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1.  Prevalence of Abnormal Glucose Tolerance and Risk Factors in Urban and Rural Malaysia 
Diabetes Care  2011;34(6):1362-1364.
To determine the prevalence of prediabetes and diabetes among rural and urban Malaysians.
This cross-sectional survey was conducted among 3,879 Malaysian adults (1,335 men and 2,544 women). All subjects underwent the 75-g oral glucose tolerance test (OGTT).
The overall prevalence of prediabetes was 22.1% (30.2% in men and 69.8% in women). Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were found in 3.4 and 16.1% of the study population, respectively, whereas 2.6% of the subjects had both IFG and IGT. Based on an OGTT, the prevalence of newly diagnosed type 2 diabetes was 12.6% (31.0% in men and 69.0% in women). The prediabetic subjects also had an increased prevalence of cardiovascular disease risk factors.
The large proportion of undiagnosed cases of prediabetes and diabetes reflects the lack of public awareness of the disease.
PMCID: PMC3114358  PMID: 21498788
2.  Intractable neonatal jaundice due to hereditary spherocytosis and Gilbert’s syndrome 
BMJ Case Reports  2011;2011:bcr0520114293.
In this article the authors present a case of pathological neonatal jaundice resistant to phototherapy in a baby with a family history of Gilbert’s syndrome and hereditary spherocytosis. Her presentation was ultimately explained with a diagnosis of both conditions, and required treatment with phenobarbitone. The authors discuss the mechanism by which Gilbert’s syndrome results in hyperbilirubinaemia and its similarities with Crigler–Najjar syndrome. The presentation of hereditary spherocystosis in the neonatal period is also explored, as is the mechanism of exaggerated hyperbilirubinaemia when the two conditions co-exist.
PMCID: PMC3149415  PMID: 22689841
3.  Pre-osteoblastic MC3T3-E1 cells promote breast cancer growth in bone in a murine xenograft model 
Chinese journal of cancer  2011;30(3):189-196.
The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cancer cells induce apoptosis in osteoblasts, which further exacerbates bone loss. However, in early stages, breast cancer cells induce osteoblasts to secrete inflammatory cytokines purported to drive tumor progression. To more thoroughly evaluate the role of osteoblasts in early stages of breast cancer metastasis to the bones, we used green fluorescent protein-labeled human breast cancer cell lines MDA-MB-231 and MDA-MB-435, which both induce osteolysis after intra-femoral injection in athymic mice, and the murine pre-osteoblastic cell line MC3T3-E1 to modulate osteoblast populations at the sites of breast cancer metastasis. Breast cancer cells were injected directly into the femur with or without equal numbers of MC3T3-E1 cells. Tumors grew significantly larger when co-injected with breast cancer cells and MC3T3-E1 cells than injected with breast cancer cells alone. Osteolysis was induced in both groups, indicating that MC3T3-E1 cells did not block the ability of breast cancer cells to cause bone destruction. MC3T3-E1 cells promoted tumor growth out of the bone into the extraosseous stroma. These data suggest that breast cancer cells and osteoblasts communicate during early stages of bone metastasis and promote tumor growth.
PMCID: PMC3661213  PMID: 21352696
MC3T3-E1; osteoblast; breast cancer; bone; metastasis
4.  Laboratory evolution of Geobacter sulfurreducens for enhanced growth on lactate via a single-base-pair substitution in a transcriptional regulator 
The ISME Journal  2011;6(5):975-983.
The addition of organic compounds to groundwater in order to promote bioremediation may represent a new selective pressure on subsurface microorganisms. The ability of Geobacter sulfurreducens, which serves as a model for the Geobacter species that are important in various types of anaerobic groundwater bioremediation, to adapt for rapid metabolism of lactate, a common bioremediation amendment, was evaluated. Serial transfer of five parallel cultures in a medium with lactate as the sole electron donor yielded five strains that could metabolize lactate faster than the wild-type strain. Genome sequencing revealed that all five strains had non-synonymous single-nucleotide polymorphisms in the same gene, GSU0514, a putative transcriptional regulator. Introducing the single-base-pair mutation from one of the five strains into the wild-type strain conferred rapid growth on lactate. This strain and the five adaptively evolved strains had four to eight-fold higher transcript abundance than wild-type cells for genes for the two subunits of succinyl-CoA synthase, an enzyme required for growth on lactate. DNA-binding assays demonstrated that the protein encoded by GSU0514 bound to the putative promoter of the succinyl-CoA synthase operon. The binding sequence was not apparent elsewhere in the genome. These results demonstrate that a single-base-pair mutation in a transcriptional regulator can have a significant impact on the capacity for substrate utilization and suggest that adaptive evolution should be considered as a potential response of microorganisms to environmental change(s) imposed during bioremediation.
PMCID: PMC3329115  PMID: 22113376
evolution; genome sequencing; geobacter; subsurface
5.  Long-term results of total knee arthroplasty following high tibial osteotomy according to Wagner 
International Orthopaedics  2011;36(4):761-764.
There is relatively little information available about the long-term results of total knee arthroplasty (TKA) following high tibial osteotomy. The aim of our study was to share our experiences and long-term results of TKA after a previous closing wedge high tibial osteotomy according to Wagner.
In a retrospective study we identified 48 consecutive patients who had undergone TKA after a previous closing wedge high tibial osteotomy according to Wagner with a follow-up of over ten years. The average duration of follow-up after the TKA was 13.3 years (min 10.0, max 15.5). X-rays were taken in two planes before TKA, one week after TKA and at the latest follow-up. Tibio-femoral alignment was measured on weightbearing long-leg anteroposterior radiographs. Radiolucent lines at the latest follow-up were documented. Functional evaluations were performed preoperatively and postoperatively (at the time of latest follow-up).
The mean Knee Society function score increased from 63.1 points preoperatively to 90.0 points postoperatively. The mean overall Knee Society score increased from 93.2 points preoperatively to 160.8 points postoperatively. The mean average femoro-tibial angle was corrected from varus 0.8° (varus 14°–valgus 8.0°) preoperatively to valgus 7.6° (valgus 2–9°) at the last follow-up.
The closing wedge high tibial osteotomy according to Wagner does not compromise subsequent total knee replacement and leads to good clinical and radiological results.
PMCID: PMC3311789  PMID: 21983941
6.  An Evaluation of Preoperative Computed Tomography on Patients with Chronic Otitis Media 
This study aimed to compare the veracity of computed tomography findings on patients undergoing surgery for chronic otitis media (COM) with the surgical findings, and to determine to what extent the preoperative computerized tomography (CT) findings are useful to the surgeon. A series of 56 patients with COM undergoing preoperative CT scanning followed by surgical exploration of the middle ear and mastoid. Operative notes were recorded and data collected on the nature of soft tissue masses, the status of the ossicles, presence or absence of facial canal dehiscence and semicircular canal (SCC) dehiscence and the presence or absence of dural plate erosion, and sigmoid sinus thrombosis. Fifty-six patients were recruited in the study, 30 males and 26 females. The age range was from 16 to 67 years with a mean of 26.51 ± 1.4 years. The preoperative CT scan imaging in cases of cholesteatoma, ossicular chain erosion and SCC dehiscence have good correlation with the intraoperative findings. The specificity of preoperative CT scan in detecting facial canal dehiscence, dural plate erosion and sigmoid sinus thrombosis in patient of COM were weak. Preoperative computed tomography evaluation is fairly useful especially in cases of cholesteatoma. According to the results of this study, CT is of value particularly in the definition of cholesteatoma, and in determining ossicular chain erosion and semicircular canal fistula.
PMCID: PMC3244578  PMID: 23449285
Chronic otitis media; Mastoidectomy; Computed tomography
Shortages of health care workers (HCWs) represents a serious challenge to ensuring effective HIV care in resource-limited settings (RLS). Stress, motivation, and job satisfaction have been linked with HCW retention and are important in addressing HCW shortages. In this cross-sectional study HCW stress, motivation, and perceived ability to meet patient needs were assessed in PEPFAR-supported urban HIV care and treatment clinics (CTCs) in Tanzania.
A self-administered questionnaire measuring motivation, stress, and perceived ability to meet patient needs was given to HCWs at 16 CTCs. Scales measuring HCW satisfaction, motivation, and stress were developed using principle components analysis. Hierarchical linear models were used to explore the association of HCW and site characteristics with reported satisfaction, stress, motivation, and ability to meet patient needs.
Seventy-three percent (279) of HCWs completed the questionnaire. Most (73%) HCWs reported minimal/no work-related stress, with 48% reporting good/excellent motivation, but 41% also reporting feeling emotionally drained. Almost all (98%) reported feeling able to help their patients, with 68% reporting work as rewarding. Most reported receipt of training and supervision, with good availability of resources. In the multivariate model, direct clinical providers reported lower motivation than management (p<0.05) and HCWs at medium-sized sites reported higher motivation than HCWs at larger sites (p<0.05). HCWs at small and medium sites were more likely to feel able to help patients than those from larger sites (p<0.05 and p<0.001 respectively).
Despite significant patient loads, HCWs in these PEPFAR-supported CTCs reported high levels of motivation, job satisfaction, ability to meet patient needs, low levels of stress but significant emotional toll. Understanding the relationship between support systems such as strong supervision and training and these outcomes is critical in designing interventions to improve motivation, reduce stress and increase retention of HCWs.
PMCID: PMC3580277  PMID: 22066277
HIV; motivation; stress; health care workers; resource limited settings
8.  Hereditary multiple intestinal atresia (HMIA) with severe combined immunodeficiency (SCID): a case report of two siblings and review of the literature on MIA, HMIA and HMIA with immunodeficiency over the last 50 years 
BMJ Case Reports  2011;2011:bcr0520103031.
Hereditary multiple intestinal atresia (HMIA), a presumed autosomal recessive disorder, is an unusual and rare form of recurrent intestinal atresia which can be associated with severe combined immunodeficiency (SCID). The combination of HMIA and SCID is invariably lethal. The authors describe this fatal association in two siblings. The parents are consanguineous and have three other normal healthy children. Both index cases had abnormal antenatal ultrasounds and were symptomatic after birth. The final diagnosis of HMIA with SCID was confirmed in both siblings. They were never able to receive enteral feeds, remained totally dependent on parenteral nutrition, had repeated episodes of sepsis and died after a very difficult neonatal intensive care course. In this article we have reviewed the clinical course and outcome of both cases. The existing literature on multiple intestinal atresia, HMIA and HMIA with immunodeficiency is also reviewed.
PMCID: PMC3062839  PMID: 22715199
9.  Conservatively treated perforation of the neovagina in a male to female transsexual patient 
BMJ Case Reports  2011;2011:bcr0820103241.
An unknown number of patients have had male to female gender transformation. Various surgical techniques have been employed to construct the neovagina. The more traditional techniques include inverted penile grafts and vascular pedicle grafts, but also the small bowel and sigmoid colon have been used. In this case, the authors present a patient who previously had a gender transformation from male to female with use of bowel for the neovagina. The patient presented with severe abdominal pain, fever and leukocytosis. A CT scan revealed retroperitoneal free air, and an x-ray examination with contrast through the neovagina showed leakage from the neovaginal top. The patient was treated conservatively with antibiotics and discharged after 7 days.
PMCID: PMC3062371  PMID: 22714607
10.  Urinary Symptoms in Breast Cancer: A Systematic Review 
Cancer  2011;118(3):582-593.
A large body of research has documented the prevalence and severity of menopausal symptoms, especially vasomotor symptoms, in breast cancer survivors and their impact on quality of life. Urinary symptoms as part of the constellation of menopausal symptoms, however, have received relatively little attention. Thus, less is known about the prevalence and severity of urinary symptoms in breast cancer survivors.
We conducted a systematic review of studies published between 1990 and 2010 to describe the prevalence and severity of urinary symptoms in breast cancer survivors.
We identified 16 eligible studies involving more than 2,500 women. Studies varied with respect to purpose, design, and nature of samples included; the majority used the same definition and assessment approach for urinary symptoms. Prevalence rates for symptoms ranged from 12% of women reporting burning or pain on micturition to 58% reporting difficulty with bladder control. Although in many studies the largest percentage of women rated symptoms as mild, as many as 23% reported severe symptoms.
Mild to moderate urinary symptoms are common in breast cancer survivors and some women report severe symptoms. Symptoms appear to adversely affect women’s quality of life. There is a need for additional research assessing the natural history of urinary symptoms using consensus definitions and validated measures in diverse populations. Nevertheless, this review suggests that clinicians should screen for urinary symptoms in breast cancer survivors and offer treatment recommendations or make referrals as appropriate.
PMCID: PMC3193898  PMID: 21751193
breast cancer; menopause; urogenital system; survivorship
11.  Use of Insulin Sensitizers for the Treatment of Major Depressive Disorder: A Pilot Study of Pioglitazone for Major Depression Accompanied by Abdominal Obesity 
Journal of Affective Disorders  2011;136(3):1164-1173.
This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder.
In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference >35 in. in women and >40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (≥25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months.
Pioglitazone decreased depression symptom severity from a total IDS score of 40.3 ± 1.8 to 19.2 ± 1.8 at week 12 (p<.001). Among partial responders (≥ 25% decrease in IDS total score), an improvement in depressive symptoms was maintained during an additional 3-month extension phase (total duration = 24 weeks) according to IDS total scores (p<.001). Patients experienced a reduction in insulin resistance from baseline to Week 12 according to the log homeostasis model assessment (−0.8 ± 0.75; p<.001) and a significant reduction in inflammation as measured by log highly- sensitive C-reactive protein (−0.87 ± 0.72; p<.001). During the current episode, the majority of participants (74%, n=17), had already failed at least one antidepressant trial. The most common side effects were headache and dizziness; no patient discontinued due to side effects.
These data are limited by a small sample size and an open-label study design with no placebo control.
Although preliminary, pioglitazone appears to reduce depression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. Larger, placebo-controlled studies are indicated.
PMCID: PMC3225727  PMID: 21782251
Clinical Cancer Research  2011;18(3):748-757.
Compared to the numerous broad screens for oncogene mutations in adult cancers, very few have been performed in pediatric solid tumors. To identify novel mutations and potential therapeutic targets in pediatric cancers, we performed a high-throughput Sequenom-based analysis in large sets of several major pediatric solid cancers, including neuroblastoma (NB), Ewing sarcoma (ES), rhabdomyosarcoma (RMS), and desmoplastic small round cell tumor (DSRCT).
Experimental Design
We designed a highly multiplexed Sequenom-based assay to interrogate 275 recurrent mutations across 29 genes. Genomic DNA was extracted from 192 NB, 75 ES, 89 RMS, and 24 DSRCT samples. All mutations were verified by Sanger sequencing.
Mutations were identified in 13% of NB samples, 4% of ES samples, 21.1% of RMS samples, and no DSRCT samples. ALK mutations were present in 10.4% of NB samples. The remainder of NB mutations involved the BRAF, RAS, and MAP2K1 genes and were absent in samples harboring ALK mutations. Mutations were more common in embryonal RMS (ERMS) samples (28.3%) than alveolar RMS (ARMS) (3.5%). In addition to previously identified RAS and FGFR4 mutations, we report for the first time PIK3CA and CTNNB1 (Beta-Catenin) mutations in 4.9% and 3.3% of ERMS, respectively.
In ERMS, ES, and NB, we identified novel occurrences of several oncogene mutations recognized as drivers in other cancers. Overall, NB and ERMS contain significant subsets of cases with non-overlapping mutated genes in growth signaling pathways. Tumor profiling can identify a subset of pediatric solid tumor patients as candidates for kinase inhibitors or RAS-targeted therapies.
PMCID: PMC3271129  PMID: 22142829
mutation; rhabdomyosarcoma; neuroblastoma; Ewing sarcoma; desmoplastic small round cell tumor
13.  Manipulating Cofactor Binding Thermodynamics in an Artificial Oxygen Transport Protein 
Biochemistry  2011;50(47):10254-10261.
We report the mutational analysis of an artificial oxygen transport protein, HP-7, which operates via a mechanism akin to human neuroglobin and cytoglobin. This protein destabilizes one of two heme-ligating histidine residues by coupling histidine side chain ligation with the burial of three charged glutamate residues on the same helix. Replacement of these glutamate residues with alanine, which is uncharged, increases the affinity of the distal histidine ligand by a factor of thirteen. Paradoxically, it also decreases heme binding affinity by a factor of five in the reduced state and sixty in the oxidized state. Application of a three-state binding model, in which an initial pentacoordinate binding event is followed by a protein conformational change to hexacoordinate, provides insight into the mechanism of this seemingly counterintuitive result: the initial pentacoordinate encounter complex is significantly destabilized by the loss of the glutamate side chains, and the increased affinity for the distal histidine only partially compensates. These results point to the importance of considering each oxidation and conformational state in the design of functional artificial proteins.
PMCID: PMC3561710  PMID: 22004125
14.  Subsets of ATP-Sensitive Potassium Channel (KATP) inhibitors increase gap junctional intercellular communication in metastatic cancer cell lines independent of SUR expression 
FEBS letters  2011;586(1):27-31.
Gap junctional intercellular communication (GJIC) regulates cellular homeostasis by propagating signaling molecules, exchanging cellular metabolites, and coupling electrical signals. In cancer, cells exhibit altered rates of GJIC which may play a role in neoplastic progression. KATP channels help maintain membrane polarity; and, linkages between KATP channel activity and rates of GJIC have been established. The mechanistic relationship has not been fully elucidated. We report the effects of treatment with multiple KATP antagonist compounds on GJIC in metastatic cell lines demonstrating an increase in communication rates following treatment with compounds possessing specificities towards the SUR2 subunit of KATP. These effects remained consistent using cell lines with different expression levels of SUR1 and SUR2, suggesting possible off target effects on GJIC by these compounds.
PMCID: PMC3249498  PMID: 22119728
Sulfonylurea; KATP; gap junction; glibenclamide
15.  Acute renal failure following lung transplantation: risk factors, mortality, and long-term consequences 
Acute renal failure (ARF) frequently complicates lung transplantation. This study determined the prevalence, predictive factors, and consequences of ARF on long-term renal function and survival.
One hundred and seventy-four lung transplantation recipients were divided into two groups based on the presence or absence of ARF defined as a 50% decrease in creatinine clearance from baseline (group I: 67 patients with ARF; group II: 107 patients without ARF). Multivariate analysis compared pre-operative, operative, and post-operative risk factors to assess predictive factors. Renal function over time was assessed by two-way repeated measures analysis of variance (ANOVA).
ARF developed in 67 (39%) of patients. Multivariate analysis identified aprotinin (OR 2.20 (1.11; 4.36), p = 0.02) and double lung transplantation (OR 2.61 (1.32; 5.15), p = 0.006) as risk factors for post-operative renal failure. At 5 years following transplant, creatinine clearance was similar between the two groups (group I CrCl: 73 ml s−1; group II CrCl: 53 ml s−1; p = 0.54). Survival at 5 years was the same in the two groups. Multivariate analysis associated age at the time of transplantation (HR 1.030 (1.004; 1.057), p = 0.02) and intensive care unit (ICU) length of stay (HR 1.029 (1.008; 1.051), p = 0.007) with decreased survival.
The use of aprotinin and double lung transplantation are associated with ARF following lung transplantation. Age at the time of transplantation and a longer intensive care stay predict decreased survival. ARF after lung transplantation is not predictive of late renal dysfunction or decreased long-term survival.
PMCID: PMC3241081  PMID: 21665487
Lung transplantation; Acute renal failure; Aprotinin
17.  Serum anti-Müllerian hormone and antral follicle count as predictive markers of OHSS in ART cycles 
To evaluate predictive role of day–3 serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) in ovarian hyperstimulation syndrome (OHSS) in patients undergoing IVF/ICSI cycles.
Materials and methods
Forty-one women with moderate/severe OHSS and 41 age matched women without OHSS were compared to evaluate the predictive value of certain risk factors for OHSS. AFC, and E2, FSH, LH, AMH, inhibin-B levels measured on day 3 of the menstrual cycle before controlled ovarian hyperstimulation.
Mean FSH was significantly lower (p < 0.0001); and mean LH, AFC and AMH were significantly higher in women with OHSS compared to women without OHSS (p = 0.049, p < 0.0001 and p < 0.0001, respectively). There was no significant difference in inhibin B (p = 0.112) and estradiol (p = 0.706) between the groups. The ROC area under curve (AUC) for AMH presented the largest AUC among the listed risk factors. AMH (AUC = 0.87) and AFC (AUC = 0.74) had moderate accuracy for predicting OHSS while Inhibin B (AUC = 0.58) and LH (AUC = 0.61) had low accuracy. The cut-off value for AMH 3.3 ng/mL provided the highest sensitivity (90%) and specificity (71%) for predicting OHSS. It’s positive (PPV) and negative predictive values (NPV) were 61% and 94%, respectively. The cut-off value for AFC was 8 with 78% sensitivity, 65% specificity, 52% PPV and 86% NPV.
Measurement of basal serum AMH and AFC can be used to determine the women with high risk for OHSS.
PMCID: PMC3241835  PMID: 21882017
Antimullerian hormone; Ovarian hyperstimulation syndrome; Antral follicle count
18.  Attention-deficit hyperactive disorder presenting with school truancy in an adolescent: a case report 
Mental Health in Family Medicine  2011;8(4):249-254.
Attention-deficit hyperactive disorder (ADHD) is a psychiatric illness commonly diagnosed during the early years of childhood. In many adolescents with undiagnosed ADHD, presentation may not be entirely similar to that in younger children. These adolescents pose significant challenges to parents and teachers coping with their disability. Often adolescents with behavioural problems are brought to medical attention as a last resort. This case describes an adolescent who presented to a primary care clinic with school truancy. He was initially treated for depression with oppositional defiant disorder and sibling rivalry. Only following a careful detailed history and further investigations was the diagnosis of ADHD made. He showed a positive improvement with the use of methylphenidate for his ADHD and escitalopram for his depression. The success of his management was further supported by the use of behavioural therapy and parenting interventions. There is a need to increase public awareness of ADHD, especially among parents and teachers so that early intervention can be instituted in these children.
PMCID: PMC3487600  PMID: 23205066
attention-deficit hyperactive disorder; primary care; school truancy
19.  Increased Phagocyte-Like NADPH Oxidase and ROS Generation in Type 2 Diabetic ZDF Rat and Human Islets 
Diabetes  2011;60(11):2843-2852.
To determine the subunit expression and functional activation of phagocyte-like NADPH oxidase (Nox), reactive oxygen species (ROS) generation and caspase-3 activation in the Zucker diabetic fatty (ZDF) rat and diabetic human islets.
Expression of core components of Nox was quantitated by Western blotting and densitometry. ROS levels were quantitated by the 2′,7′-dichlorofluorescein diacetate method. Rac1 activation was quantitated using the gold-labeled immunosorbent assay kit.
Levels of phosphorylated p47phox, active Rac1, Nox activity, ROS generation, Jun NH2-terminal kinase (JNK) 1/2 phosphorylation, and caspase-3 activity were significantly higher in the ZDF islets than the lean control rat islets. Chronic exposure of INS 832/13 cells to glucolipotoxic conditions resulted in increased JNK1/2 phosphorylation and caspase-3 activity; such effects were largely reversed by SP600125, a selective inhibitor of JNK. Incubation of normal human islets with high glucose also increased the activation of Rac1 and Nox. Lastly, in a manner akin to the ZDF diabetic rat islets, Rac1 expression, JNK1/2, and caspase-3 activation were also significantly increased in diabetic human islets.
We provide the first in vitro and in vivo evidence in support of an accelerated Rac1–Nox–ROS–JNK1/2 signaling pathway in the islet β-cell leading to the onset of mitochondrial dysregulation in diabetes.
PMCID: PMC3198065  PMID: 21911753
20.  Sleep Disturbances and Their Relationship to Glucose Tolerance in Pregnancy 
Diabetes Care  2011;34(11):2454-2457.
To explore relationships among sleep disturbances, glucose tolerance, and pregnancy outcomes.
Four validated sleep questionnaires were administered to 169 pregnant women at the time of 50-g oral glucose tolerance testing (OGTT) during the second trimester. Pregnancy outcomes were analyzed in 108 women with normal glucose tolerance (NGT).
Of the participants, 41% had excessive daytime sleepiness (Epworth Sleepiness Scale [ESS] >8); 64% had poor sleep quality; 25% snored frequently; 29% had increased risk of sleep-disordered breathing (SDB); 52% experienced short sleep (SS); 19% had both increased SDB risk and SS (SDB/SS); and 14% had daytime dysfunction. Reported sleep duration inversely correlated with glucose values from 50-g OGTT (r = −0.21, P < 0.01). Each hour of reduced sleep time was associated with a 4% increase in glucose levels. Increased likelihood of gestational diabetes mellitus (GDM) was found in subjects with increased SDB risk (odds ratio 3.0 [95% CI 1.2–7.4]), SS (2.4 [1.0–5.9]), SDB/SS (3.4 [1.3–8.7]), and frequent snoring (3.4 [1.3–8.8], after adjustment for BMI). Among NGT subjects, preterm delivery was more frequent in those with increased ESS (P = 0.02), poor sleep quality (P = 0.02), and SS (P = 0.03). Neonatal intensive care unit admissions were associated with increased ESS (P = 0.03), SDB/SS (P = 0.03), and daytime dysfunction (P < 0.01) in mothers.
Pregnant women experience significant sleep disturbances that are associated with increased risk of GDM and unfavorable pregnancy outcomes. Pregnant women with increased SDB risk, frequent snoring, and sleep duration of <7 h/night have increased risk of developing GDM.
PMCID: PMC3198297  PMID: 21926292
21.  Evaluation of a Brief Tailored Motivational Intervention to Prevent Early Childhood Caries 
This pragmatic randomized trial evaluated the effectiveness of a tailored educational intervention on oral health behaviors and new untreated carious lesions in low-income African-American children in Detroit, Michigan.
Participating families were recruited in a longitudinal study of the determinants of dental caries in 1,021 randomly selected children (0–5 years) and their caregivers. The families were examined at baseline in 2002–04 (Wave I), 2004–05 (Wave II) and 2007 (Wave III). Prior to Wave II, the families were randomized into two educational groups. An interviewer trained in applying motivational interviewing principles (MI) reviewed the dental exam findings with caregivers assigned to the intervention group (MI+DVD) and engaged the caregiver in a dialogue on the importance of and potential actions for improving the child’s oral health. The interviewer and caregiver watched a special 15-minute DVD developed specifically for this project based on data collected at Wave I and focused on how the caregivers can “keep their children free from tooth decay”. After the MI session the caregivers developed their own preventive goals. Some families in this group chose not to develop goals and were offered the project-developed goals. The goals, if defined, were printed on glossy paper that included the child’s photograph. Families in the second group (DVD-only) were met by an interviewer, shown the DVD, and provided with the project’s recommended goals. Both groups of families received a copy of the DVD. Families in the MI+DVD group received booster calls within 6 months of the intervention. Both caregivers and the children were interviewed and examined after approximately 2 years (Wave III: 2007).
After 6-month of follow-up, caregivers receiving MI+DVD were more likely to report checking the child for “pre-cavities” and making sure the child brushes at bedtime. Evaluation of the final outcomes approximately 2 years later found that caregivers receiving the MI+DVD were still more likely to report making sure the child brushed at bedtime, yet were no more likely to make sure the child brushed twice per day. Despite differences in one of the reported behaviors, children whose caregivers received the motivational intervention did not have fewer new untreated lesions at the final evaluation.
This study found that a single motivational interviewing intervention may change some reported oral health behaviors, it failed to reduce the number of new untreated carious lesions.
PMCID: PMC3177165  PMID: 21916925
Motivational Interviewing; Early Childhood Caries
22.  Raising the Breast Health Awareness amongst Women in an Urban Slum Area in Alexandria, Egypt 
Breast Care  2011;6(5):375-379.
Breast Cancer (BC) is the most frequently occurring cancer among Egyptian women. This study aimed to determine the effectiveness of a health education program on raising the knowledge related to BC, its risk factors, and some related preventive practices among women living in an urban slum area in Alexandria.
Patients and Methods
A pre-/post-test interventional study was conducted during 2009–2010 on a random sample of women aged 30–65 years (n = 486) living in a slum area in Alexandria, Egypt. 20 health education sessions were carried out to educate the women on BC risk factors and some preventive practices. Previously trained nurses educated the sampled women on breast self-examination (BSE). The women's knowledge and opinion about BC and their practice of BSE were evaluated before and 3 months after the intervention.
The findings indicated a significant increase in the mean knowledge score regarding BC and the mean opinion score regarding some BC risk factors. A significant increase in the practice of BSE was observed post intervention.
This study confirms the effectiveness of intervention programs in improving the knowledge about BC risk factors and practice of BSE even in a group of women with a low literacy rate living in a slum area.
PMCID: PMC3357171  PMID: 22619648
Breast cancer; Breast self-examination; Breast awareness; Knowledge; Egypt
23.  Expression of P-glycoprotein, Cyclin D1 and Ki-67 in Acute Lymphoblastic Leukemia: Relation with Induction Chemotherapy and Overall Survival 
Previous studies showed that non-cycling cells have a higher multidrug resistance (MDR) expression, which may be down-regulated by proliferation induction. Triggering these cells into proliferation down-regulates high MDR expression. The aim of this study was to determine the expression of P-glycoprotein (PGP) and cell cycle parameters (cyclin D1 and Ki-67) in acute lymphoblastic leukemia (ALL) at diagnosis, and to evaluate the correlation between the expressions of each marker, and the clinical significance of such expression with response to induction chemotherapy and overall survival. A total of 78 newly diagnosed ALL patients were enrolled in our study. PGP, cyclin D1 and Ki-67 were determined by flow cytometry. PGP expression was encountered in 10/78 (12.8%) of ALL cases. Cyclin D1 and Ki-67 were expressed in 16/77 (20.6%) and 27/76 (34.6%) of ALL cases, respectively. None of the parameters were associated with response to induction chemotherapy and overall survival. Based on the current analysis, we conclude that a joint immunophenotypic evaluation of PGP and cell cycle parameters like that adopted in this study is unlikely to reveal mechanisms of multidrug resistance associated with the clinical outcome.
PMCID: PMC3155713  PMID: 22942566
P-gp; Cyclin D1; Ki-67; Acute lymphoblastic leukemia (ALL); Multidrug resistance (MDR)
24.  Long-term alteration of anxiolytic effects of ovarian hormones in female mice by a peripubertal immune challenge 
Hormones and behavior  2011;60(4):318-326.
Recent reports indicate that exposure to some stressors, such as shipping or immune challenge with the bacterial endotoxin, lipopolysaccharide (LPS), during the peripubertal period reduces sexual receptivity in response to ovarian hormones in adulthood. We hypothesized that a peripubertal immune challenge would also disrupt the response of a non-reproductive behavior, anxiety-like behavior, to ovarian hormones in adulthood. Female C57Bl/6 mice were injected with LPS during the peripubertal period and tested for anxiety-like behavior in adulthood, following ovariectomy and ovarian hormone treatment. Treatment with estradiol followed by progesterone reduced anxiety-like behavior in control, but not LPS-treated females. We next determined if the disruptive effect of LPS on adult behavior were limited to the peripubertal period by treating mice with LPS either during this period or in adulthood. LPS treatment during the peripubertal period disrupted the anxiolytic effect of ovarian hormones, whereas treatment in adulthood did not. We further tested if this model of peripubertal immune challenge was applicable to an outbred strain of mice (CD-1). Similar to C57Bl/6 mice, LPS treatment during the peripubertal period, but not later, disrupted the anxiolytic effect of estradiol and progesterone. These data suggest that a peripubertal immune challenge disrupts the regulation of anxiety-like behavior by ovarian hormones in a manner that persists at least for weeks after the termination of the immune challenge.
PMCID: PMC3166431  PMID: 21722643
anxiety; estradiol; progesterone; puberty; adolescence; stress; immune challenge; lipopolysaccharide
25.  Detailed protocol for evaluation of dynamic perifusion of human islets to assess β-cell function 
Islets  2011;3(5):284-290.
The definitive measure of β-cell quality in an islet is the measurement of β-cell function, i.e., the ability of the islets to release insulin in a controlled manner in response to minute changes in ambient glucose levels. Continuous flow or dynamic perifusion of the solution containing glucose and secretagogues through the islets is the most accurate assessment of regulated insulin release in vitro. Here, we describe in detail a low cost, mini-perifusion system that can be adapted to any laboratory to assess islet function by examining dynamic insulin release in response to elevated glucose concentrations and addition of secretagogues. Human islets with purity >80% and viability >90% were perifused with low glucose (1 mM) and subsequently challenged with high glucose (16.8 mM ± KCl, 25 mM). A prototypical biphasic response to elevated glucose concentrations was observed with an average 8-fold (above basal) increase in insulin concentration at peak values. Similarly, perifusion with carbachol or exendin-4 (Byetta) with glucose (6 mM) resulted in 1.32- and 1.35-fold increase in insulin secretion above basal. Islets could be maintained in the perifusion apparatus and continued to respond to glucose for up to 3 h. At minimal financial cost and technical expertise, this apparatus can be set-up in any biological laboratory to evaluate regulated hormone release from many cell types in less than 6 h. This will allow other laboratories to measure insulin responses to their drug or modifier of interest in vitro, in a manner that better approximates islet function in vivo.
PMCID: PMC3219161  PMID: 21811103
human islets of Langerhans; insulin release; glucose; exendin-4

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