Behavioral Health Assessments and Interventions of Psychology Trainees and Residents During Dual Interviewing: Replication and Extension.

The integration of psychologists and other behavioral health providers in primary care practice continues to evolve and reshape approaches to patient care. This study is a replication and extension of a 2013 study describing dual interviewing encounters involving psychology trainees and family medicine residents within an integrated primary care clinic as it relates to behavioral health assessments and interventions. Psychology trainees provided descriptions of 400 collaborative patient encounters involving 337 single and 63 repeat encounters. Psychology trainees coded the frequency of behavioral health assessments and interventions by the psychology trainee, family medicine resident, or both. Seventy-eight percent of encounters contained an assessment, and 20% contained interventions. Compared to the 2013 study, there were significantly fewer behavioral health interventions offered and a significantly greater number of psychoeducation/supportive interventions offered collaboratively. It was discovered that discussions between psychology trainees and family medicine residents immediately after patient encounters occurred 50% of the time and involved issues of case conceptualization. These informal discussions may be an important source of behavioral health education for family medicine residents. This study adds to efforts to better understand what occurs during these encounters.

The Use of the Social Cognition and Object Relations Scale in a Primary Care Setting.

Research has indicated that as many as 10% to 15% of primary care patients have symptoms that are not well explained medically. These patients could be labeled as "somatizers." This study assessed the extent to which underlying psychological characteristics contribute to a person's level of somatization and service utilization. The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G; Stein, Hilsenroth, Slavin-Mulford, & Pinsker, 2011; Westen, 1995) was used to rate early memory narratives of 100 patients in a suburban primary care setting. Using principal axis factoring, the SCORS-G was divided into 2 components and these components (cognitive and affective) were used in subsequent analyses. The affective component was significantly negatively correlated with 2 measures of somatization and positively related to physician ratings of global health. The affective component also showed a trend toward significance on overnight hospital stays and patient-rated health. The cognitive component showed a trend toward significance with both measures of somatization, but it was not correlated with other measures of health. This study demonstrates the value of assessing underlying processes (via SCORS-G ratings of early memory narratives) that contribute to increased rates of somatization and health care utilization. Clinical implications for the relationship between affect and physical health are explored.

Convergent Validity of the Early Memory Index in Two Primary Care Samples.

Karliner, Westrich, Shedler, and Mayman (1996) developed the Early Memory Index (EMI) to assess mental health, narrative coherence, and traumatic experiences in reports of early memories. We assessed the convergent validity of EMI scales with data from 103 women from an urban primary care clinic (Study 1) and data from 48 women and 24 men from a suburban primary care clinic (Study 2). Patients provided early memory narratives and completed self-report measures of psychopathology, trauma, and health care utilization. In both studies, lower scores on the Mental Health scale and higher scores on the Traumatic Experiences scale were related to higher scores on measures of psychopathology and childhood trauma. Less consistent associations were found between the Mental Health and Traumatic Experiences scores and measures of health care utilization. The Narrative Coherence scale showed inconsistent relationships across measures in both samples. In analyses assessing the overall fit between hypothesized and actual correlations between EMI scores and measures of psychopathology, severity of trauma symptoms, and health care utilization, the Mental Health scale of the EMI demonstrated stronger convergent validity than the EMI Traumatic Experiences scale. The results provide support for the convergent validity of the Mental Health scale of the EMI.

The Patient-Doctor Relationship Questionnaire (PDRQ-9) in Primary Care: A Validity Study.

This study assessed the validity of the Patient-Doctor Relationship Questionnaire-9 (PDRQ-9) in a primary care sample (N = 180). Convergent validity was assessed through a correlation between the patient-rated PDRQ-9 and the physician-rated Difficult Doctor Patient Relationship Questionnaire-10 (DDPRQ-10). Discriminant validity was assessed through correlations between the PDRQ-9 and patient age, patient- and physician-reported health and psychological distress. To determine if the PDRQ-9 could discriminate between groups, patient PDRQ-9 ratings were compared between patients who were treated by faculty physicians versus those who were treated by residents. An exploratory factor analysis confirmed that the PDRQ-9 was made up of a single factor. The PDRQ-9 scale was internally consistent (α = .96) and significantly and negatively correlated with the DDPRQ-10 (r = -.22, p = .003) and was not significantly correlated with patient age, health, or psychological distress. PDRQ-9 ratings were statistically greater in patients who were treated by faculty physicians than those who were treated by residents (p = .01). This study provides additional support for the reliability and validity of the PDRQ-9 as a measure of the doctor-patient relationship in a primary care sample.

Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity.

Acid-active cell-penetrating peptides for in vivo tumor-targeted drug delivery.

Cell-penetrating peptides (CPPs) such as transactivator of transcription (TAT) peptide have long been explored for promoting in vitro cell penetration and nuclear targeting of various cargos, but their positive charges cause strong nonspecific interactions, making them inapplicable for many in vivo applications. In this work, we used TAT to demonstrate a molecular modification approach for inhibiting nonspecific interactions of CPPs in the bloodstream while reactivating their functions in the targeted tissues or cells. The TAT lysine residues' amines were amidized to succinyl amides ((a)TAT), completely inhibiting TAT's nonspecific interactions in the blood compartment; once in the acidic tumor interstitium or internalized into cell endo/lysosomes, the succinyl amides in the (a)TAT were quickly hydrolyzed, fully restoring TAT's functions. Thus, (a)TAT-functionalized poly(ethylene glycol)-block-poly(ε-caprolactone) micelles achieved long circulation in the blood compartment and efficiently accumulated and delivered doxorubicin to tumor tissues, giving rise to high antitumor activity and low cardiotoxicity. This amidization strategy effectively and easily enables in vivo applications of CPPs.

Maternal nutrient restriction in the ewe from early to midgestation programs reduced steroidogenic enzyme expression and tended to reduce progesterone content of corpora lutea, as well as circulating progesterone in nonpregnant aged female offspring.

BACKGROUND: Previously we reported decreased circulating progesterone and fertility in one and two year old ewes born to undernourished mothers. This study was designed to investigate if this reduction in progesterone persisted into old age, and if it did, what mechanisms are involved. METHODS: Ewes were fed a nutrient restricted (NR, 50% of NRC recommendations) or control (C, 100% of NRC) diets from day 28 to 78 of gestation, then all were fed to requirements through parturition and weaning. Female offspring (4 per treatment group) were maintained as a group and fed to requirements from weaning until assigned to this study at 6 years of age. Ewes were synchronized for estrus (day 0) and blood samples were collected daily from day 0 to day 11 before necropsy on day 12. Blood serum and luteal tissue were assayed for progesterone concentrations by validated radioimmunoassay. RESULTS: Circulation progesterone concentrations tended to be lower (P = 0.06) in NR than C offspring from day 0 to 11 of the estrous cycle. While total luteal weight was similar across groups, total progesterone content also tended to be reduced (P = 0.07) in luteal tissue of NR than C offspring. Activity of hepatic progesterone catabolizing enzymes and selected angiogenic factors in luteal tissue were similar between groups. Messenger RNA expression of steroidogenic enzymes StAR and P450scc were reduced (P < 0.05), while protein expression of StAR tended to be reduced (P < 0.07) and P450scc was reduced (P < 0.05) in luteal tissue of NR versus C offspring. CONCLUSIONS: There appears to be no difference in hepatic steroid catabolism that could have led to the decreased serum progesterone. However, these data are consistent with the programming of decreased steroidogenic enzyme expression in CL of NR offspring, leading to reduced synthesis and secretion of progesterone.

Bioreducible poly(amido amine)s with different branching degrees as gene delivery vectors.

Based on the knowledge that cationic polymers with different topographical structures behave differently in gene transfection process, herein, we synthesized three biodegradable poly(amido amine)s (PAAs) with the same repeating units and molecular weights except for degree of branching: linear PAA (LPAA), low-branched PAA (LBPAA), and high-branched PAA (HBPAA). We found that LBPAA could more effectively compact pDNA into positively charged nanoparticles than both HBPAA and LPAA. LBPAA polyplexes had the highest transfection efficiency among the three PAA polyplexes, and the difference in transfection efficiency is mainly attributed to the endocytosis rate. The cytotoxicity of PAAs was negligible at the transfection doses, probably due to the degradable disulfide bonds. Therefore, we could use branching as a parameter to simply tune a polymer's cellular uptake behavior and transfection efficiency.

Using return on investment to maximize conservation effectiveness in Argentine grasslands.

The rapid global loss of natural habitats and biodiversity, and limited resources, place a premium on maximizing the expected benefits of conservation actions. The scarcity of information on the fine-grained distribution of species of conservation concern, on risks of loss, and on costs of conservation actions, especially in developing countries, makes efficient conservation difficult. The distribution of ecosystem types (unique ecological communities) is typically better known than species and arguably better represents the entirety of biodiversity than do well-known taxa, so we use conserving the diversity of ecosystem types as our conservation goal. We define conservation benefit to include risk of conversion, spatial effects that reward clumping of habitat, and diminishing returns to investment in any one ecosystem type. Using Argentine grasslands as an example, we compare three strategies: protecting the cheapest land ("minimize cost"), maximizing conservation benefit regardless of cost ("maximize benefit"), and maximizing conservation benefit per dollar ("return on investment"). We first show that the widely endorsed goal of saving some percentage (typically 10%) of a country or habitat type, although it may inspire conservation, is a poor operational goal. It either leads to the accumulation of areas with low conservation benefit or requires infeasibly large sums of money, and it distracts from the real problem: maximizing conservation benefit given limited resources. Second, given realistic budgets, return on investment is superior to the other conservation strategies. Surprisingly, however, over a wide range of budgets, minimizing cost provides more conservation benefit than does the maximize-benefit strategy.

COVID-19-Induced Cardiomyopathy in a Young Nulliparous Woman.

A young nulliparous woman presented with new-onset heart failure several weeks after an asymptomatic coronavirus disease 2019 (COVID-19) infection. Investigation revealed non-ischemic cardiomyopathy without apical ballooning. A literature review demonstrates other reported cases of COVID-19-induced cardiomyopathy; however, our patient was demographically unique from previously described cases, presented later, and did not have Takotsubo-like findings. Our patient continued to have evidence of cardiac remodeling and a reduced ejection fraction months after presentation. This case highlights the importance of surveilling for the post-infectious sequelae of COVID-19, along with the wide demographic range of patients susceptible to such outcomes.

Prodrugs forming high drug loading multifunctional nanocapsules for intracellular cancer drug delivery.

Anticancer drugs embedded in or conjugated with inert nanocarriers, referred to as nanomedicines, show many therapeutic advantages over free drugs, but the inert carrier materials are the major component (generally more than 90%) in nanomedicines, causing low drug loading contents and thus excessive uses of parenteral excipients. Herein, we demonstrate a new concept directly using drug molecules to fabricate nanocarriers in order to minimize use of inert materials, substantially increase the drug loading content, and suppress premature burst release. Taking advantage of the strong hydrophobicity of the anticancer drug camptothecin (CPT), one or two CPT molecule(s) were conjugated to a very short oligomer chain of ethylene glycol (OEG), forming amphiphilic phospholipid-mimicking prodrugs, OEG-CPT or OEG-DiCPT. The prodrugs formed stable liposome-like nanocapsules with a CPT loading content as high as 40 or 58 wt % with no burst release in aqueous solution. OEG-DiCPT released CPT once inside cells, which showed high in vitro and in vivo antitumor activity. Meanwhile, the resulting nanocapsules can be loaded with a water-soluble drug-doxorubicin salt (DOX.HCl)-with a high loading efficiency. The DOX.HCl-loaded nanocapsules simultaneously delivered two anticancer drugs, leading to a synergetic cytotoxicity to cancer cells. The concept directly using drugs as part of a carrier is applicable to fabricating other highly efficient nanocarriers with a substantially reduced use of inert carrier materials and increased drug loading content without premature burst release.

Conserving biodiversity efficiently: what to do, where, and when.

Conservation priority-setting schemes have not yet combined geographic priorities with a framework that can guide the allocation of funds among alternate conservation actions that address specific threats. We develop such a framework, and apply it to 17 of the world's 39 Mediterranean ecoregions. This framework offers an improvement over approaches that only focus on land purchase or species richness and do not account for threats. We discover that one could protect many more plant and vertebrate species by investing in a sequence of conservation actions targeted towards specific threats, such as invasive species control, land acquisition, and off-reserve management, than by relying solely on acquiring land for protected areas. Applying this new framework will ensure investment in actions that provide the most cost-effective outcomes for biodiversity conservation. This will help to minimise the misallocation of scarce conservation resources.

"I fired my last doctor for not taking me seriously": collaborating with a difficult medical patient in a multidisciplinary primary care facility.

We present the case of a multidisciplinary primary care assessment of a 32-year-old woman with multiple medical and psychological complaints. Following the collaborative care model, this assessment was conducted by a team consisting of a clinical health psychologist, Dr. J. L. Skillings, and a family physician, Dr. W. J. Murdoch. We describe the primary care environment in which this referral was made including the methods that were utilized to insure a successful professional collaboration. We report the results and recommendations from a comprehensive biopsychosocial assessment; we place emphasis on the psychological diagnosis and pain symptoms. We also describe the feedback session in which the assessment results were provided to the patient and her spouse by both physician and psychologist. Multiperspective commentary about the assessment is offered by the patient and her husband as well as the physician and psychologist assessors.

Skewed attacks, stability, and host suppression.

It is well known that the model equilibrium in the Nicholson-Bailey framework for parasitoid-host interactions can be stabilized if there is variation in the risk of parasitism among individual hosts. We show that the shape of the distribution of risk among hosts is crucial in determining stability. Stability for all values of the reproduction rate R of the host requires the distribution to be skewed, with a modal risk of zero. As a consequence, a distribution of risk with nonzero mode but otherwise sufficiently high variability will not stabilize the host-parasitoid equilibrium for certain values of R. We also develop a new, simple, and general criterion for stability, according to which the host-parasitoid equilibrium is stable if and only if the adult host equilibrium density increases as host reproductive rate R increases. This reinforces previous results that skewed risk of the type needed for stability reduces parasitoid efficiency and hence the parasitoid's ability to suppress the host. Finally, we identify appropriate measures that can be made in the field to relate skew in risk of parasitism to stability.

Degradable poly(beta-amino ester) nanoparticles for cancer cytoplasmic drug delivery.

Fast cytoplasmic drug delivery can overcome cancer cells' drug resistance and thus have an enhanced therapeutic efficacy. Such a drug delivery regime requires drug carriers capable of entering cancer cells, localizing and rapidly releasing the drug into endosomes/lysosomes, and subsequently disrupting their membranes to release the drug into the cytosol. We herein report a low-toxic and degradable poly(beta-amino ester)-graft-polyethylene glycol (BAE-PEG) co-polymer forming pH-responsive nanoparticles capable of cytoplasmic drug delivery. BAE-PEG was synthesized by condensation polymerization of diacrylate and piperazine in the presence of a PEG-diacrylate macromonomer. BAE-PEG with 2% or 5% PEG side chains formed micelles (nanoparticles) with diameters of about 100 nm. The BAE-PEG nanoparticles were shown to rapidly enter cancer cells, localize in their endosomes/lysosomes, and subsequently disrupt them to release the drugs into the cytosol. Camptothecin loaded in the nanoparticles had a higher cytotoxicity to SKOV-3 ovarian cancer cells than free camptothecin.

Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts.

OBJECTIVES: The underlying premise of these investigations was that the lipophilic hormone progesterone, which partitions into and (at relatively high concentrations) impedes the fluid mechanics of the plasmalemma, would perturb integral associations between membrane lipids and exporter pumps that otherwise confer drug resistance. That progesterone can affect susceptibility of ovarian adenocarcinoma cells and xenografts to cisplatin was tested. METHODS: The cisplatin-resistant human cell lines SKOV-3 and OVCAR-3 were treated for 24 hours with cisplatin (0.1 microg/ml)+/-progesterone (0.01, 0.1 microg/ml). Cytotoxicity and platinum were measured by MTT assay and inductively coupled plasma mass spectrometry, respectively. Athymic mice were inoculated intraperitoneal (ip) with SKOV-3 cells. Cisplatin (2 mg/kg/week)+/-progesterone (25 mg sustained-release pellet) regimens were initiated ip at one week (when micrometastases were present) and continued to six weeks post-xenograft. Tumor burdens, histopathology, and platinum concentrations were assessed upon necropsy at 24 hours after the final injection of cisplatin. RESULTS: There were no significant in vitro/vivo anticancer effects of cisplatin alone. High-dose progesterone enhanced platinum accretion and induced drug toxicity in both cell lines. Tumorigenesis was suppressed by cisplatin+progesterone. The treatment synergy was related to elevated tumor platinum and morphological evidence of apoptosis. CONCLUSION: It appears that the addition of progesterone to ovarian cancer therapeutic modalities represents a step in improving responses.

pH-responsive nanoparticles for cancer drug delivery.

Solid tumors have an acidic extracellular environment and an altered pH gradient across their cell compartments. Nanoparticles responsive to the pH gradients are promising for cancer drug delivery. Such pH-responsive nanoparticles consist of a corona and a core, one or both of which respond to the external pH to change their soluble/insoluble or charge states. Nanoparticles whose coronas become positively charged or become soluble to make their targeting groups available for binding at the tumor extracellular pH have been developed for promoting cellular targeting and internalization. Nanoparticles whose cores become soluble or change their structures to release the carried drugs at the tumor extracellular pH or lysosomal pH have been developed for fast drug release into the extracellular fluid or cytosol. Such pH-responsive nanoparticles have therapeutic advantages over the conventional pH-insensitive counterparts.

Improving wellbeing and reducing future world population.

Almost 80% of the 4 billion projected increase in world population by 2100 comes from 37 Mid-African Countries (MACs), caused mostly by slow declines in Total Fertility Rate (TFR). Historically, TFR has declined in response to increases in wellbeing associated with economic development. We show that, when Infant Survival Rate (ISR, a proxy for wellbeing) has increased, MAC fertility has declined at the same rate, in relation to ISR, as it did in 61 comparable Other Developing Countries (ODCs) whose average fertility is close to replacement level. If MAC ISR were to increase at the historic rate of these ODCs, and TFR declined correspondingly, then the projected world population in 2100 would be decreasing and 1.1 billion lower than currently projected. Such rates of ISR increase, and TFR decrease, are quite feasible and have occurred in comparable ODCs. Increased efforts to improve the wellbeing of poor MAC populations are key.

Morphologic responses of the mouse ovarian surface epithelium to ovulation and steroid hormonal milieu.

Ovarian cancer of surface epithelial origin is an ovulation- and endocrine-related disease. It appears that a cell transformed by genotoxins generated at follicular rupture is propagated during postovulatory wound repair. A consequent steroid hormonal imbalance favoring the mitogenic estrogens is a prospective predisposing factor in ovarian neoplasia. Protection against epithelial ovarian cancer is conferred by progesterone. The objective of this study was to characterize the acute effects of ovulation and steroid hormonal exposure on morphologic responses of surface epithelial cells of mouse ovaries. Follicular development and ovulation were induced in immature animals with equine and human (=Day 0) choriogonadotropins, respectively. On Day 2 (approximately 36 hrs after ovulation), surface epithelial classifications presented in histologic sections were altered from simple (single-layered) squamous and cuboidal toward stratification; this trend was reversed (i.e., reverted to the control status) on Days 4-8. Shifts in the ovarian epithelium from simple to stratified were accentuated following postovulatory (Days 1-8) treatment with estradiol. Surface epithelia of ovaries obtained after 1 week of progesterone administration were exclusively of a simple phenotype. We conclude that the proliferative/procarcinogenic reaction of the ovarian surface epithelium to ovulation is exacerbated by estrogen and counteracted by progesterone.

Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation.

OBJECTIVE: Vascular smooth muscle cell (VSMC) migration, proliferation, and collagen synthesis are key events involved in the pathogenesis of cardiovascular disease. Growth factors, such as platelet-derived growth factor (PDGF) and fibroblast growth factor, released during vascular injury plays a pivotal role in regulating these events. Curcumin (diferuloyl methane), a major component of the spice turmeric (Curcuma longa), has been shown recently to have beneficial effects in chronic conditions, such as inflammation, cancer, cystic fibrosis, and Alzheimer's disease. The objective of this study was to investigate the ability of curcumin to inhibit PDGF-stimulated migration, proliferation, and collagen synthesis in cultured VSMCs and neointima formation after carotid artery injury in rats. METHODS AND RESULTS: Curcumin (1 to 25 microM) produced a concentration-dependent inhibition of PDGF-elicited VSMC migration, proliferation, and collagen synthesis assessed by chemotaxis, [3H]thymidine incorporation, and [3H]-L-proline incorporation, respectively. Curcumin blocked PDGF-induced VSMC actin-cytoskeleton reorganization, attenuated PDGF signal transduction, and inhibited the binding of PDGF to its receptors. Carotid artery neointima formation was significantly attenuated by perivascular curcumin compared with vehicle controls 14 days after injury, characterized by reduced DNA synthesis, collagen synthesis, and PDGF receptor phosphorylation. CONCLUSIONS: These data suggest that curcumin is a potent inhibitor of key PDGF-stimulated VSMC functions and may play a critical role in regulating these events after vascular injury.