(Complex) PTSD in Ukrainian refugees: Prevalence and association with acts of war in the Danish refugee cohort (DARECO).

BACKGROUND: The Russian invasion of Ukraine has driven millions of Ukrainians away from their homes. Among these, the majority have likely experienced war-related potentially traumatic events, and some will experience symptoms of posttraumatic stress disorder (PTSD). The aims of the study are to estimate the prevalence of PTSD and Complex PTSD (CPTSD) in displaced Ukrainians and examine associations between war- and other potentially traumatic exposures and (C)PTSD. METHODS: Questionnaires were distributed to all registered adult Ukrainians (18+) who arrived in Denmark between February 24th 2022 and February 15th 2023 (N = 18,389). We estimate the prevalence of war exposures, other potentially traumatic exposures, and (C)PTSD. In logistic regression analyses, we test if exposure to war and other potentially traumatic events are associated with PTSD and CPTSD. RESULTS: The final sample size was 6993 (38.0 %). Responders were more likely to be female and younger than non-responders. Prevalence of PTSD and CPTSD was 15.9 % and 13.5 %, respectively. Female gender, high education, and loss of a relative due to the war were associated with (C)PTSD. Direct and indirect exposure to war and combat was related to PTSD but not CPTSD, while exposure to war prior to the 2022 invasion was related to CPTSD but not PTSD. LIMITATIONS: The study is cross-sectional and based on self-report. CONCLUSION: Close to one third of the sample fulfill the criteria of PTSD or CPTSD. War exposures are differentially related to PTSD and CPTSD. The findings illustrate that trauma-related psychopathology is a pertinent problem in displaced Ukrainians.

Selective deficits in the sense of smell caused by chemical modification of the olfactory epithelium.

A chemically selective procedure for covalent modification of Schiff base-forming binding sites in proteins is demonstrated in vitro. In vivo studies show that the same procedure produces a selective anosmia ("odor blindness") when applied to the olfactory epithelia of experimental animals. Surgical experiments confirm that the sense of smell is specifically affected.

Culturally competent methods to promote organ donation rates among African-Americans using venues of the Bureau of Motor Vehicles.

BACKGROUND: The diversity of the nation is one of society's greatest assets, but this feature is overshadowed by the disproportionate burden of disease that exists among America's minorities. Evidence of the disparate health status has been documented in low life expectancy, cancer, diabetes, cardiovascular, and kidney disease as well as a plethora of disorders that necessitate organ transplantation. Many minorities have been reluctant to register to become organ donors. This circumstance can be alleviated by educating the public regarding the necessity of organ transplantation. We have developed a "unique" collaborative outreach program designed to promote acceptance of organ donation in African-Americans (AAs). Our outreach curriculum at Bureau of Motor Vehicles (BMV) has resulted in increased registrations and awareness regarding the need and positive perceptions toward donation. METHODS: We developed a culturally sensitive outreach program: cultural sensitivity indicates how culture has the ability to influence communication between patients and health providers. An "Outreach Promotional Contest" was strategically targeted toward 28 Ohio BMVs to promote and assist in an outreach educational program regarding organ donation/registry. RESULTS: The consequence/results has been an increase of 3.4% in the BMV locations. The one BMV, with the highest increase was attended predominantly by AAs which moreover, won first place in the contest (6.425%; P < .05). CONCLUSION: To increase the number of people willing to register, we believe that both community education regarding the need and importance, as well as culturally sensitive promotion of organ donation, is the best way to increase organ donor registries particularly among minority populations.

Phase I study of a five-day dose schedule of 4-Ipomeanol in patients with non-small cell lung cancer.

The mammalian pulmonary toxin 4-ipomeanol (IPO) is activated by the cytochrome P450 system in bronchial Clara cells in animals. The resulting metabolites bind rapidly to macromolecules, producing localized cytotoxicity. IPO has in vitro and in vivo antitumor activity in non-small cell lung cancer (NSCLC) and thus was proposed as a lung cancer-specific antitumor agent. We have completed a directed Phase I trial in patients with NSCLC. Forty-four patients (34 men and 10 women) with NSCLC were treated with IPO. All but two patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. They received 91 courses of therapy with i.v. IPO; 82 courses were administered daily for five days, and 9 were single bolus doses. The dose-limiting toxicity of elevated serum transaminases was observed in three of seven patients at 922 mg/m2/day. The maximum tolerated dose was 693 mg/m2/day on 5 consecutive days every 3 weeks. One patient developed grade 4 pulmonary toxicity at 167 mg/m2/day. There was no significant hematological or renal toxicity. No objective antitumor responses were observed. Pharmacokinetic analysis of 39 patients from day 1 of IPO administration showed biexponential elimination with mean half-lives of 8.6 (alpha half-life) and 76 min (beta half-life). There was a linear relationship between the area under the plasma drug concentration-time curve and the dose of IPO. There was no significant difference between the pharmacokinetic parameters measured on day 1 and day 5. Using a 4-day in vitro cytotoxicity assay, two tumor cell lines established from patients treated at 693 mg/m2/day had IC50s of approximately 6 mM, a concentration more than 75-fold higher than the plasma levels measured in these patients. Thus, although the total amount of drug administered per cycle on a daily times five dose schedule is more than 2.5-fold higher than the recommended single daily dose, IPO is unlikely to be a useful drug for patients with lung cancer.

Oral manifestations of chronic graft-v-host disease.

Sixty patients were studied 180 to 500 days after allogeneic marrow transplantation to determine if late oral abnormalities were associated with the presence of chronic graft-v-host disease (GVHD). Lip and intraoral mucosal surfaces were evaluated for color, keratinization, atrophy, and erythema. Subjective complaints of oral pain and xerostomia were also recorded. Abnormalities were scored on a scale of 0 to 3 and tested for association with GVHD by chi 2 test. Oral manifestations most strongly associated with chronic GVHD included atrophy and erythema or lichenoid lesions of the buccal and labial mucosa and oral pain. Oral manifestations resembled several naturally occurring autoimmune disorders. Recognition of these changes can aid in the clinical diagnosis and assessment of established chronic GVHD.

Launching the Tidal Model: evaluating the evidence.

Launching the Tidal Model: evaluating the evidence This paper reports on two evaluations of the Tidal Model, in the context of two separate acute admission wards, one in Birmingham (2004) and the other in Newcastle (2001), and makes recommendations concerning the criteria and type of reasoning appropriate to evaluating the evidence the two projects have generated. In the Birmingham study, results showed that in the year following the introduction of the Tidal Model, the total number of serious untoward incidents such as physical assault, violence and harassment, decreased by 57%. Nurse satisfaction with their work also improved with nurses rating the model superior to their previous way of working. Inpatient service user assessment of the overall quality of their care was also positive. These findings are then compared with the positive results of an earlier study of the Tidal Model undertaken in Newcastle in 2001. That study was criticized, however, for not showing conclusively that the positive results of the evaluation correlated with the introduction of the Tidal Model. This criticism is briefly examined in the light of both ancient (Aristotle) and modern (Charles Peirce) understandings of the nature of evidence and suggests that such criticism begs the question of the nature of proof. The paper concludes by arguing that, according to both Aristotle and the procedures of abductive reasoning advocated by Charles Peirce, inferring a positive correlation between the results of both studies and the introduction of Tidal Model is a good example of reasonable inference to the best explanation. The available evidence suggests that the results of both studies render the conclusion probable and thus 'good enough' to warrant serious consideration for implementing the Tidal Model more widely within and across Mental Health NHS Trusts.

Kinetic analysis of ligand binding to interleukin-2 receptor complexes created on an optical biosensor surface.

The interleukin-2 receptor (IL-2R) is composed of at least three cell surface subunits, IL-2R alpha, IL-2R beta, and IL-2R gamma c. On activated T-cells, the alpha- and beta-subunits exist as a preformed heterodimer that simultaneously captures the IL-2 ligand as the initial event in formation of the signaling complex. We used BIAcore to compare the binding of IL-2 to biosensor surfaces containing either the alpha-subunit, the beta-subunit, or both subunits together. The receptor ectodomains were immobilized in an oriented fashion on the dextran matrix through unique solvent-exposed thiols. Equilibrium analysis of the binding data established IL-2 dissociation constants for the individual alpha- and beta-subunits of 37 and 480 nM, respectively. Surfaces with both subunits immobilized, however, contained a receptor site of much higher affinity, suggesting the ligand was bound in a ternary complex with the alpha- and beta-subunits, similar to that reported for the pseudo-high-affinity receptor on cells. Because the binding responses had the additional complexity of being mass transport limited, obtaining accurate estimates for the kinetic rate constants required global fitting of the data sets from multiple surface densities of the receptors. A detailed kinetic analysis indicated that the higher-affinity binding sites detected on surfaces containing both alpha- and beta-subunits resulted from capture of IL-2 by a preformed complex of these subunits. Therefore, the biosensor analysis closely mimicked the recognition properties reported for these subunits on the cell surface, providing a convenient and powerful tool to assess the structure-function relationships of this and other multiple subunit receptor systems.

Effects of psychotherapy with children and adolescents revisited: a meta-analysis of treatment outcome studies.

A meta-analysis of child and adolescent psychotherapy outcome research tested previous findings using a new sample of 150 outcome studies and weighted least squares methods. The overall mean effect of therapy was positive and highly significant. Effects were more positive for behavioral than for nonbehavioral treatments, and samples of adolescent girls showed better outcomes than other Age x Gender groups. Paraprofessionals produced larger overall treatment effects than professional therapists or students, but professionals produced larger effects than paraprofessionals in treating overcontrolled problems (e.g., anxiety and depression). Results supported the specificity of treatment effects: Outcomes were stronger for the particular problems targeted in treatment than for problems not targeted. The findings shed new light on previous results and raise significant issues for future study.

Radioprotection by WR-2721 of gamma-irradiated rat parotid gland: effect on gland weight and secretion at 8-10 days post irradiation.

Changes in rat parotid salivary gland weight and functional parameters were evaluated at 8 to 10 days post irradiation in WR-2721 protected and non-protected animals following exposure to a single 15.3 Gy dose of Cs-137 radiation to the head. Glandular fluid secretory capacity was assessed by maximum flow rate, total volume of saliva and duration of secretion following pilocarpine stimulation. Protection against radiomucositis was also evaluated indirectly by daily monitoring of food and water intake, body weight and paraoral symptomatology. WR-2721 provided a significant degree of protection for all glandular functional parameters as well as gland weight. Relative protective factors (RPF) were computed for irradiated protected and non-protected animals compared to their sham-irradiated, pair-fed controls. The calculated RPFs were: Gland weight 1.9, maximum flow rate 2.9, volume of saliva 2.1 and duration of secretion 2.1 for a mean "relative protection" of 2.25. Substantial protection against radiomucositis in protected animals was evident by a progressive gain in body weight and lack of oral signs and symptoms as compared to non-protected animals. Protection against radiomucositis and preservation of residual parotid gland secretory capacity as determined by functional parameters suggests that WR-2721 may be of significant benefit in alleviating oral symptoms and maintaining salivary gland function for patients receiving radiotherapy for head and neck tumors.

Antibody HMB-45 identifies the cells of blue nevi. An immunohistochemical study on paraffin sections.

Sixteen cases of blue nevi were investigated using the anti-melanoma specific antibody HMB-45. This antibody has been found to react with junctional but not with intradermal nevus cells, and with fetal and neonatal, but not with adult, melanocytes. Our study shows that HMB-45 also reacts with cells of the blue nevus, a unique type of intradermal nevus. The origin of blue nevus cells is controversial, and the results of this study support the hypothesis that blue nevus cells are not of purely melanocytic or Schwannian origin, but are derived from a precursor cell that has some common features of both melanocyte and Schwann cell.

Disordered salivary immunoglobulin secretion and sodium transport in human chronic graft-versus-host disease.

Whole saliva samples and lip biopsies were collected from 12 allogeneic bone marrow transplant recipients who developed extensive chronic graft-versus-host disease (GVHD) and from 10 healthy allogeneic and syngeneic recipients without GVHD. Six of ten biopsies from patients with chronic GVHD had lichenoid stomatitis or sialadenitis, or both, with sialodochitis. Seven of nine biopsies from patients free of chronic GVHD were entirely normal, and two had either mild glandular or mucosal changes. Salivary gland involvement in chronic GVHD was associated with decreased or absent levels of salivary IgA and inorganic phosphate, decreased salivary flow rates, and increased concentrations of salivary sodium, albumin, and IgG. The most striking abnormalities were found in patients with histologic evidence of sialadenitis. In contrast, marrow transplant recipients without chronic GVHD had normal salivary immunoglobulin and electrolyte levels. Secretory IgA deficiency may contribute to the frequent sinobronchial infections observed in patients with chronic GVHD.

The predictive value of elevated labial saliva sodium concentration: its relation to labial gland pathology in bone marrow transplant recipients.

Labial minor gland salivary flow rate and sodium concentration were analyzed in relation to 1) histologic findings in labial biopsy specimens and 2) the occurrence of chronic graft-versus-host disease (GVHD) in patients who received bone marrow transplants. Biopsy specimens and samples were obtained from 61 recipients of marrow transplants (including three twins) 51 to 1,260 days post transplantation. Labial saliva sodium concentrations were elevated in some patients, and these increases were associated with inflammation and destruction of minor salivary gland acini and ducts by chronic GVHD or other factors. The predictive value of the salivary sodium changes in evaluating labial salivary gland pathologic changes was 91 per cent, and the sensitivity was 74 per cent. Thus, if a transplant recipient is found to have an elevated labial saliva sodium level, then the probability that he has pathologic labial gland changes is 91 per cent. When analyses were restricted to include only patients who received no irradiation during transplantation, then elevated labial saliva sodium concentration was significantly associated with the occurrence of chronic GVHD. The sensitivity of this relationship was 42 per cent, but the predictive value was 100 per cent. Thus, if a nonirradiated transplant recipient is found to have an elevated labial saliva sodium concentration, then it is virtually certain that he has chronic GVHD. We found no significant changes in labial saliva flow rates in these bone marrow transplant recipients.

Mupirocin resistance: clinical and molecular epidemiology.

The antistaphylococcal activity of topical mupirocin has made it an attractive agent for the treatment of asymptomatic colonization with Staphylococcus aureus. Increasing use has been associated with the emergence of mupirocin resistance in staphyloccoci, and failure of therapy has been associated with the isolation of strains exhibiting high-level resistance (MIC > 500 micrograms/mL). Fortunately, low-level mupirocin resistance (MIC < 100 micrograms/mL) occurs most commonly. Because a novel gene encoding for mupirocin resistance resides in both low-level and high-level resistant strains, the emergence of low-level mupirocin resistance may not be as epidemiologically insignificant as previously thought.

Identification of Merkel cells in oral epithelium using antikeratin and antineuroendocrine monoclonal antibodies.

Merkel cells are a rare cell type located at or near the basal lamina of oral epithelia and epidermis. They are associated with nerves, and may function as touch receptors. Merkel cells are difficult to identify by routine light microscopy, but have been identified by electron microscopy and specific antibodies. We demonstrate here that Merkel cells can be identified by immunohistochemistry, using a monoclonal antibody (LK2H11, Lloyd and Wilson, 1983) to neuroendocrine granules, and a monoclonal antibody (35 beta H11, Gown and Vogel, 1982) to a 54-kD keratin generally located in simple epithelia but not in stratified epithelia. Human oral tissue was fixed in Carnoy's fixative, and adjacent serial sections were stained with the two antibodies. Individual positively-stained cells were generally located at the bases of rete ridges. Cells in the same position in adjacent sections stained with both antibodies. Essentially all cells (94%) staining for neuroendocrine granules also gave a positive reaction for the 54-kD keratin, evidence that a single Merkel cell contains neuroendocrine granules and the 54-kD keratin. Staining of epithelial sheets of human oral tissues revealed a linear distribution of Merkel cells along the bases of rete ridges. We concluded that antibodies to simple epithelial keratins and neuroendocrine granules may be excellent immunohistochemical markers for Merkel cells, thus facilitating future studies to examine changes in Merkel cells and their distribution in pathologic conditions. The observation that Merkel cells can be stained with an antikeratin antibody strongly supports the epithelial origin of these cells.

Expression of the antimicrobial peptide, human beta-defensin 1, in duct cells of minor salivary glands and detection in saliva.

The oral cavity is exposed to a variety of environmental insults. Salivary secretions play a critical role in maintaining oral health via innate host defense mechanisms and secretion of secretory IgA. Human beta-defensins (hBD) are antimicrobial peptides that are a component of the innate immune response; they are expressed in epithelia and are proposed to have a role in mucosal defense. hBD-1 mRNA is constitutively expressed in numerous mucosal tissues, including human gingiva and submandibular and parotid glands. Our objective was to detect the expression and localization of hBD-1 peptide in human salivary glands and in saliva. Minor salivary gland tissue was obtained from biopsies of patients with mucoceles (n = 20). hBD-1 peptide was detected by immunohistochemistry; expression was localized to the ductal cells and not the acinar cells of these glands. The peptide was located apically, toward the lumen in the duct cells. Further evaluation showed stronger hBD-1 expression in ducts with periductal inflammation, as indicated by the immunostaining of serial sections with anti-CD45 specific for B- and T-lymphocytes. Statistical analysis showed a strong correlation of hBD-1 staining and inflammation. Results of immunolocalization suggest that hBD-1 functions to protect salivary glands from retrograde infection, that expression of the peptide is enhanced in inflamed sites, and that post-transcriptional regulatory mechanisms may be involved in hBD-1 peptide expression. Western immunoblot analysis also detected hBD-1 peptide in unstimulated, whole, acidified saliva from normal volunteers. However, hBD-1 peptide associated with salivary mucin resulted in loss of the detection in a dot-immunoblot assay. Association of hBD-1 with salivary mucin may facilitate peptide distribution and adherence to oral surfaces and aid its function within the oral cavity.

Kinetic analysis of a protein antigen-antibody interaction limited by mass transport on an optical biosensor.

Using BIAcore technology, we determined the rate constants for a protein antigen-antibody interaction that was mass transport limited on the optical biosensor. The antigen consisted of a soluble form of the human T-cell receptor CD4 (two amino terminal domains, D1D2) and the antibody was an anti-CD4 monoclonal from monkey engineered with the constant domains from human IgG1. High quality response data were obtained for this interaction by orienting the attachment of the antibody on the sensor surface and correcting for instrument artifacts with control experiments. Using numerical integration and global fitting, we demonstrate that a mass transport limited reaction was the only model of those tested that described well D1D2 binding to three different surface densities of the antibody. Statistical profiling techniques showed that the error space and correlation for the parameters in the non-linear model were essentially linear, but only when the model was simultaneously fitted to data from multiple surface densities. The "on" and "off" rate constants (1.2 x 10(-6) M-1 s-1 and 2.9 x 10(-4) s-1) determined from the kinetic analysis predict an equilibrium dissociation constant (KD = 0.24 +/- 0.01 nM) that agrees with the value measured in solution by titration calorimetry (KD = 0.2 +/- 0.1 nM). The results indicate that, although the D1D2-antibody reaction is partially controlled by mass transport on the optical biosensor, by optimizing the experimental design and analyzing data from multiple surface densities it is possible to determine accurate estimates of the intrinsic equilibrium and kinetic rate constants.

[[(18)F]N-(4'-fluorobenzyl)-4-(3-bromophenyl) acetamide for imaging the sigma receptor status of tumors: comparison with [(18)F]FDG, and [(125)I]IUDR.

A series of biodistribution studies were conducted with the radiotracer, [(18)F]N-(4'-fluorobenzyl)-4-(3-bromophenyl)acetamide, [(18)F]1 in nude mice bearing tumor xenografts of the mouse mammary adenocarcinoma, line 66. This radiotracer has a high affinity for both sigma(1) and sigma(2) receptors. In vivo studies were also conducted in order to assess the effect of blocking sigma(1) receptors on tumor uptake and the tumor:background ratio of this radiotracer. The results of these studies revealed that blocking the sigma(1) receptor so that only the sigma(2) receptors are labeled in vivo, results in a higher tumor:background ratio with only a small reduction in the tumor uptake of the radiotracer relative to the no-carrier-added (i.e., nonselective) conditions. Comparative in vivo studies were also conducted with the anatomic and metabolic imaging agent, [(18)F]FDG, and a radiolabeled DNA precursor, [(125)I]IUdR. Both of these radiolabeled compounds represent classes of agents that have been proposed for imaging the proliferative status of solid tumors. The results of these studies indicated that a sigma(2)-selective imaging agent may be, 1) a better anatomic imaging agent for breast cancer than [(18)F]FDG, and 2) a better functional imaging agent than the radiolabeled DNA precursors, [(123/124)I]IUdR and [(11)C]thymidine, for measuring the proliferative status of breast tumors with PET and SPECT. However, additional studies will be needed to compare sigma(2)-selective imaging agents with [(18)F]FLT in order to determine which is the more appropriate imaging agent for measuring the proliferative status of breast tumors with PET.

Synthesis and in vivo evaluation of [18F]-N-(p-nitrobenzyl)spiperone ([18F]PNBS) in rats.

[18F]-N-(p-nitrobenzyl)spiperone, [18F]PNBS, was prepared and its in vivo uptake in rat brain was measured. A temporal increase in striatum:cerebellum ratio and frontal cortex:cerebellum (FC:Cb) ratio was observed. Blocking studies suggested the formation of a radiolabeled metabolite, presumably [18F]spiperone, that is capable of crossing the blood-brain barrier and labeling cortical 5-HT2 receptors. This was confirmed using the ISRP method of metabolite analysis indicating [18F]PNBS is not a suitable tracer for studying D2 receptors in vivo with PET.

(+)-p-([18F]fluorobenzyl)spirotrozamicol [(+)-[18F]spiro-FBT]: synthesis and biological evaluation of a high-affinity ligand for the vesicular acetylcholine transporter (VAChT).

(+)-1'-[4-Hydroxy-1-(4-fluorobenzyl)piperidin-3-yl]spiro[1H- indene-1,4'- piperidine] {(+)-Spiro-FBT}, a high-affinity vesicular acetylcholine transporter ligand, was labeled with fluorine-18, and evaluated in the rat and monkey. In the rat brain, (+)-[18F]Spiro-FBT accumulated preferentially in the striatum, hippocampus, and cortex, brains regions containing high-to-moderate densities of cholinergic terminals. However, due to rapid metabolism, no preferential accumulation of the radiotracer was observed in corresponding regions of the monkey brain. Consequently, rapid metabolism renders (+)-[18F]Spiro-FBT unsuitable for studying cholinergic function with positron emission tomography.

The use of [18F]4-fluorobenzyl iodide (FBI) in PET radiotracer synthesis: model alkylation studies and its application in the design of dopamine D1 and D2 receptor-based imaging agents.

[18F]4-Fluorobenzyl iodide ([18F]FBI) was prepared, and a series of model alkylation studies were conducted to determine its chemical reactivity toward nitrogen and sulfur nucleophiles of varying nucleophilicities. [18F]FBI was found to react rapidly with secondary amines and anilines to give the corresponding N-[18F]4-fluorobenzyl analogue in high yield. Amides and thiol groups required the use of a base catalyst. The utility of [18F]FBI was documented by investigation of dopamine D1 and D2 receptor-based radiotracers.