Is provision of contraception at discharge following delivery associated with postpartum visit attendance?

OBJECTIVES: We examined whether provision of contraception at discharge following delivery was associated with lower rates of postpartum visit (PPV) attendance. METHODS: We conducted a retrospective cohort study of women who received pregnancy care at a Midwestern medical center in 2013. Attendance at the postpartum visit was compared for women with sterilization, contraception initiated prior to discharge (depot medroxyprogesterone acetate or etonogestrel implant), hormonal contraception prescription, or no contraception provided at postpartum discharge. Poisson regression models with robust standard errors were used to estimate the relative risk of postpartum visit attendance controlling for age, race, and parity, insurance status, and histories of both depression and drug abuse. RESULTS: Of the 1015 women who met inclusion criteria, 55% had been prescribed contraception, had initiated contraception prior to discharge, or were sterilized at the time of discharge following delivery. After adjustment for confounders, there was no association between receiving contraception and PPV attendance (relative risk for prescribed contraception = 1.09 [95% CI 0.85, 1.39], for contraception initiated prior to discharge = 0.83 [95% CI 0.67, 1.03], for sterilization = 0.86 [95% CI 0.63, 1.17] compared to no contraception). CONCLUSIONS: We found no evidence that prescribing or administering contraception post-delivery was associated with lower rates of return for postpartum follow up. IMPLICATIONS: This single site study suggests that providing effective contraception at discharge following delivery does not appear to impact PPV attendance.

Cardiovascular death and progression to end-stage renal disease after major surgery in elderly patients.

BACKGROUND: Reliable estimates for risk of cardiovascular-specific mortality and progression to end-stage renal disease (ESRD) among elderly patients undergoing major surgery are not available. This study aimed to develop simple risk scores to predict these events. METHODS: In a single-centre cohort of elderly patients undergoing major surgery requiring hospital stay longer than 24 h, progression to ESRD and long-term cardiovascular-specific mortality were modelled using multivariable subdistribution hazard models, adjusting for co-morbidity, frailty and type of surgery. RESULTS: Before surgery, 2·9 and 11·9 per cent of 16 655 patients had ESRD and chronic kidney disease (CKD) respectively. During the hospital stay, 46·9 per cent of patients developed acute kidney injury (AKI). Patients with kidney disease had a significantly higher risk of cardiovascular-specific (CV) mortality compared with patients without kidney disease (adjusted hazard ratio (HR) for CKD without AKI 1·60, 95 per cent c.i. 1·25 to 2·01; AKI without CKD 1·70, 1·52 to 1·87; AKI with CKD 2·80, 2·50 to 3·20; ESRD 5·21, 4·32 to 6·27), as well as increased progression to ESRD (AKI without CKD 5·40, 3·44 to 8·35; CKD without AKI 8·80, 4·60 to 17·00; AKI with CKD 31·60, 19·90 to 49·90). CV Death and ESRD Risk scores were developed to predict CV mortality and progression to ESRD. Calculated CV Death and ESRD Risk scores performed well with c-statistics: 0·77 (95 per cent c.i. 0·76 to 0·78) and 0·82 (0·78 to 0·86) respectively at 1 year. CONCLUSION: Kidney disease in elderly patients undergoing major surgery is associated with a high risk of CV mortality and progression to ESRD. Risk scores can augment the shared decision-making process of informed consent and identify patients requiring postoperative renal-protective strategies.

ANTECEDENTES: No se dispone de estimaciones fiables acerca del riesgo de mortalidad cardiovascular y de progresión a insuficiencia renal terminal (end-stage renal disease, ESRD) en pacientes longevos a los que se realiza cirugía mayor. Este estudio tiene como objetivo desarrollar un sistema de puntuación simple de riesgos para predecir estos eventos. MÉTODOS: En una cohorte de un solo centro de 16.655 pacientes longevos a los que se realizó cirugía mayor con hospitalización de más de 24 horas, se estimó la progresión a ESRD y la mortalidad cardiovascular a largo plazo utilizando modelos multivariables de subdistribucion de riesgos ajustados por comorbilidades, fragilidad y tipo de cirugía. RESULTADOS: Antes de la cirugía, presentaron ESRD y enfermedad renal crónica (chronic kidney Disease, CKD) un 2,9% y un 12,3% de los pacientes, respectivamente. Durante la hospitalización, el 46,9% de los pacientes desarrollaron insuficiencia renal aguda (acute kidney injury, AKI). Los pacientes con enfermedad renal tenían un riesgo significativamente mayor de mortalidad cardiovascular (CV) en comparación con los pacientes sin enfermedad renal para presentar AKI (cociente de riesgos instantáneos, hazard ratio, HR ajustado) 1,6 (i.c. del 95% 1,3-2,0), AKI sin CKD 1,7 (1,5-1,9), AKI en presencia de CKD 2,8 (2,5-3,2) y ESRD 5,2 (4,3-6,3), así como una mayor progresión a ESRD (AKI sin CKD 5,4 (3,4-8,4), CKD sin AKI 8,8 (4,6-17), y AKI en presencia de CKD 31,6 (19,9-49,9)). Se desarrollaron las escalas CV Death y ESRD Risk para predecir la mortalidad cardiovascular y la progresión a ESRD. Ambas escalas funcionaron bien a 1 año con un coeficiente de concordancia de 0,77 (i.c. del 95% 0,76-0,78) y 0,82 (0,78-0,86) respectivamente. CONCLUSIÓN: La enfermedad renal en pacientes longevos tras cirugía mayor se asocia con un elevado riesgo de mortalidad cardiovascular y de progresión a ESRD. Las escalas de riesgo pueden facilitar la toma de decisiones en el momento del consentimiento informado e identificar los pacientes que requieren estrategias de protección renal postoperatorias.

Temporal stability of MGMT promoter methylation in glioblastoma patients undergoing STUPP protocol.

Epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT) promoter via methylation in a glioblastoma (GBM), has been correlated with a more favourable response to alkylating chemotherapeutic agents such as temozolomide. The use of global methylation surrogates such as Long Interspersed Nucleotide Element 1 (LINE1) may also be valuable in order to fully understand these highly heterogeneous tumours. In this study, we analysed both original and recurrent GBMs in 22 patients (i.e. 44 tumours), for both MGMT and LINE1 methylation status. In the 22 patients: 14 (63.6%) displayed MGMT methylation stability in the recurrent GBM versus 8 (36.4%), with instability of methylation status. No significant differences in overall and progression free survival was evident between these two groups. LINE1 methylation status remained stable for 12 (54.5%) of recurrent GBM patients versus 9 (41%) of the patients with instability in LINE1 methylation status (p = 0.02), resulting in an increase in overall survival of the stable LINE1 group (p = 0.04). The results obtained demonstrated major epigenetic instability of GBMs treated with temozolomide as part of the STUPP protocol. GBMs appear to undergo selective evolution post-treatment, and have the ability to recur with a newly reprogrammed epigenetic status. Selective targeting of the altered epigenomes in recurrent GBMs may facilitate the future development of both prognostic biomarkers and enhanced therapeutic strategies.

Brain biopsies requiring Creutzfeldt-Jakob disease precautions in the Republic of Ireland 2005-2016.

AIMS: Creutzfeldt-Jakob disease (CJD) risk precautions are required when performing brain biopsies on patients with a dementing illness and in 'risk' groups. The impact on a diagnostic neuropathology service is considerable. We sought to determine if better case selection might reduce the necessity for application of CJD risk precautions. METHODS: We reviewed the clinical information, contributory investigations and final neuropathologic diagnosis in a cohort of patients (n = 21), referred to the National CJD Surveillance Centre between January 1, 2005, and December 31, 2016. RESULTS: Of this 21-patient cohort, five were positive for CJD, four belonged to the 'at risk of CJD' category requiring brain surgery, while the remaining 12 were referred to the National CJD Surveillance Unit with CJD as part of their differential diagnosis. CJD was confirmed in 5/21 (three sporadic [s]CJD, one variant [v]CJD and one iatrogenic [i] CJD). CJD was clinically probable in 4/5 proven CJD patients (80%). The patients (n = 4) in the 'at risk of CJD' group were diagnosed with tumour (n = 2), inflammation (n = 1) and non-specific changes (n = 1). Of the remaining 12 patients (in whom CJD was included in the differential diagnosis), the final neuropathologic diagnoses included tumour (n = 2), neurodegenerative (n = 2), inflammatory (n = 1), metabolic (n = 2), vascular (n = 2) and non-specific gliosis (n = 3). CONCLUSIONS: More often than not, the clinical suspicion of CJD was not borne out by the final neuropathological diagnosis. Failure by clinicians to adhere to the recommended CJD investigation algorithm impacts adversely on the neuropathology workload and causes unnecessary concern among operating theatre, laboratory and nursing personnel.

Intravascular large B-cell lymphoma presenting clinically as rapidly progressive dementia.

BACKGROUND: In patients presenting with rapidly progressive dementia, prion disease may enter the differential diagnosis. The commonest malignancies masquerading as prion disease are primary CNS lymphoma and intravascular large B-cell lymphoma, both rare and difficult to diagnose without brain biopsy. CASE PRESENTATION: This 82-year-old lady with a past history of hypertension, presented with rapidly progressive cognitive impairment and ataxia. The possibility of sCJD was raised. Brain biopsy was carried out. Western blot for prion protein was negative. Brain biopsy showed intravascular large B-cell lymphoma. She died shortly afterwards. CONCLUSION: The clinical presentation of intravascular large B-cell lymphoma is diverse. Patients may present as in this case with dementia, seizures, and myoclonus leading to a clinical diagnosis of sCJD. The diagnosis here was made at biopsy but is made at autopsy in over 50% of cases.

Measurement of linear stark interference in 199Hg.

We present measurements of Stark interference in the (61)S(0)→6(3)P(1) transition in (199)Hg, a process whereby a static electric field E mixes magnetic dipole and electric quadrupole couplings into an electric dipole transition, leading to E-linear energy shifts similar to those produced by a permanent atomic electric dipole moment (EDM). The measured interference amplitude, a(SI) = (a(M1) + a(E2)) = (5.8 ± 1.5) × 10(-9) (kV / cm)(-1), agrees with relativistic, many-body predictions and confirms that earlier central-field estimates are a factor of 10 too large. More importantly, this study validates the capability of the (199)Hg EDM search apparatus to resolve nontrivial, controlled, and sub-nHz Larmor frequency shifts with EDM-like characteristics.

Improved limit on the permanent electric dipole moment of 199Hg.

We report the results of a new experimental search for a permanent electric dipole moment of 199Hg utilizing a stack of four vapor cells. We find d(199Hg)=(0.49+/-1.29_{stat}+/-0.76_{syst})x10;{-29} e cm, and interpret this as a new upper bound, |d(199Hg)|<3.1x10;{-29} e cm (95% C.L.). This result improves our previous 199Hg limit by a factor of 7, and can be used to set new constraints on CP violation in physics beyond the standard model.

Resonant control of elastic collisions in an optically trapped fermi gas of atoms.

We have loaded an ultracold gas of fermionic atoms into a far-off resonance optical dipole trap and precisely controlled the spin composition of the trapped gas. We have measured a magnetic-field Feshbach resonance between atoms in the two lowest energy spin states, /9/2,-9/2> and /9/2,-7/2>. The resonance peaks at a magnetic field of 201.5+/-1.4 G and has a width of 8.0+/-1.1 G. Using this resonance, we have changed the elastic collision cross section in the gas by nearly 3 orders of magnitude.

Instability and pulse area quantization in accelerated superradiant atom-cavity systems.

We study the interaction of pulsed excitation fields with optically thin atomic ensembles subject to strong cavity-accelerated superradiance. In homogeneously broadened atom-field systems the excitation of superradiant instabilities is seen to lead to a quantization of the total pulse area accrued during excitation and subsequent superradiant decay. In inhomogeneously broadened systems, quasidiscretized area values and pulse area gaps (i.e., forbidden area values) are found. Predicted area discontinuities are demonstrated in cryogenically coherence-stabilized Tm(3+) ions.

Synthesis and anti-HIV activity of cosalane analogues incorporating two dichlorodisalicylmethane pharmacophore fragments.

A new series of cosalane analogues incorporating two fragments of the dichlorodisalicylmethane pharmacophore has been synthesized. In order to identify the position for the attachment of the pharmacophore fragments to the steroid ring that results in the most potent analogues, two types of compounds were designed. In the first type, the two pharmacophore fragments were attached at C-3 and C-17 of the steroid ring by using appropriate linker units. In the second type, both pharmacophore groups were connected to C-3 of the steroid through an alkenyl chain containing an amide moiety. All of the new compounds displayed antiviral activity versus HIV-1(RF), HIV-1(IIIB), and HIV-2(ROD) in cell culture. The relative potencies of the compounds resulting from the two attachment strategies were found to depend on the viral strain as well as the cell type. Overall, the attachment of the second pharmacophore did not result in either a large gain or a large loss in anti-HIV activity, and the results are therefore consistent with the hypothesis that the two pharmacophores act independently, and one at a time, with positively charged amino acid side chains present on the surface of gp120 and CD4.

Solid-phase synthesis of the alkenyldiarylmethane (ADAM) series of non-nucleoside HIV-1 reverse transcriptase inhibitors.

The Sonogashira and Stille cross-coupling reactions have been employed in the synthesis of several non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the alkenyldiarylmethane (ADAM) series. The synthesis has been carried out both in solution and on a solid support. In contrast to previous syntheses of NNRTIs in the ADAM series, the present strategy allows the incorporation of differently substituted aromatic rings in a stereochemically defined fashion. The most potent of the new ADAMs inhibited the cytopathic effect of HIV-1RF in CEM-SS cell culture with an EC50 value of 20 nM.

Land-use dynamics in a southern Illinois (USA) watershed.

The Cache River of southernmost Illinois is used as a case study for developing and demonstrating an approach to quantitatively link (1) national agricultural policy and global agricultural markets, (2) landowner's decisions on land use, (3) spatial patterns of land use at a watershed scale, and (4) hydrologic impacts, thus providing a basis to predict, under a certain set of circumstances, the environmental consequences of economic and political decisions made at larger spatial scales. The heart of the analysis is an estimation, using logistic regression, of the affect of crop prices and Conservation Reserve Program (CRP) rental rates on farmland owner's decisions whether to reenroll in the CRP or return to crop production. This analysis shows that reasonable ranges for crop prices (80%-150% of 1985-1995 values) and CRP rental rates (0-125% of 1985-1995 rates) result in a range of 3%-92% of CRP lands being returned to crop production, with crop prices having a slightly greater effect than CRP rental rates. Four crop price/CRP rental rate scenarios are used to display resulting land-use patterns, and their effect on sediment loads, a critical environmental quality parameter in this case, using the agricultural non point source (AGNPS) model. These scenarios demonstrate the importance of spatial pattern of land uses on hydrological and ecological processes within watersheds. The approach developed can be adapted for use by local governments and watershed associations whose goals are to improve watershed resources and environmental quality.

Correlation of anti-HIV activity with anion spacing in a series of cosalane analogues with extended polycarboxylate pharmacophores.

Cosalane and its synthetic derivatives inhibit the binding of gp120 to CD4 as well as the fusion of the viral envelope with the cell membrane. The binding of the cosalanes to CD4 is proposed to involve ionic interactions of the negatively charged carboxylates of the ligands with positively charged arginine and lysine amino acid side chains of the protein. To investigate the effect of anion spacing on anti-HIV activity in the cosalane system, a series of cosalane tetracarboxylates was synthesized in which the two proximal and two distal carboxylates are separated by 6--12 atoms. Maximum activity was observed when the proximal and distal carboxylates are separated by 8 atoms. In a series of cosalane amino acid derivatives containing glutamic acid, glycine, aspartic acid, beta-alanine, leucine, and phenylalanine residues, maximum activity was displayed by the di(glutamic acid) analogue. A hypothetical model has been devised for the binding of the cosalane di(glutamic acid) conjugate to CD4. In general, the compounds in this series are more potent against HIV-1(RF) in CEM-SS cells than they are vs HIV-1(IIIB) in MT-4 cells, and they are least potent vs HIV-2(ROD) in MT-4 cells.

SJ-3366, a unique and highly potent nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2.

We have identified and characterized a potent new nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1) that also is active against HIV-2 and which interferes with virus replication by two distinct mechanisms. 1-(3-Cyclopenten-1-yl)methyl-6-(3,5-dimethylbenzoyl)-5-ethyl-2,4-pyrimidinedione (SJ-3366) inhibits HIV-1 replication at concentrations of approximately 1 nM, with a therapeutic index of greater than 4 x 10(6). The efficacy and toxicity of SJ-3366 are consistent when evaluated with established or fresh human cells, and the compound is equipotent against all strains of HIV-1 evaluated, including syncytium-inducing, non-syncytium-inducing, monocyte/macrophage-tropic, and subtype virus strains. Distinct from other members of the pharmacologic class of NNRTIs, SJ-3366 inhibited laboratory and clinical strains of HIV-2 at a concentration of approximately 150 nM, yielding a therapeutic index of approximately 20,000. Like most NNRTIs, the compound was less active when challenged with HIV-1 strains possessing the Y181C, K103N, and Y188C amino acid changes in the RT and selected for a virus with a Y181C amino acid change in the RT after five tissue culture passages in the presence of the compound. In combination anti-HIV assays with nucleoside and nonnucleoside RT and protease inhibitors, additive interactions occurred with all compounds tested with the exception of dideoxyinosine, with which a synergistic interaction was found. Biochemically, SJ-3366 exhibited a K(i) value of 3.2 nM, with a mixed mechanism of inhibition against HIV-1 RT, but it did not inhibit HIV-2 RT. SJ-3366 also inhibited the entry of both HIV-1 and HIV-2 into target cells. On the basis of its therapeutic index and multiple mechanisms of anti-HIV action, SJ-3366 represents an exciting new compound for use in HIV-infected individuals.

Treasure of the Past IX: Exposure Standardization of Iodine-125 Seeds Used for Brachytherapy.

A method for calibrating iodine-125 seeds in terms of exposure has been established. The standard free-air ionization chamber, used for measuring soft x rays, was chosen for the measurements. Arrays of four to six seeds were used to enhance the ionization-current-to-background-current ratio. Seeds from an array were measured individually in a re-entrant chamber. The quotient of the exposure rate for the array by the sum of the ionization currents in the re-entrant chamber is the calibration factor for the re-entrant chamber. Calibration factors were established for three types of iodine-125 seeds. The overall uncertainty for the seed exposure calibrations is less than 6%.

Anti-HIV activity of a series of cosalane amino acid conjugates.

The binding of the anti-HIV agent cosalane to CD4 is thought to involve ionic interactions of negatively charged carboxylates of the ligand with positively charged residues on the surface of the protein. The purpose of the present study was to examine the hypothesis that the two carboxyl groups of cosalane could be sacrificed through conjugation to amino acids, and the anti-HIV activity still be retained, provided that at least two new carboxyl groups are contributed by the amino acid residues.

Identification of optimal anion spacing for anti-HIV activity in a series of cosalane tetracarboxylates.

The binding of the anti-HIV agent cosalane to CD4 is thought to involve ionic interactions of negatively charged carboxylates of the ligand with positively charged residues on the surface of the protein. An investigation of the optimal anion distances for anti-HIV activity in a series of cosalane tetracarboxylate analogues has been completed, and maximal activity results when the two proximal and the two distal carboxylates are separated by eight atoms.

Induction of apoptosis by conjugated linoleic acid in cultured mammary tumor cells and premalignant lesions of the rat mammary gland.

Conjugated linoleic acid (CLA) is an effective agent in preventing mammary cancer in rats treated with a carcinogen. The appearance of a tumor mass is the net result of cell proliferation minus cell death. Thus, apoptosis could be an important mechanism in controlling clonal expansion of the early premalignant lesions. The overall objective of this report was to determine whether CLA stimulated apoptosis. In the first part of the study, CLA was found to increase chromatin condensation (visualized through fluorescent 4',6-diamidino-2-phenylindole staining to DNA) and to induce DNA laddering, both evidence of apoptosis, in a rat mammary tumor cell line. The second part was to investigate the effect of CLA feeding on the development of histologically identifiable premalignant lesions in the rat mammary gland, as well as on the quantification of apoptosis (by terminal uridyltransferase nick end labeling assay) and the expression by immunohistochemistry of apoptosis regulatory proteins (bcl-2, bak, and bax) in normal versus premalignant mammary structures. CLA inhibited the formation of premalignant lesions by approximately 50%. It also significantly increased apoptosis and reduced the expression of bcl-2 in these lesions, but it did not modulate the levels of bak or bax. In contrast, neither apoptosis nor any of the apoptosis regulatory proteins was affected by CLA in normal mammary gland alveoli or terminal end buds. The data suggest that early pathological lesions may be particularly sensitive to CLA. In addition to providing a molecular basis for elucidating the mechanism of action of CLA in cancer prevention, the research on CLA-responsive biomarkers also has a practical side because these assays can be applied to biopsied human tissue samples in future CLA intervention trials.

Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors.

With the escalation of obesity-related disease, there is great interest in defining the mechanisms that control appetite and body weight. We have identified a link between anabolic energy metabolism and appetite control. Both systemic and intracerebroventricular treatment of mice with fatty acid synthase (FAS) inhibitors (cerulenin and a synthetic compound C75) led to inhibition of feeding and dramatic weight loss. C75 inhibited expression of the prophagic signal neuropeptide Y in the hypothalamus and acted in a leptin-independent manner that appears to be mediated by malonyl-coenzyme A. Thus, FAS may represent an important link in feeding regulation and may be a potential therapeutic target.