Factors associated with hypoglycemia episodes in hospitalized type 2 diabetes mellitus patients in a tertiary health facility in Malaysia

Purpose: To determine the factors associated with severity of hypoglycemia in hospitalized type 2 diabetes mellitus patients in a tertiary health facility in Malaysia. Methods: This retrospective study involved 207 hospitalised T2DM patients with hypoglycaemia episodes from January 2008 to December 2012 and was conducted in University Malaya Medical Centre, Petaling Jaya, Malaysia. Patients were classified into 2 groups, viz, those who had hypoglycaemia on admission and those who had hypoglycaemia during hospital stay. Patients with hypoglycemia on admission were those admitted due to hypoglycemia while patients with hypoglycemia during hospital stay were those admitted due to other causes but subsequently developed hypoglycemia during hospitalization. Results: The results for the 207 patients investigated show that most of the patients (72.2 %) were asymptomatic during hypoglycemic episodes. The majority of the episodes (57.4 %) experienced by the patients were mild hypoglycemia (< 3.9 mmol/L). Old age (p = 0.011) and presence of stroke (p = 0.033) were found to be significantly associated with severe hypoglycemia (< 2.2 mmol/L) while concurrent use of opioid (p = 0.008) was associated with mild hypoglycemia. Conclusion: The identification of the underlying factors associated with severity of hypoglycemia may help in preventing and resolving hypoglycemia in T2DM patients.

Epileptic and developmental encephalopathies: clinical and genetic study of adult patients attending a tertiary Epilepsy Centre

Objectives: To fully re-evaluate patients with early-onset epilepsy and intellectual disability with neurological, neurophysiological and neuropsychological examination in order to contribute to expanding the phenotypic spectrum of known epileptic encephalopathy (EE)-related genes and to identify novel genetic defects underlying EEs. Methods: We recruited patients with epilepsy and intellectual disability (ID) referring to our Epilepsy Centre. Patients underwent full clinical and neurophysiologic evaluation. When possible they underwent neuroradiologic investigations. Selected cases also underwent genetic analysis. Results: We recruited 200 patients (109 M, 91 F; mean age 36 years old). Mean age at epilepsy onset was 4 years old. The degree of ID was borderline in 4.5% of patients, mild in 25%, moderate in 38% and severe in 32.5%. EEG showed epileptiform abnormalities in 79.5% of patients. One hundred and thirty-one patients out of the 200 recruited (65.5%) did not have an aetiological diagnosis. All the patients underwent full clinical reassessment and when necessary they performed neuroradiologic and genetic investigations as well. We identified 35 patients with a genetic aetiology. In 8 cases a structural brain lesion was observed. In 33 patients, a genetic aetiology was identified. In 2 patients with drug-resistant seizures video-EEG allowed the identification of non-epileptic seizures, and in one patient we discontinued anti-epileptic drugs. In these patients, the aetiological diagnosis was made after 30 years (range 9-60 years) from the disease onset. Conclusions: In a population of 200 adult patients with epilepsy and ID, an aetiological cause was identified in 45 patients after 30 years from the disease onset. Aetiological diagnosis, especially if genetic, has significant positive implications for patients, even if it has been made after years from the beginning of the disease. Benefits include better-focused antiepileptic drug (AED) choice, sparing of further unnecessary investigations and improved knowledge of comorbidities.

Rhodium clusters: investigation of the reactivity towaeds phosphines and selected d- and p-metals

During my PhD we focused on different research projects concerning the synthesis and characterization of new rhodium carbonyl clusters. More specifically, we studied the reactivity between Rh4(CO)12 and different bidentate phosphines, obtaining seven different species: Rh4(CO)10(dppe), Rh4(CO)8(dppe)2, Rh4(CO)10(dppf), {Rh4(CO)10(dpp-hexane)}2, {Rh4(CO)10(t-dppe)}2, Rh2(CO)2(dppf)2 and Rh4(CO)9(μ2-dppe)(μ1-dppeO). The reactivity of [Rh7(CO)16]3- with [AuCl4]- and Au(Et2S)Cl led to the formation of seven bimetallic clusters, of which four new ones, namely [Rh16Au6(CO)36]6-, [Rh10Au(CO)26]3-, [Rh16Au6(CO)36]4-, [Rh16Au6(CO)36]5-, [Rh22Au3(CO)47]5-, [Rh19Au5(CO)40]4- and [Rh20Au7(CO)45]5-. The reactivity of [Rh16Au6(CO)36]6- and [Rh10Au(CO)26]3- was studied as well. The reactivity of [Rh7(CO)16]3- with AgBF4, AgNO3 and with Pt(Et2S)2Cl2 was investigated, yielding only to the already known [Rh6N(CO)15]-, [PtRh5(CO)15]- and [PtRh4(CO)14]2- compounds. [Rh7(CO)16]3- war reacted with SnCl2·2H2O in acetone obtaining [Rh7Sn4Cl10(CO)14]5-, and [Rh12Sn(CO)23Cl2]4- was reacted with H+ obtaining [Rh18Sn3Cl2(CO)44]4-. Reactivity of [Rh7(CO)16]3- with InCl3 resulted in the isolation of [Rh12In(CO)28]3- and [Rh11In3(CO)25Cl2]3-, already known in our research lab, and the new [HRh11In(CO)26]3-. Moreover, a more straightforward synthesis for [Rh6InCl3(CO)15]2- was found, and this also led to the isolation of the [Rh6InCl2(DMF)(CO)15]-. The recover or rhodium as valuable carbonyl compound was also studied, and starting from a mixture of by-products it was possible to obtain the starting material [Rh7(CO)16]3-.

The Effect Of Celastrol, A Triterpene With Antitumorigenic Activity, On Conformational And Functional Aspects Of The Human 90kda Heat Shock Protein Hsp90α, A Chaperone Implicated In The Stabilization Of The Tumor Phenotype.

Hsp90 is a molecular chaperone essential for cell viability in eukaryotes that is associated with the maturation of proteins involved in important cell functions and implicated in the stabilization of the tumor phenotype of various cancers, making this chaperone a notably interesting therapeutic target. Celastrol is a plant-derived pentacyclic triterpenoid compound with potent antioxidant, anti-inflammatory and anticancer activities; however, celastrol's action mode is still elusive. In this work, we investigated the effect of celastrol on the conformational and functional aspects of Hsp90α. Interestingly, celastrol appeared to target Hsp90α directly as the compound induced the oligomerization of the chaperone via the C-terminal domain as demonstrated by experiments using a deletion mutant. The nature of the oligomers was investigated by biophysical tools demonstrating that a two-fold excess of celastrol induced the formation of a decameric Hsp90α bound throughout the C-terminal domain. When bound, celastrol destabilized the C-terminal domain. Surprisingly, standard chaperone functional investigations demonstrated that neither the in vitro chaperone activity of protecting against aggregation nor the ability to bind a TPR co-chaperone, which binds to the C-terminus of Hsp90α, were affected by celastrol. Celastrol interferes with specific biological functions of Hsp90α. Our results suggest a model in which celastrol binds directly to the C-terminal domain of Hsp90α causing oligomerization. However, the ability to protect against protein aggregation (supported by our results) and to bind to TPR co-chaperones are not affected by celastrol. Therefore celastrol may act primarily by inducing specific oligomerization that affects some, but not all, of the functions of Hsp90α. To the best of our knowledge, this study is the first work to use multiple probes to investigate the effect that celastrol has on the stability and oligomerization of Hsp90α and on the binding of this chaperone to Tom70. This work provides a novel mechanism by which celastrol binds Hsp90α.

Relationship Between Lower-limb Muscle Strength And Functional Independence Among Elderly People According To Frailty Criteria: A Cross-sectional Study.

Muscle strength and functional independence are considered to be determinants of frailty levels among elderly people. The aim here was to compare lower-limb muscle strength (LLMS) with functional independence in relation to sex, age and number of frailty criteria, and to ascertain the influence of these variables on elderly outpatients' independence. Quantitative cross-sectional study, in a tertiary hospital. The study was conducted on 150 elderly outpatients of both sexes who were in a cognitive condition allowing oral communication, between October 2005 and October 2007. The following instruments were used: five-times sit-to-stand test (FTSST), Functional Independence Measurement (FIM) and Lawton's Instrumental Activities of Daily Living Scale (IADL). Descriptive, comparative, multivariate, univariate and Cronbach alpha analyses were performed. The mean time taken in the FTSST was 21.7 seconds; the mean score for FIM was 82.2 and for IADL was 21.2; 44.7% of the subjects presented 1-2 frailty criteria and 55.3% > 3 criteria. There was a significant association between LLMS and functional independence in relation to the number of frailty criteria, without homogeneity regarding sex and age. Functional independence showed significant influence from sex and LLMS. Elderly individuals with 1 or 2 frailty criteria presented greater independence in all FTSST scores. The subjects with higher LLMS presented better functional independence.

Respiratory Viruses Are Continuously Detected In Children With Chronic Tonsillitis Throughout The Year.

To evaluate the oscillations on the viral detection in adenotonsillar tissues from patients with chronic adenotonsillar diseases as an indicia of the presence of persistent viral infections or acute subclinical infections. Cross-sectional prospective study. Tertiary hospital. The fluctuations of respiratory virus detection were compared to the major climatic variables during a two-year period using adenoids and palatine tonsils from 172 children with adenotonsillar hypertrophy and clinical evidence of obstructive sleep apnoea syndrome or recurrent adenotonsillitis, without symptoms of acute respiratory infection (ARI), by TaqMan real-time PCR. The rate of detection of at least one respiratory virus in adenotonsillar tissue was 87%. The most frequently detected viruses were human adenovirus in 52.8%, human enterovirus in 47.2%, human rhinovirus in 33.8%, human bocavirus in 31.1%, human metapneumovirus in 18.3% and human respiratory syncytial virus in 17.2%. Although increased detection of human enterovirus occurred in summer/autumn months, and there were summer nadirs of human respiratory syncytial virus in both years of the study, there was no obvious viral seasonality in contrast to reports with ARI patients in many regions of the world. Respiratory viruses are continuously highly detected during whole year, and without any clinical symptomatology, indicating that viral genome of some virus can persist in lymphoepithelial tissues of the upper respiratory tract.

Sinonasal Disorders In Hematopoietic Stem Cell Transplantation.

hematopoietic stem cell transplantation (HSCT) is associated with more respiratory infections due to immunosuppression. this study aimed to verify the frequency of rhinosinusitis after HSCT, and the association between rhinosinusitis and chronic graft vs. host disease (GVHD) and type of transplantation, clinical treatment, surgical treatment, and survival. this was a retrospective study in a tertiary university hospital. A total of 95 patients with hematological diseases undergoing HSCT between 1996 and 2011 were selected. chronic myeloid leukemia was the most prevalent disease. The type of transplant most often performed was the allogenic type (85.26%). The frequency of rhinosinusitis was 36%, with no difference between the autologous and the allogenic types. Chronic GVHD occurred in 30% of patients. Patients with GVHD had a higher frequency and recurrence of rhinosinusitis, in addition to more frequent need for endoscopic sinusectomy and decreased overall survival. there was a higher frequency of rhinosinusitis in HSCT and GVHD. The type of transplant does not appear to predispose to the occurrence of rhinosinusitis. GVHD seems to be an aggravating factor and requires a more stringent treatment.

[balloon Laryngoplasty For Acquired Subglottic Stenosis In Children: Predictive Factors For Success].

The treatment of subglottic stenosis in children remains a challenge for the otorhinolaryngologist, and may involve both endoscopic and open surgery. To report the experience of two tertiary facilities in the treatment of acquired subglottic stenosis in children with balloon laryngoplasty, and to identify predictive factors for success of the technique and its complications. Descriptive, prospective study of children diagnosed with acquired subglottic stenosis and submitted to balloon laryngoplasty as primary treatment. Balloon laryngoplasty was performed in 37 children with an average age of 22.5 months; 24 presented chronic subglottic stenosis and 13 acute subglottic stenosis. Success rates were 100% for acute subglottic stenosis and 32% for chronic subglottic stenosis. Success was significantly associated with acute stenosis, initial grade of stenosis, children of a smaller age, and the absence of tracheostomy. Transitory dysphagia was the only complication observed in three children. Balloon laryngoplasty may be considered the first line of treatment for acquired subglottic stenosis. In acute cases, the success rate is 100%, and although the results are less promising in chronic cases, complications are not significant and the possibility of open surgery remains without prejudice.

Oligomerization, Membrane Association, And In Vivo Phosphorylation Of Sugarcane Udp-glucose Pyrophosphorylase.

Sugarcane is a monocot plant that accumulates sucrose to levels of up to 50% of dry weight in the stalk. The mechanisms that are involved in sucrose accumulation in sugarcane are not well understood, and little is known with regard to factors that control the extent of sucrose storage in the stalks. UDP-glucose pyrophosphorylase (UGPase; EC 2.7.7.9) is an enzyme that produces UDP-glucose, a key precursor for sucrose metabolism and cell wall biosynthesis. The objective of this work was to gain insights into the ScUGPase-1 expression pattern and regulatory mechanisms that control protein activity. ScUGPase-1 expression was negatively correlated with the sucrose content in the internodes during development, and only slight differences in the expression patterns were observed between two cultivars that differ in sucrose content. The intracellular localization of ScUGPase-1 indicated partial membrane association of this soluble protein in both the leaves and internodes. Using a phospho-specific antibody, we observed that ScUGPase-1 was phosphorylated in vivo at the Ser-419 site in the soluble and membrane fractions from the leaves but not from the internodes. The purified recombinant enzyme was kinetically characterized in the direction of UDP-glucose formation, and the enzyme activity was affected by redox modification. Preincubation with H2O2 strongly inhibited this activity, which could be reversed by DTT. Small angle x-ray scattering analysis indicated that the dimer interface is located at the C terminus and provided the first structural model of the dimer of sugarcane UGPase in solution.

[should Pediatric Parenteral Nutrition Be Individualized?].

Parenteral nutrition (PN) formulations are commonly individualized, since their standardization seem inadequate for the pediatric population. This study aimed to evaluate the nutritional state and the reasons for PN individualization in pediatric patients using PN hospitalized in a tertiary hospital in Campinas, São Paulo. This longitudinal study comprised patients using PN followed by up to 67 days. Nutritional status was classified according to the criteria established by the World Health Organization (WHO) (2006) and WHO (2007). The levels of the following elements on blood were analyzed: sodium, potassium, ionized calcium, chloride, magnesium, inorganic phosphorus and triglycerides (TGL). Among the criteria for individualization, were considered undeniable: significant reduction in blood levels of potassium (<3 mEq/L), sodium (<125 mEq/)L, magnesium (<1 mEq/L), phosphorus (<1.5 mEq/L), ionic calcium (<1 mmol) and chloride (<90 mEq/L) or any value above the references. Twelve pediatric patients aged 1 month to 15 years were studied (49 individualizations). Most patients were classified as malnourished. It was observed that 74/254 (29.2%) of examinations demanded individualized PN by indubitable reasons. The nutritional state of patients was considered critical in most cases. Thus, the individualization performed in the beginning of PN for energy protein adequacy was indispensable. In addition, the individualized PN was indispensable in at least 29.2% of PN for correction of alterations found in biochemical parameters.

[preservation Of The Fertility And The Ovaries In Women With Benign Adnexal Tumors].

To evaluate the sparing of fertility and ovaries in women submitted to surgical treatment for benign adnexal tumors. Between February 2010 and January 2014, 206 patients were included in this observational study as they were submitted to surgical treatment for benign ovarian tumors at CAISM, a tertiary hospital. Fertility sparing surgery was defined as tumorectomy or unilateral salpingoophorectomy without hysterectomy in premenopausal women. Preservation of the ovary occurred when at least one ovary or part of it was mantained. Of the 206 women with benign tumors, 120 (58%) were premenopausal and 86 (42%) were postmenopausal. There were 36 (30%) ovarian germ cell tumors, 31 (26%) epithelial neoplasms and 11 (9%) sex-cord stromal tumors among premenopausal women. In the group of postmenopausal women, 35 (41%) epithelial neoplasms, 27 (31%) sex-cord stromal tumors and 8 (9%) ovarian germ cell tumors were identified. Among 36 women with non-neoplastic ovarian tumors, 21 (58%) had endometriomas and 8 (22%) functional cysts. Among 22 women with extra-ovarian tumors, uterine leiomyomatosis was the most frequent finding (50%). In the group of women who were ≤ 35 years old, 26 (57%) were treated by tumorectomy and 18 (39%) were submitted to unilateral salpingoophorectomy with sparing of the uterus and the contralateral ovary. Women who were ≤ 35 years old were more frequently operated by laparoscopy which was associated with a higher number of fertility sparing procedures when compared to laparotomy (p<0.01). Twenty-six (28%) women submitted to hysterectomy with bilateral salpingoophorectomy were premenopausal. Although there is a trend to perform only tumorectomy in women who are ≤ 35 years old, a significant number of young women is still treated by salpingoophorectomy. Among 36- to 45-year-old women, only 70% had their fertility spared, while 20% had both ovaries removed. However, whenever possible, we must try to preserve the ovaries, mainly in premenopausal women.

Polycystic Ovary Syndrome And Chronic Autoimmune Thyroiditis.

Polycystic ovary syndrome (PCOS) has been associated with an autoimmune origin, either per se or favoring the onset of autoimmune diseases, from a stimulatory action on the inflammatory response. Thus, autoimmune thyroiditis (AIT) could be more prevalent among women with PCOS. To evaluate the prevalence of AIT in women with PCOS. It was a cross-sectional study, in a tertiary center, including 65 women with PCOS and 65 women without this condition. Clinical and laboratory parameters were evaluated and a thyroid ultrasound scan was performed. Levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), anti-thyroid peroxidase (anti-TPO) antibodies, anti-thyroglobulin (anti-TG) antibodies, and thyroid ultrasound findings were evaluated. The prevalence of subclinical hypothyroidism (SCH) in women with PCOS was 16.9% and 6.2% in the non-PCOS group. AIT was more common in the PCOS group compared with the non-PCOS group (43.1% versus 26.2%). But, when it was adjusted by weight and insulin resistance, the difference in the thyroiditis risk was not observed (OR 0.78, CI 0.28-2.16). AIT risk was similar in the PCOS and the non-PCOS group. SCH are more common in women with PCOS, highlighting a need for periodic monitoring of thyroid function.

In Adolescents With Epilepsy, High Scores Of Anxiety And Depression Are Associated With Occurrence Of Seizures In Public Places.

Objective To assess depression and anxiety symptoms of adolescents with epilepsy compared with adolescents without epilepsy. Method The study sample consisted of: case participants (50 subjects) attending the pediatric epilepsy clinic of a tertiary hospital and control participants (51 subjects) from public schools. The instruments utilized were: identification card with demographic and epilepsy data, Beck Depression Inventory and State-Trait Anxiety Inventory. Results No significant differences were founded between the groups regarding scores for depression and anxiety symptoms but both groups presented moderate scores of anxiety. A correlation was found between low scores anxiety and not frequent seizures, low scores anxiety and perception of seizure control, high scores of anxiety and depression and occurrence of seizures in public places. Conclusion Low scores of anxiety are associated with not frequent seizures; high scores of anxiety and depression are associated with occurrence of seizures in public places.

Impact Of Drug Formulation And Free Platinum/cisplatin Ratio On Hypersensitivity Reactions To Cisplatin: Formulation Matters.

Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.

The C-terminal Region Of The Human P23 Chaperone Modulates Its Structure And Function.

The p23 protein is a chaperone widely involved in protein homeostasis, well known as an Hsp90 co-chaperone since it also controls the Hsp90 chaperone cycle. Human p23 includes a β-sheet domain, responsible for interacting with Hsp90; and a charged C-terminal region whose function is not clear, but seems to be natively unfolded. p23 can undergo caspase-dependent proteolytic cleavage to form p19 (p231-142), which is involved in apoptosis, while p23 has anti-apoptotic activity. To better elucidate the function of the human p23 C-terminal region, we studied comparatively the full-length human p23 and three C-terminal truncation mutants: p23₁₋₁₁₇; p23₁₋₁₃₁ and p23₁₋₁₄₂. Our data indicate that p23 and p19 have distinct characteristics, whereas the other two truncations behave similarly, with some differences to p23 and p19. We found that part of the C-terminal region can fold in an α-helix conformation and slightly contributes to p23 thermal-stability, suggesting that the C-terminal interacts with the β-sheet domain. As a whole, our results suggest that the C-terminal region of p23 is critical for its structure-function relationship. A mechanism where the human p23 C-terminal region behaves as an activation/inhibition module for different p23 activities is proposed.