Oral Microbiota and the Risk of Gastrointestinal Cancers-A Narrative Literature Review.

The human body is colonized by trillions of microorganisms in a symbiotic relationship. The oral cavity represents one of the most abundant microbial habitats in our body. Advances in sequencing techniques provide a more detailed understanding of the oral microbiota and how imbalances between bacteria, the phenomenon of dysbiosis, can affect not only the development of dental caries or inflammation within the oral cavity but also systemic diseases and cancers in distant locations. This narrative review evaluates the relationship between oral microbiota and its impact on gastrointestinal cancers. Using the keywords "oral microbiota 'AND' gastrointestinal cancers", the PubMed Web of Science and Scopus databases were searched for articles published between 2014 and 2024. Based on the review, the relationship between oral microbiota and oral, esophageal, gastric, colorectal, hepatocellular, and pancreatic cancers was described. Potential oncogenic mechanisms exploited by the microbiota such as the production of pro-inflammatory cytokines, induction of abnormal immune responses, and disruption of cell metabolic pathways were assessed. Further research and a thorough understanding of the impact of the oral microbiota on the development of cancers of the gastrointestinal tract may play a key role in their prevention, diagnosis, and treatment in the future.

Managing Post-Transplant Diabetes Mellitus after Kidney Transplantation: Challenges and Advances in Treatment.

Kidney transplantation is the most effective treatment for end-stage renal failure but is associated with complications, including post-transplant diabetes mellitus (PTDM). It affects the quality of life and survival of patients and the transplanted organ. It can cause complications, including infections and episodes of acute rejection, further threatening graft survival. The prevalence of PTDM, depending on the source, can range from 4 to 30% in transplant patients. This article aims to discuss issues related to diabetes in kidney transplant patients and the latest treatments. Knowledge of the mechanisms of action of immunosuppressive drugs used after transplantation and their effect on carbohydrate metabolism is key to the rapid and effective detection of PTDM. Patient therapy should not only include standard management such as lifestyle modification, insulin therapy or pharmacotherapy based on well-known oral and injection drugs. New opportunities are offered by hypoglycemic drugs still in clinical trials, including glucokinase activators, such as dorzagliatin, ADV-1002401, LY2608204, TMG-123, imeglimine, amycretin and pramlintide. Although many therapeutic options are currently available, PTDM often creates uncertainty about the most appropriate treatment strategy. Therefore, more research is needed to individualize therapeutic plans and monitor these patients.

Production of Cu/Diamond Composite Coatings and Their Selected Properties.

This article presents Cu/diamond composite coatings produced by electrochemical reduction on steel substrates and a comparison of these coatings with a copper coating without diamond nanoparticles (<10 nm). Deposition was carried out using multicomponent electrolyte solutions at a current density of 3 A/dm2 and magnetic stirring speed of 100 rpm. Composite coatings were deposited from baths with different diamond concentrations (4, 6, 8, 10 g/dm3). This study presents the surface morphology and structure of the produced coatings. The surface roughness, coating thickness (XRF), mechanical properties (DSI), and adhesion of coatings to substrates (scratch tests) were also characterized. The coatings were also tested to assess their solderability, including their spreadability, wettability of the solder, durability of solder-coating bonds, and a microstructure study.

Treatment of Patients After Lung Transplantation With Covid Infection During Long-Term Follow-Up.

BACKGROUND: Patients undergoing lung transplantation are routinely managed with lifelong immunosuppression, which is associated with a heightened risk for infections. This study delves into the therapeutic challenges and strategies for managing lung transplant recipients (LTRs) infected with COVID-19 during long-term follow-up. METHODS: The was a case series analysis, among which nonstandard therapies consisting of targeted antibody treatment, antiviral drugs, or anti-interleukin-6 drugs were applied in patients after lung transplantation. Additional analysis of laboratory test results for systemic inflammation and imaging studies was also carried out. The study was limited to a dedicated COVID-19 center, commonly known as a temporary hospital, and included patients infected with COVID-19 in the late post-lung transplant period (home-related infection). RESULTS: Fifteen post-lung transplantation patients with current COVID-19 infection were treated with antibodies such as tocilizumab, casirivimab, imdevimab, and regdanvimab. Of these patients, 1 was given tocilizumab (7%), 8 casirivimab and imdevimab (53%), and 2 regdanvimab (13%). Of the 15 lung transplant recipients studied, 8 presented COVID-19-associated lung changes in computed tomography scans (53%). Common clinical manifestations included dyspnea, fever, and fatigue. Antiviral agents, like remdesivir, were employed in the remaining 4 cases (27%), and adjunctive therapies, such as corticosteroids and anticoagulants, were used selectively. All treated patients survived the infection without complications; the treatment proved effective and safe.

Anti-HLA Immunization in Patients After Lung Transplantation: A Comparative Study Before and During the Pandemic.

Anti-human leukocyte antigen (anti-HLA) sensitization in lung transplant recipients (LTRs) can significantly impact graft survival and patient outcomes. The global pandemic, induced by the SARS-CoV-2 virus, brought about numerous challenges in the medical sphere, including potential alterations in HLA immunization patterns among LTRs. A retrospective analysis of LTRs group transplanted from July 2018 to 1 March 2020 (pre-pandemic) was compared with patients transplanted from 1 March 2020 to December 2022 (during the pandemic). Totally 92 patients were controlled. Patients were also divided into 2 groups: vaccinated and non-vaccinated. The results of cytotoxic crossmatch, results of anti-HLA antibody testing, presence of DSA before and after transplantation, and early and late graft function were compared between groups. In the pandemic and vaccinated groups, an increase was observed in the number of positive crossmatch tests performed with a pool of B lymphocytes. However, the presence of dithiothreitol abolished the positive reaction in 90% of cases. We also observed an increased percentage of patients immunized based on the results of solid phase tests both in the pandemic group and in the group of patients who received vaccination against the SARS-CoV-2 virus. It might be that the pandemic/vaccination has influenced the prevalence of anti-HLA immunization in LTRs. Further studies are essential to establish causative factors and develop targeted interventions for this population of patients.

Impact of Circulating Lymphoma Cells on HLA Typing Outcomes in Patients with Diffuse Large B-Cell Lymphoma: A Case Report.

BACKGROUND: Recipient's high resolution HLA typing is required in allogeneic hematopoietic cell transplantation from unrelated donors, as well as for haploidentical family donors. For these purposes, Next-Generation Sequencing (NGS) methods are the gold standard. METHODS: We present a case of a patient with an incorrect HLA typing result caused by the population of circulating lymphoma cells. The first HLA examination was performed from peripheral blood (PB) using NGS in the active phase of diffuse large B-cell lymphoma with bone marrow involvement. RESULTS: Because of rare and inconclusive results, confirmed twice for the A* locus (A*02:32N), real-time polymerase chain reaction (RT-PCR)was performed. With RT-PCR method, we obtained more expected results according to the population allele frequency: in HLA-A locus (A*02:01) but also in DQB1 (DQB1*03:01, not as in NGS - DQB1*03:10). For the final verification, we used swab material and we obtained unambiguous NGS result with expected, frequent HLA-A*02:01 and DQB1*03:01 alleles corresponding to the RT-PCR result from PB. CONCLUSIONS: To conclude, we suspect that the discrepancies between NGS and RT-PCR results were caused by the presence of a significant amount of circulating lymphoma cells in the peripheral blood sample. Lymphomagenic mutations may involve the histocompatibility antigen coding region and affect HLA expressed on malignant cells. This finding may be relevant for the selection of test material in primary and confirmatory HLA testing in patients with active hematological malignancies because of the strong impact of incorrect HLA typing on the procedure of a donor selection.

Incidence and Role of Recipient-Specific Antibodies in Allogeneic Hematopoietic Cell Transplantation from Mismatched Related Donors.

High titer of donor-specific antibodies (DSAs) increases the risk of graft rejection after mismatched related hematopoietic cell transplantation (HCT). There are no data regarding the incidence of anti-HLA recipient-specific antibodies (RSAs) and their role after transplantation. Here we aimed to identify the incidence of RSAs in a mismatched related hematopoietic cell donor population and their possible impact on immune-mediated complications, such as acute graft-versus-host disease (aGVHD), and complications resulting from endothelial injury, such as transplantation-associated thrombotic microangiopathy (TA-TMA) and veno-occlusive disease (VOD). We prospectively analyzed the incidence of anti-HLA antibodies in 28 mismatched related pairs of recipients and their donors who underwent HCT at our center between 2020 and 2022. In positive samples screened for anti-HLA class I and/or II antibodies, the specificity of the HLA antibodies was analyzed. All recipients had a hematologic malignancy and received a myeloablative conditioning regimen and immunosuppression consisting of post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Patients were tested for TA-TMA and aGVHD development during routine post-transplantation visits up to 100 days post-transplantation. We used modified Jodele criteria for TA-TMA diagnosis, and based aGVHD grading on the MAGIC criteria. VOD was assessed using the European Society for Blood and Marrow Transplantation. Anti-HLA antibodies were detected in 12 donors (43%) and in 9 recipients (32%). There were no significant differences between donors and recipients according to age (median, 42 years [range, 17 to 69 years] versus 39 years [range, 8 to 68 years]), sex, or pregnancy history. No transfusion history was noted in the donor group (P < .05). RSA antibodies were present more often than DSAs and were detected in 9 out of 12 (75%) anti-HLA-positive donors and in only 2 out of 9 (22%) recipients, respectively (P < .05). During the follow-up, 11 patients (39%) developed aGVHD, including grade I-II in 9 (32%) and grade III-IV in 2 (7%). Twelve patients (43%) met the criteria for TA-TMA, and only 1 patient (3.5%) was diagnosed with VOD by day 100 post-HCT. RSAs were detected significantly more often in the TA-TMA group; among 12 patients diagnosed with TA-TMA, 7 (58%) had RSAs (P < .05). We did not find a correlation between RSAs and aGVHD. The patient with VOD did not have an RSA-positive donor. There was no difference in membrane attack complex (MAC) concentration in the RSA-positive group on day 30 and day 60 post-HCT; however, there was a trend toward higher MAC concentration in the RSA-positive group on day 100 (median, 912 ng/mL [range, 788 to 1120 ng/mL] versus 616 ng/mL [range, 352 to 1244 ng/mL]; P = .055). Patients with RSA suffered more often from platelet and red blood cell decreases or transfusion refractoriness, and increased lactate dehydrogenase activity was observed in all RSA-positive cases. The donor immune status and the presence of RSA may be associated with higher rates of TA-TMA in mismatched HCT recipients. Antibody-mediated complement activation might be an additional factor influencing TA-TMA occurrence.

Antibody-mediated rejection with detection of de novo donor-specific anti-human leukocyte antigen Class II antibodies after lung transplantation: Problems in diagnosis, treatment and monitoring on a case report basis.

Lung transplantation, like other transplants, carries a risk of graft rejection due to genetic differences between the donor and the recipient. In this paper, we focus on antibody-mediated rejection, which can cause acute and more importantly chronic graft dysfunction and subsequently shortened allograft survival. We present the case of a 46-year-old patient who, two months after lung transplantation (LTx), developed AMR manifested by the deterioration of graft function and de novo production of donor-specific antibodies (DSA): DQ3 (DQ7, DQ8, DQ9). As the patient was after left single LTx and heavily oxygen dependent a transbronchial biopsy was deemed to be high risk and it was decided to determine the clinical significance of the detected antibodies by their ability to bind complement. The test confirmed that the detected DSAs have the ability cause cytotoxicity of the transplanted organ. After treatment with methotrexate, intravenous immunoglobulin G (IVIg) and alemtuzumab, the patient's condition improved and a complete decrease in DSA was obtained. However, after a year, the production of antibodies increased sharply. Treatment with IVIg, cyclophosphamide and plasmapheresis slightly improved the patient's condition, reducing the MFI DSA values by half, but leaving them at high levels. Based on this clinical case, we discuss problems with making a diagnosis, choosing the right AMR treatment and monitoring the patient's condition during treatment. We also indicate a poor prognosis in the case of the production of DSA antibodies at the DQ locus.

Successful complex percutaneous intervention in patient with Fontan circulation and severe heart failure: A case report.

We report the case of a successful complex percutaneous intervention in a patient with Fontan circulation and severe heart failure. The patient presented with cyanosis; Fontan conduit stenosis was detected, and the fenestration was patent. The complex interventional procedure allowed for a long-term stabilization of the patient's condition.

Local T cell infiltrates are predominantly associated with corneal allograft rejection.

BACKGROUND: Corneal transplantations (CTXs) are a vision-saving procedure. Routinely, while CTXs' survival rates remain high, the risk of graft failure increases significantly for repeated CTXs. The reason is an alloimmunization following previous CTXs and development of memory T (Tm) and B (Bm) cells. METHODS: We characterized populations of cells present in explanted human corneas from patients receiving the first CTX and marked as a primary CTX (PCTX) or the second or more CTXs and marked as a repeated CTX (RCTX). Cells extracted from resected corneas and from peripheral blood mononuclear cells (PBMCs) were analyzed by the flow cytometry method using multiple surface and intracellular markers. RESULTS: Overall, the number of cells was similar in PCTX and RCTX patients. Extracted infiltrates from PCTXs and RCTXs contained similar numbers of T cell subsets, namely CD4+, CD8+, CD4+ Tm, CD8+ Tm, CD4+Foxp3+ T regulatory (Tregs), CD8+ Treg cells, while very few B cells (all p = NS). However, when compared to peripheral blood, PCTX and RCTX corneas contained significantly higher percentages of effector memory CD4+ and CD8+ T cells (both p < 0,05). In comparison to PCTX, RCTX group had the highest levels of Foxp3 in T CD4+ Tregs (p = 0,04) but decreased percentage of Helios-positive CD4+ Tregs. CONCLUSION: PCTXs and especially RCTXs are rejected mainly by local T cells. The accumulation of effector CD4+ and CD8+ T cells, as well as CD4+ and CD8+ Tm cells is associated with the final rejection. Furthermore, local CD4+ and CD8+ Tregs expressing Foxp3 and Helios are probably insufficient to impose the acceptance of CTX.

17-ß-Estradiol-ß-Cyclodextrin Complex as Solid: Synthesis, Structural and Physicochemical Characterization.

17-ß-estradiol (EST) is the most potent form of naturally occurring estrogens; therefore, it has found a wide pharmaceutical application. The major problem associated with the use of EST is its very low water solubility, resulting in poor oral bioavailability. To overcome this drawback, a complexation with cyclodextrins (CD) has been suggested as a solution. In this work, the host-guest inclusion complex between the ß-CD and EST has been prepared using four different methods. The obtained samples have been deeply characterized using 13C CP MAS solid state NMR, PXRD, FT-IR, TGA, DSC, and SEM. Using SCXRD, the crystal structure of the complex has been determined, being to the best of our knowledge the first solved crystal structure of an estrogen/CD complex. The periodic DFT calculations of NMR properties using GIPAW were found to be particularly helpful in the analysis of disorder in the solid state and interpretation of experimental NMR results. This work highlights the importance of a combined ssNMR/SCXRD approach to studying the structure of the inclusion complexes formed by cyclodextrins.

A Review of Applications of Solid-State Nuclear Magnetic Resonance (ssNMR) for the Analysis of Cyclodextrin-Including Systems.

Cyclodextrins, cyclic oligosaccharides composed of five or more α-D-glucopyranoside units linked by α-1,4 glycosidic bonds, are widely used both in their native forms as well as the components of more sophisticated materials. Over the last 30 years, solid-state nuclear magnetic resonance (ssNMR) has been used to characterize cyclodextrins (CDs) and CD-including systems, such as host-guest complexes or even more sophisticated macromolecules. In this review, the examples of such studies have been gathered and discussed. Due to the variety of possible ssNMR experiments, the most common approaches have been presented to provide the overview of the strategies employed to characterize those useful materials.

Current Status of Quantum Chemical Studies of Cyclodextrin Host-Guest Complexes.

This article aims to review the application of various quantum chemical methods (semi-empirical, density functional theory (DFT), second order Møller-Plesset perturbation theory (MP2)) in the studies of cyclodextrin host-guest complexes. The details of applied approaches such as functionals, basis sets, dispersion corrections or solvent treatment methods are analyzed, pointing to the best possible options for such theoretical studies. Apart from reviewing the ways that the computations are usually performed, the reasons for such studies are presented and discussed. The successful applications of theoretical calculations are not limited to the determination of stable conformations but also include the prediction of thermodynamic properties as well as UV-Vis, IR, and NMR spectra. It has been shown that quantum chemical calculations, when applied to the studies of CD complexes, can provide results unobtainable by any other methods, both experimental and computational.

In-Depth Analysis of Anti-HLA Antibodies Using C1q Assay.

Alloantibodies are significant biomarkers of posttransplant kidney rejection. With solid-phase assays, the presence of alloantibodies and complement-binding capacities can be tested. It has been noted that complement-binding anti-HLA (C1q) correlates well with high titers of anti-HLA antibodies (single antigen bead, SAB), but we have recently shown that lower SAB titers may be associated with complement in the complement cytotoxicity test. If so, low titers of donor-specific antibodies could be stratified for complement binding and used for better donor-recipient matching. To study this, we tested 268 patients awaiting kidney transplantation for SAB and C1q and stratified them into positive (Allo+) and negative (Allo-) cohorts. Next, all assayed specificities of SAB were matched with the corresponding C1q in order to correlate mean fluorescence intensity levels. We found a strong correlation between SAB and C1q for all HLA loci apart from HLA-DP. Moreover, there was no strict cutoff for C1q prediction on SAB mean fluorescence intensity level. In addition, an unusual laboratory phenotype was found; that is, a positive C1q result without corresponding SAB specificity. We tested this phenomenon and found positive IgM SAB. CONCLUSIONS: Simultaneous C1q and SAB testing may serve as a tool for in-depth analysis of alloantibodies before transplantation.

Qualitative and quantitative analysis of energy drinks using 1H NMR and HPLC methods.

Energy drinks (EDs) are widely consumed to stimulate psychomotor functions and improve the efficiency of the human body. They typically contain caffeine, taurine, sugars or sweeteners, vitamins and organic acids. EDs were selected for the study in terms of composition diversity, reflecting the variety of products available on the Polish market. The analysis of the composition of energy drinks was performed using 1H NMR spectroscopy, HPLC-DAD, titration and refractometric methods. Diagnostic signals in 1H NMR spectra of the citric acid, caffeine and niacinamide were used for quantitative analysis. The citric acid content in energy drinks ranged from 140 to 780 mg per 100 mL. The niacinamide content in the tested energy drinks varied from 3.4 to 9.7 mg per 100 mL and was usually higher than it was reported on the label. The amount of caffeine (from 19 to 40 mg) was slightly lower than labeled. Quantitative determinations by 1H NMR and HPLC are compatible and can be successfully used interchangeably. In the so-called "sugar-free" drinks, no simple sugars or sucrose were found, thus 1H NMR can easily and quickly recognize ED without the addition of sugar. Our studies showed that 1H NMR spectroscopy is a valuable tool for quality control of energy drinks.

Anti-HLA immunization of patients qualified for lung transplantation - Single center study.

For lung transplantation, the presence of donor-specific anti-HLA antibodies (DSA) is an important factor of antibody-mediated rejection (AMR) in its hyperacute, acute or chronic form during long-term follow up. The aim of the study was to assess the allosensitization of Polish patients qualified for a lung transplantation in our center. A retrospective study of 161 potential lung allograft recipients, also of 31 patients transplanted in the University Hospital of Gdansk, between June 2018 and December 2020 were performed. 121 potential recipients were thoroughly tested for immunization status before eventual lung transplantation. SAB-testing, PRA-CDC and vPRA assessment, and HLA typing were performed to guide donor-recipient matching and risk stratification. Then 73 patients were separated and qualified for the list of patients awaiting lung transplantation. Then 31 patients were transplanted based on a negative biological crossmatch result. The patients were generally not sensitized, as the median PRA-CDC was 0% (min 0; max 53), and the vPRA, calculated according to HLA ABDR (>2000 cut-off MFI), was 8% (min 0; max 99). If the cut-off was split into 2000 MFI for HLA ABDR, 10,000 MFI for HLAC, and 7000 MFI for HLA-DQ, the vPRA increased to 20% (min 0; max 99). The immunization status was assessed with single antigen-SAB assays. For class I, the number of any detectable alloantibodies was 14 (11.6%) 21 (17.35%) 16 (13.22%) for locus HLA-A/B/C, and 28 (23.14%) 30 (24.8%) 24 (19.8%) for locus HLA-DR/DQ/DP, respectively. The immunization of the transplanted patients was then analyzed in detail. Summarizing, the study is an analysis of the degree of anti-HLA immunization in the population of patients eligible for lung transplantation, which showed that this degree is of low intensity and can be effectively and safely and very precisely diagnosed before transplantation.

CD5-Positive B Lymphocytes after Kidney Transplantation.

Kidney transplantation is the treatment of choice for end-stage kidney diseases. Unfortunately, kidney allograft recipients rarely develop tolerance or accommodation and require life-long immunosuppression. Among many other regulatory mechanisms, CD5+ B lymphocytes (mainly B-1a) seem to be involved in the process of allograft acceptance. These cells are the major source of natural, low-affinity antibodies, which are polyreactive. Thus, we hypothesized that CD5+ B cells could be referred to as a biomarker in those patients who developed accommodation towards kidney allotransplant. In this study, 52 low-immunized kidney transplant recipients were evaluated for transplant outcome up to 8 y post-transplant. The follow up included anti-HLA antibodies, B cells phenotype and cytokines. We have identified a cohort of recipients who produced alloantibodies (Abs+), which was associated with increased levels of CD5+ B cells, mainly during the first year after transplantation but also later on. Importantly, creatinine levels were comparable between Abs+ and Abs- allorecipients at 2 years after the transplantation and graft survival rate was comparable between these groups even eight years post-transplant. So, it seems that despite the presence of alloantibodies the graft function was sustained when the level of CD5+ B cells was increased. Targeting CD5+ B cells may be a valuable therapeutic option to increase transplant success. The phenotype can be also tried as a biomarker to increase the effectiveness of individualized post-transplant treatments.

Can We Predict the Isosymmetric Phase Transition? Application of DFT Calculations to Study the Pressure Induced Transformation of Chlorothiazide.

Isosymmetric structural phase transition (IPT, type 0), in which there are no changes in the occupation of Wyckoff positions, the number of atoms in the unit cell, and the space group symmetry, is relatively uncommon. Chlorothiazide, a diuretic agent with a secondary function as an antihypertensive, has been proven to undergo pressure-induced IPT of Form I to Form II at 4.2 GPa. For that reason, it has been chosen as a model compound in this study to determine if IPT can be predicted in silico using periodic DFT calculations. The transformation of Form II into Form I, occurring under decompression, was observed in geometry optimization calculations. However, the reverse transition was not detected, although the calculated differences in the DFT energies and thermodynamic parameters indicated that Form II should be more stable at increased pressure. Finally, the IPT was successfully simulated using ab initio molecular dynamics calculations.

Application of Molecular Dynamics Simulations in the Analysis of Cyclodextrin Complexes.

Cyclodextrins (CDs) are highly respected for their ability to form inclusion complexes via host-guest noncovalent interactions and, thus, ensofance other molecular properties. Various molecular modeling methods have found their applications in the analysis of those complexes. However, as showed in this review, molecular dynamics (MD) simulations could provide the information unobtainable by any other means. It is therefore not surprising that published works on MD simulations used in this field have rapidly increased since the early 2010s. This review provides an overview of the successful applications of MD simulations in the studies on CD complexes. Information that is crucial for MD simulations, such as application of force fields, the length of the simulation, or solvent treatment method, are thoroughly discussed. Therefore, this work can serve as a guide to properly set up such calculations and analyze their results.

KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease.

Natural killer (NK) cells are part of the cellular immune response. They target mainly cancer and virally infected cells. To a high extent cytotoxic activity of NK cells is regulated inter alia by signals from killer immunoglobulin-like receptors (KIR). The major histocompatibility complex (MHC) class I molecules are important ligands for KIR receptors. Binding of ligands (such as MHC I) to the KIR receptors has the important role in solid organ or hematopoietic cell transplantation. Of note, the understanding of the relationship between KIR and MHC receptors may contribute to the improvement of transplant results. Donor-recipient matching, which also includes the KIR typing, may improve monitoring, individualize the treatment and allow for predicting possible effects after transplantation, such as the graft-versus-leukemia effect (GvL) or viral re-infection. There are also less evident implications of KIR/MHC matching, such as with pregnancy and cancer. In this review, we present the most relevant literature reports on the importance of the KIR/MHC relationship on NK cell activity and hematopoietic stem cell transplantation (HSCT)/solid organ transplantation (SOT) effects, the risk of allograft rejection, protection against post-transplant cytomegalovirus (CMV) infection, pregnancy complications, cancer and adoptive therapy with NK cells.