Restricted and Repetitive Behaviors in Individuals with a History of ASDs Who Have Achieved Optimal Outcomes

Studies of autism spectrum disorders (ASDs) suggest that restricted and repetitive behaviors (RRBs) are particularly difficult to remediate. We examined present and past RRBs in 34 individuals who achieved optimal outcomes (OOs; lost their ASD diagnosis), 45 high-functioning individuals with ASD (HFA) and 34 typically developing (TD) peers. The OO group exhibited minimal residual RRBs at the time of the study. All OO participants were reported to have at least one RRB in early childhood and almost 90 % met the RRB cutoff for ASD in early childhood, but RRBs were not more present in the OO than the TD group at the time of the study. History of RRBs in the HFA and OO groups differed only in oversensitivity to noise and insistence on sameness. Reports of current behavior indicated that RRB’s had almost totally disappeared in the OO group. Thus, although RRB’s were present in the OO group in childhood, they resolved along with social and communication deficits.     

Associations Between Preconception Counseling and Maternal Behaviors Before and During Pregnancy

Preconception counseling (PCC) is a vital component of preconception care. Through counseling, providers educate and recommend strategies to improve health and birth outcomes for women of reproductive age. The objective of our analysis was to assess the associations between receipt of PCC and positive maternal behaviors before and during pregnancy. We analyzed 2004?C2008 Pregnancy Risk Assessment Monitoring System data from Maine, New Jersey, Utah, and Vermont. Multivariable logistic regression was used to investigate the associations between receipt of PCC and prepregnancy daily multivitamin consumption, first-trimester entry into prenatal care, and cessation of smoking and drinking before pregnancy among women who smoked/drank in the 2?years preceding the survey, adjusting for a wide range of maternal characteristics. Overall, 32% of women reported receipt of PCC, with particularly low rates reported among women with an unintended pregnancy (14%) and no health insurance prior to pregnancy (14%). Receipt of PCC was associated with daily prepregnancy multivitamin consumption (adjusted odds ratio [AOR]?=?4.4; 95% confidence interval [CI]?=?4.0, 4.7), first-trimester entry into prenatal care for women with an intended pregnancy (AOR?=?2.1; 95% CI?=?1.8, 2.4), and drinking cessation before pregnancy among women who drank in the 2?years preceding the survey (AOR?=?1.3; 95% CI?=?1.2, 1.5). PCC was associated with positive maternal behaviors that increase the likelihood of a healthy woman, pregnancy, and infant. Unfortunately, less than one-third of women with a recent live birth reported receiving PCC. These data provide population-based evidence suggesting the value of PCC in the promotion of healthy maternal behaviors for women with intended or unintended pregnancies.     

Choice in HIV testing: the acceptability and anticipated use of a self-administered at-home oral HIV test among South Africans

Combination HIV prevention is being widely promoted by funders. This strategy aims to offer HIV prevention choices that can be selected and combined to decrease HIV risk in ways that fit with each individual’s situation. Treatment as prevention and pre-exposure prophylaxis are two new evidence-based strategies to decrease HIV incidence, both of which require high HIV testing rates to be effective, and the Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a goal of 90% of HIV-positive individuals knowing their status by 2030. However, HIV testing rates in many countries remain suboptimal. Just as no single HIV prevention method is ideal for all people in all situations, no single HIV testing modality is likely to be acceptable to everyone. By offering HIV testing choices, we may be able to increase testing rates. However, many low-resourced countries have been slow to take up new HIV testing options such as the self-administered at-home oral HIV test that is currently available in the United States. In this paper, we present findings from 20 in-depth interviews, conducted in 2010, documenting opinions about self-administered at-home oral HIV testing, a testing modality still largely unavailable in Africa. Participants were clients of three primary healthcare clinics in South Africa. Self-testing was seen as enabling confidentiality/privacy, saving time, and facilitating testing together with partners. However, concerns were raised about psychological distress when testing at home without a counsellor. Some suggested this concern could be minimised by having experienced clinic-based HIV testing and counselling before getting self-testing kits for home use. Thus, self-administered HIV testing could be an option added to the current testing modalities to address some important barriers to testing.     

Posterior reversible encephalopathy syndrome and eclampsia: pressing the case for more aggressive blood pressure control

OBJECTIVE: To assess the prevalence, clinical presentations, and neuroimaging abnormalities in a series of patients treated for eclampsia at Mayo Clinic in Rochester, MN.PATIENTS AND METHODS: We reviewed the records of all pregnant patients diagnosed as having eclampsia at Mayo Clinic in Rochester, MN, between January 1, 2001, and December 31, 2008. All patients who underwent neuroimaging were identified, and all studies were reviewed by an independent neuroradiologist. Comparisons were made between groups who did and did not undergo imaging to identify differentiating clinical or laboratory variables.RESULTS: Thirteen cases of eclampsia were found, with neuroimaging studies available for 7: magnetic resonance imaging (n=6) and computed tomography (n=1). All 7 patients developed eclamptic seizures, and 2 of 7 patients had severe hypertension, with recorded systolic blood pressures exceeding 180 mm Hg. Neuroimaging showed characteristic changes of posterior reversible encephalopathy syndrome (PRES) in all patients. Follow-up imaging showed resolution in 2 of 3 patients; 1 patient had residual neuroimaging abnormalities.CONCLUSION: Our results suggest that the clinical syndrome of eclampsia is associated with an anatomical substrate that is recognizable by neuroimaging as PRES. The levels of blood pressure elevation are lower than those reported in cases of PRES because of hypertensive encephalopathy. Further studies are needed to determine whether more aggressive blood pressure control and early neuroimaging may have a role in the management of these patients.ADC = apparent diffusion coefficient; DBP = diastolic blood pressure; DWI = diffusion-weighted imaging; MRI = magnetic resonance imaging; PRES = posterior reversible encephalopathy syndrome; SBP = systolic blood pressure.Preeclampsia is a pregnancy-specific disorder clinically characterized by hypertension (blood pressure ≥140/90 mm Hg) and proteinuria (≥300 mg in a 24-hour urine collection) occurring after 20 weeks of gestation in a previously normotensive patient.¹ Preeclampsia and its variants affect approximately 5% of pregnancies and remain leading causes of both maternal and fetal morbidity and mortality world-wide.² The incidence of progression to the convulsive form (ie, eclampsia) occurs in approximately 0.5% of patients with mild preeclampsia and 2% to 3% of those with severe preeclampsia, as defined by a systolic blood pressure (SBP) of 160 mm Hg or greater, a diastolic blood pressure (DBP) of 100 mm Hg or greater, nephrotic-range proteinuria (>3.5 g/24-hour urine), renal function impairment, thrombocytopenia, and/or evidence of microangiopathic hemolytic anemia, hepatocellular injury, pulmonary edema, and neurologic disturbances.³ The incidence of eclampsia in developed countries averages 1 in 2000 to 3000 deliveries.^4,5 Seizure activity can manifest as 1 or more generalized convulsions with or without coma.In 1992, Douglas and Redman⁶ prospectively studied all cases of eclampsia in the United Kingdom. They identified 383 confirmed cases of eclampsia and described the occurrence of 1 or more of the following antecedent symptoms within hours before the onset of an eclamptic seizure: prodromal headache, visual disturbance (scotomata, amaurosis fugax, blurred vision, diplopia, homonymous hemianopsia), and epigastric pain. The relationship between the level of blood pressure and seizure onset, although considered relevant by most, remains controversial.Posterior reversible encephalopathy syndrome (PRES) is a clinically recognizable entity that presents with neurologic signs and symptoms (headache, altered consciousness, visual abnormalities, and seizures) in conjunction with the unique neuroimaging findings of vasogenic edema involving the posterior circulation. An association between eclampsia and PRES was first described by Hinchey et al⁷ in 1996. In this initial series, 3 of 15 patients with PRES had eclampsia, with other etiologies including hypertensive encephalopathy and immunosuppressive medications. Although this study established a clear association between eclampsia and PRES, few clinical studies followed to further document and support these associations.^8-10Our study aimed to assess the prevalence and clinical presentation, along with the distribution and extent of neuroimaging abnormalities, among patients treated for eclampsia at Mayo Clinic in Rochester, MN, between 2001 and 2008. In addition, we reviewed their follow-up neuroimaging studies, when available, for evidence of persistent brain damage.     

Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10(-18)), rs3803662 (16q12) (P = 3.7 × 10(-5)), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10(-6) and P = 4.1 × 10(-4), respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.     

GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway

Alterations of the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway occur broadly in cancer via multiple mechanisms including mutation of the PIK3CA gene, loss or mutation of phosphatase and tensin homolog (PTEN), and deregulation of mammalian target of rapamycin (mTOR) complexes. The dysregulation of this pathway has been implicated in tumor initiation, cell growth and survival, invasion and angiogenesis, thus, PI3K and mTOR are promising therapeutic targets for cancer. We discovered GDC-0980, a selective, potent, orally bioavailable inhibitor of Class I PI3 kinase and mTOR kinase (TORC1/2) with excellent pharmacokinetic and pharmaceutical properties. GDC-0980 potently inhibits signal transduction downstream of both PI3K and mTOR, as measured by pharmacodynamic (PD) biomarkers, thereby acting upon two key pathway nodes to produce the strongest attainable inhibition of signaling in the pathway. Correspondingly, GDC-0980 was potent across a broad panel of cancer cell lines, with the greatest potency in breast, prostate, and lung cancers and less activity in melanoma and pancreatic cancers, consistent with KRAS and BRAF acting as resistance markers. Treatment of cancer cell lines with GDC-0980 resulted in G1 cell-cycle arrest, and in contrast to mTOR inhibitors, GDC-0980 induced apoptosis in certain cancer cell lines, including those with direct pathway activation via PI3K and PTEN. Low doses of GDC-0980 potently inhibited tumor growth in xenograft models including those with activated PI3K, loss of LKB1 or PTEN, and elicited an exposure-related decrease in PD biomarkers. These preclinical data show that GDC-0980 is a potent and effective dual PI3K/mTOR inhibitor with promise for the clinic.     

Collaborative evaluation of an erythromycin-clindamycin combination well for detection of inducible clindamycin resistance in beta-hemolytic streptococci by use of the CLSI broth microdilution method

Constitutive or inducible clindamycin resistance can occur in beta-hemolytic streptococci due to the presence of an erm gene. The Clinical and Laboratory Standards Institute (CLSI) has recommended a disk approximation test (D-zone test) with erythromycin and clindamycin disks and a single-well broth test combining erythromycin and clindamycin for detection of inducible clindamycin resistance in staphylococci, but only a disk approximation test for the beta-hemolytic streptococci. This collaborative study assessed two different erythromycin and clindamycin concentration combinations in single wells (1 μg/ml + 0.25 μg/ml [erythromycin plus clindamycin] and 1 μg/ml + 0.5 μg/ml) with three different brands of Mueller-Hinton broth supplemented with 3% lysed horse blood for testing of frozen panels prepared for this study. All labs performed the D-zone test as described by the CLSI. A total of 155 nonduplicate streptococcal isolates (50 group A, 48 group B, 28 group C, and 29 group G isolates) were tested; 99 isolates showed inducible resistance by the D-zone test. There were some differences noted based upon the test medium. The sensitivity of the erythromycin plus clindamycin combination of 1 μg/ml + 0.25 μg/ml was 91 to 100%, while the sensitivity of the combination of 1 μg/ml + 0.5 μg/ml was 95 to 100%. Specificity overall was 98%. The slightly higher sensitivity of the combination of 1 μg/ml + 0.5 μg/ml is recommended. This study has demonstrated that a single-well microdilution test incorporating erythromycin and clindamycin in combination is a sensitive and specific indicator of inducible clindamycin resistance and could be included in routine test panels.     

Evaluation of disk approximation and single-well broth tests for detection of inducible clindamycin resistance in Streptococcus pneumoniae

This study evaluated an agar disk diffusion D-zone test and an erythromycin-clindamycin (ERY + CLI) single-well broth test for inducible CLI resistance in Streptococcus pneumoniae. The standard CLSI disk approximation test and a single-well combination test incorporating 1 plus 0.5 μg/ml ERY + CLI detected >96% of isolates containing the ermB determinant.