The effect of COVID-19 on cancer incidences in the U.S.

Fundamental data analysis assists in the evaluation of critical questions to discern essential facts and elicit formerly invisible evidence. In this article, we provide clarity into a subtle phenomenon observed in cancer incidences throughout the time of the COVID-19 pandemic. We analyzed the cancer incidence data from the American Cancer Society [1]. We partitioned the data into three groups: the pre-COVID-19 years (2017, 2018), during the COVID-19 years (2019, 2020, 2021), and the post-COVID-19 years (2022, 2023). In a novel manner, we applied principal components analysis (PCA), computed the angles between the cancer incidence vectors, and then added lognormal probability concepts in our analysis. Our analytic results revealed that the cancer incidences shifted within each era (pre, during, and post), with a meaningful change in the cancer incidences occurring in 2020, the peak of the COVID-19 era. We defined, computed, and interpreted the exceedance probability for a cancer type to have 1000 incidences in a future year among the breast, cervical, colorectal, uterine corpus, leukemia, lung & bronchus, melanoma, Hodgkin's lymphoma, prostate, and urinary cancers. We also defined, estimated, and illustrated indices for other cancer diagnoses from the vantage point of breast cancer in pre, during, and post-COVID-19 eras. The angle vectors post the COVID-19 were 72% less than pre-pandemic and 28% less than during the pandemic. The movement of cancer vectors was dynamic between these eras, and movement greatly differed by type of cancer. A trend chart of cervical cancer showed statistical anomalies in the years 2019 and 2021. Based on our findings, a few future research directions are pointed out.

Technology alone does not achieve error reduction - a study of handwritten, tick-sheet, ink stamp and electronic medical prescriptions.

BACKGROUND: Technology in the form of electronic record systems and prescriptions have been touted as a potential solution to human error. In South Africa, a middle-income country where health facilities have large variations in technological capacity, prescription errors can be complex and varied. We evaluated different prescribing methods to find if the increased use of technology in prescriptions will assist in reducing error rates. METHODS: A retrospective, non-randomised study compared prescriptions, error rates and types in four hospitals with different prescribing methods: these were handwritten, ink stamp, tick-sheet and electronic prescriptions. A modern human error theory data collection tool was designed which included patient complexity. Cataract surgery was chosen as the single common procedure. RESULTS: One thousand six hundred and sixty-one individual scripts had 1 307 prescription errors. Increasing patient complexity was not an indicator of error rate. Handwritten and tick-sheet prescriptions had the fewest errors (49% and 51%, respectively). Electronic (96%) and ink stamp scripts (101%) had almost twice as many errors as handwritten scripts (p < 0.001) mainly due to systemic inbuilt errors. CONCLUSION: The application of increasing degrees of technological complexity does not automatically reduce error rate. This is especially apparent when technology is not integrated into human factors engineering and persistent critical assessment.

Striking a balance between usability and quality control in electronic health records.

BACKGROUND: This project is the first formal usability review of the hybrid electronic medical registry (HEMR) since its implementation in 2012. METHODS: A synchronous usability evaluation by novice operators was followed by a survey of veteran users. The usability evaluation was done by moderated think-aloud interview while completing tasks for a mock patient. The veteran survey was paper-based and focused on satisfaction of the system. RESULTS: A total of 141 comments on system errors were identified by the novice doctors. These consisted of 123 unique problems, of which three were hardware faults and were thus excluded. The identified issues were categorised into errors of control (27%), minimalist (21%), error (17%), match (13%), flexibility, visibility and consistency (9% each), and history (4%). Every unique usability violation was evaluated by the three experts who agreed that 82 of the 141 errors (58%) were valid and applicable. The other 59 items were rejected, not only because of the inability to reproduce some errors or programme shortcomings, but also because a series of "hurdles" were purposely included in the software to decrease cognitive dissonance and reduce error by the users. The survey of veteran users showed high levels of contentment with the system with regards to efficiency, satisfaction and preference. CONCLUSION: Despite many usability complaints by novices, almost half of them were rejected. Although usability in electronic health systems is important, it can often be sacrificed for more imperative aims such as safety, error filtering and clinical decision support.

Surgical data recording in the operating room: a systematic review of modalities and metrics.

INTRODUCTION: Operating room recording, via video, audio and sensor-based recordings, is increasingly common. Yet, surgical data science is a new field without clear guidelines. The purpose of this study is to examine existing published studies of surgical recording modalities to determine which are available for use in the operating room, as a first step towards developing unified standards for this field. METHODS: Medline, EMBASE, CENTRAL and PubMed databases were systematically searched for articles describing modalities of data collection in the operating room. Search terms included 'video-audio media', 'bio-sensing techniques', 'sound', 'movement', 'operating rooms' and others. Title, abstract and full-text screening were completed to identify relevant articles. Descriptive statistical analysis was performed for included studies. RESULTS: From 3756 citations, 91 studies met inclusion criteria. These studies described 10 unique data-collection modalities for 17 different purposes in the operating room. Data modalities included video, audio, kinematic and eye-tracking among others. Data-collection purposes described included surgical trainee assessment, surgical error, surgical team communication and operating room efficiency. CONCLUSION: Effective data collection and utilization in the operating room are imperative for the provision of superior surgical care. The future operating room landscape undoubtedly includes multiple modalities of data collection for a plethora of purposes. This review acts as a foundation for employing operating room data in a way that leads to meaningful benefit for patient care.

The management of ocular and peri-ocular trauma needs to be co-ordinated according to ATLS principles and requires multi-disciplinary collaboration.

INTRODUCTION: This project set out to focus on ocular (globe) and peri-ocular trauma and to describe the spectrum of injuries seen in a busy South African trauma unit and to document their management and outcome. RESULTS: During the period November 2012 to April 2020, a total of 12 115 patients were managed by the Pietermaritzburg Metropolitan Trauma Service (PMTS) at Greys Hospital in Pietermaritzburg, South Africa. Of these 2194 (11%) sustained ocular or peri-ocular injury. Of these 2194 patients, 1069 (83%) were male. 83% of injuries (n=1076) were classified as primarily blunt injury and 17% as a primarily sharp/penetrating mechanism. A substantial number of patients required a life-saving emergency intervention. These included resuscitation in 242 cases (19%) and active airway intervention was in 290 (22%). In total 919 (71%) patients required urgent surgery to the peri-ocular region. Slightly over half (55%) of these the surgery was performed by a single discipline. The rest needed procedures by two or more disciplines. The disciplines involved included ophthalmology, maxillofacial, plastic, ENT and neurosurgery. Plastic surgery was involved in 683 cases (53%). A total of 341 distant surgeries were required - These included orthopaedic operations, laparotomy and vascular operations. Of the 1294 cases in this study, 42 (3%) died before discharge and 99 (8%) were discharged with a GCS lower than 10. The primary skill set for management of these injuries is identified. CONCLUSION: Although the management of immediate life and organ threatening injuries takes priority, ocular and peri-ocular trauma may damage a number of important structures and their comprehensive management requires a multi-disciplinary team of specialists or, in austere environments, a font-line medical team with a diverse skill set.

Obesity and Morbidity Risk in the U.S. Veteran.

The obesity epidemic in the United States has been well documented and serves as the basis for a number of health interventions across the nation. However, those who have served in the U.S. military (Veteran population) suffer from obesity in higher numbers and have an overall disproportionate poorer health status when compared to the health of the older non-Veteran population in the U.S. which may further compound their overall health risk. This study examined both the commonalities and the differences in obesity rates and the associated co-morbidities among the U.S. Veteran population, utilizing data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS). These data are considered by the Centers for Disease Control and Prevention (CDC) to be the nation's best source for health-related survey data, and the 2018 version includes 437,467 observations. Study findings show not only a significantly higher risk of obesity in the U.S. Veteran population, but also a significantly higher level (higher odds ratio) of the associated co-morbidities when compared to non-Veterans, including coronary heart disease (CHD) or angina (odds ratio (OR) = 2.63); stroke (OR = 1.86); skin cancer (OR = 2.18); other cancers (OR = 1.73); chronic obstructive pulmonary disease (COPD) (OR = 1.52), emphysema, or chronic bronchitis; arthritis (OR = 1.52), rheumatoid arthritis, gout, lupus, or fibromyalgia; depressive disorders (OR = 0.84), and diabetes (OR = 1.61) at the 0.95 confidence interval level.

Impact of cone beam computed tomography on periapical assessment and treatment planning five to eleven years after surgical endodontic retreatment.

AIM: To evaluate how additional information from Cone Beam CT (CBCT) impacts on periapical assessment and treatment planning based on clinical examination and periapical radiographs (PR) in cases followed up five to eleven years after surgical endodontic retreatment (SER). METHODOLOGY: Patients receiving SER during 2004-2010 were reinvited for follow-up examination including clinical examination, PR, and CBCT. In total, 108 patients (119 teeth) were reinvited, 74 patients (83 teeth) accepted to participate. Three observers initially assessed PR according to the four-scaled, increasing disease severity criteria by Rud et al. (International Journal of Oral Surgery, 1, 1972 and 195) and Molven et al. (International Journal of Oral and Maxillofacial Surgery, 16, and 432): 'Radiographic assessment A'. By including clinical information 'Treatment plan A' was made as follows: 1) no treatment, 2) further observation, 3) SER reoperation (SER-R), or 4) extraction. Hereafter, the CBCT volume was assessed and the information incorporated for 'Radiographic assessment B' followed by 'Treatment plan B'. Agreement between radiographic assessments and between treatment plans was recorded and assessed statistically by Stuart-Maxwell test for marginal homogeneity. RESULTS: Nine teeth had been extracted; thus, the final analysis included 74 teeth (66 patients). The radiographic assessment was changed as a result of the CBCT evaluation in 38 cases (51.4%), of which 35 (47.3%) were to a higher Rud & Molven score, P < 0.001. The treatment plan was changed for 18 teeth (24.3%). For 14 teeth (18.9%), the change was from no treatment or further observation to a more invasive treatment plan (SER-R or extraction), P = 0.005. CONCLUSION: The use of CBCT for long-term follow-up after SER led to more cases diagnosed with persisting or recurrent apical periodontitis and hence often to the recommendation of a more invasive treatment modality.

The selective 5-HT6 receptor antagonist SLV has putative cognitive- and social interaction enhancing properties in rodent models of cognitive impairment.

In the present study, our aim was to investigate whether the novel highly selective 5-hydroxytryptamine6 (5-HT6) receptor antagonist SLV can ameliorate impairments in cognition and social interaction with potential relevance for both schizophrenia and Alzheimer's disease (AD). SLV sub-chronically - treated Wistar rats reared in isolation showed significantly enhanced prepulse inhibition (PPI) and object recognition performance when compared to vehicle - treated rats. In the isolated rats, also a significant reduction in expression of hippocampal neural cell adhesion molecule polysialylation (NCAM-PSA) was found which was ameliorated following treatment with SLV (30mg/kg). The social engagement deficit in rats exposed in utero (on gestational day 12.5) to valproic acid (VPA) was reversed by treatment with SLV (30mg/kg). SLV (20 and 30mg/kg, p.o.) fully reversed MK-801 - induced deficits in the ORT and also scopolamine - induced deficits in both the Object Recognition Task (ORT) and Object Location Task (OLT) in Wistar rats. In addition, a combination of sub-optimal doses of SLV and donepezil attenuated scopolamine-induced ORT deficits. Furthermore, SLV (10mg/kg, p.o.) reversed spontaneous alternation deficits in the T-maze induced by MK-801 administration in Swiss mice and in aged C57Bl/6J mice. SLV additionally improved T-Maze spatial learning and passive avoidance learning in Sprague-Dawley rats with amyoid-beta (Aß) injections into the hippocampus. In contrast, no benefits were found with SLV or the tested reference compounds (donepezil and RVT-101) on cognitive performance of 12months old Tg2576 mice. Also, in the social recognition task, an absence of cognitive enhancing properties was observed with SLV on "normal forgetting" in Wistar rats. Finally, analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) frequency recorded from pyramidal cells revealed a reduction in the presence of 1µM of SLV. In conclusion, SLV was investigated in several rodent animal models and found to be effective at a least effective dose (LED) of 20mg/kg and 10mg/kg (p.o.) in the rat and the mouse, respectively.

Hyponatremia and osteoporosis: insights from the Danish National Patient Registry.

UNLABELLED: The association between hyponatremia and osteoporosis was evaluated in humans. A significant association was found between low sodium levels, lower bone mineralization in the hip, and with several common conditions. Hyponatremia could be used as a marker of osteoporosis and systemic disease. INTRODUCTION: The objective of this study was to evaluate the association between hyponatremia and osteoporosis in humans through a cross-sectional study. METHODS: Patient information was gathered from regional and national Danish patient databases, both in- and outpatient settings, from 2004 to 2011. Patients with dual-energy x-ray absorptiometry (DXA) scans performed within this time were included if accompanied [Na+] was measured within 14 days prior or past the scan date. A total of 1575 patients were included. RESULTS: A total of 104 patients were hyponatremic (6.6 %). Total hip and lumbar spine bone mineral content (BMC) and densities (BMD) and T-scores were all significantly lower with hyponatremia. The odds ratio (OR) of osteoporosis significantly increased among hyponatremic patients at both total hip (unadjusted OR = 2.17, 95% CI = [1.40-3.34], p < .05) and lumbar spine (unadjusted OR = 1.83, 95% CI = [1.20-2.80], p < .05) regions. Dose-response found between increasing [Na+] and increasing total hip BMC (slope .174, adjusted p < .05), BMD (slope .004, adjusted p < .05), and T-score (slope .034, adjusted p < .05). Systemic disease was more prevalent in hyponatremia. CONCLUSION: The presence of hyponatremia increases the risk of concurrent osteoporosis at both the total hip and lumbar spine in humans. Hyponatremia could be used a screening tool and marker of secondary osteoporosis.

The potential for genetically altered microglia to influence glioma treatment.

Diffuse and unstoppable infiltration of brain and spinal cord tissue by neoplastic glial cells is the single most important therapeutic problem posed by the common glioma group of tumors: astrocytoma, oligoastrocytoma, oligodendroglioma, their malignant variants and glioblastoma. These neoplasms account for more than two thirds of all malignant central nervous system tumors. However, most glioma research focuses on an examination of the tumor cells rather than on host-specific, tumor micro-environmental cells and factors. This can explain why existing diffuse glioma therapies fail and why these tumors have remained incurable. Thus, there is a great need for innovation. We describe a novel strategy for the development of a more effective treatment of diffuse glioma. Our approach centers on gaining control over the behavior of the microglia, the defense cells of the CNS, which are manipulated by malignant glioma and support its growth. Armoring microglia against the influences from glioma is one of our research goals. We further discuss how microglia precursors may be genetically enhanced to track down infiltrating glioma cells.

A novel highly selective 5-HT6 receptor antagonist attenuates ethanol and nicotine seeking but does not affect inhibitory response control in Wistar rats.

Recent studies suggest a potential role for 5-hydroxytryptamine(6) (5-HT(6)) receptors in the regulation of addictive behavior. In the present study, our aim was to investigate whether the novel highly selective 5-HT(6) receptor antagonist compound (CMP) 42 affected nicotine and ethanol seeking behavior in Wistar rats. We have also studied whether CMP 42 had beneficial effects in a model of impulse control, as measured in the 5-choice serial reaction time task (5-CSRTT). Rats were trained to nose poke to receive intravenous infusions of nicotine or an ethanol drop. CMP 42 (3-30 mg/kg intraperitoneally, i.p.) was administered to investigate the effects on nicotine self-administration. Rats were also tested for cue-induced reinstatement of nicotine and ethanol seeking. In addition, the effects of CMP 42 were studied on the number of anticipatory responses in the 5-CSRTT. CMP 42 was effective in reducing nicotine self-administration and reinstatement of nicotine seeking at a dose of 30 mg/kg (i.p.). CMP 42 was also effective in reducing reinstatement of ethanol seeking (30 mg/kg i.p.). In contrast, CMP 42 did not affect anticipatory responding at doses tested, indicating no effects on impulse control. These results add to a body of evidence implicating the 5-HT(6) receptor as a viable target for the control of drug abuse. Specifically, we demonstrated for the first time effects on nicotine self-administration and on nicotine and ethanol reinstatement. Further, these effects are probably not mediated by effects on impulse control.

Pancreatic carcinoma cell lines reflect frequency and variability of cancer stem cell markers in clinical tissue.

BACKGROUND: Pancreatic cancer is one of the most deadly malignancies with insufficient therapeutic options and poor outcome. Cancer stem cells (CSCs) are thought to be responsible for progression and therapy resistance. We investigated the potential of pancreatic cell lines for CSC research by analyzing to what extent they contain CSC populations and how representative these are compared to clinical tissue. METHODS: Six pancreatic cancer cell lines were analyzed by flow cytometry for CD326, CD133, CD44, CD24, CXCR4 and ABCG2. Subsequently, 70 primary pancreatic tissues were evaluated for CD326, CD133 and CD44 by immunohistochemistry. RESULTS: All the cell lines but one showed a stable expression pattern throughout biological replicates. Marker expression in clinical tissue of CD44 distinguished normal patients from pancreatic carcinoma patients with a sensitivity of 50% at 80% specificity and metastasized from nonmetastasized carcinomas with 69% sensitivity at 100% specificity. CONCLUSIONS: Our results indicate a link between elevated CD44 expression, malignancy and metastasis of pancreatic tissue. Furthermore, individual pancreatic cell lines show a substantial amount of cells with CSC properties which is comparable with interpatient variability detected in primary tissue. These pancreatic cancer cell lines could thus serve for urgently needed pharmacological CSC in vitro research.

SLV330, a cannabinoid CB(1) receptor antagonist, attenuates ethanol and nicotine seeking and improves inhibitory response control in rats.

Cannabinoid CB(1) receptor (CB(1)R) signaling has been shown to play a role in the regulation of addictive behavior. In the present study, our aim was to investigate whether the CB(1)R antagonist SLV330 could reduce ethanol and nicotine self-administration and cue-induced reinstatement of ethanol and nicotine seeking behavior in Wistar rats. In operant chambers, rats were learned to emit a specific response (nose poke) in order to receive an ethanol solution or intravenous injections of nicotine. Discrete light and tone cues were presented during ethanol and nicotine delivery. These cues are particularly important for drug self-administration behavior and, through Pavlovian conditioning, acquire conditioned reinforcing and motivational properties and are therefore able to generate and maintain drug-seeking behavior. Subsequently, the CB(1)R antagonist SLV330 (doses ranging from 1 to 10mg/kg, given orally, p.o.) was administered to investigate the effects on drug self-administration. In addition, responding for ethanol and nicotine was extinguished. Then, the animals were tested for cue-induced reinstatement of ethanol and nicotine seeking and treated with vehicle or SLV330. Finally, the effects of SLV330 were studied on the number of anticipatory responses in the 5-choice serial reaction time task (5-CSRTT) in order to determine whether this compound could also increase impulse control in Wistar rats. The CB(1) antagonist SLV330 was effective in reducing ethanol self-administration at a lowest effective dose (LED) of 10mg/kg (p.o.) and reinstatement of ethanol seeking at a LED of 3mg/kg (p.o.). SLV330 was also effective in reducing nicotine self-administration and reinstatement of nicotine seeking, although at a LED of 10mg/kg (p.o.). Finally, SLV330 decreased time delay-dependent anticipatory responding (LED of 3.0mg/kg, p.o.), indicating an increased inhibitory control. These findings are in agreement with results reported with other CB(1) antagonists. The combined action of reducing the reinforcing and motivational properties of nicotine and alcohol and the improvement of impulse control supports the idea that the cannabinoid system is a promising target for anti-relapse medication.

Immunotherapy of malignant gliomas using autologous and allogeneic tissue cells.

Immunotherapy of brain tumors is rapidly emerging as a potential clinical option [1-3]. The quality and magnitude of immune responses evoked by the new generation anti-tumor vaccines is in general highly dependent on the source or choice of peptide antigens, and as well, a suitable immunopotentiator. Poorly immunogenic antigens, such as those present in tumor cell lysates, may not reliably provide stimulation like recombinant or DNA-encoded protein antigens might be expected to. In addition, the efficacy of the vaccine may depend on inherent counteracting measures of the tumor which dampen immune surveillance and immune effector activity triggered by immunization [4]. Our body has many means of limiting an immune response to our own (self) proteins. In particular, patients with gliomas exhibit a broad suppression of cell-mediated immunity [5-8]. Unfortunately, for most tumor vaccines the induction of local or systemic immune effector cells does not necessarily translate into objective clinical responses or increased survival [9]. Here we review immunotherapeutic approaches against gliomas and recent pre-clinical and clinical initiatives based on cellular or active immunization of the patient's immune system using autologous and allogeneic tissues or cultured cells. Available evidence shows that single modality cancer therapies likely remain suboptimal. Combination regimens targeting the immune system at multiple coordinated levels must be developed, and possibly combined with strategies to inhibit immune suppressive factors if significant clinical benefit is to be achieved.

The influence of pancreas-derived stem cells on scaffold based skin regeneration.

It has been shown that Pancreatic Stem Cells (PSCs) share many features with skin stem cells. Yet, their potential role in skin regeneration remains to be elucidated. 5x10(5) PSCs from male Rattus norwegicus were seeded on Matriderm scaffold overnight. Cells survival and proliferation were then tested in vitro showing the survival of the cells and their homogenous distribution in the scaffolds. Afterwards, scaffolds were used to replace bilateral full-thickness skin wounds made on the dorsum of Nu/Nu mice. A control group of nude mice received the Matriderm scaffolds without cells. Two weeks after transplantation, wound areas were harvested and analyzed with respect to epithelialization, vascularization and wound closure. The healing area and regeneration rate were significantly increased in the group used the PSCs-seeded scaffolds (factor of 2.1). Vascularization rate showed a significant increase in the PSCs-seeded scaffolds(factor of 1.5). Morphology and immunohistochemistry showed new skin-like structures positive to epidermal markers in the healing wound bed. PSCs were detected in the regenerated tissues. This study showed that the combined use of PSCs with the Matriderm as a scaffold for dermal regeneration significantly increased the epidermalization, vascularization and healing in full-thickness wounds.

Sulfur-enhanced defence: effects of sulfur metabolism, nitrogen supply, and pathogen lifestyle.

Evidence from field experiments indicates differential roles of sulfur and nitrogen supply for plant resistance against pathogens. Dissection of these observations in defined pathosystems and controlled nutritional conditions indicates an activation of plant sulfur metabolism in several incompatible and compatible interactions. Contents of cysteine and glutathione as markers of primary sulfate assimilation and stress response show increases in ARABIDOPSIS THALIANA upon infection, coinciding with the synthesis of sulfur-containing defence compounds. Similar increases of thiols were observed with necrotrophic, biotrophic, and hemibiotrophic pathogens. Sulfate supply was found to be neutral or beneficial for tolerance against fungal but neutral for bacterial pathogens under IN VITRO conditions. According to various reports and own observations the effects of nitrogen supply appeared to be neutral or harmful, depending on the pathogen. The activation of sulfur metabolism was a consequence of activation of gene expression as revealed by macroarray analysis of an A. THALIANA/ALTERNARIA BRASSICICOLA pathosystem. This activation appeared to be largely independent from sufficient or optimal sulfate supply and from the established sulfate deficiency response. The data suggest that plant-pathogen interactions and sulfur metabolism are linked by jasmonic acid as signal.

Permanent, lowered HLA class I expression using lentivirus vectors with shRNA constructs: Averting cytotoxicity by alloreactive T lymphocytes.

Transplantation of many tissues requires histocompatibility matching of human leukocyte antigens (HLA) to prevent graft rejection, to reduce the level of immunosuppression needed to maintain graft survival, and to minimize the risk of graft-versus-host disease, particularly in the case of bone marrow transplantation. However, recent advances in fields of gene delivery and genetic regulation technologies have opened the possibility of engineering grafts that display reduced levels of HLA expression. Suppression of HLA expression could help to overcome the limitations imposed by extensive HLA polymorphisms that restrict the availability of suitable donors, necessitate the maintenance of large donor registries, and complicate the logistics of procuring and delivering matched tissues and organs to the recipient. Accordingly, we investigated whether knockdown of HLA by RNA interference (RNAi), a ubiquitous regulatory system that can efficiently and selectively inhibit the expression of specific gene products, would enable allogeneic cells to evade immune recognition. For efficient and stable delivery of short hairpin-type RNAi constructs (shRNA), we employed lentivirus-based gene transfer vectors, which provide a delivery system that can achieve integration into genomic DNA, thereby permanently modifying transduced graft cells. Our results show that lentivirus-mediated delivery of shRNA targeting pan-Class I and allele-specific HLA can achieve efficient and dose-dependent reduction in surface expression of HLA in human cells, associated with enhanced resistance to alloreactive T lymphocyte-mediated cytotoxicity, while avoiding MHC-non-restricted killing. We hypothesize that RNAi-induced silencing of HLA expression has the potential to create histocompatibility-enhanced, and, eventually, perhaps "universally" compatible cellular grafts.

X-ray microbeams: Tumor therapy and central nervous system research.

Irradiation with parallel arrays of thin, planar slices of X-ray beams (microplanar beams, or microbeams) spares normal tissue, including the central nervous system (CNS), and preferentially damages tumors. The effects are mediated, at least in part, by the tissue's microvasculature that seems to effectively repair itself in normal tissue but fails to do so in tumors. Consequently, the therapeutic index of single-fraction unidirectional microbeam irradiations has been shown to be larger than that of single-fraction unidirectional unsegmented beams in treating the intracranial rat 9L gliosarcoma tumor model (9LGS) and the subcutaneous murine mammary carcinoma EMT-6. This paper presents results demonstrating that individual microbeams, or arrays of parallel ones, can also be used for targeted, selective cell ablation in the CNS, and also to induce demyelination. The results highlight the value of the method as a powerful tool for studying the CNS through selective cell ablation, besides its potential as a treatment modality in clinical oncology.

[Intestinal malperfusion in critical care patients]. / Intestinale Perfusionsstörungen beim Intensivpatienten.

Due to the bowel's poor tolerance of hypoxia, intestinal malperfusion presents as a grave disease with high mortality. The intensivist is confronted with this condition in association with other underlying diseases, in the course of surgery, during application of medication or associated with invasive therapy. In a critical care setting, the non-occlusive mesenteric ischemia (NOMI) is of increasing importance. Since critical care patients often lack clinical symptoms, special attention is required and one main factor of the patient's prognosis is early diagnosis. This review summarizes pathophysiology and diagnostic aspects and the range of therapeutic and preventive measures.