Second Job Holding Among Direct Care Workers and Nurses: Implications for COVID-19 Transmission in Long-Term Care.

One reason that nursing homes are a primary source of COVID-19 infections and deaths in the United States may be that workers hold multiple jobs. We use 2010-2019 Current Population Survey data to document the rate of second jobholding among nursing and long-term care workers. On average, 6.41% of personal care and nursing aides and 6.23% of licensed practical nurses and registered nurses hold second jobs; second job holding rates are 35% and 32% higher than those of other workers, respectively. Both wages and hours in the primary job are negatively associated with the probability of holding a second job for personal care and nursing aides, while lower hours are more strongly correlated with a second job for registered nurses and licensed practical nurses. Many of these workers move across health settings from their first to second jobs, and 15% of second jobs for personal care and nursing aides are in other "essential" occupations.

Protein kinase C zeta regulates human pancreatic cancer cell transformed growth and invasion through a STAT3-dependent mechanism.

Pancreatic cancer is a very aggressive disease with few therapeutic options. In this study, we investigate the role of protein kinase C zeta (PKCζ) in pancreatic cancer cells. PKCζ has been shown to act as either a tumor suppressor or tumor promoter depending upon the cellular context. We find that PKCζ expression is either maintained or elevated in primary human pancreatic tumors, but is never lost, consistent with PKCζ playing a promotive role in the pancreatic cancer phenotype. Genetic inhibition of PKCζ reduced adherent growth, cell survival and anchorage-independent growth of human pancreatic cancer cells in vitro. Furthermore, PKCζ inhibition reduced orthotopic tumor size in vivo by inhibiting tumor cell proliferation and increasing tumor necrosis. In addition, PKCζ inhibition reduced tumor metastases in vivo, and caused a corresponding reduction in pancreatic cancer cell invasion in vitro. Signal transducer and activator of transcription 3 (STAT3) is often constitutively active in pancreatic cancer, and plays an important role in pancreatic cancer cell survival and metastasis. Interestingly, inhibition of PKCζ significantly reduced constitutive STAT3 activation in pancreatic cancer cells in vitro and in vivo. Pharmacologic inhibition of STAT3 mimicked the phenotype of PKCζ inhibition, and expression of a constitutively active STAT3 construct rescued the transformed phenotype in PKCζ-deficient cells. We conclude that PKCζ is required for pancreatic cancer cell transformed growth and invasion in vitro and tumorigenesis in vivo, and that STAT3 is an important downstream mediator of the pro-carcinogenic effects of PKCζ in pancreatic cancer cells.

Exploring the spatial wage penalty for women: Does it matter where you live?

Inequality between men and women has decreased over the past four decades in the US, but wage inequality among groups of women has increased. As metropolitan women's earnings grew by 25% over the past four decades, nonmetropolitan women's earnings only grew by 15%. In the current study we draw on data from the Current Population Survey to analyze the spatial wage gap among women. We explore differences in the spatial wage gap by education, occupation, and industry. Regression models that control for marriage, motherhood, race, education, region, age, and work hours indicate that metropolitan women earn 17% more per hour than nonmetropolitan women. Nonmetropolitan women earn less than metropolitan women who live in central cities and outside central cities. The gap in metropolitan-nonmetropolitan wages is higher for more educated women than for less educated women. The wage gap is only 5% for women without a high school degree, but it is 15% for women with a college degree and 26% for women with an advanced degree. Nonmetropolitan college graduates are overrepresented in lower-paying occupations and industries. Metropolitan college graduates, however, are overrepresented in higher-paying occupations and industries, such as professional services and finance.

NTS1 and NTS2 mediate analgesia following neurotensin analog treatment in a mouse model for visceral pain.

Neurotensin (NT) analogs, NT69L, NT72, and NT79, differentially bind the two major neurotensin receptors, NTS1 and NTS2, to elicit effects similar to those of endogenous NT, including analgesia. Previous data strongly suggest NTS2 as the main receptor involved in NT- and NT analog-mediated visceral analgesia. However, this idea has yet to be confirmed with the use of mice lacking the NTS2 receptor. Here we use the writhing assay, a model of visceral pain, to investigate the analgesic effects of NT69L (binds NTS1 and NTS2 equally), NT79 (NTS2-selective), NT72 (NTS1 selective) and levocabastine (NTS2-selective) in WT, NTS1 knock-out, and NTS2 knock-out mice. Additionally, we investigate the role of NTS2 in the development of tolerance to NT69L-mediated visceral analgesia. All three NT analogs reduced writhing in the WT mice. NT79 and levocabsatine reduced writhing in the NTS1(-/-) mice while NT69L and NT72 showed significant analgesic effect in the NTS2(-/-) mice. In conclusion, the data shows that (1) both NTS1 and NTS2 are involved in mediating visceral analgesia and their respective roles appear to be NT analog-dependent; (2) NTS1 may inhibit NTS2-mediated analgesia; and (3) NTS2 is necessary for the development of tolerance to NT69L-mediated analgesia.

Protein kinase C iota regulates pancreatic acinar-to-ductal metaplasia.

Pancreatic acinar-to-ductal metaplasia (ADM) is associated with an increased risk of pancreatic cancer and is considered a precursor of pancreatic ductal adenocarcinoma. Transgenic expression of transforming growth factor alpha (TGF-α) or K-ras(G12D) in mouse pancreatic epithelium induces ADM in vivo. Protein kinase C iota (PKCι) is highly expressed in human pancreatic cancer and is required for the transformed growth and tumorigenesis of pancreatic cancer cells. In this study, PKCι expression was assessed in a mouse model of K-ras(G12D)-induced pancreatic ADM and pancreatic cancer. The ability of K-ras(G12D) to induce pancreatic ADM in explant culture, and the requirement for PKCι, was investigated. PKCι is elevated in human and mouse pancreatic ADM and intraepithelial neoplastic lesions in vivo. We demonstrate that K-ras(G12D) is sufficient to induce pancreatic ADM in explant culture, exhibiting many of the same morphologic and biochemical alterations observed in TGF-α-induced ADM, including a dependence on Notch activation. PKCι is highly expressed in both TGF-α- and K-ras(G12D)-induced pancreatic ADM and inhibition of PKCι significantly reduces TGF-α- and K-ras(G12D)-mediated ADM. Inhibition of PKCι suppresses K-ras(G12D)-induced MMP-7 expression and Notch activation, and exogenous MMP-7 restores K-ras(G12D)-mediated ADM in PKCι-depleted cells, implicating a K-ras(G12D)-PKCι-MMP-7 signaling axis that likely induces ADM through Notch activation. Our results indicate that PKCι is an early marker of pancreatic neoplasia and suggest that PKCι is a potential downstream target of K-ras(G12D) in pancreatic ductal metaplasia in vivo.

Slc4-like anion transporters of the larval mosquito alimentary canal.

Mosquito larvae exhibit luminal pH extremes along the axial length of their alimentary canal that range from very alkaline (pH>10) in the anterior midgut to slightly acid in the hindgut. The principal buffer in the system is thought to be bicarbonate and/or carbonate, because the lumen is known to contain high levels of bicarbonate/carbonate and is surrounded by various epithelial cell types which express a variety of carbonic anhydrases. However, the precise mechanisms responsible for the transport of bicarbonate/carbonate into and out of the lumen are unclear. In the present study, we test the hypothesis that SLC4-like anion transporters play a role in bicarbonate/carbonate accumulation in the larval mosquito alimentary canal. Molecular, physiological and immnuohistochemical characterizations of Slc4-like transporters in the gut of larval mosquitoes (Aedes aegypti and Anopheles gambiae) demonstrate the presence of both a Na(+)-independent chloride/bicarbonate anion exchanger (AE) as well as a Na(+)-dependent anion exchanger (NDAE). Notably, immunolocalization experiments in Malpighian tubules show that the two proteins can be located in the same tissue, but to different cell types. Immunolabeling experiments in the gastric caecae show that the two proteins can be found in the same cells, but on opposite sides (basal vs. apical). In summary, our results indicate that the alimentary canal of larval mosquitoes exhibits robust expression of two SLC4-like transporters in locations that are consistent with a role in the regulation of luminal pH. The precise physiological contributions of each transporter remain to be determined.

Labor mobility of the direct care workforce: implications for the provision of long-term care.

This study provides the first comprehensive analysis of the dynamics of labor supply of direct care workers, the lower-skill nursing workers who provide the bulk of long-term care for the elderly in the USA. Our estimates from the 1996 and 2001 panels of the Survey of Income and Program Participation (SIPP) show that the mean (median) duration of employment spells for the same direct care employer is only 9.7 (5.0) months. We find that fewer than one-third of direct care workers leave a job to take another job in the direct care field. There is also little indication of upward mobility in the health sector; direct care workers are approximately equally likely to transition to working as Registered Nurses as they are to working in household service jobs. Additionally, the rate at which spells end in work-limiting disability (5.4%) is very high compared with rates in similar occupations. We estimate duration models of direct care job spell length and find that, after correcting for the endogenous relationship between wages and tenure, wages appear to have a modest effect in preventing turnover; this effect is concentrated among the shortest spells.

The role of NTS2 in the development of tolerance to NT69L in mouse models for hypothermia and thermal analgesia.

NT69L is a neurotensin (NT)(8-13) analog that binds the two major NT receptors, NTS1 and NTS2, and elicits similar behavioral effects as endogenous NT. Tolerance develops rapidly to some, but not to all of NT69L's effects, and to date, little is known about the mechanisms responsible for this tolerance. The development of tolerance appears to be more prevalent in behavioral effects mediated by NTS1 than by those mediated by NTS2, including hypothermia and thermal analgesia. However, we hypothesize that both NTS1 and NTS2 have important roles in mediating the effects of NT69L. Here, we investigate the role of NTS2 on NT69L-mediated hypothermia and thermal analgesia with the use of NTS2 knock-out mice. We show that tolerance develops to NT69L-mediated hypothermia and thermal analgesia following sub-chronic treatment in wild-type (WT) mice, and that NTS2 is necessary for the development of that tolerance. Additionally, we suggest potential means by which NTS2 influences these NT69L-mediated behaviors.

Physiological and pharmacological characterizations of the larval Anopheles albimanus rectum support a change in protein distribution and/or function in varying salinities.

Ion regulation is a biological process crucial to the survival of mosquito larvae and a major organ responsible for this regulation is the rectum. The recta of anopheline larvae are distinct from other subfamilies of mosquitoes in several ways, yet have not yet been characterized extensively. Here we characterize the two major cell types of the anopheline rectum, DAR and non-DAR cells, using histological, physiological, and pharmacological analyses. Proton flux was measured at the basal membrane of 2%- and 50%-artificial sea water-reared An. albimanus larvae using self-referencing ion-selective microelectrodes, and the two cell types were found to differ in basal membrane proton flux. Additionally, differences in the response of that flux to pharmacological inhibitors in larvae reared in 2% versus 50% ASW indicate changes in protein function between the two rearing conditions. Finally, histological analyses suggest that the non-DAR cells are structurally suited for mediating ion transport. These data support a model of rectal ion regulation in which the non-DAR cells have a resorptive function in freshwater-reared larvae and a secretive function in saline water-reared larvae. In this way, anopheline larvae may adapt to varying salinities.

Silencing of carbonic anhydrase in an Anopheles gambiae larval cell line, Ag55.

RNAi has been used extensively to down-regulate proteins in adult mosquitoes; however, it is not well adapted for use in larvae. Larval mosquitoes can generate a pH as high as 10.5 in the anterior region of their midgut. The mechanisms responsible for the generation and maintenance of this pH are not entirely understood, but members of the carbonic anhydrase (CA) family of enzymes have been implicated. Here we use an An. gambiae larval cell line, Ag55 cells, to demonstrate that application of full-length double-stranded RNA specific to one CA, AgCA9, is sufficient to silence AgCA9 mRNA and down-regulate the corresponding protein. This is a first step towards determining the role(s) of these enzymes in pH regulation.

Carbonic anhydrases and anion transport in mosquito midgut pH regulation.

Mosquito larvae use a digestive strategy that is relatively rare in nature. The anterior half of the larval mosquito midgut has a luminal pH that ranges between 10.5 and 11.5. Most other organisms, both large and small, initiate digestion in an acid medium. The relative uniqueness of the highly alkaline digestive strategy has been a long-standing research focus in larval lepidopterans. More recently, the disease vector potential of mosquitoes has fueled specific interest in larval mosquito biology and the alkaline digestive environment in the midgut. The probable principle anion influencing the highly alkaline gut lumen is bicarbonate/carbonate. Bicarbonate/carbonate is regulated at least in part by the activity of carbonic anhydrases. Hence, we have focused attention on the carbonic anhydrases of the mosquito larva. Anopheles gambiae, the major malaria mosquito of Africa, is an organism with a published genome which has facilitated molecular analyses of the 12 carbonic anhydrase genes annotated for this mosquito. Microarray expression analyses, tissue-specific quantitative RT-PCR, and antibody localization have been used to generate a picture of carbonic anhydrase distribution in the larval mosquito. Cytoplasmic, GPI-linked extracellular membrane-bound and soluble extracellular carbonic anhydrases have been located in the midgut and hindgut. The distribution of the enzymes is consistent with an anion regulatory system in which carbonic anhydrases provide a continuous source of bicarbonate/carbonate from the intracellular compartments of certain epithelial cells to the ectoperitrophic space between the epithelial cells and the acellular membrane separating the food bolus from the gut cells and finally into the gut lumen. Carbonic anhydrase in specialized cells of the hindgut (rectum) probably plays a final role in excretion of bicarbonate/carbonate into the aquatic environment of the larva. Detection and characterization of classic anion exchangers of the SLC4A family in the midgut has been problematic. The distribution of carbonic anhydrases in the system may obviate the requirement for such transporters, making the system more dependent on simple carbon dioxide diffusion and ionization via the activity of the enzyme.

Larval anopheline mosquito recta exhibit a dramatic change in localization patterns of ion transport proteins in response to shifting salinity: a comparison between anopheline and culicine larvae.

Mosquito larvae live in dynamic aqueous environments, which can fluctuate drastically in salinity due to environmental events such as rainfall and evaporation. Larval survival depends upon the ability to regulate hemolymph osmolarity by absorbing and excreting ions. A major organ involved in ion regulation is the rectum, the last region for modification of the primary urine before excretion. The ultrastructure and function of culicine larval recta have been studied extensively; however, very little published data exist on the recta of anopheline larvae. To gain insight into the structure and functions of this organ in anopheline species, we used immunohistochemistry to compare the localization of three proteins [carbonic anhydrase (CA9), Na+/K+ P-ATPase and H+ V-ATPase] in the recta of anopheline larvae reared in freshwater and saline water with the localization of the same proteins in culicine larvae reared under similar conditions. Based on the following key points, we concluded that anophelines differ from culicines in larval rectal structure and in regulation of protein expression: (1) despite the fact that obligate freshwater and saline-tolerant culicines have structurally distinct recta, all anophelines examined (regardless of saline-tolerance) have a structurally similar rectum consisting of distinct DAR (dorsal anterior rectal) cells and non-DAR cells; (2) anopheline larvae undergo a dramatic shift in rectal Na+/K+-ATPase localization when reared in freshwater vs saline water. This shift is not seen in any culicine larvae examined. Additionally, we use these immunohistochemical analyses to suggest possible functions for the DAR and non-DAR cells of anopheline larvae in freshwater and saline conditions.

Cloning and characterization of AgCA9, a novel alpha-carbonic anhydrase from Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) larvae.

Mosquito larvae generate a luminal pH as high as 10.5 in the anterior region of their midgut. The mechanisms responsible for the generation and maintenance of this alkaline pH are largely unknown, but there is evidence suggesting a role for the enzyme carbonic anhydrase (CA). CA has been cloned from the alimentary canal epithelium of Anopheles gambiae larvae and can generate bicarbonate, which is implicated as a buffer for the larval lumen. The question remains as to how the bicarbonate is transported from the cells into the lumen. We hypothesize the presence of a CA within the lumen itself to generate bicarbonate from CO(2) produced by the metabolically active alimentary canal cells. Here, we report the cloning and characterization of a novel cytoplasmic-type alpha-CA from the larval An. gambiae alimentary canal. Antibody immunolocalization reveals a unique protein distribution pattern that includes the ectoperitrophic fluid, 'transitional region' of the alimentary canal, Malpighian tubules and a subset of cells in the dorsal anterior region of the rectum. Localization of this CA within the lumen of the alimentary canal may be a key to larval pH regulation, while detection within the rectum reveals a novel subset of cells in An. gambiae not described to date. Phylogenetic analysis of members of the alpha-CA family from the Homo sapiens, Drosophila melanogaster, Aedes aegypti and An. gambiae genomes shows a clustering of the novel CA with Homo sapiens CAs but not with other insect CAs. Finally, a universal system for naming newly cloned An. gambiae CAs is suggested.

Preliminary study of the relationship between thyroid status and cognitive and neuropsychiatric functioning in euthyroid patients with Alzheimer dementia.

OBJECTIVE: To investigate whether variations within normal ranges of thyroid functioning are related to cognitive and neuropsychiatric functioning in Alzheimer disease (AD). BACKGROUND: Mild alterations of thyroid hormone levels, even in the normal range, are associated with changes in mood and cognitive functioning in older, nondemented adults, and lower concentrations of thyroid hormones have been shown to be associated with an increased risk for cognitive decline. Less is known about the relationship between thyroid hormone levels and cognitive and neuropsychiatric dysfunction in AD. METHOD: Twenty-eight euthyroid patients with AD on donepezil underwent evaluation of thyroid status, including measures of thyroid-stimulating hormone (TSH) and free thyroxine (FT4), and cognitive and neuropsychiatric assessment with the Alzheimer's Disease Assessment Scale, Neuropsychiatric Inventory, and Visual Analog Mood Scales. RESULTS: Correlational analyses indicated statistically significant associations between FT4 concentrations and self-reported feelings of fear and fatigue. Fear and fatigue were negatively correlated with FT4. There were no significant relationships between thyroid hormones and cognition and other depressive and anxiety symptoms. CONCLUSIONS: Results of this preliminary study support a relationship between thyroid status and neuropsychiatric symptoms in euthyroid individuals with AD, with lower concentrations of FT4 associated with fear and fatigue.

Self-care: why do parents leave their children unsupervised?

We used a preferences-and-constraints model to develop four hypotheses to explain why parents may choose self-care (an unsupervised arrangement) as the primary child care arrangement for their children over supervised alternatives and tested them in a multivariate framework using 1995 data from the Survey of Income and Program Participation. We found that the choice of self-care over supervised care alternatives is linked to the availability of parents' time to care for children, the child's level of responsibility and maturity, and the neighborhood context. However, we found no evidence that parents' ability to pay for child care is related to the choice of self-care. The results also suggest that parents use different decision-making processes, depending on their children's ages.

The influence of cognitive reserve on memory following electroconvulsive therapy.

Cognitive reserve (CR) theory proposes that certain genetic and nonacquired variables, such as larger head size and greater neuronal density, and some life experiences, such as higher educational and occupational attainment, provide a buffer against brain dysfunction in the face of acquired central nervous system (CNS) dysfunction. This study examined CR in the pseudoexperimental paradigm of electroconvulsive therapy (ECT). Subjects included fifty (N = 50) depressed patients treated with bilateral ECT. Subjects were placed in high (n = 27) or low (n = 23) CR groups based on years of education and occupational attainment. At baseline, no significant differences were observed between the groups in the amount of information forgotten on a verbal memory measure (Randt stories) after a 30-minute delay. Following three ECT treatments, however, the high CR group forgot significantly less information after a 30-minute delay, as compared to the low CR group (p < 0.01). These data provide further support for CR theory and suggest that CR may be an underlying factor in differential memory loss in ECT.