Partner bereavement and risk of psoriasis and atopic eczema: cohort studies in the U.K. and Denmark.

BACKGROUND: Stress is commonly cited as a risk factor for psoriasis and atopic eczema, but such evidence is limited. OBJECTIVES: To investigate the association between partner bereavement (an extreme life stressor) and psoriasis or atopic eczema. METHODS: We conducted cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). The exposed cohort was partners who experienced partner bereavement. The comparison cohort was up to 10 nonbereaved partners, matched to each bereaved partner by age, sex, county of residence (Denmark) and general practice (U.K.). Outcomes were the first recorded diagnosis of psoriasis or atopic eczema. We estimated hazard ratios (HRs) and confidence intervals (CIs) using a stratified Cox proportional hazards model in both settings, which were then pooled in a meta-analysis. RESULTS: The pooled adjusted HR for the association between bereavement and psoriasis was 1·01 (95% CI 0·98-1·04) across the entire follow-up. Similar results were found in other shorter follow-up periods. Pooled adjusted HRs for the association between bereavement and atopic eczema were 0·97 (95% CI 0·84-1·12) across the entire follow-up, 1·09 (95% CI 0·86-1·38) within 0-30 days, 1·18 (95% CI 1·04-1·35) within 0-90 days, 1·14 (95% CI 1·06-1·22) within 0-365 days and 1·07 (95% CI 1·02-1·12) within 0-1095 days. CONCLUSIONS: We found a modest increase in the risk of atopic eczema within 3 years following bereavement, which peaked in the first 3 months. Acute stress may play a role in triggering onset of new atopic eczema or relapse of atopic eczema previously in remission. We observed no evidence for increased long-term risk of psoriasis and atopic eczema following bereavement.

The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.

BACKGROUND: Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited. OBJECTIVES: This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma. METHODS: We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis. RESULTS: In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60). CONCLUSIONS: We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.

Risk factors for falls in patients with total hip arthroplasty and total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: Falls are common after total hip arthroplasty (THA) and total knee arthroplasty (TKA). While previous studies have investigated various risk factors for falls in patients following THA and TKA, no systematic reviews have summarized these risk factors. Therefore, the current systematic review aimed to summarize evidence regarding risk factors for falls in patients after THA and/or TKA. METHODS: MEDLINE, EMBASE, CINAHL, SPORTDiscus, and Physiotherapy Evidence Database (from inception to June 30, 2018) were searched. The methodological quality and quality of evidence of the included studies were assessed by two independent reviewers. Relevant data regarding participants' characteristics, study design, follow-up time points, and identified risk factors were extracted. Meta-analyses and narrative syntheses were performed. RESULTS: Twelve studies with a total of 1,292,689 participants were included. Twenty-nine identified risk factors for post-THA/TKA falls were classified into either inpatient or post-discharge risk factors. Key risk factors for both post-THA and/or post-TKA inpatient falls that showed moderate level of evidence included: postoperative complications or comorbidities and revision THA/TKA. Likewise, risk factors for post-discharge falls after THA and/or TKA that demonstrated moderate level of evidence included: medications, psychiatric diseases, living alone, prior history of TKA, falls history and female gender. The quality of the included studies varied and sample sizes were not justified. CONCLUSIONS: This review summarized both non-modifiable and modifiable risk factors for post-THA/TKA falls. Our findings highlight the importance of developing strategies to lower the falls risk among patients following THA/TKA.

Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis.

Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-nuclear factor of activated T cells (NFAT) pathway, including cyclosporine A or tacrolimus, is commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threatening conditions. A component of the A. fumigatus cell wall, ß-glucan, is recognized by dendritic cells (DCs) via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important antifungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.

Severe prothrombin deficiency caused by prothrombin-Edmonton (R-4Q) combined with a previously undetected deletion.

BACKGROUND: During infancy, a male patient experienced several life-threatening bleeding episodes. Standard coagulation tests revealed that the patient's plasma prothrombin activity was 8%, while his father's and mother's levels were 74% and 62%, respectively. OBJECTIVES: A molecular genetic approach was used to determine the molecular basis of prothrombin deficiency within the family. PATIENT/METHODS: Prothrombin genomic DNA fragments were amplified by using the polymerase chain reaction (PCR). In addition, liver cDNA fragments were amplified from the patient by using reverse transcription (RT) and PCR. The nucleotide sequences of the DNA fragments were determined. RESULTS: A novel, heterozygous point mutation (g.1755 G > A, named prothrombin-Edmonton) was detected in the patient and his mother, resulting in the mutation of Arg-4 in the prothrombin propeptide to Gln (R-4Q). RT-PCR analysis of the patient's liver sample demonstrated the presence of two mRNA transcripts that differed by the presence or absence of exon 11. Real-time PCR analysis on genomic DNA and cDNA confirmed a deletion (g.10435_10809del) in the paternal allele. CONCLUSIONS: The patient has a maternally-inherited point mutation (R-4Q) and a paternally-inherited deletion. By analogy with the previously reported factor IX San Dimas, the R-4Q mutation probably causes under-carboxylation of prothrombin and poor cleavage of the propeptide in the hepatocyte. The deletion probably results in a polypeptide that lacks 50 amino acids from the protease domain; this is likely to impair folding, secretion, stability and/or activity of the truncated prothrombin. The two mutations combine to give the prothrombin deficiency observed in the patient.

Direct acceleration of solid-density plasma bunch by ultraintense laser.

The interaction of a petawatt laser with a small solid-density plasma bunch is studied by particle-in-cell simulation. It is shown that when irradiated by a laser of intensity >10(21) W/cm2, a dense plasma bunch of micrometer size can be efficiently accelerated. The kinetic energy of the ions in the high-density region of the plasma bunch can exceed ten MeV at a density in the 10(23)-cm(-3) level. Having a flux density orders of magnitude higher than that of the traditional charged-particle pulses, the laser-accelerated plasma bunch can have a wide range of applications. In particular, such a dense energetic plasma bunch impinging on the compressed fuel in inertial fusion can significantly enhance the nuclear-reaction cross section and is thus a promising alternative for fast ignition.

Red cell flux during the cardiac cycle in the rabbit myocardial microcirculation.

OBJECTIVE: (1) To measure regional phasic myocardial red cell flux during a cardiac cycle using a laser Doppler velocimeter. (2) To test the responses of regional red cell flux to a vasodilator (adenosine), a vasoconstrictor (angiotensin II), and an inotrope (isoproterenol). METHODS: Using an anaesthetised open-chest rabbit with the pericardium intact a 140-micron-tip fibre optic probe was placed in the left ventricular myocardium in various locations. With the fibre in place drugs were given to alter myocardial loading conditions while red cell flux was registered. RESULTS: Phasic red cell flux was similar in the epicardium to endocardium giving an average endo/epi ratio of 1.14 in the rabbit heart. At least two peaks of increased red cell flux within a single cardiac cycle were observed. Some unique patterns for red cell flux were observed in specialised myocardial structures. Adenosine increased red cell flux but minimally changed the pattern of phasic flux throughout the cycle. CONCLUSIONS: Laser Doppler velocimetry permits the recording of phasic red cell flux during the cardiac cycle in the myocardial microcirculation. Its pattern is determined by both coronary arterial inflow and venous outflow. The pattern of red cell flux may be characteristic for a region-probably determined by difference in tissue pressure (attributable to the pattern of muscle fibre shortening and collagen tethering) and changes in capillary length and density.

A model of calcium regulation in smooth muscle cell.

A model of smooth muscle cell is proposed to describe the mechanisms by which intracellular calcium (Cai) is regulated when the cell is stimulated by noradrenaline (NA)/agonist (Ag) or depolarized. The intracellular Ca2+ store is comprised of two calcium pools: A-store which is sensitive to inositol 1,4,5 trisphosphate (IP3) and C-store, insensitive to IP3 but sensitive to Cai. The A-store is refilled by Ca2+ from C-store and reuptake of Cai. The uptake rate is dependent on the degree of filling in the A-store. The C-store, activated by Cai, is replenished by extracellular Ca2+ (Cao). IP3 generated by NA or Ag changes the A-store permeability, discharging its Ca2+ into the cytosol. Depolarization activates Ca2+ current through the L-type channels. The following events are simulated and compared with experimental observations: (a) Cai transient stimulated by high K+; (b) Cai transient and Ca2+ efflux induced by shortlasting and longlasting NA in the absence of Cao; (c) effect of lanthanum on NA-induced Cai and Ca2+ efflux; and (d) effects of nifedipine, ryanodine, BAY K 8644 and cyclopiazonic acid on Cai.

Pigmented central neurocytoma: case report and literature review.

A case of pigmented central neurocytoma is reported. The tumor showed histologic, immunophenotypic, and ultrastructural features of central neurocytoma. The pigment consisted of an intimate association of lipofuscin and neuromelanin. Pigmented neuroepithelial tumors are rare, and the pigments may be neuromelanin or melanin. Pigmented central neurocytoma has not been described to date. The low proliferation rate of the tumor suggests a delayed turnover of tumor cells as a possible cause of lipofuscin accumulation. Autocatalytic peroxidation of lipofuscin is a possible mechanism of neuromelanin formation.

Stepwise pain score analysis of the effect of local lignocaine on outpatient hysteroscopy: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the efficacy of lignocaine gel in reducing the overall pain and pain of individual steps during outpatient hysteroscopy in comparison with placebo (no anesthesia). DESIGN: A prospective, randomized, double-blind, placebo-controlled trial. SETTING: Outpatient hysteroscopy clinic in a regional hospital in Hong Kong. PATIENT(S): A total of 500 Chinese patients undergoing outpatient hysteroscopy. INTERVENTION(S): Application of lignocaine gel to the cervix during outpatient hysteroscopy. MAIN OUTCOME MEASURE(S): Mean pain score using present pain intensity, overall pain score measured by total area under the curve, and the pain score of individual steps in the procedure in patients receiving lignocaine gel were compared with those of patients having no anesthesia. The failure rate and poor-view rate in both groups were also compared. RESULT(S): There were no statistically significant differences in mean pain score, overall pain score, and pain score of individual steps between the lignocaine group and controls. The failure rate and poor-view rate also showed no statistically significant differences. CONCLUSION(S): Outpatient hysteroscopy without anesthesia is acceptable to most Chinese women, and the local application of lignocaine gel is not effective in reducing pain.

Mucinous anal gland carcinoma with perianal Pagetoid spread.

We report a case of well differentiated perianal mucinous carcinoma with associated dysplasia of the adjacent anal gland epithelium. Anal gland dysplasia is only rarely demonstrable histologically in cases of adenocarcinoma of suspected anal gland origin. The tumor was not associated with chronic perianal abscess or fistula formation, which had been regarded as important in the pathogenesis of perianal mucinous carcinoma. There was associated, clinically unsuspected Pegetoid intra-epidermal spread of adenocarcinoma in the perianal skin.

The dynamics of the coronary venous system in the dog.

The coronary vascular system is characterised by a small blood-volume, high resistance arterial system, in which flow is primarily diastolic, a capillary-venule exchange system and a large blood volume, low resistance venous system with predominantly systolic flow. In order to understand the venous component we measured intramyocardial pressure (IMP), peripheral (PVP) and central (CVP) coronary venous pressure, as well as phasic coronary sinus outflow. Based on the experimental data, a model is proposed to describe the hemodynamics of the coronary venous system. This model consists of an intramyocardial vascular storage region into which the arterial blood flows during diastole. During systole, the pressure in the storage vessels increases, pushing the peripheral and epicardial venous system. Blocking the inflow tends to empty the 'storage' and the peripheral regions, reducing venous pressures. Occlusion of the outflow increases the blood volume in these regions, elevating venous pressures. The observations of peak (IMP-PVP) vs peak venous flow during vagal, right abd left stellate stimulation conform satisfactorily with the model.

Vaginal misoprostol compared with vaginal gemeprost in termination of second trimester pregnancy. A randomized trial.

A prospective randomized trial was conducted in 140 women to compare the efficacy of vaginal gemeprost with vaginal misoprostol for termination of second trimester pregnancy. Women requesting termination of second trimester pregnancy were randomized into two groups. Group A women were given 1 mg vaginal gemeprost every 3 h for a maximum of five doses in the first 24 h, whereas group B women were given 400 micrograms vaginal misoprostol every 3 h for a maximum of five doses in 24 h. The median induction-abortion interval in the vaginal misoprostol group (14.1 h) was significantly shorter than that in the gemeprost group (19.5 h). The percentage of women who achieved successful abortion within 24 h in the misoprostol group (80.0%) was significantly higher than that in the gemeprost group (58.6%). There was no significant difference in the incidence of side effects between the two groups except for diarrhea, which was more common in the gemeprost group. The incidence of fever was more common in the misoprostol group. It is concluded that vaginal misoprostol is more effective than gemeprost in termination of second trimester pregnancy.

PIP: The efficacies of vaginal gemeprost and vaginal misoprostol for the termination of second-trimester pregnancies were compared in a prospective, randomized trial conducted in Hong Kong, China. 140 women 16-40 years of age requesting pregnancy termination at gestational ages of 14-20 weeks were allocated to receive either 1 mg of gemeprost every 3 hours up to 5 doses (n = 70) or 400 mcg of misoprostol every 3 hours up to 5 doses (n = 70). 56 women (80.0%) in the misoprostol group and 41 (58.6%) in the gemeprost group aborted within 24 hours. In primigravidas, the rate of successful abortion was significantly higher in the misoprostol group (83.3%) than the gemeprost group (55.3%). There were no significant between-group differences in this rate for multigravid women. The median induction-abortion interval was significantly shorter in the misoprostol group (14.1 hours) than the gemeprost group (19.5 hours). Blood loss during the procedure was similar in both groups. Although there was no significant difference in the incidence of side effects, diarrhea was less common in misoprostol acceptors (24.3%) than in women who received gemeprost (40.0%). In addition to being more effective at inducing abortion, misoprostol is substantially less expensive than gemeprost and does not require refrigerated transport and storage facilities. Thus, misoprostol, with or without mifepristone, should be the drug of choice for termination of mid-trimester pregnancies. Further studies are needed, however, to determine the optimal dose and frequency of administration.

The kinetics of Ca-Na exchange in excitable tissue.

A model is proposed to describe the Na-Ca exchange in excitable tissues. The present scheme requires a carrier mechanism that exchanges 3Na for 1Ca across the membrane under the electrochemical gradient of Na. The carriers, assumed to be trivalent anions, have monovalent and divalent sites; Ca and Na can compete only at the second site. The partially and fully loaded carrier-ion complexes are mobile and diffusible across the membrane. Subsequently, analytical expressions for Na and Ca unidirectional flux at steady state are derived in terms of intracellular concentration (Na(i) and Ca(i)) and extracellular concentration (Na(o) and Ca(o)) as well as membrane potential, E(M). Published experimental flux data on cardiac muscle, squid axon, and rat synaptosomes can be satisfactorily fitted with the flux equation simply by adjusting the numerical constants.

Outpatient diagnostic hysteroscopy: analysis of 429 cases.

OBJECTIVE: To evaluate the diagnostic accuracy of outpatient hysteroscopy. METHODS: Outpatient CO2 hysteroscopy using video-camera for monitoring was performed on 429 patients from November 1995 to December 1996. The indications included post-menopausal bleeding (32.2%), menorrhagia (25.4%), irregular bleeding (24.7%), intermenstrual spotting (10.2%) and others (7.5%). RESULTS: Hysteroscopy was successfully performed on 420 (97.9%) patients. Although no anaesthetics were used, only two (0.47%) patients complained of severe pain during the procedure. Twenty-one (4.9%) patients had poor view due to submucosal fibroid or bloody view. There were no operative complications. Normal uterine cavity was found in 36.8% and atrophic endometrium in 34.7% of patients. The pathologies included submucosal fibroid (10.7%), endometrial polyp (5.8%) and fibroid polyp (2.8%). Five (1.2%) out of 429 patients were confirmed histologically to have endometrial carcinoma. No malignant lesions were missed. A total of 372 (86.7%) patients had histological confirmation of hysteroscopic findings. In 57 (13.2%) patients, the histological results did not correlate with the hysteroscopic findings. CONCLUSIONS: Outpatient hysteroscopy and suction curettage is a safe, cost-effective and acceptable procedure.

Critical care in obstetrical patients: an eight-year review.

OBJECTIVE: To review the clinical characteristics and outcomes of critically ill obstetrical patients and to determine the outcome predictability using the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system. METHODS: A retrospective data collection of all obstetrical patients (n = 49) admitted for more than 24 hours to the Intensive Care Unit at Kwong Wah Hospital from 1988 to 1995 was conducted. Demographics, obstetric data, preexistent medical problems, diagnosis, days staying in the ICU and ICU related data were recorded for each patient. RESULTS: Obstetric admissions to ICU during the study period represented 0.12% of all deliveries during this period. There was a predominance of postpartum admissions and obstetric diagnosis responsible for the patients' critical illness. Massive postpartum haemorrhage was the single most common cause of ICU admission, representing 53.0% of all patients. Preeclampsia and eclampsia (14.3%), anaesthesia related complications (14.3%), and medical diseases complicating pregnancy (14.3%) were the other common disease categories for ICU admission. Two cases (4.1%) of surgical disease complicating pregnancy were admitted. The maternal mortality rate was 5.1 deaths per 100,000 total births, or 2 maternal deaths in 39,354 total deliveries in this study period. All deaths were due to nonobstetric causes. The perinatal mortality rate was 10.0% (5 cases) in this study group. CONCLUSIONS: When applying the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system in predicting the final outcome in this group of obstetric patients, we found that our obstetric patients requiring intensive care had a better outcome than predicted, as expressed by a low mortality ratio (0.25).

Attitude towards rape among doctors working in the emergency department.

In this study, a 29-item questionnaire survey was conducted to explore the attitude and knowledge toward rape amongst doctors working in Hong Kong. The Likert scale was used for questions on attitude and knowledge. A composite score was computed for both attitude and knowledge. Comparisons of the attitude and knowledge scores were made between doctors of different genders and ranks. Existing practices in the handling of rape cases were also explored. The response rate was 58%; 175 questionnaires were completed by 147 (84%) male and 28 (16%) female doctors. There were 12 (6.3%) consultants, 44 (23%) senior medical officers and 119 (62%) medical officers. The average length of emergency department experience was 4.7 years. Most doctors held a favourable attitude towards rape victims, and there was no significant difference between senior and junior doctors (P=0.062) or between doctors of different genders (P=0.793). However, 36% of the doctors agreed that 'a women should be responsible for preventing her own rape', and more female doctors agreed that 'a woman can successfully resist rape if she tries hard enough' (P<0.042). Senior doctors had a higher knowledge score (P<0.0001). The correlation between knowledge and attitude scores was low (Spearman coefficient 0.258; P<0.05). In conclusion, doctors working in the emergency department generally held favourable attitudes towards rape victims. However, there is still room for improvements in attitude and knowledge. A one-stop service is suggested to avoid fragmentation and prevent 'revictimization'.

A method for measuring systolic and diastolic microcirculatory red cell flux within the canine myocardium.

BACKGROUND: Knowledge of the patterns of movement of red cells during the cardiac cycle in the microcirculation within the contracting myocardium is largely unknown. We describe a method of making such measurements in the canine myocardium using the technique of laser Doppler velocimetry. METHODS: A lensed 100 microm fiber-optic probe was inserted into the beating myocardium at various sites. Using an ultra-stable laser and achieving measurement stability by heterodyning the laser light and reflected light from the tissue, it was possible to obtain a stable high quality measurement of predominately red cell movement in the microcirculation. RESULTS: Unique regional patterns of red cell movement within the myocardium were observed. Epicardial flux was continuous with peaks while endocardial flux was predominately diastolic. Stopping flow in the epicardial artery for 5-6 s demonstrated that red cell movement continues in the microcirculation with some reduction followed by a delayed reactive hyperemia. Modeling demonstrates an important role for the small coronary veins in control of microcirculatory red cell movement. CONCLUSIONS: It is possible using laser Doppler velocimetry to measure red blood cell flux in the beating canine myocardium. Such measurements demonstrate a high degree of complexity which is not reflected in epicardial coronary arterial or venous flow.

Evaluation of predictor variables for a self-instructional preclinical course.

Several studies have shown that the Dental Admission Test and predental grade point average have validity in predicting performance in dental school. The purpose of this two-year study is to compare these predictors with a manual skill exercise to determine their usefulness in predicting manual dexterity success in operative dentistry. Sophomore students were instructed to make preparations on an Ivorine block following imprinted outlines. Correlation to performance on laboratory examinations was computed. Results indicate the traditional predictors have limited usefulness in manual skill prediction while the Ivorine block exercise demonstrated consistent correlation over both years. The emphasis on manual dexterity in preclinical dental courses requires that appropriate variables be used in selecting students.