Hemispheric black carbon increase after the 13th-century Maori arrival in New Zealand.

New Zealand was among the last habitable places on earth to be colonized by humans1. Charcoal records indicate that wildfires were rare prior to colonization and widespread following the 13th- to 14th-century Maori settlement2, but the precise timing and magnitude of associated biomass-burning emissions are unknown1,3, as are effects on light-absorbing black carbon aerosol concentrations over the pristine Southern Ocean and Antarctica4. Here we used an array of well-dated Antarctic ice-core records to show that while black carbon deposition rates were stable over continental Antarctica during the past two millennia, they were approximately threefold higher over the northern Antarctic Peninsula during the past 700 years. Aerosol modelling5 demonstrates that the observed deposition could result only from increased emissions poleward of 40° S-implicating fires in Tasmania, New Zealand and Patagonia-but only New Zealand palaeofire records indicate coincident increases. Rapid deposition increases started in 1297 (±30 s.d.) in the northern Antarctic Peninsula, consistent with the late 13th-century Maori settlement and New Zealand black carbon emissions of 36 (±21 2 s.d.) Gg y-1 during peak deposition in the 16th century. While charcoal and pollen records suggest earlier, climate-modulated burning in Tasmania and southern Patagonia6,7, deposition in Antarctica shows that black carbon emissions from burning in New Zealand dwarfed other preindustrial emissions in these regions during the past 2,000 years, providing clear evidence of large-scale environmental effects associated with early human activities across the remote Southern Hemisphere.

Lewy body dementia: Overcoming barriers and identifying solutions.

Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public-health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public-domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor. HIGHLIGHTS: A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research. Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field.

LATE-NC staging in routine neuropathologic diagnosis: an update.

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.

Percentage of change and increment of the glucose level after a normal oral tolerance curve between 24 and 28 weeks of pregnancy.

AIM: To determine the percentage of change and increment in glucose levels after a normal oral glucose tolerance test between 24 and 28 weeks of pregnancy. METHODS: We studied 3510 pregnant women who attended their obstetric delivery at a tertiary care hospital in Guadalajara, Mexico in 2018, according to characteristics and risk 1647 (47%) patients were screened for diabetes diagnosis using the oral glucose tolerance test, 501 patients reported normal values between their 24th and 28th week of pregnancy, only 400 patients had their fasting glucose level measured on the same day of their obstetric delivery, to be compared. RESULTS: Average age was 30 years, with an average of 25.3 weeks of pregnancy. The fasting serum glucose levels taken after 28 weeks of pregnancy and before the obstetrical delivery showed an increase of 1.1 mmol/L in women who develop gestational diabetes mellitus, in contrast to women who did not develop gestational diabetes mellitus after 28 weeks their blood glucose only increased on average 0.4 mmol/L. The incidence of gestational diabetes mellitus in the study population during 2018 was 32.7%. Patients who developed gestational diabetes mellitus after a normal oral glucose tolerance test had greater body mass index before the pregnancy and newborns had a higher weight than babies born to mothers without gestational diabetes mellitus. CONCLUSION: Changes in glucose levels after the oral tolerance test of normal glucose require strict monitoring, in that it was demonstrated that 3% of patients developed gestational diabetes mellitus after week 28 of gestation.

Neuronal loss of the nucleus basalis of Meynert in primary progressive aphasia is associated with Alzheimer's disease neuropathological changes.

INTRODUCTION: Imaging studies indicated basal forebrain reduction in primary progressive aphasia (PPA), which might be a candidate marker for cholinergic treatment. Nucleus basalis of Meynert (nbM) neuronal loss has been reported, but a systematic quantitative neuropathological assessment including the three clinical PPA variants is lacking. METHODS: Quantitative assessment of neuronal density and pathology was performed on nbM tissue of 47 cases: 15 PPA, constituting the different clinicopathological phenotypes, 14 Alzheimer's disease (AD), and 18 cognitively normals. RESULTS: Group-wise, reduced nbM neuronal density was restricted to AD. At the individual level, semantic variant PPA with underlying AD neuropathological change (ADNC) had lower neuronal densities, while those with frontotemporal lobar degeneration (FTLD) transactive response DNA binding protein 43 kDa (TDP-43) type C pathology were unaffected. Higher Braak stages and increased numbers of nbM-related pretangles were associated with nbM neuronal loss. DISCUSSION: nbM neuronal loss in PPA is related to ADNC. This study cautions against overinterpreting MRI-based basal forebrain volumes in non-AD PPA as neuronal loss.

Association of Netrin 1 with hsCRP in Subjects with Obesity and Recent Diagnosis of Type 2 Diabetes.

Netrin 1 (Ntn1) is a cell migration protein with an anti-inflammatory effect, which may play a key role in the pathological development of type 2 diabetes (T2D). In this study, we evaluate the relationships between the serum concentrations of Ntn1, glucose, and high-sensitivity C-reactive Protein (hsCRP). We carried out a cross-sectional study including 90 individuals divided into three groups (n = 30): healthy subjects, individuals with obesity without glucose alterations, and individuals with newly diagnosed T2D. Serum concentrations of Ntn1 and hs-CRP were determined by enzyme-linked immunosorbent assay (ELISA). The serum concentration of Ntn1 was higher in individuals with newly diagnosed T2D (0.33 ± 0.22 ng/mL), in comparison to healthy subjects and individuals with obesity (0.13 ± 0.06 and 0.15 ± 0.07 ng/mL, respectively). In addition, we observed a positive association between the levels of Ntn1 and hsCRP (rho = 0.443; p < 0.001) as well as with serum glucose (rho = −0.110; p = 0.05). The serum concentration of Ntn1 was higher in individuals with T2D, in comparison with the other groups in this study, and presented a positive correlation with hsCRP. Therefore, Ntn1 can be considered a promising risk biomarker and a potential therapeutic target for T2D.

Increased pyroptosis activation in white matter microglia is associated with neuronal loss in ALS motor cortex.

Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motor neurons in the motor cortex, brainstem, and spinal cord. Although ALS is considered a motor neuron disorder, neuroinflammation also plays an important role. Recent evidence in ALS disease models indicates activation of the inflammasome and subsequent initiation of pyroptosis, an inflammatory type of cell death. In this study, we determined the expression and distribution of the inflammasome and pyroptosis effector proteins in post-mortem brain and spinal cord from ALS patients (n = 25) and controls (n = 19), as well as in symptomatic and asymptomatic TDP-43A315T transgenic and wild-type mice. Furthermore, we evaluated its correlation with the presence of TDP-43 pathological proteins and neuronal loss. Expression of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, pyroptosis effector protein cleaved Gasdermin D (GSDMD), and IL-18 was detected in microglia in human ALS motor cortex and spinal cord, indicative of canonical inflammasome-triggered pyroptosis activation. The number of cleaved GSDMD-positive precentral white matter microglia was increased compared to controls and correlated with a decreased neuronal density in human ALS motor cortex. Neither of this was observed in the spinal cord. Similar results were obtained in TDP-43A315T mice, where microglial pyroptosis activation was significantly increased in the motor cortex upon symptom onset, and correlated with neuronal loss. There was no significant correlation with the presence of TDP-43 pathological proteins both in human and mouse tissue. Our findings emphasize the importance of microglial NLRP3 inflammasome-mediated pyroptosis activation for neuronal degeneration in ALS and pave the way for new therapeutic strategies counteracting motor neuron degeneration in ALS by inhibiting microglial inflammasome/pyroptosis activation.

My life, my story: Teaching patient centered care competencies for older adults through life story work.

We implemented "My Life, My Story" as an educational activity for enhancing patient-centered care (PCC) competencies across health professions trainees. Four hundred and eighty-two stories were completed for patients (M age = 72.5, SD = 12.7) primarily in inpatient medical settings, by trainees from seven disciplines. Trainees spent approximately 2 hours on the assignment; 84% felt this was a good use of their time. A mixed method survey evaluated the effectiveness of the activity on enhancing PCC competencies using open ended questions and ratings on the Consultation and Relational Empathy (CARE) Measure adapted for this project. The assignment most influenced trainees' ability to understand the patient as a "whole person" along with other PCC competencies such as showing empathy, really listening, building knowledge of values and goals, and building relationships. In addition, trainees perceived the activity enhanced patient care and was a positive contrast to usual care.

Maturation of neuronal AD-tau pathology involves site-specific phosphorylation of cytoplasmic and synaptic tau preceding conformational change and fibril formation.

In Alzheimer's disease (AD), tau-protein undergoes a multi-step process involving the transition from a natively unfolded monomer to large, aggregated structures such as neurofibrillary tangles (NFTs). However, it is not yet clear which events initiate the early preclinical phase of AD tauopathy and whether they have impact on the propagation of tau pathology in later disease stages. To address this question, we analyzed the distribution of tau species phosphorylated at T231, S396/S404 and S202/T205, conformationally modified at the MC1 epitope and fibrillary tau detected by the Gallyas method (Gallyas-tau), in the brains of 15 symptomatic and 20 asymptomatic cases with AD pathology as well as of 19 nonAD cases. As initial tau lesions, we identified phosphorylated-T231-tau diffusely distributed within the somatodendritic compartment (IC-tau) and phosphorylated-S396/pS404-tau in axonal lesions of the white matter and in the neuropil (IN-tau). The subcellular localization of pT231-tau in the cell body and pS396/pS404-tau in the presynapse was confirmed in hP301L mutant Drosophila larvae. Phosphorylated-S202/T205-tau, MC1-tau and Gallyas-tau were negative for these lesions. IC- and IN-tau were observed in all analyzed regions of the human brain, including early affected regions in nonAD cases (entorhinal cortex) and late affected regions in symptomatic AD cases (cerebellum), indicating that tau pathology initiation follows similar processes when propagating into previously unaffected regions. Furthermore, a sequence of AD-related maturation of tau-aggregates was observed, initiated by the appearance of IC- and IN-tau, followed by the formation of pretangles exhibiting pT231-tau, pS396/pS404-tau and pS202/pT205-tau, then by MC1-conformational tau, and, finally, by the formation of Gallyas-positive NFTs. Since cases classified as nonAD [Braak NFT stages < I (including a-1b)] already showed IC- and IN-tau, our findings suggest that these lesions are a prerequisite for the development of AD.

Assessment of nitric oxide metabolites concentrations in plasma, saliva, and breast milk and their relationship in lactating women.

Nitric oxide (NO) plays a role in many biological mechanisms. The amounts of physiologically produced NO are associated with the concentrations of its metabolites nitrate and nitrite. This study investigated whether there is any association between the concentrations of NO metabolites nitrate, nitrite, and nitrosylated species (RXNO) in mature breast milk, saliva, and plasma in healthy lactating women (N = 30). We hypothesized that the NO metabolites concentrations in plasma are associated with those found in saliva and in breast milk. NO metabolites concentrations were measured using chemiluminensce-based assays. Nitrate concentrations in breast milk are twice as much as plasma concentrations, whereas nitrate concentrations in saliva are about eightfold higher (both P < 0.001). Similar differences were found when nitrite concentrations were taken into consideration. RXNO concentrations in breast milk were negligible, and RXNO concentrations in saliva were approximately sixfold higher than those found in plasma samples (P < 0.0001). Nitrate concentrations in plasma are associated with nitrate concentrations in saliva (rs = 0.474, P = 0.004). However, no significant association was found between nitrate concentrations in breast milk and in plasma (P > 0.05). Our results show a significant association between nitrate concentrations in plasma with those found in saliva, whereas all other relationships were not significant. In conclusion, this report shows for the first time that the physiological concentrations of NO metabolites in human breast milk are probably independent of circulating NO metabolites concentrations and may depend mostly on endogenous NO synthesis in the breast. These findings may have clinical implications for newborns and lactating women.

Prediction of thromboembolic events and mortality by the CHADS2 and the CHA2DS2-VASc in COVID-19.

AIMS: Age, sex, and cardiovascular disease have been linked to thromboembolic complications and poorer outcomes in COVID-19. We hypothesize that CHADS2 and CHA2DS2-VASc scores may predict thromboembolic events and mortality in COVID-19. METHODS AND RESULTS: COVID-19 hospitalized patients with confirmed SARS-CoV-2 infection from 1 March to 20 April 2020 who completed at least 1-month follow-up or died were studied. CHADS2 and CHA2DS2-VASc scores were calculated. Given the worse prognosis of male patients in COVID-19, a modified CHA2DS2-VASc score (CHA2DS2-VASc-M) in which 1 point was given to male instead of female was also calculated. The associations of these scores with laboratory results, thromboembolic events, and death were analysed. A total of 3042 patients (mean age 62.3 ± 20.3 years, 54.9% male) were studied and 115 (3.8%) and 626 (20.6%) presented a definite thromboembolic event or died, respectively, during the study period [median follow 59 (50-66) days]. Higher score values were associated with more marked abnormalities of inflammatory and cardiac biomarkers. Mortality was significantly higher with increasing scores for CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M (P < 0.001 for trend). The CHA2DS2-VASc-M showed the best predictive value for mortality [area under the receiver operating characteristic curve (AUC) 0.820, P < 0.001 for comparisons]. All scores had poor predictive value for thromboembolic events (AUC 0.497, 0.490, and 0.541, respectively). CONCLUSION: The CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M scores are significantly associated with all-cause mortality but not with thromboembolism in COVID-19 patients. They are simple scoring systems in everyday use that may facilitate initial 'quick' prognostic stratification in COVID-19.

Thoughts about health and patient-reported outcomes among people with diabetes mellitus: results from the DiaDec-study.

BACKGROUND: There is considerable evidence that repetitive negative thoughts are often associated with adverse health outcomes. The study aims are (i) to identify the frequency and valence of thoughts about health in people with diabetes mellitus using questions based on the day reconstruction method (DRM) and (ii) to analyse associations between thoughts about health and health-related quality of life (HRQoL), diabetes-related distress and depressive symptoms. METHODS: Cross-sectional study of a random sample of a German statutory health insurance population with diabetes aged between 18 and 80 linking questionnaire and claims data. Associations between frequency and valence of thoughts about health on a previous day and HRQoL assessed by a 12-Item Short-Form Health Survey, diabetes-related distress assessed using the Problem Areas in Diabetes scale and depressive symptoms assessed by Patient Health Questionnaire-9 were analysed using linear and logistic regression analysis, adjusting for sociodemographic and clinical characteristics. RESULTS: Thoughts about health were analysed in 726 participants (86% type 2 diabetes, 62% male, mean age 67.6 ± 9.7 years). A total of 46% had not thought about their health the day before, 17.1% reported low frequency and negative thoughts, 21.4% low frequency and positive thoughts, 12.1% high frequency and negative thoughts and 3.4% high frequency and positive thoughts. The presence of thoughts about health irrespective of their frequency and valence is associated with a lower physical and mental component summary score of the 12-Item Short-Form Health Survey. Negative thoughts are associated with high diabetes-related distress. Frequent or negative thoughts are associated with depressive symptoms. CONCLUSIONS: Thoughts about health are a part of everyday life for a substantial number of people with diabetes. Surprisingly, even positive thoughts are associated with poorer HRQoL in our study. Further research within the DRM paradigm is needed to understand how thoughts about health may affect people's (assessment of) state of health. Thoughts about health should be considered in diabetes education and patient counselling with a view to preventing and treating emotional disorders. More attention should be paid to the outcomes of interventions that may themselves lead to an increase in the frequency of thoughts about health.

Different information needs in subgroups of people with diabetes mellitus: a latent class analysis.

BACKGROUND: Current evidence suggests that the information needs of people with diabetes mellitus differ across patient groups. With a view to being able to provide individualized information, this study aims to identify (i) the diabetes-related information needs of people with diabetes mellitus; (ii) different subgroups of people with specific information needs; and (iii) associated characteristics of the identified subgroups, such as sociodemographic characteristics, diabetes-related comorbidities, and well-being. METHODS: This cross-sectional study was based on data from 837 respondents with diabetes mellitus who participated in the population-based KORA (Cooperative Health Research in the Augsburg Region) Health Survey 2016 in Southern Germany (KORA GEFU 4 study) (45.6% female, mean age 71.1 years, 92.8% Type 2 diabetes). Diabetes-related information needs were assessed with a questionnaire asking about patients' information needs concerning 11 diabetes-related topics, e.g. 'long-term complications' and 'treatment/therapy'. Subgroups of people with different information needs and associated characteristics were identified using latent class analysis. RESULTS: We identified the following four classes of people with different information needs: 'high needs on all topics', 'low needs on all topics', 'moderate needs with a focus on complications and diabetes in everyday life', and 'advanced needs with a focus on social and legal aspects and diabetes research'. The classes differed significantly in age, years of education, type of diabetes, diabetes duration, diabetes-related comorbidities, smoking behaviour, diabetes education, current level of information, and time preference. CONCLUSIONS: Knowledge about different patient subgroups can be useful for tailored information campaigns or physician-patient interactions. Further research is needed to analyse health care needs in these groups, changes in information needs over the course of the disease, and prospective health outcomes.

In situ thermal ablation augments antitumor efficacy of adoptive T cell therapy.

Purpose: The aim of this study is to investigate whether radiofrequency ablation (RFA) improves the efficacy of adoptive T cell immunotherapy in preclinical mouse cancer models.Method: Mice implanted subcutaneously (sc) with syngeneic colon adenocarcinoma or melanoma were treated with sub-curative in situ RFA (90 °C, 1 min). Trafficking of T cells to lymph nodes (LN) or tumors was quantified by homing assays and intravital microscopy (IVM) after sham procedure or RFA. Expression of trafficking molecules (CCL21 and intercellular adhesion molecule-1 [ICAM-1]) on high endothelial venules (HEV) in LN and tumor vessels was evaluated by immunofluorescence microscopy. Tumor-bearing mice were pretreated with RFA to investigate the therapeutic benefit when combined with adoptive transfer of in vitro-activated tumor-specific CD8+ T cells.Results: RFA increased trafficking of naïve CD8+ T cells to tumor-draining LN (TdLN). A corresponding increase in expression of ICAM-1 and CCL21 was detected on HEV in TdLN but not in contralateral (c)LN. IVM revealed that RFA substantially enhanced secondary firm arrest of lymphocytes selectively in HEV in TdLN. Furthermore, strong induction of ICAM-1 in tumor vessels was associated with significantly augmented trafficking of adoptively transferred in vitro-activated CD8+ T cells to tumors after RFA. Finally, preconditioning tumors with RFA augmented CD8+ T cell-mediated apoptosis of tumor targets and delayed growth of established tumors when combined with adoptive T cell transfer immunotherapy.Conclusions: These studies suggest that in addition to its role as a palliative therapeutic modality, RFA may have clinical potential as an immune-adjuvant therapy by augmenting the efficacy of adoptive T cell therapy.

Bovine scavenger receptor class A (SR-A) exhibit specific patterns of regulation in the endometrium during the oestrous cycle and early pregnancy.

In mammals, tight regulation of maternal endometrial function is critical for pregnancy success. In bovine species, endometrial expression of members of the scavenger receptor class A (SR-A) has been listed in high-throughput analyses, but very little is known about the involvement of these immune factors during implantation in mammals. To provide first insights into the contribution of SR-A to endometrial physiology, we analysed the expression and regulation of all members of SR-A (SR-A1, SR-A3-SR-A6) during the oestrous cycle and early pregnancy in cattle. Levels of SR-A1 were increased on Day 20 of pregnancy, whereas SR-A3 levels were increased on Day 13 of the oestrous cycle and of the pregnancy. Although SR-A4 levels were reduced on Day 20 of the oestrous cycle, they remained high in pregnant animals. SR-A5 levels increased by Day 13 of the oestrous cycle and decreased on Day 20, but remained high in pregnant animals. Interferon-τ does not affect SR-A gene expression, whereas progesterone regulates the expression of the SR-A3 and SR-A5 transcripts. Endometrial SR-A3 appeared significantly higher in cows carrying invitro-produced embryos than in AI cows. Our data suggest that members of the SR-A family are involved in endometrial remodelling and regulation of endometrial gland physiology, both processes being critical for implantation in mammals.

Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8+ T-cell axis.

Activation of an anticancer innate immune response is highly desirable because of its inherent ability to generate an adaptive antitumor T-cell response. However, insufficient safety of innate immune modulators limits clinical use to topical applications. Toll-like receptor 5 (TLR5) agonists are favorably positioned as potential systemic immunotherapeutic agents because of unusual tissue specificity of expression, uniquely safe profile of induced cytokines, and antitumor efficacy demonstrated in a number of animal models. Here, we decipher the molecular and cellular events underlying the metastasis suppressive activity of entolimod, a clinical stage TLR5 agonist that activates NF-κB-, AP-1-, and STAT3-driven immunomodulatory signaling pathways specifically within the liver. Used as a single agent in murine colon and mammary metastatic cancer models, entolimod rapidly induces CXCL9 and -10 that support homing of blood-borne CXCR3-expressing NK cells to the liver predominantly through an IFN-γ signaling independent mechanism. NK cell-dependent activation of dendritic cells is followed by stimulation of a CD8(+) T-cell response, which exert both antimetastatic effect of entolimod and establishment of tumor-specific and durable immune memory. These results define systemically administered TLR5 agonists as organ-specific immunoadjuvants, enabling efficient antitumor vaccination that does not depend on identification of tumor-specific antigens.

Tumor-associated myeloid cells promote tumorigenesis of non-tumorigenic human and murine prostatic epithelial cell lines.

The etiology of prostate cancer is poorly understood, but it is a multi-step process that has been linked to environmental factors that induce inflammation within the gland. Glands of prostate cancer patients frequently contain multiple zones of disease at various stages of progression. The factors that drive disease progression from an indolent benign stage to aggressive disease are not well-defined. Prostate inflammation and carcinoma are associated with high levels of myeloid cell infiltration; these cells are linked to disease progression in other cancers, but their role in prostate cancer is unclear. To determine whether myeloid cells contribute to prostate cancer progression, the ability of prostate tumor-associated CD11b+ cells (TAMC) to drive prostate epithelial cell tumorigenesis was tested. Co-culture of CD11b+ TAMC with non-tumorigenic genetically primed prostate epithelial cells resulted in stable transformation and induction of tumorigenesis. RNA sequencing identified the IL-1α pathway as a potential molecular mechanism responsible for tumor promotion by TAMC. Inhibition of IL-1α delayed growth of TAMC-induced tumors. Further analysis showed that IL-1α inhibition led to decreased angiogenesis within tumors, suggesting that IL-1α promotes prostate tumor progression, potentially through augmentation of angiogenesis.

Photodynamic therapy of cancer: an update.

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.