Elevated risk of multimorbidity post-COVID-19 infection: protective effect of vaccination.

BACKGROUND: It is unclear how the coronavirus disease 2019 (Covid-19) pandemic has affected multimorbidity incidence among those with one pre-existing chronic condition, as well as how vaccination could modify this association. AIM: To examine the association of Covid-19 infection with multimorbidity incidence among people with one pre-existing chronic condition, including those with prior vaccination. DESIGN: Nested case-control study. METHODS: We conducted a territory-wide nested case-control study with incidence density sampling using Hong Kong electronic health records from public healthcare facilities and mandatory Covid-19 reports. People with one listed chronic condition (based on a list of 30) who developed multimorbidity during 1 January 2020-15 November 2022 were selected as case participants and randomly matched with up to 10 people of the same age, sex and with the same first chronic condition without having developed multimorbidity at that point. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of multimorbidity. RESULTS: In total, 127 744 case participants were matched with 1 230 636 control participants. Adjusted analysis showed that there were 28%-increased odds of multimorbidity following Covid-19 [confidence interval (CI) 22% to 36%] but only 3% (non-significant) with prior full vaccination with BNT162b2 or CoronaVac (95% CI -2% to 7%). Similar associations were observed in men, women, older people aged 65 or more, and people aged 64 or younger. CONCLUSIONS: We found a significantly elevated risk of multimorbidity following a Covid-19 episode among people with one pre-existing chronic condition. Full vaccination significantly reduced this risk increase.

Effects of a recovery swim on subsequent running performance.

The effects of a swimming-based recovery session implemented 10 h post high intensity interval running on subsequent run performance the next day was investigated. Nine well trained triathletes performed two high intensity interval running sessions (HIIS) (8x3 min at 85-90% VO(2peak) velocity), followed 10 h later by either a swim recovery session (SRS) (20x100 m at 90% of 1 km time trial speed), or a passive recovery session (PRS). Subsequently, a time to fatigue run (TTF) was completed 24 h post-HIIS. Venous blood samples were taken pre-HIIS and pre-TTF to determine the levels of circulating C-Reactive Protein (CRP). Subjects were also asked to rate their perceived recovery prior to commencing the TTF run. The SRS resulted in a significantly longer (830+/-198 s) TTF as compared to PRS (728+/-183 s) ( P=0.005). There was also a significant percentage change from baseline in the CRP levels 24 h post-HIIS (SRS=-23%, PRS=+/-5%, P=0.007). There were no significant differences in perceived recovery between two conditions ( P=0.40) . The findings of the present study showed that a swimming-based recovery session enhanced following day exercise performance, possibly due to the hydrostatic properties of water and its associated influence on inflammation.

Physiologic and anatomic assessment of a canine carotid artery stenosis model utilizing phase contrast with vastly undersampled isotropic projection imaging.

BACKGROUND AND PURPOSE: Noninvasive assessment of the hemodynamic significance of carotid stenosis is often performed with MR angiography and supplemented with carotid Doppler sonography. Phase contrast with vastly undersampled isotropic projection reconstruction (PC-VIPR), a novel MR imaging technique, accelerates phase-contrast MR flow imaging and provides both images of the vessels and measurements of blood-flow velocities. For this study, we determined the accuracy of PC-VIPR blood-flow velocity measurements to determine pressure gradients across an experimental carotid stenosis. MATERIALS AND METHODS: A focal stenosis was surgically created in each common carotid artery of 6 canines. Digital subtraction angiography (DSA) was performed, and the degree of stenosis was determined using the North American Symptomatic Carotid Endarterectomy Trial methodology. A microcatheter was positioned in the carotid artery proximal and distal to the stenosis, and pressures were measured in the vessel through the catheter. PC-VIPR was then performed on a 1.5T MR imaging scanner with parameters producing 0.8-mm isotropic voxel resolution. From the velocity measurements, pressure gradients were calculated from the Navier-Stokes relationship to compare with the pressures measured by a catheter. RESULTS: Carotid stenoses in the 50%-85% range were produced in the 12 arteries. Pressure gradients across the stenoses ranged from 6 to 26 mm Hg. The pressure gradient calculated from the PC-VIPR data correlated (r = 0.91, P < .0001) with the actual pressure measurements. CONCLUSION: With PC-VIPR, a novel MR imaging technique, the hemodynamic effect of a stenosis on flow and pressure can be evaluated.

Extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer screening: a pilot study.

BACKGROUND: Caecal intubation can be achieved by extended flexible sigmoidoscopy in 32% of patients. AIM: To assess the feasibility of extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer screening. METHODS: We enrolled 41 patients referred for screening flexible sigmoidoscopy. After purging, examination was performed with a colonoscope. All patients completed sigmoidoscopy (success in meeting referral goal); 93% and 71% had examination to the transverse or ascending colon, and caecum, respectively. Overall yield and right-sided polyps was 56% and 27%, respectively. Caecal intubation and complete examination with polypectomy took 6.0 +/- 2.5 and 18.3 +/- 5.1 min, respectively; with no complications. Twelve patients requested colonoscope withdrawal because of discomfort. Although 46% reported moderate to severe discomfort, 39% and 36%, respectively, were definitely or probably willing to repeat flexible sigmoidoscopy. RESULTS: Unsedated colonoscopy introduced as extended flexible sigmoidoscopy emphasizes the benefits of added yield rather than the negative image of withholding of discomfort relief. The patient can choose to accept the equivalent of an unsedated colonoscopy or reject the option based on perceived discomfort during extended flexible sigmoidoscopy performed by the colonoscopist. CONCLUSION: Extended flexible sigmoidoscopy is a feasible option in carefully selected patients, fully prepared and by an experienced colonoscopist.

Comparison of automatic quantification software for the measurement of ventricular volume and ejection fraction in gated myocardial perfusion SPECT.

The aim of this study was to compare the performance of three different software packages for the calculation of ejection fraction (EF) and end diastolic volume (EDV) from gated myocardial single photon emission computed tomography studies. Two hundred patients undergoing gated stress myocardial perfusion scans were analysed retrospectively. Patients were grouped as follows: small heart (n=31), normal perfusion scan (n=71), and scan with perfusion defects (n=98). EF and EDV were calculated for each using QGS (Cedars Sinai, Los Angeles, CA), 4D-MSPECT (University of Michigan, Ann Arbor, MI), and ECT (Emory University, Atlanta, GA). Bland-Altman plots, repeated measures ANOVA, and linear regression analysis were used to compare methods. Correlation coefficients between the methods for both EF and EDV were high, greater than 0.9. However, Bland-Altman plots revealed a large standard deviation of the difference between methods, preventing the confident estimate of the value of one method from an observation of another. Despite good correlation, the variance between methods was high. These algorithms behave differently, produce widely variable results from one another, and should not be used interchangeably. It may prove prudent for laboratories to independently validate the software algorithm that is chosen against a 'gold standard' using their own population.

Direct protein-protein interaction between the intracellular domain of TRA-2 and the transcription factor TRA-1A modulates feminizing activity in C. elegans.

In the nematode Caenorhabditis elegans, the zinc finger transcriptional regulator TRA-1A directs XX somatic cells to adopt female fates. The membrane protein TRA-2A indirectly activates TRA-1A by binding and inhibiting a masculinizing protein, FEM-3. Here we report that a part of the intracellular domain of TRA-2A, distinct from the FEM-3 binding region, directly binds TRA-1A. Overproduction of this TRA-1A-binding region has tra-1-dependent feminizing activity in somatic tissues, indicating that the interaction enhances TRA-1A activity. Consistent with this hypothesis, we show that tra-2(mx) mutations, which weakly masculinize somatic tissues, disrupt the TRA-2/TRA-1A interaction. Paradoxically, tra-2(mx) mutations feminize the XX germ line, as do tra-1 mutations mapping to the TRA-2 binding domain. We propose that these mutations render tra-2 insensitive to a negative regulator in the XX germ line, and we speculate that this regulator targets the TRA-2/TRA-1 complex. The intracellular domain of TRA-2A is likely to be produced as a soluble protein in vivo through proteolytic cleavage of TRA-2A or through translation of an XX germ line-specific mRNA. We further show that tagged derivatives of the intracellular domain of TRA-2 localize to the nucleus, supporting the hypothesis that this domain is capable of modulating TRA-1A activity in a manner reminiscent of Notch and Su(H).

Development of speechreading supplements based on automatic speech recognition.

In manual-cued speech (MCS) a speaker produces hand gestures to resolve ambiguities among speech elements that are often confused by speechreaders. The shape of the hand distinguishes among consonants; the position of the hand relative to the face distinguishes among vowels. Experienced receivers of MCS achieve nearly perfect reception of everyday connected speech. MCS has been taught to very young deaf children and greatly facilitates language learning, communication, and general education. This manuscript describes a system that can produce a form of cued speech automatically in real time and reports on its evaluation by trained receivers of MCS. Cues are derived by a hidden markov models (HMM)-based speaker-dependent phonetic speech recognizer that uses context-dependent phone models and are presented visually by superimposing animated handshapes on the face of the talker. The benefit provided by these cues strongly depends on articulation of hand movements and on precise synchronization of the actions of the hands and the face. Using the system reported here, experienced cue receivers can recognize roughly two-thirds of the keywords in cued low-context sentences correctly, compared to roughly one-third by speechreading alone (SA). The practical significance of these improvements is to support fairly normal rates of reception of conversational speech, a task that is often difficult via SA.

Murine CD1d-restricted T cell recognition of cellular lipids.

NKT cells are associated with immunological control of autoimmune disease and cancer and can recognize cell surface mCD1d without addition of exogenous antigens. Cellular antigens presented by mCD1d have not been identified, although NKT cells can recognize a synthetic glycolipid, alpha-GalCer. Here we show that after addition of a lipid extract from a tumor cell line, plate-bound mCD1d molecules stimulated an NKT cell hybridoma. This hybridoma also responded strongly to three purified phospholipids, but failed to recognize alpha-GalCer. Seven of sixteen other mCD1d restricted hybridomas also showed a response to certain purified phospholipids. These findings suggest NKT cells can recognize cellular antigens distinct from alpha-GalCer and identify phospholipids as potential self-antigens presented by mCD1d.

1. Positron Emission Tomography of Thoracic Malignancies. Reduction of Myocardial Fluorodeoxyglucose Uptake Artifacts With a Carbohydrate Restricted Diet.

Purpose: To reduce the artifact caused by cardiac uptake of F-18 fluorodeoxyglucose (FDG); we investigated the change in myocardial FDG uptake after placing a group of patients on a carbohydrate-restricted diet.Methods: Case control study involving 130 whole body FDG PET scans. 73 scans were of patients on carbohydrate-restriction; the remaining 57 were without dietary restrictions. Dietary intake for the last meal prior to scanning was recorded for both groups. Coronal and axial images were assessed and scored based on myocardial FDG uptake the presence of associated image artifacts.Results: Of the 73 patients on the diet, 50 did not consume carbohydrates, while of the 57 patients without dietary restriction, 13 did not consume carbohydrates. Of the 67 patients from both groups who consumed carbohydrates prior to their PET scan, 17 (25.4%) had a clinically significant image artifact versus only 6 (9.5%) of the 63 patients who did not consume carbohydrates (P = 0.018) in their meals prior to scanning. The odds ratio was calculated to be 3.23 (confidence interval 1.09-10.00), indicating that the risk a clinically significant image artifact will occur is 3.23 times higher for patients who consume carbohydrates in their last meal prior to scanning.Conclusion: A substantial reduction in the prevalence of myocardial FDG uptake image artifacts among patients who did not consume carbohydrates was observed. A carbohydrate dietary restriction prior to scanning may play a significant role in increasing lesion detectability and in preventing false negative scans when imaging for thoracic neoplasm.

Coordinate up-regulation of low-density lipoprotein receptor and cyclo-oxygenase-2 gene expression in human colorectal cells and in colorectal adenocarcinoma biopsies.

Many colorectal cancers have high levels of cyclo-oxygenase 2 (COX-2), an enzyme that metabolizes the essential fatty acids into prostaglandins. Since the low-density lipoprotein receptor (LDLr) is involved in the uptake of essential fatty acids, we studied the effect of LDL on growth and gene regulation in colorectal cancer cells. DiFi cells grown in lipoprotein-deficient sera (LPDS) grew more slowly than cells with LDL. LDLr antibody caused significant inhibition of tumor cell growth but did not affect controls. In addition, LDL uptake did not change in the presence of excess LDL, suggesting that ldlr mRNA lacks normal feedback regulation in some colorectal cancers. Analysis of the ldlr mRNA showed that excess LDL in the medium did not cause down-regulation of the message even after 24 hr. The second portion of the study examined the mRNA expression of ldlr and its co-regulation with cox-2 in normal and tumor specimens from patients with colorectal adenocarcinomas. The ratio of tumor:paired normal mucosa of mRNA expression of ldlr and of cox-2 was measured in specimens taken during colonoscopy. ldlr and cox-2 transcripts were apparent in 11 of 11 carcinomas. There was significant coordinate up-regulation both of ldlr and of cox-2 in 6 of 11 (55%) tumors compared with normal colonic mucosa. There was no up-regulation of cox-2 without concomitant up-regulation of ldlr. These data suggest that the LDLr is abnormally regulated in some colorectal tumors and may play a role in the up-regulation of cox-2.

Razor blade surgery: use of the Castroviejo blade breaker and holder.

BACKGROUND: To remove skin lesions, many dermatologists use the razor blade which may be manipulated with or without the aid of an instrument. However, the techniques previously described employ the use of an entire razor blade. OBJECTIVE: To outline a technique that is easily performed with better control of the blade and with more precise cutting than by holding the blade by hand. This report reviews the merits of razor blade use in cutaneous surgery as well as the advantages of using the Castroviejo razor blade breaker. METHODS: The method for cutting double-edged razor blades and holding the sections with a Castroviejo blade breaker is described as well as a basic guide for selecting blade size for performing shave biopsies and shave excisions. CONCLUSIONS: Using the Castroviejo razor blade breaker and holder with cut razor blades is safe and allows better control and more precise cutting than using a complete double-edged blade alone.

Graphing health status can help pinpoint patient problems.

Diagnosing the cause of a patient's complaints by reviewing physical symptoms alone may overlook indicators of psychological and emotional problems that need to be considered. A health status assessment (see "Health Status Assessment--A Vital Sign for Planning Patient Therapy," pages 2-9) using the Health Status Questionnaire enables a clinician to rapidly sort through the bases of presenting symptoms in physical and psychological terms. After a patient fills out the form, the data are input into a computer, which translates the results into a graph. The physician and patient then use the graph to review the results and develop a plan of therapy. The scenario below demonstrates use of the graph by Northfield, Minn., family practitioner Donald Lum, M.D., along with a standardized, scripted interpretation-and-questions process developed by Atlanta practitioner Dwana Bush, M.D., and Dr. Lum to plan patient therapy.

Needle stick injuries in country general practice.

AIMS: The aims of this study were to determine the frequency of needle stick injury (NSI) in general practice, to determine what measures were being taken to protect against needle stick injury, and to gather other information regarding work practices, risk perception, and knowledge of transmission. METHODS: A postal survey was undertaken of all general practitioners and one practice nurse per practice address in selected areas of New Zealand. RESULTS: The response rate was 82%. An incidence rate of 22 needle stick injuries in 100 health care workers per 6 month period was found. For general practitioners alone the incidence rate was 25 in 100 per 6 month period and for practice nurses it was 17 in 100 per 6 month period. Recommended precautionary measures were not being followed by most individuals. CONCLUSIONS: Needle stick injury is a substantial problem in general practice and exposes general practitioners and practice nurses to a serious risk of infection from bloodborne transmissible agents. All patients should be considered to pose a potentially high risk of infection and recommended precautionary measures should be followed at all times.

Dominant enhancers of Egfr in Drosophila melanogaster: genetic links between the Notch and Egfr signaling pathways.

The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed an F1 screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context.

Endoscopic hemostasis of nonvariceal, non-peptic ulcer hemorrhage.

The majority of patients who present with acute upper gastrointestinal hemorrhage are found to be bleeding from acid peptic disease including ulcer, esophagitis and gastritis, and variceal disease. Mallory-Weiss tear, Dieulafoy's lesion, cancer, and other rare lesions account for the bleeding source in the remaining patients. Endoscopic hemostasis may be effective in many of the conditions, but only Mallory-Weiss tear and Dieulafoy's lesion are encountered frequently enough to be clinically significant.

Benign colorectal polyps. Endoscopic surveillance guidelines and effects on colorectal cancer risk.

In the past several years, there have been major advances in the understanding of colorectal cancer from both the clinical and basic science level. Although there are various techniques for colorectal cancer screening and surveillance, the most cost-effective approach has yet to be determined. As molecular biology techniques are improved and incorporated into clinical practice, identification of high-risk populations seems possible. With future advances in endoscopy and imaging, patient compliance can be improved. With the proper combination of both clinical and basic science techniques, it seems reasonable that a further reduction in the mortality from colorectal cancer can be accomplished.