This report details the comprehensive, gamified cardiopulmonary rehabilitation of a 6-year-old girl undergoing a complex clinical journey from left ventricular assist device (LVAD) bridge therapy to successful heart transplantation. Given the paucity of standardised protocols for this high-risk population, a structured, multidisciplinary team (MDT)-guided pathway was implemented, adapting interventions to the distinct phases of LVAD support and post-transplant recovery. Key nursing and rehabilitation strategies included initiating very early mobilisation in the cardiac intensive care unit (CICU) with meticulous safety precautions for the LVAD driveline and post-sternotomy incision, implementing a tiered programme of play-based respiratory training games to improve pulmonary function, and guiding the patient through a progressive, gamified exercise regimen encompassing low-intensity aerobic games and combined resistance-aerobic training. Throughout, continuous risk monitoring and dynamic adjustment based on haemodynamic and device-specific parameters were paramount. This individualised, phased approach effectively improved the patient's cardiopulmonary function, muscle strength and exercise tolerance. She was discharged on postoperative Day 44 with a left ventricular ejection fraction of 69%, NYHA Class I cardiac function, grade 5 muscle strength and a 6-min walk distance of 260 m, without rehabilitation-related adverse events. This case demonstrates a feasible and effective model for rehabilitating paediatric patients across the challenging continuum from mechanical circulatory support to heart transplantation. This case provides a structured, reproducible framework for cardiopulmonary rehabilitation in paediatric patients transitioning from LVAD support to heart transplantation. It emphasises the necessity of phase-adapted interventions, rigorous safety monitoring and the integration of gamification to enhance engagement and outcomes, offering practical guidance for nurses and therapists in this specialised field.

Orexin receptors (OXRs) have emerged as promising therapeutic targets for insomnia. Our preliminary research suggested that neferine (NEF)-a bisbenzylisoquinoline alkaloid derived from Nelumbinis plumula-is a potential antagonist of OXRs in vitro. However, it remains poorly understood whether NEF affects sleep architecture and quality, as well as the underlying neurobiological mechanisms. To explore this, a chronic sleep-deprived (CSD) mouse model was established using a multi-platform method. The pentobarbital-induced sleep test and HomeCageScan system analysis showed that 3 weeks of CSD prolonged sleep latency, decreased sleep duration and reduced sleep behavior, and NEF treatment (80 mg/kg) could obviously reverse these effects. Telemetric EEG/EMG recordings revealed that NEF administration increased the delta power ratio (sleep depth) and reduced sleep fragmentation (sleep stability) in chronically sleep-deprived mice. Mechanistically, Ca[2+] influx assays and immunofluorescence staining demonstrated that NEF effectively antagonized OXRs both in vitro and in vivo. Bioinformatics analysis revealed that OXRs are highly expressed in monoaminergic neurons within the locus coeruleus (LC) and the dorsal raphe nucleus (DRN). NEF treatment suppressed the activities of noradrenergic-LC and serotonergic-DRN neurons, and reduced the levels of their corresponding neurotransmitters, norepinephrine (NE) and serotonin (5-HT). Together, these findings indicate that NEF exerts desirable sleep-promoting effects by improving sleep depth and sleep stability in sleep-deprived mice, and these effects are potentially mediated by antagonizing OXRs in noradrenergic and serotonergic neurons. This study provides a theoretical basis for the application of NEF in insomnia and offers a new scaffold for insomnia drug development.

The oxygen reduction reaction limits the energy efficiency of H2 fuel cells and Li-air batteries, yet, it remains poorly understood within popular kinetic frameworks. Here, we study the oxygen reduction reaction on Pt/C, Ir/C, Ru/C and Rh/C nanoparticles as a function of electrochemical bias, temperature and O2 pressure at industrially-relevant conditions in membrane electrode assemblies. Bias-, and pressure-dependent Arrhenius analysis reveals distinct changes in the (apparent) activation energy and pre-exponential factor that we relate to kinetics that cascade through a series of rate-limiting steps and transition states. Further, while the kinetics are accelerated by the pressure and bias, they remain pinned to pseudo-capacitive reduction processes and structural changes at the water-solid interface. Collectively, our study informs on how the free energy driving force and pressure tune the degree of rate control of rate-limiting steps and transition states of (electro)catalytic multi-step reactions and how this is related to structural and chemical changes at the interface. This is at the very heart of catalysis.

LIM protein-domain containing protein Ajuba (encoded by AJUBA) functions as a scaffold protein to regulate protein-protein interactions, signalling transduction and genes transcription. AJUBA expression is higher in colorectal cancer (CRC) tissues than normal tissues, but its specific molecular function in CRC progression is still not very clear. Here, we found that, in CRC cancer cell lines, overexpression of AJUBA decreased p53 levels, whereas knock-down of AJUBA significantly increased p53 levels. Although the presence of Ajuba did not influence p53 transcription, it formed a complex with p53 and MDM2 to promote the degradation of p53. AJUBA overexpression reduced the sensitivity of cancer cells to chemotherapeutic drugs and vice versa. In addition, chemotherapeutic drugs significantly induced AJUBA expression, which was largely dependent on the presence of p53. Therefore, Ajuba formed a negative feedback loop to regulate p53 expression and activity. In conclusion, as a novel p53-negative regulator, Ajuba inhibits the apoptosis of CRC cells induced by chemotherapeutic drugs and it may be a new therapeutic target for CRC treatment.

A 62-year-old man underwent successful coronary artery bypass for unstable angina 34 years after a complete repair of tetralogy of Fallot. Coronary risk factors were hypertension and a positive family history. While coronary disease was the presenting complaint, he had evidence of widespread atherosclerosis. He is the first patient reported to undergo coronary artery bypass following repair of tetralogy of Fallot. Coronary artery disease complicating tetralogy of Fallot has been mentioned five times in the literature. As the population of patients who have undergone tetralogy of Fallot ages, the number showing signs of coronary disease will likely rise. Thus, vigilance regarding risk factor modification must encompass these patients as they age.

The brain stems of 17 squirrel monkeys (Saimiri sciureus) were systematically explored for vocalization-related single-unit activity during calls electrically elicited from the periaqueductal grey. Of 12,280 cells tested, 1151 fired in relation to vocalization. Of these, 587 reacted to external acoustic stimuli and started firing after vocalization onset. As most of these cells were located in classical auditory relay structures, they probably represent auditory neurones reacting indirectly to self-produced vocalization due to auditory feedback. Seven cells reacted to acoustic stimuli but fired in advance of self-produced vocalization. These cells were located in the pericentral inferior colliculus, dorsal nucleus of the lateral lemniscus, dorsomedial to the ventral nucleus of the lateral lemniscus and immediately lateral to the central grey. They are probably engaged in tuning the auditory system to process self-generated sounds differently from external sounds. 261 neurones reacted to nonphonatory oral movements (chewing, swallowing) and started firing after vocalization onset. These neurones were widely distributed within the brain stem, with the highest density in the spinal trigeminal nucleus and medially adjacent reticular formation. The majority of these cells seem to react to proprioceptive and tactile stimuli generated by phonatory and nonphonatory oral activities. Some of them may exert motor control on muscles that come into play at later stages of phonation. 57 neurones reacted to nonphonatory oral movements but fired in advanced of vocalization onset. These neurones were located mainly in the trigeminal motor nucleus, nucl. ambiguous, reticular formation around these nuclei, parabrachial region and lateral vestibular nucleus. Their role in motor control seems to be related to specific muscles rather than specific functions. 100 of the vocalization-related cells showed a correlation with respiration. Expiration-related cells were found in and around the rostral nucl. ambiguous and in the reticular formation dorsal to the facial nucleus. Inspiration-related cells were located in the rostral and caudal nucl. ambiguous regions, ventrolateral solitary tract nucleus and the lateral reticular formation below the trigeminal motor nucleus. Most of these cells probably represent premotor neurones of respiratory muscles and laryngeal motoneurones of the cricothyroid and posterior cricoarytenoid muscles. Finally, a last group of cells was found that was unresponsive to chewing and swallowing movements, quiet breathing and acoustic stimuli, but changed activity during vocalization. 38 of them became active before vocalization and cricothyroid activity, and 101 afterward.(ABSTRACT TRUNCATED AT 400 WORDS)

Binding of tracer or competing steroids to transcortin can compromise specificity studies on receptors for adrenal steroids. Recently Alexis et al. have used cortisol 17 beta acid at high concentrations to prevent steroid binding to any transcortin possibly contaminating rat brain cytosol preparations. On the basis of limited specificity studies of [3H]dexamethasone and [3H]corticosterone binding under such conditions, it was claimed that binding sites for the two steroids are indistinguishable, and it is thus unnecessary to invoke distinct binding sites for each glucocorticoid. We have extended these competition studies in the presence of cortisol 17 beta acid, and shown that in rat hippocampus Type I, corticosterone-preferring glucocorticoid receptors can be clearly distinguished both from transcortin and from Type II, dexamethasone-binding glucocorticoid receptors.

Pulmonary toxicity due to cytotoxic drugs is well described in the literature. This is most commonly described in association with bleomycin, busulfan, and methotrexate. This report presents a case of interstitial pneumonitis with a normal chest x-ray that is most certainly due to procarbazine. In addition, the role of gallium-67 citrate scintigraphy in early diagnosis is discussed. This is especially important since discontinuation of the drug before radiographic manifestations of pulmonary toxicity become evident may prevent permanent pulmonary injury and its sequelae.

Although exposure to many industrially important monomers is controlled by law, few of these reactive chemicals have been determined in human tissues. Analogy with other fat-soluble organic substances strongly implies that these monomers may be retained in tissue, subject to the usual physiological constraints of metabolism, solubility and volatility. The storage of DDT and PCBs is discussed, as well as tetrachloro-ethylene (PCE) and trichloroethylene (TCE), which are chemically similar to many industrially used monomers. Styrene in blood and breath and its metabolites in urine have been studied in humans. Styrene and vinyl chloride have been measured in fat tissue of polymerization workers.

The results of EEG investigations after Spiller-Frazier's operation for trigeminal neuralgia in 112 patients are reported. Follow-up EEGs were recorded within 1-8 years after surgery; two to three follow-up tracings were available in 53 patients. Two distinct phases of EEG alterations were noted: 1) The immediate postoperative phase characterized by bilateral delta waves of maximal distribution in the frontal-precentral area and in the temporal area on the side of surgery. Such alterations are supposedly due to postoperative edema or associated metabolic disturbances. 2) Several months after surgery focal abnormalities of the temporal lobe develop, which consist of high amplitude alpha-, beta- or theta-waves, sharp waves, spikes and occasional stypical spike-and-wave complexes. These abnormalities are reflected on the contralateral side in approximately one third of the case. Repeated EEGs confirmed the consistency of degree and location of these findings with the exception of a less constant incidence of spikes and sharp waves. Severity of EEG abnormalities and incidence of potentially epileptogenic discharges increases with age. In spite of the precarious location of such focal abnormalities in the temporal lobe only 3 of 112 patients (2.7%) reported seizures with temporal lobe features. The age of the three patients was below the average age of 59.1 years. Seizures occurred sporadically beginning approximately 2 years after surgery. The low incidence of seizures may in our opinion be due to the advanced age of most patients.

In some subjects with increased light sensitivity to intermittent photic stimulation it could be observed: (1) a photomyoclonic response (PMR)--(in the EEG: muscular and ocular artefacts and probably spikes) including twitching of the facial, and sometimes muscles (Fig. 1 and 2) a photoconvulsive response (PKR), which deals in EEG with paroxismal cerebral potentials (Fig. 2). 20 min after consumation of small doses of alcohol (60 ml brandy) the PMR persists, while the photomyoclunus response gets extinguished (Fig. 3). In special terms there can be a development of epileptic seizures without alcohol (Fig. 4a-b), which fail to appear after alcohol up to 3 hours. This effect is demonstrated in six cases (Tab. 1). A partial anticonvulsive effect of alcohol is possible to be involved, especially in cases of fits with motoric actions (myoclunisms). The cilical valence of PMR and PKR seems to be the same, as a conductive factor to the liability to cerebral fits.

The changes in the EEG were put in relation to the clinical course and liver function tests in 3 cases of acute poisoning by Amanita phalloides. Within discrete disturbances of liver function, distinct paroxysmal changes and increased interspersion of epsilon waves in the EEG are already found on the second day after taking the fungi. The liver dystrophy developing in the later course, recognisable by Quick values below 2%, at first only produces a small increase in the EEG changes. On the 5th or 6th day, severe general changes in the EEG appear along with symptoms of confusion to delirium. At this time, no further deterioration of the laboratory findings were demonstrable, but on the contrary we already even found a distinct improvement in the liver function. With further continuous increase in the clotting factors, the EEG becomes increasing slower in the next 4 days and after surviving this stage, improves very quickly thereafter. Our findings show that in poisoning with Amanita phalloides, EEG changes may become manifest even before the appearance of psycho-pathological changes and do not correlate directly with the tangible technical liver function tests of the laboratory.

For the visual evaluation of the EEG in children (awake) 17 items are formulated and defined. They are to be examined and determined as beeing either optimal or non-optimal, as it is easier to define what is optimal, than what is normal. The non-optimal items are summed up for a total score. It could be shown that this score discriminates between sample groups of 50 children each, one with "minimal brain dysfunction" and another with normal controls of the same age and sex. There are also several distinct differences within the particular items. The objectivity of the items was proved by fourfold examination of the same sample group. The concept of optimality therefore offers a valid and objective method of quantifying the visual EEG evaluation, thus improving the interpretation of minor abnormalities in the EEG.

The study's goal was the examination of the hypothesis that transsexualism develops on a diminution of sexual drive which itself is a result of temporal lobe dysfunction. 28 transsexuals were examined. More than 30% of this group showed pathologic findings in EEG recordings. Most of the pathological findings were situated in the temporal region. Four transsexuals with pathologic EEG findings mentioned a brain injury in their personal history. In all but one case this injury had taken place after manifestation of transsexual behavior. There was no correlation between depressed sexual drive and pathologic electroencephalographic changes. Generally genetic male transsexuals showed a diminuation of sexual drive only by taking estradiol. This is interpreted as a hypogonadotropic hypogonadism. The electroencephalographic findings in 9 or 28 cases of transsexualism with an increase of epsilon-waves mostly in the temporal region are discussed in the context of single case studies and regarded as a reference to temporal lobe dysfunction. This dysfunction is interpreted as a biologic factor in the etiology of transsexualism.

Cyclic Cushing syndrome, a rare endocrine disorder marked by periodic fluctuations of cortisol secretion and clinical manifestations, is diagnostically challenging. This study integrates clinical and multi-omics data to advance early diagnosis. We analyzed four patients with pituitary cyclic Cushing syndrome and fifty-six patients with conventional Cushing disease. Proteomics profiling identified differentially expressed proteins; Annexin A1 expression was validated via immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay. Single-cell RNA sequencing mapped its cellular origin. Annexin A1 expression was significantly elevated in pituitary tumors and serum of patients with cyclic Cushing syndrome. Serum Annexin A1 measured during the remission phase in patients with cyclic Cushing syndrome demonstrated promising diagnostic ability, and a related diagnostic approach was proposed. Single-cell transcriptomics revealed a distinct Annexin A1-enriched tumor subpopulation, predominantly in patients with cyclic Cushing syndrome. Multi-omics and clinical integration identify Annexin A1 as a diagnostic biomarker for cyclic Cushing disease.

Renal fibrosis is a critical pathological hallmark of chronic kidney disease. Although nonalcoholic fatty liver disease (NAFLD) has been implicated in kidney disease progression, its specific role and underlying mechanisms in renal fibrosis remain poorly understood. This study aims to investigate these mechanisms by establishing a mouse model of renal fibrosis through unilateral ureteral obstruction (UUO) combined with a high-fat diet-induced NAFLD. Single-cell RNA sequencing, untargeted metabolomics, flow cytometry, and immunofluorescence are performed, along with in vitro experiments involving primary renal macrophages and coculture models. It is demonstrated that NAFLD exacerbates renal fibrosis, as HFD-induced hepatocytes release significant levels of ANGPTL8, which activates renal CCR2+PIRB+ macrophages. These specialized macrophages disrupt linoleic acid metabolism and increase the production of inflammatory cytokines, aggravating renal fibrosis. In addition, CCR2+PIRB+ macrophages promote the activation and proliferation of Th17 cells, which can further contribute to the worsening of renal fibrosis. Thus, the ANGPTL8/PIRB/ALOX5AP axis is a crucial signaling pathway between the liver and kidneys, and CCR2+PIRB+ macrophages play a pivotal role in the progression of NAFLD-induced renal fibrosis. These findings suggest potential therapeutic targets to treat NAFLD-related renal fibrosis.

Decreased expression of sirtuin 1 (SirT1) has been implicated in Alzheimer's disease (AD), and as we previously reported, is related to transcriptional repression by the major risk factor for sporadic AD, apolipoprotein E4 (ApoE4). Herein we describe the discovery of an orally brain-permeable small-molecule, DDL-218, that enhanced SirT1 in ApoE4-expressing neuronal cells and a murine AD model. DDL-218 increased the transcription factor NFYb resulting in upregulation of PRMT5. Mechanistic and modeling studies show that binding of ApoE4 to the SirT1 gene promoter can be displaced by PRMT5 leading to increased SirT1 transcription. DDL-218 treatment elicited improvement in memory in the AD model, suggesting that DDL-218 enhancement of neurotrophic SirT1 in the brain has potential to modulate neuronal activity that may clinically provide an improvement in cognitive function and complement the current anti-Aβ antibody monotherapy. Our findings support further development of DDL-218 as a novel ApoE4-targeted therapeutic candidate for AD.

Carbon dots (CDs) are new types of fluorescent nanomaterials with particle diameters of 1∼10 nm and have excellent photoluminescence (PL) properties, good biocompatibility, simple preparation methods and numerous raw materials; consequently, they are promising in the biomedical field. In recent years, to overcome drug resistance and toxic side effects of traditional organic drugs, the synthesis of CDs from drug molecules has become an effective strategy, which produces CDs with the same therapeutic effects as the raw drugs and even possessing new properties. At present, many CDs derived from organic drugs have been developed, which can be classified according to their sources such as antibiotics, anti-inflammatory drugs, and guanidine drugs. This article focuses on the progress of the above-mentioned drug-derived CDs compared with their drug precursors in terms of therapeutic efficacy, enhanced performance and new additional functions, with special attention to the structure-activity relationship between the drug precursors and the CD-based therapeutic agents. It demonstrates the feasibility of designing new drug-derived CDs for clinical applications, summarizes the shortcomings and research gaps of the existing work, and provides a reference for related work in the future.

Implantable cardioverter-defibrillators (ICDs) are recommended to reduce the risk of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF). The landmark studies leading to the current guideline recommendations preceded the 4 pillars of guideline-directed medical therapies (GDMTs). Therefore, some have questioned the role of ICDs for primary prevention in current clinical practice. In this paper, the authors provide an overview of the current ICD recommendations, including the instrumental clinical trials, the risk of SCD as observed in clinical trials vs real-world scenarios, disparities in ICD use among different patient populations, the impact of contemporary GDMT on outcomes, and ongoing and future trials and methodologies to help identify patients who are at an increased risk of SCD and who may benefit from an ICD. The authors also propose a pragmatic guidance for clinicians when they engage in the shared decision-making discussions for primary ICD implantation.

Helicobacter pylori is a prevalent, global infectious disease that causes dyspepsia, peptic ulcer disease, and gastric cancer. The American College of Gastroenterology commissioned this clinical practice guideline (CPG) to inform the evidence-based management of patients with H. pylori infection in North America. This CPG used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology to systematically analyze 11 Population, Intervention, Comparison, and Outcome questions and generate recommendations. Where evidence was insufficient or the topic did not lend itself to GRADE, expert consensus was used to create 6 key concepts. For treatment-naive patients with H. pylori infection, bismuth quadruple therapy (BQT) for 14 days is the preferred regimen when antibiotic susceptibility is unknown. Rifabutin triple therapy or potassium-competitive acid blocker dual therapy for 14 days is a suitable empiric alternative in patients without penicillin allergy. In treatment-experienced patients with persistent H. pylori infection, "optimized" BQT for 14 days is preferred for those who have not been treated with optimized BQT previously and for whom antibiotic susceptibility is unknown. In patients previously treated with optimized BQT, rifabutin triple therapy for 14 days is a suitable empiric alternative. Salvage regimens containing clarithromycin or levofloxacin should only be used if antibiotic susceptibility is confirmed. The CPG also addresses who to test, the need for universal post-treatment test-of-cure, and the current evidence regarding antibiotic susceptibility testing and its role in guiding the choice of initial and salvage treatment. The CPG concludes with a discussion of proposed research priorities to address knowledge gaps and inform future management recommendations in patients with H. pylori infection from North America.

The aim of this study was to establish an evidence-based guideline for the antibiotic treatment of Corynebacterium striatum infections. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with systemic inflammatory response syndrome, harboring C. striatum isolated from body fluids or tissues in which it is not normally present. C. striatum had to be identified as the only causative agent of the invasive infection, and its isolation from blood, body fluids or tissues had to be confirmed by one of the more advanced diagnostic methods (biochemical methods, mass spectrometry and/or gene sequencing). This systematic review included 42 studies that analyzed 85 individual cases with various invasive infections caused by C. striatum. More than one isolate of C. striatum exhibited 100% susceptibility to vancomycin, linezolid, teicoplanin, piperacillin-tazobactam, amoxicillin-clavulanate and cefuroxime. On the other hand, some strains of this bacterium showed a high degree of resistance to fluoroquinolones, to the majority majority of β-lactams, aminoglycosides, macrolides, lincosamides and cotrimoxazole. Despite the antibiotic treatment, fatal outcomes were reported in almost 20% of the patients included in this study. Gene sequencing methods should be the gold standard for the identification of C. striatum, while MALDI-TOF and the Vitek system can be used as alternative methods. Vancomycin should be used as the antibiotic of choice for the treatment of C. striatum infections, in monotherapy or in combination with piperacillin-tazobactam. Alternatively, linezolid, teicoplanin or daptomycin may be used in severe infections, while amoxicillin-clavulanate may be used to treat mild infections caused by C. striatum.

The growing popularity of unpasteurized milk in the United States raises public health concerns. We estimated outbreak-related illnesses and hospitalizations caused by the consumption of cow's milk and cheese contaminated with Shiga toxin-producing Escherichia coli, Salmonella spp., Listeria monocytogenes, and Campylobacter spp. using a model relying on publicly available outbreak data. In the United States, outbreaks associated with dairy consumption cause, on average, 760 illnesses/year and 22 hospitalizations/year, mostly from Salmonella spp. and Campylobacter spp. Unpasteurized milk, consumed by only 3.2% of the population, and cheese, consumed by only 1.6% of the population, caused 96% of illnesses caused by contaminated dairy products. Unpasteurized dairy products thus cause 840 (95% CrI 611-1,158) times more illnesses and 45 (95% CrI 34-59) times more hospitalizations than pasteurized products. As consumption of unpasteurized dairy products grows, illnesses will increase steadily; a doubling in the consumption of unpasteurized milk or cheese could increase outbreak-related illnesses by 96%.

The authors describe the fibro-granulomatous lesions with scar formation on a splenectomy specimen removed for familial spherocytosis, eight weeks after the onset of cat scratch disease. This original observation, apparently unique in the literature, is in favour of the blood spread of the agent responsible for benign inoculation lymphoreticulosis, and suggests a pathogenic theory for the unusual visceral manifestations.

The 2020 clinical practice guideline for the treatment of non-tuberculous mycobacterial pulmonary disease (NTM-PD) by the American Thoracic Society, European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, and Infectious Diseases Society of America; and the 2017 management guideline by the British Thoracic Society covered pulmonary diseases in adults caused by Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium xenopi, and Mycobacterium abscessus. In order to provide evidence-based recommendations for the treatment of less common non-tuberculous mycobacterial (NTM) species in adult patients without cystic fibrosis or HIV infection, our expert panel group performed systematic literature searches to provide management guidance for pulmonary diseases caused by seven additional organisms: Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium genavense, Mycobacterium gordonae, Mycobacterium malmoense, Mycobacterium simiae, and Mycobacterium szulgai. Treatment recommendations were developed by a structured consensus process. The evidence from the scientific literature published in English for treatment recommendations for pulmonary diseases caused by other NTM species was of very low quality, with the exception of M malmoense, and based on the evaluation of case reports and case series. For M malmoense, results from two randomised controlled trials and three retrospective cohort studies provided a better evidence base for treatment recommendations, although the evidence was still of low quality.

Alloxan treatment induces a decrease of orotic acid content in various organs of carp, frog, pigeon and rat, parallel to a decrease of liver and muscle glycogen content. Loss of orotic acid and glycogen cannot be prevented by orotic acid and carbamyl phosphate given i.p. Mice, rats and pigeons use up and excrete exogenous orotic acid rapidly, but carps and frogs accumulate it.

Syncope is a common clinical problem caused by transient cerebral hypoperfusion and encompasses reflex, orthostatic, and cardiac mechanisms. Accurate diagnosis relies on careful history taking and physical examination, as well as targeted testing guided by risk stratification. Management of syncope is determined on the basis of the underlying mechanism and focuses on reducing recurrence and injury risk. In older patients, syncope may manifest as unexplained falls. Early identification of high-risk features is critical to prevent adverse cardiovascular outcomes.

Linear care cascades (the Rule of Halves and awareness-treatment-control frameworks) quantify attrition among system-recognized cases but cannot represent true disease that remains undiagnosed, system-labeled disease that is absent or non-actionable, or symptomatic individuals whose diagnostic encounters are consumed by competing labels. A structural solution to these simultaneous limitations does not exist within current population health methodology. We conducted a narrative review of prior healthcare uses of the Johari Window, empirical applications and limitations of linear gap frameworks, evidence on the burden and consequences of underdiagnosis and inappropriate labeling, and literature on diagnostic competition and competing-diagnosis bias. We searched PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE) and Google Scholar (2000 to January 2026) using terms spanning Johari Window applications in health, population care cascades, underdiagnosis, overdiagnosis, and competing diagnoses. We adapted the Johari Window by jointly classifying populations along two operational axes, true disease state and health-system labeling state, and applied a priority-ordered classification rule to yield four mutually exclusive, jointly exhaustive quadrants. The adapted framework generates four quadrants: Open (disease present, target-disease label present); Hidden (disease present, no label); Facade (label present without actionable target diagnosis, with two mechanistically distinct subtypes: type I diagnostic misclassification and type II diagnostic competition); and Unknown (disease absent, no label, stratified into at-risk and not at-risk). Four system-level diagnostic performance metrics (system sensitivity, system specificity, positive predictive value (PPV), and negative predictive value (NPV)) are derived directly from quadrant counts, supplemented by the Hidden Burden Index, Facade Burden Index, and Facade-to-Hidden Ratio. The framework is illustrated with global pools of undiagnosed diabetes (~252 million) and hypertension (~580 million), substantial proportions of clinically labeled chronic obstructive pulmonary disease lacking spirometric confirmation (30%-60%), and the diagnostic shadow cast by depression, stroke, and other competing diagnoses. The adapted Johari Window framework provides a structurally complete, operationalizable, and metric-yielding solution to limitations inherent in linear cascade models, enabling simultaneous assessment of underdiagnosis, overdiagnosis, diagnostic competition, and system-level diagnostic performance at the population scale.

Chronic kidney disease (CKD) represents a significant global health burden, highlighting the need for low-cost, easily accessible biomarkers for early risk detection. The neutrophil-to-lymphocyte ratio (NLR) has demonstrated prognostic value in established CKD; however, its association with incident CKD in the general population without uremia remains poorly understood. We conducted a prospective study of 9,631 adults with preserved renal function from the Shanghai Suburban Adult Cohort. Logistic regression analysis was performed to assess the association between baseline NLR and incident CKD. Dose-response and subgroup analyses were also conducted. During follow-up, 400 participants (4.2%) developed incident CKD. After full adjustment, each 1-unit increase in NLR was associated with a 19% increase in CKD odds (OR = 1.19, 95% CI: 1.06-1.32). A dose-response relationship was observed: compared with the low NLR group (< 1.5), the normal (1.5-3.0) and high (≥ 3.0) NLR groups exhibited 37% (OR = 1.37) and 62% (OR = 1.62) increased odds of developing CKD, respectively. In this community-based population, NLR was positively, independently, and dose-dependently associated with incident CKD risk. These findings suggest that NLR, a low-cost and easily accessible biomarker, is independently associated with incident CKD risk and warrants further validation for early risk stratification in primary care and community health settings.

Introduction With the advancement in technology as well as surgical techniques, laparoscopic ventral hernia repair (LVHR) is more commonly being performed as compared to open repair in various centres throughout the world. Our study aimed to compare the short-term operative outcomes between LVHR and open repair. Materials and methods Sixty patients diagnosed with noncomplicated ventral hernias were included in this prospective study and were randomly divided into the laparoscopic group and the open group. The two groups were compared to evaluate operative time, postoperative pain, length of hospital stay and time taken to return to normal activity. A p-value of less than 0.05 was considered to be statistically significant. Results Mean operative time was longer in LVHR (116 min) as compared to open repair (67 min)(p<0.01). Patients experienced more pain on the first and seventh postoperative days in the open group (p<0.01) and they also had a longer duration of hospital stay as compared to the laparoscopic group (6.23 ± 0.35 vs 2.17 ± 1.12 days, p = 0.02). Patients in the laparoscopic group returned to normal activity faster as compared to the open group (1.47 ± 0.11 vs 2.87 ± 0.34, p<0.01). Conclusion LVHR carries a significant advantage over open hernia repair, especially in terms of reduced postoperative pain, duration of hospital stay, and early resumption of normal activity.

Lyophilized Brucella abortus Strain 19 vaccines were prepared using five recommended mediums. These five vaccines were compared with each other and with liquid vaccine relative to their suitability for (1) maintaning distinguishing cultural characteristics; (2) maintaining viability during lyophilization; (3) quality of restoration; (4) maintaining viability under various storage temperatures and (5) maintaining stable, antigenic and virulence qualities.

The authors present their experience with manometric studies, before and after Thal's fundic patch operation, in patients with Chagas' megaesophagus. The preoperative studies showed in the majority of the patients synchronous, waves of normal duration, that had low peak pressure and were repetitive (vigorous achalasia). The postoperative studies showed disappearance of the vigorous achalasia in over half the patients and increase of the contraction peak pressure in one patient.

The evaluation of EEG-findings during the acute phase of stroke-patients is somewhat difficult particularly in regard to the voltage-production, less in regard to the temporary retardation of frequency. Within comparable neurophysiological and biochemical examinations of the experimental brain-infarct under standardized conditions of silicon-rubber-embolus was introduced intracarotideally and an occlusion of the media-trunk evoked. One day prior to the embolisation and on the first, third and fifth day thereafter EEG-derivation took place which were stored on analogous-tape, digitalized and were then confronted with the FFT-Algorithm. From the statistical point of view four animal groups were the result: HO-group (control group), H1-, H3- and H5-group (each time N = 6). Visual evaluation of the curves, descriptive and inferential statistics of the spectral EEG estimators showed a significant loss of power within five days after the infarction; it always was more distinct across the focal side than across the not immediately involved hemisphere. On the fifth day the original level of voltage was almost reached again. From the clinical standpoint the neurological deficits had practically been disappeared. The biochemical finishing of the dog-brains -- the results of which are planned to be confronted with the electrophysiological results in another paper -- in accordance with the papers of other authors brings close the assumption that the decrease of tension i.e. the loss of power of the electric potential during the first days after infarction is combined with a temporary decrease of the energetic potential of the metabolically active corticocerebral cells which is tied to the phosphagene-system of the highly energetical phosphates and metabolites of the energy-metabolism in the brain.

In a strictly selected material of 80 patients, who were all outpatients of a special nephrological clinic, with chronic renal insufficiency with retention values of 1.4-14.5 mg% serum creatinine, an EEG was done besides thorough neurological and internal examinations. In 21 cases (26.2%) a pathological EEG in the form of background slowing and general dysrhythmia. There was a tendency to increase in pathological EEG findings in correlation with increase of the retention values. The patients with pathological EEG had on the average a creatinine value of 5.89 mg%, those without EEG findings had an average creatinine value of 3.98 mg%. The difference is statistically significant (alpha less than or equal to 0.015). It is notable that there is a statistical correlation (alpha less than or equal to 0.005) between the presence of pathological EEG and the motor conduction velocity of the peroneal nerve: only 12% of the patients with a conduction velocity of less than 43 m/sec had a pathological EEG while 60% of the patients with a conduction velocity of more than 43 m/sec had EEG findings. No statistical correlation were found between the EEG changes and other neurological and internal signs and symptoms, including cardiovascular findings like the blood pressure.

Two patients from families with hereditary spastic paraplegia (recessive and dominant type) were examined electromyographically. It was found that the peripheral motor neuron is involved. It is assumed that in cases of infantile recessive familial spastic paraplegia the peripheral motor neuron is rather more involved than in those of the dominant type of spastic paraplegia.

The H reflex in the triceps surae muscle was elicited by just supraliminal stimulation of the tibial nerve. It was conditioned by paired impulses to the brachial plexus or the forelimb nerves and in some cases to other sites of the body. With a conditioning test interval of 32-47 msec a facilitation occurred which reached its maximum at about 80 msec and lasted for about 400 msec. The facilitation evoked by ipsilateral conditioning had a shorter latency than that from contralateral (ipsilateral: 32-42 msec, contralateral; 37-47 msec). The facilitation at the optimum interval (about 80 msec) ranged between 1;5 and 11.3 times of the control values. Ipsilateral conditioning was slightly more effective than the contralateral one (Fig. 1, 2). Stimulation of different forelimb nerves at an interval of 80 msec showed only insignificant differences in the amount of facilitation but was more effective than skin stimulation in the most cases (Fig. 3). Varying the intensity of the conditioning stimulus showed that facilitation occurred with just perceptable stimuli but it became more pronounced as soon as pain threshold (2-3 time of perception threshold) was exceeded (Fig. 3). This suggests that facilitation was mainly due to activation of nociceptor afferents. From the onset of facilitation and the conduction velocities of the respective forelimb and hindlimb afferents (cf. 6) a central reflex lantency of about 43 msec was calculated. To get further insight into the central connections of the reflex loop the H reflex was conditioned by paravertebral stimulation at C5 and L1 level. Both stimuli caused a distinct facilitation. However, the latency of the onset was 10-15 msec shorter with lumbar stimulation than with cervical stimulation. This and the similar time course of facilitation seen in animal experiments (12) suggest that an early part of facilitation is mediated via a descending propriospinal pathway. The major part, however, is supposed to be mediated via supraspinal pathways and seems to be related to a startle response.

Several esophageal cytologic tecniques (sponge biopsy, sponge smear, and espohageal washings) were assessed and compared with endoscopy and biopsy of esophageal tumors. Esophageal cytology rendered better results than esophagoscopy or biopsy, with a 97% positivity in cases of esophageal carcinoma, when using sponge biopsy and sponge smear techniques, and of 91.4% for esophageal and gastric carcinoma of the fundus invading gastroesophageal junction, when considered together. The combination of sponge techniques was better for diagnosisng esophageal carcinoma than the application of esophageal washings, a more difficult, time consuming, and sometimes unfeasible method. However, the utilization of three mehtods enhanced the overall diagnostic possibilities in all cases of esophageal tumors when considered together.

Autoimmune diseases (AIDs) are multifaceted, chronic illnesses characterized by immune dysregulation and systemic inflammation. Newer evidence has pointed a finger at the human gut microbiota, a trillion-fold population of microorganisms that inhabits the human GI tract, as a major influential modulator of immune reactivity and a significant contributor to autoimmune pathogenesis. This systematic review will seek to address how the literature correlates with systematic changes in the gut microbiota in AIDs as well as explore mechanistic associations with biological processes like intestinal permeability and modulation of the immune system, coupled with determining the effectiveness of microbiota-directed interventions. An extensive literature search was conducted in PubMed, Embase, Cochrane Central, and Web of Science, involving the availability of studies until May 2025. The eligible studies included observational studies, randomized controlled trials, and relevant mechanistic research regarding autoimmune diseases and alterations of the gut microbiome or administered interventions. Data extraction and risk of bias (ROB) assessments were performed by two independent reviewers, and a narrative synthesis with an illustrative meta-analysis was applied. Inclusion criteria were met by 10 studies, encompassing various autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), autoimmune thyroid diseases (AITDs), and psoriasis. Familiar patterns of microbiome dysbiosis were identified, such as a reduction in microbial diversity, increased intestinal permeability, and the expansion of pro-inflammatory species like Ruminococcus gnavus. Dietary interventions, fecal microbiota transplantation, and probiotics demonstrated positive effects on clinical outcomes and immune measures across multiple studies. The meta-analysis revealed that microbiota-directed interventions significantly improved disease activity and immune response markers in AIDs, indicating a robust link between gut microbiota composition and autoimmune pathology. In autoimmune disorders, gut microbiota is a key factor in immunopathology. Gut biology as an adjunct interventional strategy provides potential in managing these diseases. Additional studies are required to help standardize methods and identify microbial targets specific to diseases that can then be addressed through therapeutic interventions.

A wearable electrochemical biosensor for real-time monitoring of neurotransmitters in sweat during physical exercise is presented. The biosensor utilizes a CuMOF@InMOF architecture, enhanced with gold nanoparticles (AuNPs), to improve electron transfer, surface area, and overall stability. Thiolate nucleic acid aptamers, highly specific to dopamine, serotonin, and epinephrine, are immobilized on the biosensor surface, enabling precise and simultaneous detection of these key neurotransmitters. The flexible, multi-electrode platform is integrated into a microfluidic patch that adheres to the skin, facilitating seamless sweat collection and continuous neurochemical analysis. Structural validation confirmed the successful synthesis of the CuMOF@InMOF architecture with enhanced surface area, stability, and electron transfer properties, contributing to the biosensor's high sensitivity and selectivity. Impressively, the biosensor achieved detection limits of 0.18 nM for dopamine, 0.33 nM for serotonin, and 0.27 nM for epinephrine, with a broad dynamic range from 1 nM to 10 µM. Performance was validated through square wave voltammetry and amperometry, demonstrating exceptional sensitivity, selectivity, and stability. This innovative biosensor offers a powerful tool for non-invasive, real-time neurochemical monitoring, with significant potential in personalized healthcare.

The prevalence of morbid obesity in today's population around the world is alarming. Morbid obesity involves substantial changes in body composition and function, which can affect the pharmacodynamics and pharmacokinetics of many drugs. This paper aims to discuss the application of muscle relaxants and their reversing agents in patients with morbid obesity. This work is based both on the available literature and the author's personal experience. Dosage recommendations for muscle relaxants in morbidly obese patients are as follows: non-depolarizing relaxants like rocuronium, vecuronium, atracurium, and cisatracurium should be based on ideal body weight. Succinylcholine dosage should be adjusted to total body weight with a 200 mg maximum, while mivacurium should also be based on total body weight. Pancuronium is not used due to its long duration. Neostigmine dosing remains uncertain, but some suggest using total body weight. When it comes to Sugammadex opinions of the authors are divided, some indicate that it should be dosed based on ideal body weight, but more recent studies show that it should be based on 40% of corrected body weight.

Kidney disease is a critical and potentially life-threatening degenerative condition that poses a significant global public health challenge due to its elevated rates of morbidity and mortality. It manifests primarily in two distinct clinical forms: acute kidney injury (AKI) and chronic kidney disease (CKD). The development of these conditions hinges on a multitude of factors, including the etiological agents and the presence of coexisting medical conditions. Despite disparities in their underlying pathogenic mechanisms, both AKI and CKD can progress to end-stage kidney disease (ESKD). This advanced stage is characterized by organ failure and its associated complications, greatly increasing the risk of mortality. There is an urgent need to delve into the pathogenic mechanisms underlying these diseases and to identify novel biomarkers that can facilitate earlier diagnosis. Such early detection is crucial for enhancing the efficacy of therapy and impeding disease progression. In this context, proteomic approaches have emerged as invaluable tools for uncovering potential new markers of different pathological conditions, including kidney diseases. In this chapter, we overview the recent discoveries achieved through diverse proteomic techniques aimed at identifying novel molecules that may play a pivotal role in kidney diseases such as diabetic kidney disease (DKD), IgA nephropathy (IgAN), CKD of unknown origin (CKDu), autosomal dominant polycystic kidney disease (ADPKD), lupus nephritis (LN), hypertensive nephropathy (HN), and COVID-19-associated acute kidney injury (COVID-AKI).

‘Nothing to be done’ (Beckett 2012: 11). Samuel Beckett’s play Waiting for Godot is not about healthcare, but its first line seems to hover between prognosis and diagnosis, suggesting that some kind of existential ‘doctoring’ is afoot, even as it is clear that no prescriptions are going to be dispensed. For the play’s two central characters, Vladimir and Estragon, ‘nothing to be done’ empties out the urgency of curative political action from Vladimir Lenin’s famous question: ‘What is to be done?’ Every possibility of change on the horizon of the play is derailed by the inertia of the fixing refrain: ‘we’re waiting for Godot’. Waiting is the nothing that famously happened twice (Mercier 1956: 6), and came to be figured, in many early critical receptions of Beckett, as a representation of the existential human condition (Graver and Federman 1979). In the early 1950s, when the play was first performed, perhaps abstractions were more available for critical absorption than the possibility that postwar Europe was still in a present denuded of an inhabitable future (Kenner 1973: 133; Gibson 2010: 108) – an endless time of living on without any real hope of change in the wake of an unspecified disaster. Beckett’s play materializes a waiting that becomes a form of endurance through the promise of what might come to change the present for there is always some orientation towards the future in such practices. But the clear unavailability of Godot decouples the for (Schweizer 2008: 11), the most obvious preposition or relation, from the action of waiting. Neither weak enough to cease and desist nor strong enough to leave, Vladimir and Estragon endure and persist, not, in the end, waiting for Godot but waiting with and sometimes even on one another. Although in this chapter we will pay close attention to existential claims about the place of waiting in human experience, we will suggest that waiting is significantly shaped by the promises and narratives of particular historical moments and lifeworlds, and their distinct ways of understanding time. Indeed, if tarrying in Godot’s waiting room seems to speak to the existential human condition, we would argue that it is because the audiences the play found and continues to find persist in a time when the promises of the future feel increasingly unavailable. Godot’s characters, alongside their audiences, wait with their diagnosis, which is also their prognosis: ‘nothing to be done’. Perhaps one reason the slow modernism of Godot found and made its mark so sharply was its insistence on attending to the disavowed underside of the dominant timescapes of modernity. In 1931, Aldous Huxley was able to state that ‘[s]peed […] provides the one genuinely modern pleasure’ (Huxley 2001: 263), and it has been a critical commonplace to read aesthetic modernism as a reflection of the shock of the new and a pacing, racing present. Planes, trains, and automobiles; ragtime and jazz; epiphanies and revolutions; telegraphs and telephones; production lines and new mass media: humanities scholarship has thoroughly mined how the modernity of the early and mid-twentieth century produced, for better and worse, accelerated lives and shaped technologies capable of both registering and increasing sensations of speed (Duffy 2009). Engaged with a more contemporary moment and less concerned with aesthetic practices, Paul Virilio (2006) has described how a logic of acceleration that has compressed, foreshortened, and fractured time still sits at the heart of modernity and its drives towards destruction; while Jonathan Crary (2013) has critiqued a culture of 24/7 availability fuelled by unsleeping technologies that has turned even the slowing of rest into an act of embodied resistance. But there were always other times folded into the modern, as Elisabeth Kirtsoglou and Bob Simpson’s idea of ‘chronocracy’ suggests (this volume). For example, the managed and mechanized time of the working classes in a newly industrialized Europe was consistently used to service a version of a progressive future that was not shaped in their interests (Thompson 1967). Craig Jeffery has also identified ‘chronic, fruitless waiting’ (Jeffery 2010: 3) as a particular temporal experience of those colonized populations who provided much of the material resources for acceleration of Empire and modernity, noting it as a prominent feature of the experience of subaltern peoples globally since the 1960s. Bendixsen and Eriksen indeed point out that for certain groups waiting can be an expression of power and domination, generating vulnerability and humiliation (2018: 92). And while a ‘new chronic’ temporal imaginary has become more generally palpable in the late liberalism of the contemporary global north (Cazdyn 2012), many of the most acute experiences of ‘chronic, fruitless waiting’ remain ‘zoned’ in specifically gendered, raced, and classed ways. As Lisa Baraitser has argued in Enduring Time (2017), despite an ever-increasing sense of acceleration, because the spooling of time towards a possible future seems to have come unravelled in the contemporary moment, experiences of interruption, suspension, delay, and slowness strongly insist in affective life in highly differential ways. Here, however, we track this sense of time enduring rather than passing back to an earlier moment in the twentieth century, noting the ways in which waiting uncoupled from a future into which one might step came to be understood as a key feature of the affective condition termed ‘melancholia’, or, in its more contemporary configuration, ‘depression’. This is not to claim that either condition is simply a response to modern times or, more strongly still, a social construction; nor is it to seek to medicalize distress that may be the result of other social relations of inequality or injustice (Thomas et al. 2018). Rather, we are interested in exploring how understandings of melancholia in twentieth-century Europe came to be focalized through particular ideas and sensations of stuck, suspended, impeded, or ungraspable time that shaped and continue to mould the contours of the temporal landscapes and psychological imaginaries of (late) modernity. Furthermore, we argue that care in the context of depression, which we understand as imbricated with psychosocial relations and experiences and therefore ‘more than biomedical’ or psychological in constitution (Hinchliffe et al. 2018), may turn out to hinge around the offer and use of extended periods of time and the capacity to stay with those whose experience is that of a temporality that no longer flows. Although the disciplinary perspective here is not anthropological, our concern with examining melancholia and depression through experiences and practices of waiting brings our chapter into contact with an important body of anthropological literature. In his interdisciplinary volume, Ghassen Hage describes waiting as an experience that is always both existential and historically articulated or situational (Hage 2009: 4, 6). Manpreet Janeja and Andreas Bandak similarly suggest that analysing waiting requires a capacity to shuttle between existential and more clearly social or institutional perspectives, as they demonstrate how focussed ethnographic work can illuminate both waiting’s poetics and its politics (Janeja and Bandak 2018: 3). But this chapter uses a more dispersed, eclectic, and textual archive of experience to open up a theoretical account of melancholia/depression as a condition fundamentally entangled with existential, cultural, and socio-historical experiences and theorisations of European (late) modernity. Remaining broadly within the climate of these anthropological approaches to waiting, however, we propose that the remarkable tradition of phenomenological psychiatry from the late nineteenth and early twentieth century provides a significant opportunity to trace the relationship between accounts of lived experience of mental distress that emerged explicitly alongside existential philosophies, and more broadly socio-historical accounts of time. As time became a topic of intense debate across the sciences and arts and humanities in early twentieth century Europe and North America, multiple disciplines explored the tension between accounts of intuitive/subjective time and understandings of mathematical/objective time (Fryxell 2019: 5–6). Phenomenological psychiatry established its distinctive approach in this context by refusing the dominant third-person approach to psychopathology exemplified by Emil Kraepelin (Broome et al. 2012: 90) in favour of paying careful attention to the first person, subjective experience of disruptions of well-being. The discipline was profoundly influenced by the new philosophies of temporality of Henri Bergson and Martin Heidegger in the first three decades of the twentieth century and one of its key insights was that chronic mental distress can be understood as a disturbance of a sense of lived time. However, phenomenological psychiatry paid scant explicit attention to the temporal demands of treatment (Fryxell 2019: 23) – the time bound up in the intersubjectivity of the clinical encounter or simply the time that treatment takes. But psychoanalysis, which emerged alongside phenomenological psychiatry in historical terms, insisted on reflecting, with particular self-consciousness, on the complex, often seemingly interminable temporality of treatment (Freud 1937). Both phenomenological psychiatry and psychoanalysis developed in explicit dialogue with the conditions of modernity and alongside the devastating experiences of industrialized warfare, but while phenomenology negatively articulated a temporal attitude of normalcy that recedes in experiences of mental illness, psychoanalysis used the rhythms of psychopathology and the inevitability of falling ill as a way of illuminating the structures of all mental life and of a psychic life of time that can never be simply linear, teleological, or smoothly flowing. Instead of suggesting that sensations of waiting without a for break apart what is proper to lived time, psychoanalysis comes to understand such experiences to be part of the inevitable conditions of psychic life. Psychoanalysis thus offers up a specifically chronic cure – the offer of time and care, and of remembering, repeating and working through (Freud 2014) – to contain, understand, and ameliorate the chronic condition of mental distress. By highlighting this link between the chronicity of the mind and the broader psychosocial contexts in which endurance plays out, this paper aims to open up a historically nuanced sense of the value of psychoanalytic temporal practices of waiting not for but with. We also suggest that by attending specifically to the relationships between depression, temporality, and historical and psychosocial experience, the urgent debates about uses of time in contemporary mental healthcare delivered by the UK’s National Health Service might tentatively be reframed.

Functional capacity is an important component of risk assessment for major surgery. Doctors' clinical subjective assessment of patients' functional capacity has uncertain accuracy. We did a study to compare preoperative subjective assessment with alternative markers of fitness (cardiopulmonary exercise testing [CPET], scores on the Duke Activity Status Index [DASI] questionnaire, and serum N-terminal pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting death or complications after major elective non-cardiac surgery.

The effect of cisapride on plasma concentrations of paracetamol was investigated with respect to hepatic metabolism. Paracetamol (1 g) together with cisapride (7.5 mg) or placebo was orally administered to five healthy male volunteers. Venous blood samples were taken before and after administration. Plasma paracetamol and its glucuronide and sulfate conjugates were measured by HPLC. The pharmacokinetic variables were calculated from the plasma concentration-time curves of each volunteer. The area under the plasma paracetamol concentration-time curve from 0 to 180 min (mean +/- s.d.) increased from 1875.0 +/- 112.8 micrg min mL(-1) (placebo coadministration) to 2238.8 +/- 125.8 microg min mL(-1) (cisapride coadministration) (P < 0.01). The mean maximum plasma paracetamol concentration(18.2 microg mL(-1))with placebo was reached 30 min after administration, whereas mean maximum plasma paracetamol concentration (21.2 microg mL(-1)) with cisapride occurred 45 min after administration. The plasma paracetamol concentrations with cisapride were significantly greater at 45 to 120 min after administration compared with placebo. Plasma paracetamol glucuronide conjugate concentrations with cisapride were decreased at 15 to 60 min compared with placebo (P< 0.05), whereas plasma paracetamol sulfate conjugate concentrations did not change significantly. Hence the coadministration of paracetamol with cisapride reduced plasma paracetamol glucuronide concentrations and increased plasma paracetamol concentrations, presumably due to inhibition of paracetamol metabolism via paracetamol glucuronyltransferase. Thus, care is necessary when paracetamol and cisapride are coadministered.

Meningococcal conjunctivitis is typically described as an acute purulent infection. An atypical case of mild catarrhal conjunctivitis occurred in a 19-year-old college student. The meningococci were identified as Neisseria meningitidis, group A, and were isolated from the throats of the patient and her roommate. The conjunctivitis responded rapidly to treatment with sodium sulfacetamide, and it was not treated systemically. A short review of the literature of meningococcal conjunctivitis is presented, and the current recommendation for prophylaxis is discussed.

Artificial air pouches in the connective tissue of mice were evaluated as a means of studying Neisseria gonorrhoeae infections. Animals inoculated with type-1 N. gonorrhoeae cells developed an infection characterised by infiltration of polymorphonuclear leucocytes. Viable cocci could be recovered from the air pouches for up to 10 days after infection and intracellular cocci were evident in electronmicrographs within connective-tissue fibroblasts for at least 35 days, indicating that a persistent infection had been established. The mouse air pouch should be of value in the study of gonococcal and other infections.

We describe nine patients with methyl alcohol poisoning who were treated with hemodialysis. The time from ingestion to dialysis varied from 4 to 100 hours. Predialysis blood methanol levels ranged from 3 to 570 mg/dl. All patients were acidotic and had an increased anion gap. Two patients died, seven recovered, but three had permanent visual impairment. There was little correlation between the blood methanol level or anion gap and visual outcome. The interval from ingestion to treatment appears to be more important than the initial biochemical status. We recommend prompt hemodialysis if the blood methanol level is above 50 mg/dl, when an amount of methanol exceeding the minimal lethal dose (30 ml) is known to have been ingested, when there is evidence of acidosis or when an abnormality has developed in vision, funduscopic examination or mental state. Concurrent therapy with alkali and ethanol is vital.

Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998-2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne illness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.