1. The mechanical effects of morphine, heroin, codeine, dilaudid, dicodid, and eukodol upon the alimentary tract are discussed and contrasted.

2. The results of these mechanical effects upon the passage of food along the alimentary canal are discussed.

3. The constipating action of morphine is explained upon an almost purely mechanical basis.

4. From experimental evidence it is concluded that dilaudid is probably a constipating drug although this effect may not be so marked as that produced by morphine.

5. There is no experimental evidence to suggest that the administration of dicodid would ever produce constipation.

6. It is suggested that small doses of eukodol are not constipating, whereas large doses, in certain circumstances which are discussed, may produce a mild degree of constipation.

In the human population, influenza A viruses are associated with acute respiratory illness and are responsible for millions of deaths annually. Avian and human influenza viruses typically have a different α2-3- and α2-6-linked sialic acid (SA) binding preference. Only a few amino acid changes in the haemagglutinin on the surface of avian influenza viruses (AIV) can cause a switch from avian to human receptor specificity, and the individuals with pathognostic chronic diseases might be more susceptible to AIV due to the decreased expression level of terminal α2-3-linked SA in their saliva. Here, using lectin and virus histochemical staining, we observed the higher expression levels of α2-3/6-linked SA influenza virus receptors in the airway of HBV-transgenic mice compared with that of control mice due to the significant decrease in control mice during ageing, which imply that this is also a risk factor for individuals with pathognostic chronic diseases susceptible to influenza viruses. Our findings will help understand the impact on influenza virus pathogenesis and transmission.

Both the sensitation of typhoid bacilli by serum and their ingestion by leucocytes when sensitised, have been shown by Ledingham (1912) to take place in accordance with the laws regulating an adsorption process, the removal of opsonin from a serum by bacteria, and of sensitised bacteria from an emulsion by leucocytes following very satisfactorily the adsorption equation y=kxn, where y= the amount adsorbed, x= the amount left free and k and n are constants.

The three heterologous anti-sera currently provided for tetanus prophylaxis have been compared with reference to the production of untoward reactions in 498 patients, and to the blood antitoxin concentrations produced in 76 patients. Equine serum, although giving rise to more reactions, was the only effective agent in terms of the levels and duration of serum antitoxin concentration produced. The local response to a test dose of any of the three sera is not a reliable guide to immediate or late general reactions.

In a series of publications issued from the Institut Prophylactique in Paris, Vernes and his co-workers (1926) described a flocculation method for the diagnosis of tuberculosis in man. This method was first elaborated for the diagnosis of syphilis. Various modifications were then introduced and it was found that the test could be applied to the diagnosis of human tuberculosis. Finally a standard technique was laid down. This consisted of measuring by means of the Vernes-Bricq-Yvon photometer the amount of flocculation which took place during 4 hours' incubation at 20° C. when 0·6 c.c. of resorcinol (1·25 per cent.) was added to an equal volume of the blood serum under test. Readings were taken immediately the resorcinol was added and again at the end of the incubation period. The difference between these readings gave the value on which the diagnosis was made. If this were below 30 the serum was considered normal. Values over 30 indicated infection, the higher the number the more advanced the infection. Correlation of these figures with clinical examination showed that very frequently the photometer value confirmed the clinical findings, and that in some cases the course of the disease could be forecast and followed by testing a number of blood samples over a period.

Sera from 203 Asian immigrants to the United Kingdom were examined for toxoplasma antibodies. The antibody titres were not significantly different from those found in the indigenous population although there was some indication that a higher domestic animal–human contact in Asia was associated with a higher positivity rate.

Rodents and shrews are major reservoirs of various pathogens that are related to zoonotic infectious diseases. The purpose of this study was to investigate co-infections of zoonotic pathogens in rodents and shrews trapped in four provinces of China. We sampled different rodent and shrew communities within and around human settlements in four provinces of China and characterised several important zoonotic viral, bacterial, and parasitic pathogens by PCR methods and phylogenetic analysis. A total of 864 rodents and shrews belonging to 24 and 13 species from RODENTIA and EULIPOTYPHLA orders were captured, respectively. For viral pathogens, two species of hantavirus (Hantaan orthohantavirus and Caobang orthohantavirus) were identified in 3.47% of rodents and shrews. The overall prevalence of Bartonella spp., Anaplasmataceae, Babesia spp., Leptospira spp., Spotted fever group Rickettsiae, Borrelia spp., and Coxiella burnetii were 31.25%, 8.91%, 4.17%, 3.94%, 3.59%, 3.47%, and 0.58%, respectively. Furthermore, the highest co-infection status of three pathogens was observed among Bartonella spp., Leptospira spp., and Anaplasmataceae with a co-infection rate of 0.46%. Our results suggested that species distribution and co-infections of zoonotic pathogens were prevalent in rodents and shrews, highlighting the necessity of active surveillance for zoonotic pathogens in wild mammals in wider regions.

Roughly half (54%) of the 910 young conscripts at a garrison in Finland were vaccinated with commercial influenza vaccines in autumn 1998. During the influenza outbreak in February 1999, 12 H3N2-subtype virus strains were isolated from vaccinated patients, and 11 such strains were isolated from unvaccinated patients. The isolates were related to the vaccine strain A/Sydney/5/97 and could be classified into three subgroups based on sequence variation in the HA1 gene coding for the variable domain of viral haemagglutinin (HA). A total of 6–10 amino-acid substitutions in HA1, three of these in the receptor-binding site, differentiated the field strains from the vaccine virus. In haemagglutination inhibition (HI) tests, eight strains from the study population exhibited reduced reactivity with a variety of antisera including human post-vaccination sera. Six of these strains were isolated from vaccinated and two from unvaccinated patients. The reduced reactivity did not correlate with particular amino-acid changes in HA1. We suggest that low-reactivity viruses may have an advantage over other co-circulating variants under some circumstances characterized by enhanced immunity-mediated selection and high infection pressure. Whether the frequency of these viruses increased in our vaccinated study population cannot be determined, nor can their effect on vaccine efficacy.

To evaluate the dynamic changes of antibody levels in different groups after inoculation with the coronavirus disease 2019 (COVID-19) vaccine. The 1493 subjects who were tested for IgM and IgG against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Qionglai Medical Center Hospital from June to October in 2021 were accepted for analyses of geometric mean titre (GMT) of IgG and IgM. The overall GMT of IgM and IgG in the population of Qionglai reached at a peak value at 1.497 (+3.810, −3.810) S/CO and 4.048 (+2.059, −2.059) S/CO in the second week, and then gradually decreased to 0.114 (+2.707, −2.707) and 1.885 (+1.506, −1.506) S/CO in the 11th–25th weeks, respectively. IgG was positive within 1 day, after that GMT increased continuously and peaked on the 13th day. There was a significant difference between male and female groups for titre of IgM during the prior 2 weeks and among three age groups for titre of IgG during the 2nd–3rd week after vaccination. The GMT level of IgG in the population vaccinated with the COVID-19 vaccine remained at a high level within 25 weeks and peaked on the 13th day, indicating that IgG could exist for a longer period and exhibiting positive SARS-CoV-2- defending effect.

Despite promising steps towards the elimination of hepatitis C virus (HCV) in the UK, several indicators provide a cause for concern for future disease burden. We aimed to improve understanding of geographical variation in HCV-related severe liver disease and historic risk factor prevalence among clinic attendees in England and Scotland. We used metadata from 3829 HCV-positive patients consecutively enrolled into HCV Research UK from 48 hospital centres in England and Scotland during 2012–2014. Employing mixed-effects statistical modelling, several independent risk factors were identified: age 46–59 y (ORadj 3.06) and ≥60 y (ORadj 5.64) relative to <46 y, male relative to female sex (ORadj 1.58), high BMI (ORadj 1.73) and obesity (ORadj 2.81) relative to normal BMI, diabetes relative to no diabetes (ORadj 2.75), infection with HCV genotype (GT)-3 relative to GT-1 (ORadj 1.75), route of infection through blood products relative to injecting drug use (ORadj 1.40), and lower odds were associated with black ethnicity (ORadj 0.31) relative to white ethnicity. A small proportion of unexplained variation was attributed to differences between hospital centres and local health authorities. Our study provides a baseline measure of historic risk factor prevalence and potential geographical variation in healthcare provision, to support ongoing monitoring of HCV-related disease burden and the design of risk prevention measures.

Numerouspapers have been published on the effect of heat on diphtheria antitoxin, but there appears to be no record of a series of observations carried out at a temperature nearly that of the human body. The object of this note is to fill in this slight gap in our knowledge.

Vaccination against hepatitis B virus (HBV) is effective at preventing vertical transmission. Sierra Leone, Liberia, and Guinea are hyperendemic West African countries; yet, childhood vaccination coverage is suboptimal, and the determinants of incomplete vaccination are poorly understood. We analyzed national survey data (2018–2020) of children aged 4–35 months to assess complete HBV vaccination (receiving 3 doses of the pentavalent vaccine) and incomplete vaccination (receiving <3 doses). Statistical analysis was conducted using the complex sample command in SPSS (version 28). Multivariate logistic regression was used to identify determinants of incomplete immunization. Overall, 11,181 mothers were analyzed (4,846 from Sierra Leone, 2,788 from Liberia, and 3,547 from Guinea). Sierra Leone had the highest HBV childhood vaccination coverage (70.3%), followed by Liberia (64.6%) and Guinea (39.3%). Within countries, HBV vaccination coverage varied by socioeconomic characteristics and healthcare access. In multivariate regression analysis, factors that were significantly associated with incomplete vaccination in at least one country included sex of the child, Muslim mothers, lower household wealth index, <4 antenatal visits, home delivery, and distance to health facility vaccination (all p < 0.05). Understanding and addressing modifiable determinants of incomplete vaccination will be essential to help achieve the 2030 viral hepatitis elimination goals.

A local COVID-19 outbreak with two community clusters occurred in a large industrial city, Shaoxing, China, in December 2021 after serial interventions were imposed. We aimed to understand the reason by analysing the characteristics of the outbreak and evaluating the effects of phase-adjusted interventions. Publicly available data from 7 December 2021 to 25 January 2022 were collected to analyse the epidemiological characteristics of this outbreak. The incubation period was estimated using Hamiltonian Monte Carlo method. A well-fitted extended susceptible-exposed-infectious-recovered model was used to simulate the impact of different interventions under various combination of scenarios. There were 387 SARS-CoV-2-infected cases identified, and 8.3% of them were initially diagnosed as asymptomatic cases. The estimated incubation period was 5.4 (95% CI 5.2–5.7) days for all patients. Strengthened measures of comprehensive quarantine based on tracing led to less infections and a shorter duration of epidemic. With a same period of incubation, comprehensive quarantine was more effective in containing the transmission than other interventions. Our findings reveal an important role of tracing and comprehensive quarantine in blocking community spread when a cluster occurred. Regions with tense resources can adopt home quarantine as a relatively affordable and low-impact intervention measure compared with centralized quarantine.

We investigated cardiovascular disease (CVD) risk associated with latent tuberculosis infection (LTBI) (Aim-1) and LTBI therapy (Aim-2) in British Columbia, a low-tuberculosis-incidence setting. 49,197 participants had valid LTBI test results. Cox proportional hazards model was fitted, adjusting for potential confounders. Compared with the participants who tested LTBI negative, LTBI positive was associated with an 8% higher CVD risk in complete case data (adjusted hazard ratio (HR): 1.08, 95% CI: 0.99-1.18), a statistically significant 11% higher risk when missing confounder values were imputed using multiple imputation (HR: 1.11, 95% CI: 1.02-1.20), and 10% higher risk when additional proxy variables supplementing known unmeasured confounders were incorporated in the highdimensional disease risk score technique to reduce residual confounding (HR: 1.10, 95% CI: 1.01-1.20). Also, compared with participants who tested negative, CVD risk was 27% higher among people who were LTBI positive but incomplete LTBI therapy (HR: 1.27, 95% CI: 1.04-1.55), whereas the risk was similar in people who completed LTBI therapy (HR: 1.04, 95% CI: 0.87-1.24). Findings were consistent in different sensitivity analyses. We concluded that LTBI is associated with an increased CVD risk in low-tuberculosis-incidence settings, with a higher risk associated with incomplete LTBI therapy and attenuated risk when therapy is completed.

Test baiting has shown that rats underground are distributed in a series of discrete colonies, each one in close association with a group of men. Interplay between colonies is rare in large mines although evident in small ones. In the absence of stables the rats must depend almost entirely on miners’ food scraps.

These observations were made during work carried out under a research grant from Safety in Mines Research Establishment, Ministry of Power, and I am indebted to the Ministry for permission to publish the results. I should like also to express my gratitude to Dr E. T. B. Francis who supervised the work, Mr. C. S. W. Grice of the Ministry of Power and Miss B. B. Jones of the Ministry of Agriculture, Fisheries and Food for their help in various aspects of the work.

This study aimed to understand rural–urban differences in the uptake of COVID-19 vaccinations during the peak period of the national vaccination roll-out in Aotearoa New Zealand (NZ). Using a linked national dataset of health service users aged 12+ years and COVID-19 immunization records, age-standardized rates of vaccination uptake were calculated at fortnightly intervals, between June and December 2021, by rurality, ethnicity, and region. Rate ratios were calculated for each rurality category with the most urban areas (U1) used as the reference. Overall, rural vaccination rates lagged behind urban rates, despite early rapid rural uptake. By December 2021, a rural–urban gradient developed, with age-standardized coverage for R3 areas (most rural) at 77%, R2 81%, R1 83%, U2 85%, and U1 (most urban) 89%. Age-based assessments illustrate the rural–urban vaccination uptake gap was widest for those aged 12–44 years, with older people (65+) having broadly consistent levels of uptake regardless of rurality. Variations from national trends are observable by ethnicity. Early in the roll-out, Indigenous Māori residing in R3 areas had a higher uptake than Māori in U1, and Pacific peoples in R1 had a higher uptake than those in U1. The extent of differences in rural–urban vaccine uptake also varied by region.

Tuberculosis (TB) is one of the top 10 leading causes of morbidity and mortality worldwide [1]. In 2017, approximately 10 million people were infected with TB and 1.3 million patients faced mortality [1]. Patients with active TB can infect up to 10–15 people over a year. There is a greater risk of transmission in overcrowded areas with limited air ventilation including large family units, prisons and slums [1, 2]. Without proper diagnosis and treatment, roughly 45% of non-HIV positive TB patients face mortality [1]. With the help of global organizations and national TB treatment and control programmes, the global incidence of TB is declining by approximately 2% each year [1]. The World Health Organization (WHO) TB-strategy aims to end the TB epidemic and encourages partners to fund national TB programmes to improve diagnosis and treatment of TB. The goal is to ultimately decrease death rates by 90% and decrease incidence rates by 80% [1]. To achieve these goals, the decline in TB incidence needs to reach approximately 4–5% per year [1]. The WHO 2018 TB report identified multidrug resistant TB (MDR-TB) as the leading factor hindering that goal [1]. The incidence and spread of MDR-TB has drastically increased, where approximately 558 000 new cases of MDR-TB were diagnosed in 2017 causing more than 230 000 deaths globally [1]. MDR-TB is identified by resistance to the two most powerful anti-TB treatment drugs including isoniazid and rifampicin [3]. Patients with MDR-TB are required to start second-line anti-TB drugs (SLDs), which are limited, expensive, less effective and more toxic [1,2]. Therapy duration is one of the major limitations of second-line treatments, which may require up to two years of consistent use. Since TB affects mostly developing countries, long treatment durations and associated costs become a major challenge. In 2015, 15% of new TB cases were reported as MDR-TB, which drastically increased to 24% by 2017 [1]. Even with significant improvements in molecular tests and diagnostic methods, MDR-TB is still on the rise where the success rate of treatments is between 50 and 60% [1]. Additional characteristics including socioeconomic and sociocultural factors need to be considered when targeting and treating patients with MDR-TB.

Contra-posing panel data on the incidence of pulmonary tuberculosis (PTB) at the provincial level in China through the years of 2004–2021 and introducing a geographically and temporally weighted regression (GTWR) model were used to explore the effect of various factors on the incidence of PTB from the perspective of spatial heterogeneity. The principal component analysis (PCA) was used to extract the main information from twenty-two indexes under six macro-factors. The main influencing factors were determined by the Spearman correlation and multi-collinearity tests. After fitting different models, the GTWR model was used to analyse and obtain the distribution changes of regression coefficients. Six macro-factors and incidence of PTB were both correlated, and there was no collinearity between the variables. The fitting effect of the GTWR model was better than ordinary least-squares (OLS) and geographically weighted regression (GWR) models. The incidence of PTB in China was mainly affected by six macro-factors, namely medicine and health, transportation, environment, economy, disease, and educational quality. The influence degree showed an unbalanced trend in the spatial and temporal distribution.

While the incidence of infections with the human immunodeficiency virus largely remained unchanged in Germany, an increase of other sexually transmitted infections (STIs) was observed. The aim was to analyse the effectiveness of our sexual education lecture for students in improving the awareness, knowledge and prevention of STIs. We conducted a cross-sectional survey after students had attended our extra-curricular lecture at the Department of Dermatology of the Ludwig-Maximilians-University of Munich, Germany (LMU). We compared the data with a previously performed study in which the same survey was carried out before the lecture had started. A total of 5866 questionnaires were included in the analysis. After attending the lecture significantly more students were aware of STIs (syphilis: 36.8% (before) vs. 63.5% (after); chlamydia: 30.5% vs. 49.3%; gonorrhoea: 22.4% vs. 38.2%; human papillomaviruses (HPV): 17.7% vs. 30.2%), the transmission pathways of STIs (oral: 36.6% vs. 82.6%; vaginal: 81.8% vs. 97.3%; anal: 42.8% vs. 94.0%; penile: 68.7% vs. 92.1%), knew that the HPV vaccination is directed against a virus (36.8% vs. 56.9%) and were interested in receiving a vaccination (57.7% vs. 78.8%). This study demonstrates the positive educative effects of our lecture for awareness and improved knowledge of STIs. To satisfy the need for a comprehensive sexual education, a combination of school and health facility-based programmes should be implemented as one single lecture cannot convey the entire information about STIs.