Five Functional Classes Identified Among Patients Hospitalized for Pneumonia Characterized by Activity Limitations With Mobility and Self-Care Tasks.

Objective: Latent class analysis was used to identify functional classes among patients hospitalized for pneumonia. Then, we determined predictors of class membership and examined variation in distal outcomes among the functional classes. Design: An observational, cross-sectional study design was used with retrospectively collected data between 2014 and 2018. Setting: The study setting was a single health system including 5 acute care hospitals. Participants: A total of 969 individuals hospitalized with the primary diagnosis of pneumonia and receipt of an occupational and/or physical therapy evaluation were included in the study. Interventions: Not applicable. Main Outcomes: The following 5 distal outcomes were examined: (1) occupational therapy treatment use, (2) physical therapy treatment use, (3) discharge to home with no services, (4) discharge to home with home health, and (5) institutional discharge. Results: Five functional classes were identified and labeled as follows: Globally impaired, Independent with low-level self-care, Independent low-level mobility, Independent self-care, and Independent. Probability of occupational therapy treatment use (χ2[4]=50.26, P<.001) and physical therapy treatment use (χ2[4]=50.86, P<.001) varied significantly across classes. The Independent with low-level self-care class had the greatest probability of occupational therapy treatment use and physical therapy treatment use. Probability of discharging to home without services (yes/no; χ2[4]=88.861, P<.001), home with home health (yes/no; χ2[4]=15.895, P=.003), and an institution (yes/no; χ2[4]=102.013, P<.001) varied significantly across the 5 classes. The Independent class had the greatest probability of discharging to home without services. Conclusions: Five functional classes were identified among individuals hospitalized for pneumonia. Functional classes could be used by the multidisciplinary team in the hospital as a framework to organize the heterogeneity of functional deficits after pneumonia, improve efficiency of care processes, and help deliver targeted rehabilitation treatment.

Identification of Disability Subgroups for Patients After Ischemic Stroke.

OBJECTIVE: The aims of this study were to identify disability subgroups among patients hospitalized for ischemic stroke and to determine the predictors and distal outcomes for the disability subgroups. METHODS: A retrospective, cross-sectional study design was used. Data on patients after ischemic stroke were collected from the electronic health records at 5 hospitals within a single health system. Covariates included social and demographic factors. Disability was characterized according to the Activity Measure for Post-Acute Care assessment. Distal outcomes were physical therapist treatment use, occupational therapist treatment use, and discharge disposition. Latent class analysis was used to identify disability subgroups of patients hospitalized for ischemic stroke. RESULTS: A total of 1549 patients were included in the analyses. Five disability subgroups were identified and labeled as follows: globally impaired (subgroup 1), impaired dynamic balance (subgroup 2), impaired self-care (subgroup 3), impaired mobility (subgroup 4), and independent (subgroup 5). Physical therapist treatment use (χ24 = 113.21 [P < .001]) and occupational therapist treatment use (χ24 = 122.97 [P < .001]) varied significantly across the disability subgroups. The globally impaired group had the highest probability of physical and occupational therapist treatment use. Similarly, discharge disposition varied across the subgroups (for home without services, χ24 = 246.61 [P < .001]; for home with home health care, χ24 = 35.49 [P < .001]; for institutional discharge, χ24 = 237.18 [P < .001]). The independent subgroup had the highest probability of discharge to home without services. CONCLUSION: Five disability subgroups were identified for patients after ischemic stroke. The disability subgroups provide a common language for clinicians to organize the heterogeneity of disability after stroke. IMPACT: Using the disability subgroups, the multidisciplinary team might be able to improve the accuracy and efficiency of care decisions. The number of current rehabilitation interventions is indeterminable; these subgroups may help to guide clinicians in selecting the most beneficial interventions for patients based on subgroup membership.

Are Social Determinants of Health Associated With Onset of Rehabilitation Services in Patients Hospitalized for Traumatic Brain Injury?

OBJECTIVE: To examine the impact of community-level social determinants of health (SDoH) on the onset of occupational therapy (OT) and physical therapy (PT) services among individuals hospitalized for traumatic brain injury (TBI). SETTING: 14 acute care hospitals in the state of Colorado. PARTICIPANTS: We studied 5825 adults with TBI. DESIGN: In a secondary analysis of de-identified electronic health record data, we performed multivariable logistic and linear regressions to calculate odds ratios (ORs) and 95% CIs for the likelihood of receiving services and duration to initiation of services among those who received them. MAIN MEASURES: Community-level SDoH, receipt of rehabilitation services, and onset of rehabilitation services. RESULTS: Multivariable logistic and linear regressions revealed that those in top quartiles for community income were associated with duration to OT services, ranging from OR = 0.33 [05% CI, 0.07, 0.60] for quartile 2 to 0.76 [0.44, 1.08] for quartile 4 compared with those with the lowest quartile. Only the top quartile differed significantly for duration to PT services (0.63 [0.28, 0.98]). Relative to those with below the median community percentage of high school degree, those with above the median were associated with duration to PT services only (-0.32 [-0.60, -0.04]). Neither community percentage with bachelor's degree nor rural-urban designation was associated with duration to either therapy service. CONCLUSION: Further research is needed to determine whether our SDoH variables were too diffuse to capture individual experiences and impacts on care or whether community-level education and income, and rurality, truly do not influence time to therapy for patients hospitalized with TBI. Other, individual-level variables, such as age, comorbidity burden, and TBI severity, demonstrated clear relationships with therapy onset. These findings may help therapists evaluate and standardize equitable access to timely rehabilitation services.

Activities of Daily Living Performance and Acute Care Occupational Therapy Utilization: Moderating Factors.

IMPORTANCE: Hospitalized patients who have difficulty performing activities of daily living (ADLs) benefit from occupational therapy services; however, disparities in access to such services are understudied. OBJECTIVE: To investigate whether need (i.e., limited ADL performance) predicts acute care occupational therapy utilization and whether this relationship differs across sociodemographic factors and insurance type. DESIGN: A secondary analysis of electronic health records data. Logistic regression models were specified to determine whether ADL performance predicted use of occupational therapy treatment. Interactions were included to investigate whether the relationship between ADL performance and occupational therapy utilization varied across sociodemographic factors (e.g., age) and insurance type. PARTICIPANTS: A total of 56,022 adults admitted to five regional hospitals between 2014 and 2018 who received an occupational therapy evaluation. INTERVENTION: None. Outcomes and Measures: Occupational therapy service utilization, Activity Measure for Post-Acute Care "6-Clicks" measure of daily activity. RESULTS: Forty-four percent of the patients evaluated for occupational therapy received treatment. Patients with lower ADL performance were more likely to receive occupational therapy treatment; however, interaction terms indicated that, among patients with low ADL performance, those who were younger, were White and non-Hispanic, had significant others, and had private insurance (vs. public) were more likely to receive treatment. These differences were smaller among patients with greater ADL performance. CONCLUSIONS AND RELEVANCE: Greater need was positively associated with receiving occupational therapy services, but this relationship was moderated by age, minoritized status, significant other status, and insurance type. The findings provide direction for exploring determinants of disparities in occupational therapy utilization. What This Article Adds: Acute care occupational therapy utilization is driven partly by patient need, but potential disparities in access to beneficial services may exist across sociodemographic characteristics and insurance type. Identifying potential determinants of disparities in acute care occupational therapy utilization is the first step in developing strategies to reduce barriers for those in need.

Activities of Daily Living Performance and Acute Care Occupational Therapy Utilization: Moderating Factors.

IMPORTANCE: Hospitalized patients who have difficulty performing activities of daily living (ADLs) benefit from occupational therapy services; however, disparities in access to such services are understudied. OBJECTIVE: To investigate whether need (i.e., limited ADL performance) predicts acute care occupational therapy utilization and whether this relationship differs across sociodemographic factors and insurance type. DESIGN: A secondary analysis of electronic health records data. Logistic regression models were specified to determine whether ADL performance predicted use of occupational therapy treatment. Interactions were included to investigate whether the relationship between ADL performance and occupational therapy utilization varied across sociodemographic factors (e.g., age) and insurance type. PARTICIPANTS: A total of 56,022 adults admitted to five regional hospitals between 2014 and 2018 who received an occupational therapy evaluation. INTERVENTION: None. Outcomes and Measures: Occupational therapy service utilization, Activity Measure for Post-Acute Care "6-Clicks" measure of daily activity. RESULTS: Forty-four percent of the patients evaluated for occupational therapy received treatment. Patients with lower ADL performance were more likely to receive occupational therapy treatment; however, interaction terms indicated that, among patients with low ADL performance, those who were younger, were White and non-Hispanic, had significant others, and had private insurance (vs. public) were more likely to receive treatment. These differences were smaller among patients with greater ADL performance. CONCLUSIONS AND RELEVANCE: Greater need was positively associated with receiving occupational therapy services, but this relationship was moderated by age, minoritized status, significant other status, and insurance type. The findings provide direction for exploring determinants of disparities in occupational therapy utilization. What This Article Adds: Acute care occupational therapy utilization is driven partly by patient need, but potential disparities in access to beneficial services may exist across sociodemographic characteristics and insurance type. Identifying potential determinants of disparities in acute care occupational therapy utilization is the first step in developing strategies to reduce barriers for those in need.

Occupational Therapist Treatment of Patients in the Neurological Critical Care Unit: Utilization and Patient Characteristics.

IMPORTANCE: Occupational therapy use in the neurological critical care unit (NCCU) may relate to patient factors, but data about these relationships remain unpublished. OBJECTIVE: To examine how patient factors predict NCCU occupational therapy use and intervention types. DESIGN: Retrospective cohort study of electronic health records data from adults admitted to the NCCU between May 2013 and September 2015. SETTING: NCCU in a large, urban academic hospital. PARTICIPANTS: Adults (age ≥18 yr; N = 1,134) admitted to the NCCU. MEASURES: Using length of stay (LOS), number of comorbidities, Glasgow Coma Scale (GCS) score, gender, age, and racial-ethnic minority status as independent variables, separate regression models identified predictors for each dependent variable: receipt of NCCU occupational therapy, occupational therapy onset (days after admission), and receipt of self-care or home management (ADL-Home); functional activities or cognitive training (Func-Cog); and therapeutic exercise (Ther-Ex). RESULTS: Four hundred twenty patients (37.0%) received occupational therapy in the NCCU. Receipt of occupational therapy was positively associated with LOS, number of comorbidities, GCS score, and age. Earlier occupational therapy onset was associated with higher GCS score and shorter LOS. Receipt of ADL-Home or Func-Cog interventions was significantly predicted by number of occupational therapy sessions, but patients with longer LOS were less likely to receive ADL-Home interventions. Receipt of Ther-Ex interventions became less likely as GCS score increased. CONCLUSIONS AND RELEVANCE: Patients are more likely to receive occupational therapy services if they are older and have a longer NCCU LOS, more comorbidities, and a higher level of consciousness. What This Article Adds: A patient's level of consciousness is clearly associated with occupational therapy utilization and hospital outcomes, but it should not be the only factor considered when prioritizing patients for NCCU occupational therapy services. Compared with patients who were more awake and alert, patients with a lower level of consciousness had a later onset of occupational therapy, which suggests an opportunity for NCCU occupational therapists to collaborate with physicians in the modification of sedation protocols to enable early rehabilitation.

The Relationship Between Fall Risk and Hospital-Based Therapy Utilization Is Moderated by Demographic Characteristics and Insurance Type.

OBJECTIVE: To investigate whether indicators of patient need (comorbidity burden, fall risk) predict acute care rehabilitation utilization, and whether this relation varies across patient characteristics (ie, demographic characteristics, insurance type). DESIGN: Secondary analysis of electronic health records data. SETTING: Five acute care hospitals. PARTICIPANTS: Adults (N=110,209) admitted to 5 regional hospitals between 2014 and 2018. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Occupational therapy (OT) and physical therapy (PT) utilization. Logistic regression models determined whether indicators of patient need predicted OT and PT utilization. Interactions between indicators of need and both demographic factors (eg, minority status, presence of significant other) and insurance type were included to investigate whether the relation between patient need and therapy access varied across patient characteristics. RESULTS: Greater comorbidity burden was associated with a higher likelihood of receiving OT and PT. Relative to those with low fall risk, those with moderate and high fall risk were more likely to receive OT and PT. The relation between fall risk and therapy utilization differed across patient characteristics. Among patients with higher levels of fall risk, those with a significant other were less likely to receive OT and PT; significant other status did not explain therapy utilization among patients with low fall risk. Among those with high fall risk, patients with VA insurance and minority patients were more likely to receive PT than those with private insurance and nonminority patients, respectively. Insurance type and minority status did not appear to explain PT utilization among those with lower fall risk. CONCLUSIONS: Patients with greater comorbidity burden and fall risk were more likely to receive acute care rehabilitation. However, the relation between fall risk and utilization was moderated by insurance type, having a significant other, and race/ethnicity. Understanding the implications of these utilization patterns requires further research.

Comparing the effects of physiologically-based metal oxide nanoparticles on ribonucleic acid and RAS/RBD-targeted triplex and aptamer interactions.

Physiological metals such as zinc, magnesium, and nickel facilitate nucleic acid and protein interactions and stability. In the nanoscale, the impact these have on nucleic acid structure-function is very poorly understood and was investigated here. Nanoparticles' (NP) RNA precipitation efficiency was in the order; NiO > MgO > ZnO > CaO > CaCO3>Cu. Gel mobility shift was observed for MgO and especially ZnO NP. Loss of staining intensity was shown for Cu suggesting this NP may denature RNA supported by the UV- and CD-spectroscopy patterns, change in area-under-the-curve (AUC) and abs260 nm measurements. Aptamer and triplex-forming oligomer (TFO) sequences were designed targeting RAS/Ras binding domain (RBD) and the impact of the NP on target interaction investigated. MgO NP promotes aptamer:RBD interaction and preserves triplex formation whereas NiO NP effects duplex migration and intensifies staining of the triplex suggesting a novel mechanism of interaction and conformation. These data strongly support the role of MgO, ZnO and NiO NP for nucleic acid nanobio interaction and suggest potential biomedical application for such novel interfaces.

Mind-body interventions utilized by an occupational therapist in a medical intensive care unit: An exploratory case study.

Patients in the medical intensive care unit (MICU) face life-threatening conditions leading to physical and psychological stress, and decreased occupational engagement. Mind-body interventions include techniques based on connecting the mind, body, brain, and behavior to positively influence health. The purpose of this study was to explore the use of mind-body interventions as a tool for use by occupational therapists (OT) to improve health and occupational performance. This was an exploratory case study completed with the patient, "Ann" in a MICU. Ann was a 57-year-old female who was admitted to the MICU for abdominal pain and later diagnosed with septic shock. Two mind-body sessions were completed with Ann and her responses were assessed via multiple variables, including: respiratory rate; blood pressure; heart rate; oxygen saturation; and anxiety. Ann stayed within normal ranges for all variables. This study demonstrates it was feasible to elicit mind-body interventions in this setting, with this patient.

Translating Nanomedicine to Comparative Oncology-the Case for Combining Zinc Oxide Nanomaterials with Nucleic Acid Therapeutic and Protein Delivery for Treating Metastatic Cancer.

The unique anticancer, biochemical, and immunologic properties of nanomaterials are becoming a new tool in biomedical research. Their translation into the clinic promises a new wave of targeted therapies. One nanomaterial of particular interest are zinc oxide (ZnO) nanoparticles (NPs), which has distinct mechanisms of anticancer activity including unique surface, induction of reactive oxygen species, lipid oxidation, pH, and also ionic gradients within cancer cells and the tumor microenvironment. It is recognized that ZnO NPs can serve as a direct enzyme inhibitor. Significantly, ZnO NPs inhibit extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) associated with melanoma progression, drug resistance, and metastasis. Indeed, direct intratumoral injection of ZnO NPs or a complex of ZnO with RNA significantly suppresses ERK and AKT phosphorylation. These data suggest ZnO NPs and their complexes or conjugates with nucleic acid therapeutic or anticancer protein may represent a potential new strategy for the treatment of metastatic melanoma, and potentially other cancers. This review focuses on the anticancer mechanisms of ZnO NPs and what is currently known about its biochemical effects on melanoma, biologic activity, and pharmacokinetics in rodents and its potential for translation into large animal, spontaneously developing models of melanoma and other cancers, which represent models of comparative oncology.

Two-Dimensional Fluorescence Difference Spectroscopy of ZnO and Mg Composites in the Detection of Physiological Protein and RNA Interactions.

Two-dimensional fluorescence difference spectroscopy (2-D FDS) was used to determine the unique spectral signatures of zinc oxide (ZnO), magnesium oxide (MgO), and 5% magnesium zinc oxide nanocomposite (5% Mg/ZnO) and was then used to demonstrate the change in spectral signature that occurs when physiologically important proteins, such as angiotensin-converting enzyme (ACE) and ribonuclease A (RNase A), interact with ZnO nanoparticles (NPs). When RNase A is bound to 5% Mg/ZnO, the intensity is quenched, while the intensity is magnified and a significant shift is seen when torula yeast RNA (TYRNA) is bound to RNase A and 5% Mg/ZnO. The intensity of 5% Mg/ZnO is quenched also when thrombin and thrombin aptamer are bound to the nanocomposite. These data indicate that RNA-protein interaction can occur unimpeded on the surface of NPs, which was confirmed by gel electrophoresis, and importantly that the change in fluorescence excitation, emission, and intensity shown by 2-D FDS may indicate specificity of biomolecular interactions.

From MSM to heteroflexibilities: Non-exclusive straight male identities and their implications for HIV prevention and health promotion.

This article examines the logics of self-identification among men who have same-sex desires and behaviours and consider themselves to be straight. We draw from interviews conducted in the USA with 100 straight-identified men who have same-sex desires and 40 partners of such men. Our data allow us to reject two misconceptions. One is the idea that these men are actually gay or bisexual but refuse to accept those identities. We argue instead that these men see themselves as straight and therefore it is important to understand what specifically they mean by that. The second misconception links straight-identified men who have same-sex desires and behaviours to the racialised discourse of the so-called down low (or 'DL') in the USA. While the DL typically is depicted as involving African American and Latino men, most of our participants are White. Moving beyond these misconceptions, we propose that health educators must acknowledge flexibilities in the definition of heterosexuality and use an expanded definition as a starting point to envision, together with these men, how to more effectively engage them in HIV prevention and health promotion.

Ferromagnetic Coupling in "Double-Bridged" Dihydrogenpyrophosphate Complexes of Cobalt(II) and Nickel(II).

Three isostructural compounds of the formula {[M(bipy)(H2O)(H2P2O7)]2·2H2O} [bipy = 2,2'-bipyridine; M = Ni (1), Co (2), Mn (3)] have been isolated from aqueous solutions containing the corresponding metal(II) chloride hydrate with a bipy and sodium pyrophosphate solution in a 1:1:2 molar ratio, and their structures were determined by single-crystal X-ray diffraction. The structures of 1-3 consist of neutral aqua(2,2'-bipyridine)metal(II) dinuclear units bridged by two dihydrogenpyrophosphate groups adopting a bidentate/monodentate mode. Each metal ion in 1-3 is six-coordinate in a distorted octahedral geometry, with the reduced value of the angle subtended by the chelating bipy at the metal ion [79.6(1)° (1), 77.32(7)° (2), and 72.9(1)° (3)] being the main source of this distortion. The values of the intramolecular metal-metal separation are 5.271(1) Å (1), 5.3065(8) Å (2), and 5.371(1) Å (3). Magnetic susceptibility measurements on polycrystalline samples of 1-3 in the temperature range 1.9-300 K shows weak intramolecular ferromagnetic [J = +1.86(2) cm(-1) (1) and +0.25(1) cm(-1) (2)] and antiferromagnetic [J = -0.48(1) cm(-1) (3)] coupling, with the spin Hamiltonian being defined as H = -JSM1·SM1a. This rarely observed coordination mode for dihydrogenpyrophosphate leads to ferromagnetic coupling in complexes of nickel(II) or cobalt(II).

Clinical isolates of Candida albicans, Candida tropicalis, and Candida krusei have different susceptibilities to Co(II) and Cu(II) complexes of 1,10-phenanthroline.

The minimal inhibitory concentrations (MICs) of copper and cobalt based dimeric pyrophosphate complexes with capping 1,10-phenanthroline groups on clinical isolates of C. albicans (28 isolates), C. krusei (20 isolates) and C. tropicalis (20 isolates) are reported. C. albicans was inhibited by the cobalt complex better than by the copper complex, while C. krusei demonstrated the opposite results. C. tropicalis showed similar sensitivities to both metals in terms of calculated MIC50 values but was more sensitive to cobalt when MIC90 values were noted. Knockout strains of C. albicans that had the copper efflux protein P-type ATPase (CRP1), the copper binding metallothionein CUP1 or both CRP1/CUP1 removed clearly demonstrate that the origins of copper resistant in C. albicans lies primarily in the P-type ATPase, with the MT playing an important secondary role in the absence of the efflux protein. This study suggests that certain strains of Candida have evolved to protect against particular metal ions and that in the case of C. albicans, a primary invasive fungal species, cobalt may be a good starting-point for new therapeutic development.

Elevating the role of finance at Mary Lanning Healthcare.

To effectively partner with hospital operations leaders, healthcare finance leaders should: Streamline and align financial planning and budgeting functions across the organization; Ensure capital planning is regarded as a strategic process; Optimize performance monitoring across management levels.

Co(II) and Cu(II) pyrophosphate complexes have selectivity and potency against Mycobacteria including Mycobacterium tuberculosis.

Tuberculosis (TB) causes up to 10 million incident cases worldwide per annum. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains are leading factors in the resurgence of TB cases and the need to produce new agents to combat such infection. Herein, we describe Co(II) and Cu(II) metal based complexes that feature the pyrophosphate ligand with notable selectivity and marked potency against Mycobacterium tuberculosis, including MDR strains. Such complexes are confirmed to be bacteriocidal and not affected by efflux inhibitors. Finally, while susceptibility to copper has recently been established for M. tuberculosis, the greater efficacy of cobalt observed herein is of considerable note and in line with the discovery of a copper metallothionein in M. tuberculosis.

Epigenetics of kidney cancer and bladder cancer.

This article focuses on the epigenetic alterations of aberrant promoter hypermethylation of genes, and histone modifications or RNA interference in cancer cells. Current knowledge of the hypermethylation of allele(s) in classical tumor suppressor genes in inherited and sporadic cancer, candidate tumor suppressor and other cancer genes is summarized gene by gene. Global and array-based studies of tumor cell hypermethylation are discussed. The importance of standardization of scoring of the methylation status of a gene is highlighted. The histone marks associated with hypermethylated genes, and the miRNAs with dysregulated expression, in kidney or bladder tumor cells are also discussed. Kidney cancer has the highest mortality rate of the genito-urinary cancers. There are management issues associated with the high recurrence rate of superficial bladder cancer, while muscle-invasive bladder cancer has a poor prognosis. These clinical problems are the basis for the translational application of gene hypermethylation in the diagnosis and prognosis of kidney and bladder cancer.

Global reactivation of epigenetically silenced genes in prostate cancer.

Transcriptional silencing associated with aberrant promoter hypermethylation is a common mechanism of inactivation of tumor suppressor genes in cancer cells. To globally profile the genes silenced by hypermethylation in prostate cancer, we screened a whole genome expression microarray for genes reactivated in the LNCaP, DU-145, PC-3, and MDA2b prostate tumor cell lines after treatment with the demethylating drug 5-aza-2-deoxycytidine and the histone deacetylation-inhibiting drug trichostatin A. A total of 2,997 genes showed at least 2-fold upregulation of expression after drug treatment in at least one prostate tumor cell line. For validation, we examined the first 45 genes, ranked by upregulation of expression, which had a typical CpG island and were known to be expressed in the normal cell counterpart. Two important findings were, first, that several genes known to be frequently hypermethylated in prostate cancer were apparent, and, second, that validation studies revealed eight novel genes hypermethylated in the prostate tumor cell lines, four of which were unmethylated in normal prostate cells and hypermethylated in primary prostate tumors (SLC15A3, 66%; KRT7, 54%; TACSTD2, 17%; GADD45b, 3%). Thus, we established the utility of our screen for genes hypermethylated in prostate cancer cells. One of the novel genes was TACSTD2/TROP2, a marker of human prostate basal cells with stem cell characteristics. TACSTD2 was unmethylated in prostatic intraepithelial neoplasia and may have utility in emerging methylation-based prostate cancer tests. Further study of the hypermethylome will provide insight into the biology of the disease and facilitate translational studies in prostate cancer.

Expanding monomeric pyrophosphate complexes beyond platinum.

Four new monomeric pyrophosphate complexes, namely [Co(phen)(2)(H(2)P(2)O(7))] x 4 H(2)O (1 x 4 H(2)O), [Ni(phen)(2)(H(2)P(2)O(7))] x 8 H(2)O (2 x 8 H(2)O), [Cu(phen)(H(2)O)(H(2)P(2)O(7))] (3) and {[Cu(phen)(H(2)O)(P(2)O(7))][Na(2)(H(2)O)(8)]} x 6 H(2)O (4 x 14 H(2)O) have been isolated and structurally characterized. The impact of pH and stoichiometry in obtaining 1-4 is described. These complexes have been tested against the adriamycin-resistant ovarian cancer cell line A2780/AD, revealing highly significant (nM) IC(50) values, compared to microM IC(50) values for cisplatin controls.

Promoter hypermethylation of the PALB2 susceptibility gene in inherited and sporadic breast and ovarian cancer.

The partner and localizer of BRCA2 (PALB2) gene was recently identified as a BRCA2-interacting protein and subsequently shown to be a Fanconi anemia gene (FANCN). Disease-associated point mutations resulting in protein truncation have been found in BRCA1/2 mutation-negative breast cancer families identifying PALB2 as a susceptibility gene for breast cancer. Aberrant promoter hypermethylation is a mechanism of inactivation of many tumor suppressor genes, including BRCA1 and p16(INK4a), in breast and ovarian cancer. We therefore investigated the methylation status of a 1512 bp typical CpG island located in the promoter and exon 1 region of the PALB2 gene in 130 sporadic and familial breast and ovarian primary tumors, 9 cell lines, and 10 normal cell specimens. We found two primary breast tumors from BRCA2 mutation carriers, four sporadic primary breast tumors, and four sporadic primary ovarian tumors showed hypermethylation of the core promoter region of PALB2. All 10 normal tissue DNA had an unmethylated PALB2 promoter region. Quantitative real-time reverse transcription-PCR showed PALB2 expression to be reduced 28-fold in primary breast tumor with PALB2 promoter hypermethylation compared with matched normal breast tissue RNA. Aberrant promoter hypermethylation of PALB2 is more frequent than the reported level of PALB2 point mutations in breast tumors from BRCA1/2-negative families and is similar to the frequency of BRCA1 hypermethylation in inherited and sporadic breast and ovarian cancers.