escalation might be safe and feasible in a large proportion of patients.
Outcome of severe lactic acidosis associated with metformin accumulation
Authors: Friesecke Sigrun , Abel Peter , Roser Markus , Felix Stephan B , Runge Soeren 
Published: January 2011

Abstract
Introduction
Metformin associated lactic acidosis (MALA) may complicate metformin therapy, particularly if metformin accumulates due to renal dysfunction. Profound lactic acidosis (LA) generally predicts poor outcome. We aimed to determine if MALA differs in outcome from LA of other origin (LAOO).

Methods
We conducted a retrospective analysis of all patients admitted with LA to our medical ICU of a tertiary referral center during a 5-year period. MALA patients and LAOO patients were compared with respect to parameters of acid-base balance, serum creatinine, hospital outcome, Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) score, using Pearson's Chi-square or the Mann-Whitney U-test.

Results
Of 197 patients admitted with LA, 10 had been diagnosed with MALA. With MALA, median arterial blood pH was significantly lower (6.78 [range 6.5 to 6.94]) and serum lactate significantly higher (18.7 ± 5.3 mmol/L) than with LAOO (pH 7.20 [range 6.46 to 7.35], mean serum lactate 11.2 ± 6.1 mmol/L). Overall mortality, however, was comparable (MALA 50%, LAOO 74%). Furthermore, survival of patients with arterial blood pH < 7.00 (N = 41) was significantly better (50% vs. 0%) if MALA (N = 10) was the underlying condition compared to LAOO (N = 31).

Conclusions
Compared to similarly severe lactic acidosis of other origin, the prognosis of MALA is significantly better. MALA should be considered in metformin-treated patients presenting with lactic acidosis.
Relationship between alcohol use disorders, cortisol concentrations, and cytokine levels in patients with sepsis
Authors: de Wit Marjolein , Wiaterek Gregory K , Gray Nicole D , Goulet Keith E , Best Al M , Clore John N , Sweeney Lori B 
Published: January 2011

AbstractIntroductionPatients with alcohol use disorders (AUD) are at increased risk of developing sepsis and have higher mortality. AUD are associated with higher cortisol and anti-inflammatory cytokine profile. Higher cortisol increases risk of death in septic patients. The relationship between AUD and cortisol in septic patients is unknown. We aimed to study this relationship and postulated that AUD would be associated with higher cortisol and anti-inflammatory cytokine profile.MethodsThis was a prospective cohort study of 40 medical intensive care unit (ICU) patients admitted with sepsis. Cortisol, anti-inflammatory interleukin (IL) 10, and pro-inflammatory IL1β, IL6, tumor necrosis factor (TNF) α were measured.ResultsThirteen (32%) out of 40 patients had AUD. AUD patients had higher cortisol by univariate (39 microg/dl versus 24,P= 0.04) and multivariable analyses (44 microg/dl versus 23,P= 0.004). By univariate analyses, AUD patients had higher IL10 (198 picog/dl versus 47,P= 0.02) and IL6 (527 picog/ml versus 156,P= 0.048), but similar IL1β and TNFα. By multivariable analyses, AUD patients had higher IL10 (182 picog/dl versus 23,P= 0.049) but similar IL1β, IL6, and TNFα. AUD patients had lower IL1β/IL10 (univariate 0.01 versus 0.10,P= 0.04; multivariable 0.01 versus 0.03,P= 0.04), lower TNFα/IL10 (univariate 0.15 versus 0.52,P= 0.03; multivariable 0.11 versus 0.63,P= 0.01), but similar IL6/IL10.ConclusionsAUD are common diagnoses among medical ICU patients with sepsis. Patients with AUD have higher cortisol concentrations and have differences in cytokine expression. Future studies should seek to determine if these differences may explain the higher severity of illness seen in patients with sepsis and AUD.Trial registrationClinicalTrials.gov:NCT00615862
Pre-hospital cooling of patients following cardiac arrest is effective using even low volumes of cold saline
Authors: Škulec Roman , Truhlář Anatolij , Šeblová Jana , Dostál Pavel , Černý Vladimír 
Published: January 2011

Abstract
Introduction
Pre-hospital induction of therapeutic mild hypothermia (TH) may reduce post-cardiac arrest brain injury in patients resuscitated from out-of-hospital cardiac arrest. Most often, it is induced by a rapid intravenous administration of as much as 30 ml/kg of cold crystalloids. We decided to assess the pre-hospital cooling effectivity of this approach by using a target dose of 15-20 ml/kg of 4°C cold normal saline in the setting of the physician-staffed Emergency Medical Service. The safety and impact on the clinical outcome have also been analyzed.

Methods
We performed a prospective observational study with a retrospective control group. A total of 40 patients were cooled by an intravenous administration of 15-20 ml/kg of 4°C cold normal saline during transport to the hospital (TH group). The pre-hospital decrease of tympanic temperature (TT) was analyzed as the primary endpoint. Patients in the control group did not undergo any pre-hospital cooling.

Results
In the TH group, administration of 12.6 ± 6.4 ml/kg of 4°C cold normal saline was followed by a pre-hospital decrease of TT of 1.4 ± 0.8°C in 42.8 ± 19.6 min (p < 0.001). The most effective cooling was associated with a transport time duration of 38-60 min and with an infusion of 17 ml/kg of cold saline. In the TH group, a trend toward a reduced need for catecholamines during transport was detected (35.0 vs. 52.5%, p = 0.115). There were no differences in demographic variables, comorbidities, parameters of the cardiopulmonary resuscitation and in other post-resuscitation characteristics. The coupling of pre-hospital cooling with subsequent in-hospital TH predicted a favorable neurological outcome at hospital discharge (OR 4.1, CI95% 1.1-18.2, p = 0.046).

Conclusions
Pre-hospital induction of TH by the rapid intravenous administration of cold normal saline has been shown to be efficient even with a lower dose of coolant than reported in previous studies. This dose can be associated with a favorable impact on circulatory stability early after the return of spontaneous circulation and, when coupled with in-hospital continuation of cooling, can potentially improve the prognosis of patients.

Trial Registration
ClinicalTrials (NCT): NCT00915421
Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit
Authors: Pérez-Bárcena Jon , Crespí Catalina , Regueiro Verónica , Marsé Pedro , Raurich Joan M , Ibáñez Jordi , García de Lorenzo-Mateos Abelardo , Bengoechea José A 
Published: January 2011

Abstract
Introduction
The use of glutamine as a dietary supplement is associated with a reduced risk of infection. We hypothesized that the underlying mechanism could be an increase in the expression and/or functionality of Toll-like receptors (TLR), key receptors sensing infections. The objective of this study was to evaluate whether glutamine supplementation alters the expression and functionality of TLR2 and TLR4 in circulating monocytes of trauma patients admitted to the intensive care unit (ICU).

Methods
We designed a prospective, randomized and single-blind study. Twenty-three patients received parenteral nutrition (TPN) with a daily glutamine supplement of 0.35 g/kg. The control group (20 patients) received an isocaloric-isonitrogenated TPN. Blood samples were extracted before treatment, at 6 and 14 days. Expression of TLR2 and TLR4 was determined by flow cytometry. Monocytes were stimulated with TLR specific agonists and cytokines were measured in cell culture supernatants. Phagocytic ability of monocytes was also determined.

Results
Basal characteristics were similar in both groups. Monocytes from patients treated with glutamine expressed the same TLR2 levels as controls before treatment (4.9 ± 3.5 rmfi vs. 4.3 ± 1.9 rmfi, respectively; P = 0.9), at Day 6 (3.8 ± 2.3 rmfi vs. 4.0 ± 1.7 rmfi, respectively; P = 0.7) and at Day 14 (4.1 ± 2.1 rfim vs. 4.6 ± 1.9 rmfi, respectively; P = 0.08). TLR4 levels were not significantly different between the groups before treatment: (1.1 ± 1 rmfi vs 0.9 ± 0.1 rmfi respectively; P = 0.9), at Day 6 (1.1 ± 1 rmfi vs. 0.7 ± 0.4 rmfi respectively; P = 0.1) and at Day 14 (1.4 ± 1.9 rmfi vs. 1.0 ± 0.6 rmfi respectively; P = 0.8). No differences in cell responses to TLR agonists were found between groups. TLR functionality studied by phagocytosis did not vary between groups.

Conclusions
In trauma patients in the intensive care unit, TPN supplemented with glutamine does not improve the expression or the functionality of TLRs in peripheral blood monocytes.

Trial registration
ClinicalTrials.gov Identifier: NCT01250080.
Respiratory support withdrawal in intensive care units: families, physicians and nurses views on two hypothetical clinical scenarios
Authors: Fumis Renata RL , Deheinzelin Daniel 
Published: January 2011

Abstract
Introduction
Evidence suggests that dying patients' physical and emotional suffering is inadequately treated in intensive care units. Although there are recommendations regarding decisions to forgo life-sustaining therapy, deciding on withdrawal of life support is difficult, and it is also difficult to decide who should participate in this decision.

Methods
We distributed a self-administered questionnaire in 13 adult intensive care units (ICUs) assessing the attitudes of physicians and nurses regarding end-of-life decisions. Family members from a medical-surgical ICU in a tertiary cancer hospital were also invited to participate. Questions were related to two hypothetical clinical scenarios, one with a competent patient and the other with an incompetent patient, asking whether the ventilator treatment should be withdrawn and about who should make this decision.

Results
Physicians (155) and nurses (204) of 12 ICUs agreed to take part in this study, along with 300 family members. The vast majority of families (78.6%), physicians (74.8%) and nurses (75%) want to discuss end-of-life decisions with competent patients. Most of the physicians and nurses desire family involvement in end-of-life decisions. Physicians are more likely to propose withdrawal of the ventilator with competent patients than with incompetent patients (74.8% × 60.7%, P = 0.028). When the patient was incompetent, physicians (34.8%) were significantly less prone than nurses (23.0%) and families (14.7%) to propose decisions regarding withdrawal of the ventilator support (P < 0.001).

Conclusions
Physicians, nurses and families recommended limiting life-support therapy with terminally ill patients and favored family participation. In decisions concerning an incompetent patient, physicians were more likely to maintain the therapy.