Placental Immune Responses to Viruses: Molecular and Histo-Pathologic Perspectives.

As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection.

Antihypertensive treatment decreases arterial stiffness at night but not during the day. Results from the Hypertension in the Very Elderly Trial.

The main Hypertension in the Very Elderly Trial (HYVET) demonstrated a very marked reduction in cardiovascular events by treating hypertensive participants 80 years or older with a low dose, sustained release prescription of indapamide (indapamide SR, 1.5 mg) to which was added a low dose of an angiotensin converting enzyme inhibitor in two-thirds of cases (perindopril 2-4 mg). This report from the ambulatory blood pressure sub-study investigates whether changes in arterial stiffness and ambulatory blood pressure (BP) could both explain the benefits observed in the main trial. A total of 139 participants were randomized to placebo [67] and to active treatment [72] and had both day and night observations of BP and arterial stiffness as determined from the Q wave Korotkoff diastolic (QKD) interval. The QKD interval was 5.6 ms longer (p = 0.017) in the actively treated group at night than in the placebo group. This was not true for the more numerous daytime readings so that 24-h results were similar in the two groups. The QKD interval remained longer at night in the actively treated group even when adjusted for systolic pressure, heart rate and height. The reduced arterial stiffness at night may partly explain the marked benefits observed in the main trial.

A novel cytomegalovirus-induced regulatory-type T-cell subset increases in size during older life and links virus-specific immunity to vascular pathology.

BACKGROUND: Cytomegalovirus (CMV) infection directly targets vascular endothelium and smooth muscle and at older ages is associated with accelerated vascular pathology and mortality. CMV-specific cellular immunity might directly contribute to this process. METHODS: Conventional ex vivo activation-induced T-cell responses to 19 dominant CMV antigens, along with CMV-specific inducible regulatory-type CD4+ T cells (iTregs), were measured in healthy older people, using a novel protocol that included classic Treg markers alongside the activation marker CD134. Measurements were correlated with diastolic, systolic, and mean arterial blood pressure, a surrogate marker for arterial stiffness. RESULTS: CMV-specific iTregs recognized the same antigens as conventional CD4+ T cells and were significantly more frequent at older ages. They suppressed antigen-specific and nonspecific proliferation and in large part expressed Foxp3. Frequencies of CMV-specific iTregs and CD8+ T cells (summated response) were significantly associated with diastolic and mean arterial pressures. Confounders, including age, body mass index, smoking, antihypertensive medication use, or C-reactive protein levels, did not explain these observations. CONCLUSIONS: A novel CMV-induced regulatory-type CD4+ T-cell subset is readily detectable in CMV-infected people and, like the aggregate CD8+ T-cell response to the most dominant CMV antigens, is quantitatively associated with arterial stiffness in older life. Whereas CD8+ effector T cells might directly cause vascular injury, iTregs may attenuate this response.

Characterisation of CD154+ T cells following ex vivo birch allergen stimulation defines a close relationship between T cell subsets in healthy volunteers.

BACKGROUND: Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We hypothesised that the relationship between these T cell subsets could be better defined using a short-term allergen stimulation system followed by direct analysis of CD154-positive T cells. Using peripheral blood samples from birch pollinosis patients and healthy non-atopic controls, we sought to explore the frequencies and phenotype of birch-stimulated CD154-positive T helper cells following ex vivo birch allergen stimulation. RESULTS: Activated CD154-positive Th1, Th2 and Tr1-like cells, that co-expressed IFNγ, IL-4 and IL-10 respectively, were identified in both birch-allergic and non-allergic participants. We observed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. The relationship between Th1, Th2 and Tr1-like responses was dysregulated in birch-allergic patients, with abrogation of the IL-10 response and a higher Th2: Th1 ratio. A close correlation was observed between Th2 cell frequency and the absolute concentration of birch-specific IgE within the birch-allergic group, and we confirmed previous reports of a more differentiated T cell phenotype in allergic subjects. CONCLUSIONS: The findings demonstrate an important balance between IFNγ, IL-4 and IL-10 T cell responses to birch allergen in health, where Th2 responses to allergens were frequently observed, but apparently balanced by Th1 and regulatory responses. The detection of CD154 positive T cells after short-term antigen stimulation may be a useful method for the detection of T cell responses to allergens when cost, speed and convenience are priorities.

Characterisation of CD154+ T cells following ex vivo allergen stimulation illustrates distinct T cell responses to seasonal and perennial allergens in allergic and non-allergic individuals.

BACKGROUND: Allergic sensitisation has been ascribed to a dysregulated relationship between allergen-specific Th1, Th2 and regulatory T cells. We sought to utilise our short-term CD154 detection method to further analyse the relationship between these T cell subsets and investigate differences between seasonal and perennial allergens. Using peripheral blood samples from grass-allergic, cat-allergic and healthy non-atopic subjects, we compared the frequencies and phenotype of CD154-positive T helper cells following stimulation with seasonal (grass) and perennial (cat dander) allergens. RESULTS: We identified a higher frequency of CD154+ T cells in grass-allergic individuals compared to healthy controls; this difference was not evident following stimulation with cat allergen. Activated Th1, Th2 and Tr1-like cells, that co-express IFNγ, IL4 and IL10, respectively, were identified in varying proportions in grass-allergic, cat-allergic and non-allergic individuals. We confirmed a close correlation between Th1, Th2 and Tr1-like cell frequency in non-allergic volunteers, such that the three parameters increased together to maintain a low Th2: Th1 ratio. This relationship was dysregulated in grass-allergic individuals with no correlation between the T cell subsets and a higher Th2: Th1 ratio. We confirmed previous reports of a late-differentiated T cell phenotype in response to seasonal allergens compared to early-differentiated T cell responses to perennial allergens. CONCLUSIONS: The findings confirm our existing work illustrating an important balance between Th1, Th2 and Tr1-like responses to allergens in health, where Th2 responses are frequently observed, but balanced by Th1 and regulatory responses. We confirm previous tetramer-based reports of phenotypic differences in T cells responding to seasonal and perennial allergens.

Polyfunctional T cells accumulate in large human cytomegalovirus-specific T cell responses.

Large cytomegalovirus (CMV)-specific CD8 T-cell responses are observed in both young and, somewhat more often, old people. Frequent CMV reactivation is thought to exhaust these cells and render them dysfunctional so that larger numbers of them are needed to control CMV. Expansions of CMV-specific CD4 T cells are also seen but are less well studied. In this study, we examined the T-cell response to the dominant CMV pp65 and IE-1 antigens in healthy CMV-infected people across a wide age range (20 to 84 years) by using multicolor flow cytometry. CMV-specific T cells were characterized by the activation markers CD40 ligand (CD40L), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) and the memory markers CD27 and CD45RA. The proportions of effector memory T cells increased in large responses, as did the proportions of polyfunctional CD8 (IFN-γ(+) IL-2(+/-) TNF-α(+)) and CD4 (CD40L(+/-) IFN-γ(+) IL-2(+) TNF-α(+)) T-cell subsets, while the proportion of naïve T cells decreased. The bigger the CD4 or CD8 T-cell response to pp65, the larger was the proportion of T cells with an advanced memory phenotype in the entire (including non-CMV-specific) T-cell compartment. In addition, the number of activation markers per cell correlated with the degree of T-cell receptor downregulation, suggesting increased antigen sensitivity in polyfunctional cells. In summary, our findings show that polyfunctional CMV-specific T cells were not superseded by dysfunctional cells, even in very large responses. At the same time, however, the memory subset composition of the entire T-cell compartment correlated with the size of the T-cell response to CMV pp65, confirming a strong effect of CMV infection on the immune systems of some, but not all, infected people.

Identifying the patient at risk of acute kidney injury: a predictive scoring system for the development of acute kidney injury in acute medical patients.

BACKGROUND: Acute kidney injury (AKI) in hospitalized patients has significant implications in terms of morbidity and mortality, length of hospital stay and associated costs. To date, no interventions are proven to prevent the development of AKI but this is hampered in part by the lack of early recognition of patients at risk. We aimed to determine whether a simple system could be devised from both physiological and demographic data in order to identify individuals at increased risk from the development of inpatient AKI. METHOD: Our observational, population-based single-centred study took place in an 870-bed associated university hospital. All patients admitted to the acute medical admissions unit on the Worthing site of the Western Sussex Hospitals Trust during the study period were included. RESULTS: Multivariate logistic regression analysis demonstrated that age, respiratory rate and disturbed consciousness together with a history of chronic kidney disease, diabetes mellitus, congestive cardiac failure and liver disease were associated with an increased risk of developing AKI within 7 days of admission. We derived a simple scoring system to identify acute medical patients at greater risk of developing AKI. CONCLUSIONS: The incidence of AKI complicating inpatient admissions remains high, however with the application of the derived AKI prediction score it is hoped that early recognition will translate to improved outcomes.

Elective open versus laparoscopic sigmoid colectomy for diverticular disease: a meta-analysis with the Sigma trial.

BACKGROUND: A meta-analysis of published literature comparing open versus laparoscopic elective sigmoid resections for diverticular disease was conducted. METHODS: Electronic databases were searched for data from January 1991 to March 2009. A systematic review was performed to obtain a summative outcome. RESULTS: Twenty-two comparative studies involving 10,898 patients were analyzed; 1538 patients were in the laparoscopic group and 9360 were in the open group. The operative time for laparoscopic sigmoid resection (LSR) is longer than open resections (OSR) [random-effects model: SMD = 1.94, 95% CI = (1.14, 2.74), z = 4.74, p < 0.001]. However, patients who undergo LSR have earlier return to passage of feces [random-effects model: SMD = -1.01, 95% CI (-1.80, -0.22), z = -2.50, p = 0.013] and shorter hospital stay [random-effects model: SMD = -7.65, 95% CI (-10.96, -4.32), z = -4.52, p < 0.001]. Overall morbidity was higher in the OSR group [random-effects model: RR = 0.56, 95% CI (0.40, 0.80), z = -3.24, p < 0.001] and no difference in mortality rates was observed (p = 0.81). CONCLUSIONS: Laparoscopic sigmoid resection takes longer to perform than open procedures; however, it is safe and has lower overall morbidity, earlier return of bowel function, and shorter hospital stays. This approach should be considered for elective cases but more randomized controlled trials are required to strengthen the evidence.

Needlescopic versus laparoscopic appendectomy: a systematic review.

BACKGROUND: Needlescopic appendectomies (NA) have been performed since the 1990s. We sought to systematically analyze trials comparing NA with laparoscopic appendectomies (LA) in the management of appendicitis. METHODS: We performed a systematic review of the literature. We compared and analyzed clinical trials on NA and LA to generate summative data expressed as standardized mean differences (SMD). RESULTS: Of 5 retrieved trials from the electronic database 2 trials involving 412 patients met our inclusion criteria. In the fixed-effects models, NA took longer than LA, and this time difference was statistically significant: SMD 0.20 min, 95% confidence interval 0.01-0.40, p = 0.030, z(1) = 2.09. In both fixed-and random-effects models, the difference in total hospital stay and in perioperative complications between the NA and LA groups were nonsignificant. Furthermore, in both fixed-and random-effects models, NA was associated with a higher conversion rate to open appendectomy than LA. There was no heterogeneity between the trials (Q = 0.34, p = 0.55). CONCLUSION: Needlescopic appendectomy can be a safe and effective procedure for the management of appendicitis. It is comparable to LA in terms of hospital stay and perioperative complications. However, NA is associated with a longer duration of surgery and a higher conversion rate, indicating technical challenges of the procedure. Before recommending routine use of the needlescopic technique for appendectomy, a major multicentre randomized controlled trial is necessary.

Development of a conversion factor to facilitate comparison of National Institute of Health Stroke Scale scores with Scandinavian Stroke Scale scores.

BACKGROUND: The National Institute of Health Stroke Scale (NIHSS) and the Scandinavian Stroke Scale (SSS) are commonly used in clinical stroke trials. Use of different scales in trials makes comparison of outcomes difficult. METHODS: Adult patients with an acute stroke were recruited within 24 h of onset, and NIHSS, SSS and Glasgow Coma Scale scores were assessed at baseline and repeated at 1 week. RESULTS AND CONCLUSIONS: A total of 144 patients were included (46% males, mean age = 73 years). At presentation the median SSS score was 38 (2-58), and a week later 40 (4-58), the median NIHSS score at presentation was 5 (0-29) and a week later 3 (0-27). Changes in both scales were strongly correlated, r = 0.76, p < 0.001. Both were good predictors of mortality. Linear regression analysis produced an equation relating the two: SSS = 50 - 2 x NIHSS.

Day-night differences in oxygen saturation and the frequency of desaturations in the first 24 hours in patients with acute stroke.

BACKGROUND: Hypoxia is common after acute stroke. Most studies of oxygenation after stroke were done at night. The objective of this study was to determine whether there are differences in oxygenation between day and night early after stroke. METHODS: Patients with an acute stroke were recruited within 24 hours of admission. Patients who were hypoxic (oxygen saturation < 90%) were excluded. Oxygen saturation was assessed by pulse oximetry over 24 hours. Daytime recordings were taken from 9 am to 9 pm and nighttime recordings from 10 pm to 6 am. Respiratory rate and sleep/awake status were recorded twice during the day and the night. RESULTS: Forty patients were recruited (mean age 77 years [range 55-93 years], 53% men; median [range] Glasgow Coma Scale score 15 [10-15] and Scandinavian Stroke Scale score 31 [4-56]; 80% cerebral infarcts, 20% hemorrhages). The median (range) respiratory rate was 20 (14-30) breaths/min in the day and 18 (12-32) breaths/min in the night (P < .01, Wilcoxon paired test). The median (range) oxygen saturation was 95.5% (87%-98.6%) in the day and 94.3% (80%-98%) at night (P < .001, Wilcoxon paired test). The median (range) 4% oxygen desaturation index was 1.7 (0.0, 18.0) in the day and 3.0 (0.0, 39.4) at night (P < .001, Wilcoxon paired test). Respiratory rate, oxygen saturation, and 4% oxygen desaturation index during the day and night were strongly correlated. CONCLUSIONS: All indicators of oxygenation assessed in this study were significantly worse at night than in the day. Because daytime and nighttime results were strongly correlated, borderline hypoxia during the day is strongly predictive of overt hypoxia at night.

Validation of a Mitotic Index Cutoff as a Prognostic Marker in Undifferentiated Uterine Sarcomas.

Undifferentiated uterine sarcomas (UUS) are a heterogenous group of high-grade mesenchymal tumors. Although these tumors are highly aggressive, a subset of patients may experience long-term survival. These tumors have previously been divided morphologically into uniform and pleomorphic types. A previous study demonstrated that a mitotic index cutoff of 25 mitoses/10 high-power fields (corresponding to 11.16 mitotic figures/mm) could successfully divide tumors into 2 prognostic groups with significantly different overall survival. The goals of the current study were to (1) validate this mitotic index cutoff in an independent, multicenter cohort and (2) explore the prognostic value of the mitotic index groups in relation to other clinicopathologic variables. Cases were included from 3 independent institutions: The Norwegian Radium Hospital, The Mayo Clinic, and Skåne University Hospital. A total of 40 tumors were included after central review. All cases were negative for the YWHAE-FAM22A/B and JAZF1-JJAZ1 translocations. Survival data were available on all patients. In this study, one-third of patients with UUS survived beyond 5 years. The crude (unadjusted) Cox Proportional Hazards model revealed a number of parameters that significantly impacted overall survival, including mitotic index group, patient age, stage, and the presence of tumor necrosis. Classification into the uniform and pleomorphic types was not prognostic. Combining these parameters into an adjusted model revealed that only the mitotic index group and stage were prognostic. On the basis of these findings, it is proposed that UUS be subdivided into "mitogenic" and "not otherwise specified" types.

An observational study of comorbidity and healthcare utilisation among HIV-positive patients aged 50 years and over.

The number of HIV-positive people aged ≥50 years is rising each year. We measured the prevalence of non-infectious illnesses and their risk factors and described healthcare use in this UK population. A cross-sectional, observational study was conducted at an outpatient HIV specialist clinic in south east England. Patients age ≥50 years were invited to complete questionnaires measuring demographics, non-infectious illnesses, medication use, lifestyle and healthcare utilisation. The response rate was 67%. Of 299 participants, 84% reported ≥1 comorbid condition and 61% reported ≥2 (multimorbidity). Most commonly reported were high cholesterol, sexual dysfunction, hypertension and depression. In multivariate analyses, age, number of years HIV-positive and duration of antiretroviral therapy remained significant predictors of comorbidity when controlling for lifestyle factors (exercise, smoking and use of recreational drugs and alcohol). Use of non-HIV healthcare services was associated with increasing comorbidity, a longer duration of HIV and recreational drug use. The majority of HIV-patients aged ≥50 years reported multiple comorbidities and this was associated with polypharmacy and increased use of non-HIV services. Further research examining the quality, safety and patient experience of healthcare is needed to inform development of services to optimally meet the needs of older HIV-positive patients.

A normative database of lumbar spine ranges of motion.

The overall aim of the work was to develop a comprehensive normative database of indices for ranges of motion in the lumbar spine, in an asymptomatic sample of the general population. This was a repeated measures prospective study utilizing a reliable and valid instrument, the modified CA6000 Spine Motion Analyzer (Orthopedic Systems Inc. Union City CA & Troke/University of Brighton). The portable equipment was used to collect data in a variety of community settings (e.g. schools, GP surgeries, offices, leisure centres, emergency services stations). A total of 405 asymptomatic subjects (196 female, 209 male) aged 16-90 yr from sedentary, mixed and physically demanding occupations participated in the study and data were collected in standing, at different times of the day, following a standardized methodology for lumbar spine motion in the sagittal, coronal and horizontal planes. Age-related centile graphs were derived separately for male and female subjects in flexion, extension, left and right lateral flexion and left and right axial rotation. All 12 graphs are presented as an appendix located on the Manual Therapy website. Overall, flexion (73-40 degrees) and lateral flexion (28-14 degrees, L&R) declined 45% and 48%, respectively, across the age range. Extension (29-6 degrees) declined the greatest at 79%. By contrast, no overall decline in axial rotational RoMs was recorded, and the median RoM remained at 7 degrees each way across the age spectrum examined. A comprehensive database of indices of lumbar spine ranges of motion has thus been developed which is gender specific, age related, drawn from a wide age range and presents data for all three planes of motion. It is considered that the new database has a number of potential clinical and research applications.

Genome signature-based dissection of human gut metagenomes to extract subliminal viral sequences.

Bacterial viruses (bacteriophages) have a key role in shaping the development and functional outputs of host microbiomes. Although metagenomic approaches have greatly expanded our understanding of the prokaryotic virosphere, additional tools are required for the phage-oriented dissection of metagenomic data sets, and host-range affiliation of recovered sequences. Here we demonstrate the application of a genome signature-based approach to interrogate conventional whole-community metagenomes and access subliminal, phylogenetically targeted, phage sequences present within. We describe a portion of the biological dark matter extant in the human gut virome, and bring to light a population of potentially gut-specific Bacteroidales-like phage, poorly represented in existing virus like particle-derived viral metagenomes. These predominantly temperate phage were shown to encode functions of direct relevance to human health in the form of antibiotic resistance genes, and provided evidence for the existence of putative 'viral-enterotypes' among this fraction of the human gut virome.

Does white coat hypertension require treatment over age 80?: Results of the hypertension in the very elderly trial ambulatory blood pressure side project.

White coat hypertension is considered to be a benign condition that does not require antihypertensive treatment. Ambulatory blood pressure (ABP) was measured in 284 participants in the Hypertension in the Very Elderly Trial (HYVET), a double-blind randomized trial of indapamide sustained release 1.5 mg±perindopril 2 to 4 mg versus matching placebo in hypertensive subjects (systolic blood pressure 160-199 mm Hg) aged >80 years. ABP recordings (Diasys Integra II) were obtained in 112 participants at baseline and 186 after an average follow-up of 13 months. At baseline, clinic blood pressure (CBP) exceeded the morning ABP by 32/10 mm Hg. Fifty percent of participants fulfilled the established criteria for white coat hypertension. The highest ABP readings were in the morning (average 140/80 mm Hg), the average night-time pressure was low at 124/72 mm Hg, and the average 24-hour blood pressure was 133/77 mm Hg. During follow-up, the systolic/diastolic blood pressure placebo-active differences averaged 6/5 mm Hg for morning ABP, 8/5 mm Hg for 24-hour ABP, and 13/5 mm Hg for CBP. The lowering of blood pressure over 24 hours supports the reduction in blood pressure with indapamide sustained release±perindopril as the explanation for the reduction in total mortality and cardiovascular events observed in the main HYVET study. Because we estimate that 50% had white coat hypertension in the main study, this condition may benefit from treatment in the very elderly.

Comparative (meta)genomic analysis and ecological profiling of human gut-specific bacteriophage φB124-14.

Bacteriophage associated with the human gut microbiome are likely to have an important impact on community structure and function, and provide a wealth of biotechnological opportunities. Despite this, knowledge of the ecology and composition of bacteriophage in the gut bacterial community remains poor, with few well characterized gut-associated phage genomes currently available. Here we describe the identification and in-depth (meta)genomic, proteomic, and ecological analysis of a human gut-specific bacteriophage (designated φB124-14). In doing so we illuminate a fraction of the biological dark matter extant in this ecosystem and its surrounding eco-genomic landscape, identifying a novel and uncharted bacteriophage gene-space in this community. φB124-14 infects only a subset of closely related gut-associated Bacteroides fragilis strains, and the circular genome encodes functions previously found to be rare in viral genomes and human gut viral metagenome sequences, including those which potentially confer advantages upon phage and/or host bacteria. Comparative genomic analyses revealed φB124-14 is most closely related to φB40-8, the only other publically available Bacteroides sp. phage genome, whilst comparative metagenomic analysis of both phage failed to identify any homologous sequences in 136 non-human gut metagenomic datasets searched, supporting the human gut-specific nature of this phage. Moreover, a potential geographic variation in the carriage of these and related phage was revealed by analysis of their distribution and prevalence within 151 human gut microbiomes and viromes from Europe, America and Japan. Finally, ecological profiling of φB124-14 and φB40-8, using both gene-centric alignment-driven phylogenetic analyses, as well as alignment-free gene-independent approaches was undertaken. This not only verified the human gut-specific nature of both phage, but also indicated that these phage populate a distinct and unexplored ecological landscape within the human gut microbiome.

The phenotypic distribution and functional profile of tuberculin-specific CD4 T-cells characterizes different stages of TB infection.

BACKGROUND: Recent publications have suggested that altered proportions of functional CD4 T-cell subsets correlate with active pulmonary TB. Also, CD27-expression on tuberculin-activated IFN-γ(+) CD4 T-cells is known to differ significantly between patients with active pulmonary TB and healthy TB-unexposed BCG vaccinees. Here, we explore links between CD4 T-cell phenotype, multiple functional subsets, and control of TB. METHODS: We examined ex-vivo overnight tuberculin activated CD4 T-cells in regards to CD27-expression and the activation markers, CD154 upregulation, IFN-γ, TNF-α, IL-2, and degranulation in 44 individuals, including cases of clinically active pulmonary TB, and hospital staff with prolonged TB exposure, some of whom had latent TB. RESULTS: Active pulmonary TB generally showed an excess of TNF-α(+) subsets over IFN-γ(+) subsets, paralleled by decreased CD27 expression on activated IFN-γ(+) or CD154(+) CD4 T-cells. The single subset distinguishing best between active pulmonary TB and high TB exposure was CD154(+) /TNF-α(+) / IFN-γ(-) /IL-2(-) /degranulation(-) (AUROC 0.90). The ratio between the frequencies of TNF-α(+) /IFN-γ(+) CD4 T-cells was an effective alternative parameter (AUROC 0.87). CONCLUSIONS: Functional subsets and phenotype of tuberculin induced CD4 T-cells differ between stages of TB infection. Predominance of TNF-α(+) CD4 T-cells in active infection suggests an increased effort of the immune system to contain disease.

The role of physician reminders in faecal occult blood testing for colorectal cancer screening.

BACKGROUND: Colorectal cancer screening in the form of faecal occult blood (FOB) testing can significantly reduce the burden of this disease and has been used as early as the 1970s. Effective involvement of GPs along with reminding physicians prior to seeing a patient may improve uptake. OBJECTIVE: This article is a systematic review of published literature examining the uptake of FOB testing after physician reminders as part of the colorectal cancer screening process. METHODS: Electronic databases were searched from January 1975 to October 2010. All studies comparing physician reminders (Rem) with controls (NRem) were identified. A meta-analysis was performed to obtain a summary outcome. RESULTS: Five comparative studies involving 25 287 patients were analyzed. There were 12 641 patients were in the Rem and 12 646 in the NRem group. All five studies obtained a higher percentage uptake when physician reminders were given. However, in only two of the studies were the percentage uptake significantly higher. There was significant heterogeneity among trials (I2 = 95%). The combined increase in FOB test uptake was not statistically significant (random effects model: risk difference = 6.6%, 95% CI: -2-14.7%; z = 1.59, P = 0.112). CONCLUSION: Reminding physicians about those patients due for FOB testing may not improve the effectiveness of a colorectal cancer screening programme. Further studies are required and should focus on areas where there is a lower baseline uptake and areas with high levels of deprivation.

The effect of bangerter occlusion foils on blepharospasm and hemifacial spasm in occlusion-positive and occlusion-negative patients.

OBJECTIVE: To test the hypothesis that occlusion-positive (OP) patients with blepharospasm (BEB) or hemifacial spasm (HFS) will benefit from a Bangerter occlusion foil (BOF), compared to occlusion-negative (ON) patients. OP/ON was based on immediate improvement in spasm with placement of a hand in front of either eye. DESIGN: Prospective non-randomised single-centre pilot study. PARTICIPANTS: Fifteen-patients (6 BEB, 9 HFS). METHODS: Patients were identified as OP or ON and wore highest-density BOF tolerable over one spectacle lens for 1 month. Outcomes were assessed at 1 month. MAIN OUTCOME MEASURES: Validated quality-of-life questionnaire (CDQ-24), scores of blink-rate and spasm severity assessed by two observers from video-recordings. RESULTS: OP group had mean improvement in all scores. There was no change or worsening of scores in the ON group. In both BEB and HFS, more OP patients reported subjective benefit from wearing a foil (2 of 4 BEB, and 2 of 2 HFS) compared to the ON group (0 of 2 BEB, and 1 of 7 HFS). CONCLUSION: OP patients with BEB and HFS are more likely to experience improvement in spasms from wearing a BOF compared to ON patients. The occlusion test should be considered on all patients with BEB or HFS.