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In a recent call to action, we described pressing issues in the health-service-psychology (HSP) internship from the perspective of interns. In our article, we sought to initiate a dialogue that would include trainees and bring about concrete changes. The commentaries on our article are a testament to the readiness of the field to engage in such a dialogue, and we applaud the actionable recommendations that they make. In our response to these commentaries, we seek to move the conversation further forward. We observe two themes that cut across these responses: the impetus to gather novel data on training (the "need to know") and the importance of taking action (the "need to act"). We emphasize that in new efforts to gather data and take policy-level action, the inclusion of trainee stakeholders (as well as others involved in and affected by HSP training) is a crucial ingredient for sustainable and equitable change.

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The challenges observed in health service psychology (HSP) training during COVID-19 revealed systemic and philosophical issues that preexisted the pandemic, but became more visible during the global health crisis. In a position paper written by 23 trainees across different sites and training specializations, the authors use lessons learned from COVID-19 as a touchstone for a call to action in HSP training. Historically, trainee voices have been conspicuously absent from literature about clinical training. We describe longstanding dilemmas in HSP training that were exacerbated by the pandemic and will continue to require resolution after the pandemic has subsided. The authors make recommendations for systems-level changes that would advance equity and sustainability in HSP training. This article advances the conversation about HSP training by including the perspective of trainees as essential stakeholders.

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In the past 30 years, the incidence of esophageal adenocarcinoma (EAC) has increased more rapidly than any other cancer in the United States. The prevalence of obesity and diabetes mellitus has drastically increased as well. We explored the potential association between obesity, diabetes mellitus, and EAC. By means of retrospective interrogation of an administrative database from fiscal year 2005-2009, we identified two cohorts. The cancer cohort was defined as patients with adenocarcinoma of the distal esophagus or gastric cardia. The comparison cohort contained patients with gastroesophageal reflux disorder (GERD; diagnosis coupled with a procedure code for fundoplication). Patient data, including demographic measures, diagnoses of obesity, diabetes mellitus, dyslipidemia, alcohol abuse, and nicotine dependence were examined. A logistic regression model identified risk factors for development of EAC. The sample included 2,836 patients identified as having either EAC (1,704) or fundoplication with GERD (1,132). Although slightly higher percentages of the benign cohort were obese, the cancer cohort had more diabetics (30.8% vs. 14.8%; chi-square = 94.5; P < 0.0001). In a logistic regression analysis adjusting for comorbidity and lifestyle factors, diagnosis of diabetes mellitus was significantly associated with esophageal cancer as opposed to GERD without cancer (OR = 2.2; 95% confidence interval [CI] 1.7-2.8). Nicotine dependence was also identified as a risk factor (OR = 1.7; 95% CI 1.4-2.0). We identified a potential association between diabetes mellitus and adenocarcinoma of the esophagus or gastric cardia. This association appears to be independent of obesity. Additionally, nicotine dependence was identified as a risk factor for EAC.

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INTRODUCTION: Trophoblast inclusions (TIs) are often found in placentas of genetically abnormal gestations. Although best documented in placentas from molar pregnancies and chromosomal aneuploidy, TIs are also associated with more subtle genetic abnormalities, and possibly autism. Less than 3% of non-aneuploid, non-accreta placentas have TIs. We hypothesize that placental genetics may play a role in the development of placenta accreta and aim to study TIs as a potential surrogate indicator of abnormal placental genetics. METHODS: Forty cases of placenta accreta in the third trimester were identified in a search of the medical records at one institution. Forty two third trimester control placentas were identified by a review of consecutively received single gestation placentas with no known genetic abnormalities and no diagnosis of placenta accreta. RESULTS: Forty percent of cases with placenta accreta demonstrated TIs compared to 2.4% of controls. More invasive placenta accretas (increta and percreta) were more likely to demonstrate TIs than accreta (47% versus 20%). Prior cesarean delivery was more likely in accreta patients than controls (67% versus 9.5%). DISCUSSION: Placenta accreta is thought to be the result of damage to the endometrium predisposing to abnormal decidualization and invasive trophoblast growth into the myometrium. However, the etiology of accreta is incompletely understood with accreta frequently occurring in women without predisposing factors and failing to occur in predisposed patients. CONCLUSION: This study has shown that TIs are present at increased rates in cases of PA. Further studies are needed to discern what underlying pathogenic mechanisms are in common between abnormal placentation and the formation of TIs.

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INTRODUCTION: In an effort to improve prenatal screening for Trisomy 21, we evaluated pregnancy associated plasma protein-A2 (PAPP-A2) as a potential novel second trimester biomarker for Trisomy 21. METHODS: Trisomy 21 and normal control mid-trimester placental samples were subjected to quantitative rt PCR analysis of seven genes we had previously found to be differentially expressed in Trisomy 21 placentae. The localization and differential expression of PAPP-A2 in second trimester placentae from normal and Trisomy 21 pregnancies was determined by immunohistochemistry. PAPP-A2 maternal serum protein levels in ten Trisomy 21 and ten diploid pregnancies were compared by Western blotting. Maternal serum PAPP-A2 levels were measured in 30 Down syndrome cases and 142 normal controls, using ELISA. Regression analysis was used to determine the correlation of PAPP-A2 with other existing markers of Trisomy 21. RESULTS: PAPP-A2 (aka PLAC 3) mRNA and protein expression were both increased in Down syndrome placentae as compared to diploid placentae. PAPP-A2 was also increased in maternal serum from Down syndrome pregnancies as compared to diploid pregnancies. PAPP-A2 expression correlated weakly with established markers. DISCUSSION: This work takes advantage of our previously performed systematic approach to the discovery of novel maternal serum biomarkers for Trisomy 21, using cDNA microarray analysis. Beginning with the validation of the microarray results, we have tracked PAPP-A2 overexpression in Down syndrome from placental mRNA to maternal serum protein. CONCLUSION: PAPP-A2 could serve as an additional maternal serum marker in prenatal screening for Trisomy 21.

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Cryptococcosis during pregnancy is well documented, but transmission of infection to the fetus is rare. We describe a premature neonate born to a mother with congenitally acquired human immunodeficiency virus (HIV) and active cryptococcosis. Histological examination of the placenta revealed Cryptococcus neoformans within the maternal intervillous space with focal invasion into the chorionic villi. A positive serum cryptococcal antigen (1:2) was detected on days 1 and 5 of life. The neonate had no evidence of central nervous system disease and was treated with fluconazole with resolution of antigenemia. This case highlights both the potential for transplacental transmission of C. neoformans infection and the complexities of caring for pregnant mothers who themselves are congenitally infected with HIV.

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Facultative winter diapause in species of the genus Trichogramma Westw. (Hymenoptera, Trichogrammatidae) is regulated, like in the majority of other insects, by photoperiod and temperature. In trichograms, prepupae are diapausing, but sensitivity to length of the light day and to temperature as to the cue factors inducing diapause is characteristic of all stages of development from embryo to the egg-laying female. The action of the cue factors affects not only the current, but also the subsequent generations. Under natural conditions the photothermal regulation provides the timely induction of the diapause coordinated both with astronomical year time (the photoperiodic reaction) and with specificity of this season (the temperature reaction). In the course of special experiments in trichograms there are also revealed the "rudimentary" reactions that have lost their adaptive role. Results of these studies prove once more that specificity of photoperiodic and temperature reactions inducing diapause and their relative importance and confinement to certain sensitive stages are determined not only by peculiarities of ecology of different insect taxa, but also by the course of their previous evolution.

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The capillary-dominated regime of dynamics of electrified jets of a viscous leaky dielectric liquid is studied numerically. In this regime the effective force in the direction of an applied field due to tangential electric stresses is balanced by the gradient of liquid pressure governed by the surface-tension stresses. As is characteristic of this regime, the electric current and the characteristic jet radius are dependent on the surface-tension coefficient and not on viscosity. In the scope of this work, the conditions of the existence of this regime are determined. A qualitative order-of-magnitude analysis gives the power-law dependences of the jet radius and electric current on the parameters of the problem (conductivity, applied electric field, flow rate, and surface-tension coefficient). Numerical results are obtained for low conductive liquids for a large range of the dimensionless flow rate (capillary number, Ca). The order-of-magnitude estimations of electric current are in agreement with the numerical results given a small Ca. The corresponding numerically obtained jet shapes are discussed and explained.

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Epiphrenic diverticulum is a rare disease associated with distal esophageal obstruction and a weakened muscularis propria. We have adhered to an operative strategy of excision (diverticulectomy), repair of esophageal wall, and relief of functional and mechanical obstruction. We sought to assess this pathophysiology-directed treatment strategy. From 1987 to 2005, 44 patients underwent surgery for epiphrenic diverticulum. Diverticulectomy, repair, and relief of distal obstruction was performed in 35 (80%) and esophagectomy in nine (10%). Outcome (symptoms, diet, subsequent therapies and morbidity) was assessed by follow-up. Forty of 44 patients had preoperatively identifiable esophageal obstruction (91%). Distal obstruction was functional in 32 patients and mechanical in 24; these conditions coexisted in 16. After surgery, there were no in-hospital deaths; 15 patients experienced 22 in-hospital complications. Survival was 90% at 5 years and 72% at 10 years. Symptoms improved in most patients (P = 0.0004), except for gastroesophageal reflux; new symptoms of gastroesophageal reflux occurred in 9/27 (33%) without this symptom preoperatively. Diet was less restricted postoperatively (P < 0.0001). Of 35 patients undergoing diverticulectomy, three (8.6%) required dilatation and two (6%) reoperation; 6/9 esophagectomy patients required dilatations. Preoperative assessment must include evaluation for mechanical obstruction. Adherence to a pathophysiology-directed operative strategy is safe and will improve the symptoms of most patients, with little need for reintervention. However, occasional patients will experience new symptoms, particularly reflux. Esophagectomy is the alternative for patients who are not candidates for diverticulectomy, repair of esophageal wall, and relief of distal obstruction.

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The final glycated products forming in diabetes contribute to the higher atherogenic oxidative modification of low-density lipoproteins (LDL). The impact of glycemic control on the parameters of free radical oxidation was comparatively studied in patients with type 2 diabetes who received metformin (Glucophage, Nycomed) (Group 1, n = 40) and sulfanylurea preparations (Group 2, n - 30, out of them 15 patients took maninil and 15 had diabeton) good glycemic control caused the magnitude of oxidative stress to reduce, which appeared as the decreased levels of primary (lipid hydroperoxides) and secondary (malonic dialdehyde) products of free radical oxidation in LDL and as the enhanced activity of antioxidative defense enzymes. However, with the identical degree of glycemic control, which was determined by the level concentrations of HbA1c and lipids in both groups, the plasma levels of lipid peroxides decreased by more than 5 times in Group 1 patients receiving metformin than in Group 2 patients and the rate of LDL oxidability reduced by 4.5 times. Such a marked effect of metformin on the attenuated manifestations of oxidative stress is indicative of its antioxidative effect independent of the hypoglycemic effect of the drug.

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Abstract Effects of egg retention on movement and dispersal activity of Trichogramma principium (Hymenoptera, Trichogrammatidae) females were investigated under laboratory conditions. Individual females were observed during one minute in the absence of hosts. Movement activity and dispersal rate were estimated by the length of the track and by the distance from the start point, respectively. Before the test, all wasps during 2 - 4 days were presented with a possibility to parasitize a factitious laboratory host, Sitotroga cerealella Oliv. (Lepidoptera, Gelechiidae). Wasps that had parasitized before the test show significant reduction of spontaneous walking activity and dispersal rate when compared with females that refused to parasitize the non-preferred host (i.e. manifested egg retention). This effect cannot be considered as a direct arrestment reaction to the host because during the test period, no hosts were provided. Thus, egg retention results not only in temporal spread, but also in more intensive spatial dispersal of a group of simultaneously emerged females.

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Using a technique to identify substrates of the peptide processing enzyme carboxypeptidase E (CPE), several novel peptides were detected in the brain and pituitary of Cpe(fat)/Cpe(fat) mice and found to be derived from a single precursor, termed proSAAS. In order to gain further information regarding the potential physiological roles of these peptides, we have examined the distribution of two proSAAS-derived peptides, ARPVKEPRSLSAASAPLAETSTPLRL (SAAS) and LENSSPQAPARRLLPP (LEN), in rat neuroendocrine tissues using immunohistochemistry. Both peptides are detected throughout the brain, with the highest concentrations of SAAS peptide in the hypothalamus. In the hippocampus, both peptides are co-localized with prohormone convertase 1 in the dentate gyrus and CA1-3 region. In cerebellum, SAAS peptide is co-localized with prohormone convertase 1 in Purkinje and granular cells, whereas LEN is much more abundant in the Purkinje cells relative to the granular cells. Similarly, SAAS and prohormone convertase 1 are co-localized in the dorsal horn of the spinal cord, while LEN is mainly restricted to fibers of the white matter. In the pituitary, SAAS, LEN, and prohormone convertase 1 are detected in all three lobes. In the pancreas, SAAS, LEN, and prohormone convertase 1 are only detected in the islets, although the peptides are enriched in the peripheral cells (alpha and/or delta) while prohormone convertase 1 is only expressed in the inner cells (beta). Both SAAS and LEN are present in the adrenal medulla along with prohormone convertase 1. Taken together, these data are consistent with the proposed role for proSAAS as an endogenous inhibitor of prohormone convertase 1 in many, but not all cell types. However, the broader localization of the peptides allows for the possibility that they perform additional functions.

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Massive acute thymic haemorrhage in the neonate occurs extremely rarely and is associated with haemorrhagic disease of the newborn. A 30 year old woman with an unremarkable previous obstetric history presenting at 37 weeks and 4 days gestation with the complaint of loss of fetal movement was found to have a male fetus with findings at necropsy of massive acute thymic haemorrhage, acute intracranial haemorrhage, and hydrops fetalis. This is the first report of massive acute thymic haemorrhage in utero. Massive thymic haemorrhage should be added to the reported causes of lethal non-immunological hydrops.

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BACKGROUND: The main cause of morbidity and mortality after lung transplantation (LT) is bronchiolitis obliterans syndrome (BOS). Anti-HLA antibodies development after LT has been shown to play an important role in BOS pathogenesis. However, the nature of non-HLA antibodies developed after LT and their role in BOS pathogenesis have not been determined. METHODS: Sera from 16 BOS+ patients and 11 BOS- patients were collected at 12, 24, 36, and 48 months after LT. Anti-HLA class I and class II antibodies were absorbed with pooled human platelets and pooled human lymphoblastoid cell lines, respectively. Then, the presence of non-HLA antibodies against several cell lines from different origin was determined by flow cytometric analysis. Antibody-positive samples were tested for induction of proliferation and growth factor production in two selected airway epithelial cell (AEC) lines. RESULTS: Five of 16 BOS+ patients (31.2%) and 0 of 11 BOS- patients (0%) developed anti-AEC antibodies after LT (P=0.05). No reactivity against endothelial cells, lymphocytes, monocytes, or granulocytes was detected. Further analysis of two selected sera demonstrated the development of reactivity against a 60-kDa antigen expressed by 60% of AEC lines and only 12% of cell lines from other tissues. Antibody binding to this antigen induced intracellular Ca++ influx, tyrosine phosphorylation, proliferation, and up-regulation of transforming growth factor-beta and heparin-binding epidermal growth factor mRNA transcription in AECs. CONCLUSIONS: These results indicate that anti-AEC antibodies may play a role in the immunopathogenesis of BOS in the absence of anti-HLA antibodies.

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Metallocarboxypeptidase Z (CPZ), a new member of the regulatory metallocarboxypeptidases, contains a 120-residue cysteine-rich region that has 20-35% amino acid sequence identity to Drosophila and mammalian frizzled proteins. In order to gain insights into the function of CPZ, we have examined the distribution of the protein by immunohistochemistry throughout mouse development. The expression of CPZ peaks at E9-E12, decreases in late gestation and falls further in adult tissues. CPZ expression in amnion cells, cochlear epithelial cells and surrounding mesenchyme, ventricular lining cells in the brain and cartilagenous condensations and surrounding connective tissue in ribs remains at high levels throughout mouse gestation. The expression pattern of CPZ overlaps with the expression pattern of several Wnt genes, consistent with the putative role of CPZ in Wnt signaling.

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Carboxypeptidases perform many diverse functions in the body. The well-studied pancreatic enzymes (carboxypeptidases A1, A2 and B) are involved in the digestion of food, whereas a related enzyme (mast-cell carboxypeptidase A) functions in the degradation of other proteins. Several members of the metallocarboxypeptidase gene family (carboxypeptidases D, E, M and N) are more selective enzymes and are thought to play a role in the processing of intercellular peptide messengers. Three other members of the metallocarboxypeptidase gene family do not appear to encode active enzymes; these members have been designated CPX-1, CPX-2 and AEBP1/ACLP. In this review, we focus on the recently discovered carboxypeptidase Z (CPZ). This enzyme removes C-terminal Arg residues from synthetic substrates, as do many of the other members of the gene family. However, CPZ differs from the other enzymes in that CPZ is enriched in the extracellular matrix and is broadly distributed during early embryogenesis. In addition to containing a metallocarboxypeptidase domain, CPZ also contains a Cys-rich domain that has homology to Wnt-binding proteins; Wnts are important signaling molecules during development. Although the exact function of CPZ is not yet known, it is likely that this protein plays a role in development by one of several possible mechanisms.

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A correlation between indirect allorecognition of mismatched donor HLA class I peptides and development of bronchiolitis obliterans syndrome (BOS) after lung transplantation has been previously observed. The aim of this study was to determine whether there was a correlation between indirect allorecognition of mismatched donor HLA class II peptides and development of BOS after lung transplantation. Peripheral blood mononuclear cells from nine BOS+ and nine BOS-lung transplant recipients were cultured with synthetic peptides corresponding to the beta-chain hypervariable region of a mismatched donor HLA-DR molecule. Then, proliferative alloreactivity as well as frequency of alloreactive T cells were determined. In addition, the immunodominant epitopes from the donor HLA-DR molecules were identified in selected patients. T cells from BOS+ patients showed a dose-dependent proliferative alloreactivity against donor HLA-DR peptides that was significantly higher than that observed in BOS- patients (p=0.001). Similarly, the frequency of HLA-DR alloreactive T cells was significantly higher in BOS+ patients than in BOS- patients (p=0.001). This T-cell alloreactivity was directed against a single immunodominant HLA-DR peptide. These results suggest that indirect alloreactivity to donor HLA class II molecules may play a role in the pathogenesis of BOS after lung transplantation.

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