Demographic and Clinical Features of Dengue Fever in Pakistan from 2003–2007: A Retrospective Cross-Sectional Study

Background: Demographic features of dengue fever have changed tremendously in Pakistan over the past two decades. Small scale studies from all over the country have reported different aspects of individual outbreaks during this time. However, there is scarcity of data looking at the overall trend of dengue virus infection in the country. In this study, we examined annual trends, seasonality, and clinical features of dengue fever in the Pakistani population.Methods: Demographic information and dengue IgM status of all patients tested for dengue IgM antibody at Aga Khan University Hospital from January 2003 to December 2007 were analyzed to look for trends of IgM-positive cases in Pakistan. In addition, clinical and biochemical parameters were abstracted retrospectively from medical records of all patients hospitalized with IgM-proven dengue fever between January 2006 and December 2007. These patients were categorized into dengue fever and dengue hemorrhagic fever according to the WHO severity grading scale.Results: Out of a total of 15040 patients (63.2% male and 36.8% female), 3952 (26.3%) tested positive for dengue IgM antibody. 209 IgM proven dengue patients were hospitalized during the study period. During 2003, IgM positive cases were seen only during the months of July-December. In contrast, such cases were detected throughout the year from the 2004– 2007. The median age of IgM positive patients decreased every year from 32.0 years in 2003 to 24.0 years in 2007 (p,0.001). Among hospitalized patients, nausea was the most common presenting feature found in 124/209 (59.3%) patients. Children presented with a higher median body temperature than adults (p = 0.010). In addition, neutropenia was seen more commonly in children while raised serum ALT levels were seen more commonly in adults (both p = 0.006). While a low total white cell count was more common in patients with dengue fever as compared to Dengue Hemorrhagic Fever (p = 0.020), neutropenia (p = 0.019), monocytosis (p = 0.001) and raised serum ALT level (p = 0.005) were observed more commonly in the latter group.Conclusions: Dengue virus is now endemic in Pakistan, circulating throughout the year with a peak incidence in the post monsoon period. Median age of dengue patients has decreased and younger patients may be more susceptible. Total and differential leukocyte counts may help identify patients at risk of hemorrhage

Cancer patients' needs during hospitalisation: a quantitative and qualitative study

BACKGROUND: The evaluation of cancer patients needs, especially during that delicate period when they are hospitalized, allows the identification of those areas of care that require to be improved. Aims of the study were to evaluate the needs in cancer inpatients and to improve the understanding of the meanings of the needs expressed. METHODS: The study was conducted during a "sample day", with all the cancer patients involved having been hospitalized at the Istituto Nazionale Tumori of Milan (INT) for at least 48 hours beforehand. The study was carried out using quantitative and qualitative methodologies. The quantitative part of the study consisted in making use of the Needs Evaluation Questionnaire (NEQ), a standardized questionnaire administered by the INT Psychology Unit members, supported by a group of volunteers from the Milan section of the Italian League Against Cancer. The aim of the qualitative part of the study, by semi-structured interviews conducted with a small sample of 8 hospitalized patients, was to improve our understanding of the meanings, implications of the needs directly described from the point of view of the patients. Such an approach determines the reasons and conditions of the dissatisfaction in the patient, and provides additional information for the planning of improvement interventions. RESULTS: Of the 224 eligible patients, 182 (81%) completed the questionnaire. Four of the top five needs expressed by 40% or more of the responders concerned information needs (diagnosis, future conditions, dialogue with doctors, economic-insurance solutions related to the disease). Only one of the 5 was concerned with improved "hotel" services (bathrooms, meals, cleanliness). Qualitative analysis showed that the most expressed need (to receive more information on their future conditions) has the meaning to know how their future life will be affected more than to know his/her actual prognosis. CONCLUSIONS: Some of the needs which emerged from this investigation could be immediately satisfied (the need for psychological support, the need for economic aid, the need for spiritual support), while others will have to be faced in the longer term; for example, the presence of a high percentage of needs in patient-physician relationships and/or information-communication issues, could be resolved by setting up structured introductory training courses for all clinicians in the institution. On the other hand, the needs related to the living infrastructure (bathrooms, meals, etc...) could encourage the Institution to improve its services

Menstrual Cycle and Facial Preferences Reconsidered

Two previous articles reported that women prefer less feminized male faces during the fertile phase of their menstrual cycle, supposedly reflecting an evolved mating strategy whereby women choose mates of maximum genetic quality when conception is likely. The current article contends this theory rests on several questionable assumptions about human ancestral mating systems. A new empirical test also was conducted: 853 adults, primarily from North America, evaluated facial attractiveness of photos. The study included more complete evaluation of ovulatory status and a greater number (n = 258) of target women than past research. The results did not suggest any greater preference for masculine faces when fertilization was likely. The article concludes with general comments about evolutionary theorizing and interpersonal relationships

Long-term health outcomes in a British cohort of breast, colorectal and prostate cancer survivors: a database study

BACKGROUND: The community-based incidence of cancer treatment-related long-term consequences is uncertain. We sought to establish the burden of health outcomes that have been associated with treatment among British long-term cancer survivors. METHODS: We identified 26,213 adults from the General Practice Research Database who have survived 5 years or more following breast, colorectal or prostate cancer. Four age-, sex- and general practice-matched non-cancer controls were selected for each survivor. We considered the incidence of treatment-associated health outcomes using Cox proportional hazards models. RESULTS: Breast cancer survivors had an elevated incidence of heart failure (hazards ratio (HR) 1.95, 95% confidence interval (CI) 1.27-3.01), coronary artery disease (HR 1.27, 95% CI 1.11-1.44), hypothyroidism (HR 1.26, 95% CI 1.02-1.56) and osteoporosis (HR 1.26, 95% CI 1.13-1.40). Among colorectal cancer survivors, there was increased incidence of dementia (HR 1.68, 95% CI 1.20-2.35), diabetes (HR 1.39, 95% CI 1.12-1.72) and osteoporosis (HR 1.41, 95% CI 1.15-1.73). Prostate cancer survivors had the highest risk of osteoporosis (HR 2.49, 95% CI 1.93-3.22). CONCLUSIONS: The study confirms the occurrence of increased incidence of chronic illnesses in long-term cancer survivors attributable to underlying lifestyle and/or cancer treatments. Although the absolute risk of the majority of late effects in the cancer survivors cohort is low, identifying prior risk of osteoporosis by bone mineral density scanning for prostate survivors should be considered. There is an urgent need to improve primary care recording of cancer treatmen

On the Perception of Newcomers: Toward an Evolved Psychology of Intergenerational Coalitions

Human coalitions frequently persist through multiple, overlapping membership generations, requiring new members to cooperate and coordinate with veteran members. Does the mind contain psychological adaptations for interacting within these intergenerational coalitions? In this paper, we examine whether the mind spontaneously treats newcomers as a motivationally privileged category. Newcomers—though capable of benefiting coalitions—may also impose considerable costs (e.g., they may free ride on other members, they may be poor at completing group tasks). In three experiments we show (1) that the mind categorizes coalition members by tenure, including newcomers; (2) that tenure categorization persists in the presence of orthogonal and salient social dimensions; and (3) that newcomers elicit a pattern of impressions consistent with their probable ancestral costs. These results provide preliminary evidence for a specialized component of human coalitional psychology: an evolved concept of newcomer

Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile

In recent years it has become clear that the therapeutic properties of bone marrow-derived mesenchymal stromal cells (MSC) are related not only to their ability to differentiate into different lineages but also to their capacity to suppress the immune response. We here studied the influence of MSC on macrophage function. Using mouse thioglycolate-elicited peritoneal macrophages (M) stimulated with LPS, we found that MSC markedly suppressed the production of the inflammatory cytokines TNF-α, IL-6, IL-12p70 and interferon-γ while increased the production of IL-10 and IL-12p40. Similar results were observed using supernatants from MSC suggesting that factor(s) constitutively released by MSC are involved. Supporting a role for PGE2 we observed that acetylsalicylic acid impaired the ability of MSC to inhibit the production of inflammatory cytokines and to stimulate the production of IL-10 by LPS-stimulated M. Moreover, we found that MSC constitutively produce PGE2 at levels able to inhibit the production of TNF-α and IL-6 by activated M. MSC also inhibited the up-regulation of CD86 and MHC class II in LPS-stimulated M impairing their ability to activate antigen-specific T CD4+ cells. On the other hand, they stimulated the uptake of apoptotic thymocytes by M. Of note, MSC turned M into cells highly susceptible to infection with the parasite Trypanosoma cruzi increasing more than 5-fold the rate of M infection. Using a model of inflammation triggered by s.c. implantation of glass cylinders, we found that MSC stimulated the recruitment of macrophages which showed a low expression of CD86 and the MHC class II molecule Iab and a high ability to produce IL-10 and IL-12p40, but not IL-12 p70. In summary, our results suggest that MSC switch M into a regulatory profile characterized by a low ability to produce inflammatory cytokines, a high ability to phagocyte apoptotic cells, and a marked increase in their susceptibility to infection by intracellular pathogens

Loss of Function of the Cik1/Kar3 Motor Complex Results in Chromosomes with Syntelic Attachment That Are Sensed by the Tension Checkpoint

The attachment of sister kinetochores by microtubules emanating from opposite spindle poles establishes chromosome bipolar attachment, which generates tension on chromosomes and is essential for sister-chromatid segregation. Syntelic attachment occurs when both sister kinetochores are attached by microtubules from the same spindle pole and this attachment is unable to generate tension on chromosomes, but a reliable method to induce syntelic attachments is not available in budding yeast. The spindle checkpoint can sense the lack of tension on chromosomes as well as detached kinetochores to prevent anaphase onset. In budding yeast Saccharomyces cerevisiae, tension checkpoint proteins Aurora/Ipl1 kinase and centromere-localized Sgo1 are required to sense the absence of tension but are dispensable for the checkpoint response to detached kinetochores. We have found that the loss of function of a motor protein complex Cik1/Kar3 in budding yeast leads to syntelic attachments. Inactivation of either the spindle or tension checkpoint enables premature anaphase entry in cells with dysfunctional Cik1/Kar3, resulting in co-segregation of sister chromatids. Moreover, the abolished Kar3-kinetochore interaction in cik1 mutants suggests that the Cik1/Kar3 complex mediates chromosome movement along microtubules, which could facilitate bipolar attachment. Therefore, we can induce syntelic attachments in budding yeast by inactivating the Cik1/Kar3 complex, and this approach will be very useful to study the checkpoint response to syntelic attachments

Interaction of Pyrrolobenzodiazepine (PBD) Ligands with Parallel Intermolecular G-Quadruplex Complex Using Spectroscopy and ESI-MS

Studies on ligand interaction with quadruplex DNA, and their role in stabilizing the complex at concentration prevailing under physiological condition, has attained high interest. Electrospray ionization mass spectrometry (ESI-MS) and spectroscopic studies in solution were used to evaluate the interaction of PBD and TMPyP4 ligands, stoichiometry and selectivity to G-quadruplex DNA. Two synthetic ligands from PBD family, namely pyrene-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrid (PBD1), mixed imine-amide pyrrolobenzodiazepine dimer (PBD2) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) were studied. G-rich single-stranded oligonucleotide d(5′GGGGTTGGGG3′) designated as d(T2G8), from the telomeric region of Tetrahymena Glaucoma, was considered for the interaction with ligands. ESI-MS and spectroscopic methods viz., circular dichroism (CD), UV-Visible, and fluorescence were employed to investigate the G-quadruplex structures formed by d(T2G8) sequence and its interaction with PBD and TMPyP4 ligands. From ESI-MS spectra, it is evident that the majority of quadruplexes exist as d(T2G8)2 and d(T2G8)4 forms possessing two to ten cations in the centre, thereby stabilizing the complex. CD band of PBD1 and PBD2 showed hypo and hyperchromicity, on interaction with quadruplex DNA, indicating unfolding and stabilization of quadruplex DNA complex, respectively. UV-Visible and fluorescence experiments suggest that PBD1 bind externally where as PBD2 intercalate moderately and bind externally to G-quadruplex DNA. Further, melting experiments using SYBR Green indicate that PBD1 unfolds and PBD2 stabilizes the G-quadruplex complex. ITC experiments using d(T2G8) quadruplex with PBD ligands reveal that PBD1 and PBD2 prefer external/loop binding and external/intercalative binding to quadruplex DNA, respectively. From experimental results it is clear that the interaction of PBD2 and TMPyP4 impart higher stability to the quadruplex complex