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Background/Objectives: Despite clonal expansion during a primary immune response, or after subsequent antigen encounters, the frequency of memory B cells (Bmem) specific for an antigen remains low, making their detection difficult. However, unlike serum antibodies, which have a short half-life in vivo and thus require continuous replenishment to maintain stable titers, circulating Bmem are long-lived; they preserve immunological preparedness through their ability to rapidly engage in recall responses and differentiate into antibody-secreting cells (ASCs) upon antigen encounter. To this end, development of assays suited for the reliable detection of rare antigen-specific Bmem is critical and can provide insights into an individual's antigen exposure history and immune status beyond that offered by traditional serum antibody measurements alone. Methods: ImmunoSpot® has emerged as a suitable technique for the detection of individual antigen-specific B cells through visualizing their antibody-derived secretory footprints. Here, we report the theoretical and practical foundations for detecting rare antigen-specific Bmem in human peripheral blood mononuclear cells (PBMC). Leveraging the unique availability of verifiably naïve vs. antigen-experienced human samples, we used SARS-CoV-2 Spike (S-) and Nucleocapsid (NCAP) antigens to interrogate the presence of Bmem with these respective specificities. Results: While 100% diagnostic accuracy was achieved for both antigens, detection of NCAP-specific Bmem required reducing the lower detection limit of the standard assay. Specifically, this was achieved by testing a total of 2 million PBMC across multiple replicate assay wells and assessing the cumulative number of secretory footprints detected. Conclusion: The protocols described here should facilitate the reliable detection of ASCs present at varying precursor frequencies and serve as guidance for routine immune monitoring of rare Bmem with specificity for any antigen.

The Gypsy mushroom (Cortinarius caperatus) is prized as an edible fungus in northern climates. This species has a strong predilection for accumulating radiocaesium (134/137Cs), but the potential to accumulate other toxic nuclides is unknown. 210Po and 210Pb activity concentrations were determined in the fruiting bodies of this species and the associated forest soil (0-10 cm layer) collected at 20 sites across Northern Poland. Concentrations of 210Po and 210Pb in mushrooms ranged from 0.92 to 10.0 and 0.36 to 13.1 Bq∙kg-1 db and from 10.5 to 46.6 and 11.0 to 46.2 Bq∙kg-1 db in soils, respectively. Estimated bioconcentration factors indicated that the species exhibited bioexclusion of both 210Po and 210Pb. The effective dose from a meal containing 100 g of fresh gypsy mushroom would result in 22.0-64.4 nSv from 210Po + 210Pb decay. The highest assessed risk of cancer for adult consumers only due to 210Po and 210Pb exposure from 5 kg of fresh specimens consumed annually over 50 years was 10-6, indicating that one in a million consumers of these mushrooms might develop cancer.

The Gulf States are home to industries emitting styrene, benzene, toluene, ethylbenzene, and xylenes (SBTEX). Presently, adverse health effects of ambient SBTEX exposure in highly polluted regions, such as the Gulf States, must be evaluated. Epidemiologists, however, are limited by inadequate estimates of ambient SBTEX. Using Bayesian Maximum Entropy, SBTEX estimation methods of varying resource intensity were evaluated, including simple kriging (least intense), incorporation of observational and emissions data trends (moderately intense), and data fusion of observed and Comprehensive Air quality Model with extensions (CAMx) data (most intense). Generally, as resource intensity increased, so did SBTEX estimation performance, where SBTEX Spearman R values increased by 0.48 on average from the least to most intense methods. Data fusion of observed and CAMx data was identified as the best ambient SBTEX estimation method in the Gulf States. Exposure estimates revealed that Gulf States residences within commuting distance of high industrial activity experienced 1.64 times higher 97.5th percentile daily exposures to SBTEX on average than those living in less industrialized areas, which could contribute to total occupational and ambient exposure disparities. Furthermore, ambient benzene exposure was greater than the acceptable one-in-a-million excess cancer risk threshold for 75% of estimated residence locations in the Gulf States.

Removal of co-occurring contaminants produces significantly greater potential benefit estimates compared to evaluation of one contaminant at a time. Here we present a framework for calculating avoidable lifetime cancer cases from simultaneously reducing hexavalent chromium and arsenic concentrations in drinking water using U.S. data as a case study. We analyzed contaminant occurrence data from 2011 to 2023 in 6,831 U.S. community water systems for which testing data for Cr(VI) were available. We also extrapolated potential Cr(VI) concentrations for an additional 10,893 groundwater systems in the U.S. where total chromium test data were available. To estimate potential reductions in the theoretical lifetime cancer risk from Cr(VI) and arsenic pollution, we evaluated water quality improvement scenarios for the subset of community water systems where inorganic arsenic and Cr(VI) co-occur. For the entire U.S., an estimated 7,410 lifetime cancer cases from Cr(VI) exposure and 43,418 from arsenic exposure could be avoided if drinking water concentrations were reduced to their respective one-in-a-million cancer risk levels in systems with Cr(VI) detections. For hypothetical maximum contaminant levels of Cr(VI) at 10 and 5 μg/L, estimated avoidable lifetime cancer cases for the entire United States are 575 and 1,320, respectively. At these same hypothetical limits for Cr(VI), simultaneously reducing arsenic by 42 % and 28 %, would double the number of lifetime cases avoided. Analysis of decreased cancer risk associated with the simultaneous reduction of co-occurring drinking water contaminants provides information for establishing new frameworks for mitigating contaminants and protecting public health from pollution. Consideration of the health and economic benefits associated with removal of co-occurring contaminants may help underscore the value of regulations that encourage the use of such technologies. It could also support the development of more efficient approaches for drinking water treatment.

Epithelioid haemangioendothelioma (EHE) is a rare vascular neoplasm characterised by proliferation of vascular endothelial and pre-endothelial cells. The prevalence is less than one in a million people. It is principally observed in the soft tissues of the extremities but can also occur in the bone, brain, liver, lung and lymph nodes. EHE in the head and neck region is very rare. The most common site of occurrence in the head and neck is the submandibular region. To the best of our knowledge, there are only four cases of EHE reported in the orbit. We herein present the unusual case of a 22-year-old female patient with an EHE of the lateral wall of the right orbit and describe the clinical findings, histopathology, differential diagnoses and treatment. EHEs exhibit the potential for malignancy and recurrence, but metastasis remains rare. Due to its noticeable potential for malignancy and recurrence, complete excision and regular long-term follow-up would be the appropriate treatment protocol.

Damage to a nuclear power station resulted in radioactive contamination of certain areas of Japan in 2011. Legislation was put in place in Europe to establish controls on the import of certain types of food and feed, including a limit of 100 radioactive decays (becquerel, Bq) per second of radiocesium per kg. This legislation was retained in the United Kingdom after leaving the EU and then reviewed in 2021. A quantitative risk assessment was developed to estimate the radiological risk to public health from consuming Japanese food imported into the United Kingdom should the maximum level on radiocesium be removed. Although Japanese monitoring data indicated occurrences when products exceeded the 100 Bq per kg limit, these were found to be rare; a total of 1485 occurrences (0.0013%) of all measured foodstuff samples (>1 million) within the scope of this assessment had radiocesium activity concentrations that exceeded 100 Bq per kg. Using the recorded occurrence and level of radiocesium measured, and the current pattern and volume of food imported from Japan, there was an estimated excess risk of fatal cancer of around one in a million per year, categorized as negligible compared to the baseline 2018-2020 UK cancer fatality rate of around 1 in 4. On the basis of the described assessment and the estimated small additional risk, Great Britain lifted import controls related to radioactivity present in food from Japan. A number of recommendations to address data gaps and approaches in this assessment are made, particularly how we can improve modeling UK dietary habits for specialist foods.

Clinical guidance recommends promoting physical activity during general practice consultations. The frequency and content of physical activity discussions in UK general practice are poorly understood. To explore the content of physical activity discussions during routine consultations between patients and GPs. Secondary analysis was undertaken of video-recorded UK general practice consultations from the One in a Million study, which was conducted in the West of England. In total, 294 consultation transcripts were available; these were screened to identify consultations that included or omitted physical activity advice when recommended by National Institute for Health and Care Excellence guidance. The content, quality, and depth of advice provided by GPs were scored to ascertain how meaningful the advice was. Physical activity was relevant to management according to clinical guidance in 175/294 (59.5%) consultations. In 64 (36.6%) of these consultations, physical activity was discussed as part of clinical management; the depth of discussion was judged as 'meaningful' in 22 (12.6%) consultations. Although physical activity advice tended to be given most often for musculoskeletal problems, depth of advice did not appear to be related to the presenting problem. When physical activity advice was relevant and omitted, consultations prioritised another overriding presenting problem, or clinical management focused on another intervention. Physical activity advice, following national guidance, was potentially relevant to more than half of GP consultations; GPs delivered advice of varying depth in a third of these consultations. Future work should explore ways of delivering physical activity advice effectively, efficiently, and equitably within the constraints of general practice.

Whipple's disease (WD), triggered by Tropheryma whipplei ( T. whipplei ), is a rare, chronic, inflammatory, systemic infectious disease that typically manifests in adults. The most frequent initial manifestations include arthritis, followed by diarrhea, abdominal pain, and weight loss. Half the world's population is exposed to T. whipplei , but only one in a million develop WD. This suggests that acquired or inborn errors of immunity (IEI) may underlie WD. Anti-TNF treatment is a well established risk factor for flare-ups of WD. We have also reported two rare IEI in patients with WD. Six WD patients from two unrelated kindreds were found to have autosomal dominant IRF4 deficiency acting via a mechanism of haploinsufficiency. These patients were otherwise healthy. In addition, a single patient with a history of WD and other infections was found to have autosomal recessive CD4 deficiency. Rare IEI can underlie WD. Human genetic studies of patients with WD are warranted for the development of precision medicine for affected kindreds and to improve our understanding of the pathogenesis of this rare infectious disease.

Murine models are often used to study the pathogenicity and dissemination of the enteric pathogen Salmonella enterica serovar Typhimurium. Here, we quantified S. Typhimurium population dynamics in mice using the STAMPR analytic pipeline and a highly diverse S. Typhimurium barcoded library containing ~55,000 unique strains distinguishable by genomic barcodes by enumerating S. Typhimurium founding populations and deciphering routes of spread in mice. We found that a severe bottleneck allowed only one in a million cells from an oral inoculum to establish a niche in the intestine. Furthermore, we observed compartmentalization of pathogen populations throughout the intestine, with few barcodes shared between intestinal segments and feces. This severe bottleneck widened and compartmentalization was reduced after streptomycin treatment, suggesting the microbiota plays a key role in restricting the pathogen's colonization and movement within the intestine. Additionally, there was minimal sharing between the intestine and extraintestinal organ populations, indicating dissemination to extraintestinal sites occurs rapidly, before substantial pathogen expansion in the intestine. Bypassing the intestinal bottleneck by inoculating mice via intravenous or intraperitoneal injection revealed that Salmonella re-enters the intestine after establishing niches in extraintestinal sites by at least two distinct pathways. One pathway results in a diverse intestinal population. The other re-seeding pathway is through the bile, where the pathogen is often clonal, leading to clonal intestinal populations and correlates with gallbladder pathology. Together, these findings deepen our understanding of Salmonella population dynamics.

Aflatoxin B1 (AFB1) is widely found and substantially impends public health. The current work aimed to assess AFB1 in medical areca nuts in China. The average content of AFB1 was 13.0 μg/kg, and the maximum content was 146.0 μg/kg. Furthermore, a comprehensive probabilistic risk assessment approach considering combined utilization of a Monte Carlo simulation with the margin of exposure (MOE) and quantitative liver cancer risk (HCC) strategies was developed for assessing the human health risk of AFB1 from consuming medical areca nuts for the first time. The MOE values of AFB1 in samples for no more than the 75th percentile were less than the threshold of 10,000 for both men and women. The estimated 90th percentile to the maximum of the HCC values for males and the estimated 75th percentile to the maximum of the HCC values for females were higher than one in a million upon exposure to medical areca nuts, indicating an unacceptable liver cancer risk. Sensitivity analysis demonstrated that for both MOE and HCC approaches, AFB1 content was the parameter with the greatest effects on the results, followed by the exposure frequency (EF) and daily intake rate (IR). This study is the first of this kind, demonstrating the applicability of stochastic exposure evaluation techniques for the precise and scientific assessment of the health risk of AFB1 in medical areca nuts, with the main purpose of minimizing human cancer risk.

Ganglioneuromas are rare neuroendocrine tumors affecting around one in a million, mostly young adults. These slow-growing, well-differentiated neuroepithelial tumors originate from the neural crest and involve the sympathetic nervous system. We present an unusual case of a 47-year-old African American man with mildly elevated liver enzymes who was incidentally found to have a suspected pancreatic mass. Endoscopic ultrasound and fine-needle biopsies confirmed the diagnosis of a ganglioneuroma, inseparable and exophytic in the body of the pancreas extending into the tail.

Budd-Chiari Syndrome (BCS) is an uncommon liver disorder characterized by obstruction of hepatic venous outflow. BCS is a rare condition affecting one in a million adults. The obstruction may be thrombotic or non-thrombotic anywhere along the venous course from the hepatic venules to the junction of the inferior vena cava to the right atrium. Patient may present with abdominal pain, ascites along with hepatomegaly, jaundice, bleeding in the oesophagus, oedema in the legs, hepatic encephalopathy and liver failure. Treatment for Budd-Chiari syndrome in modern science are dissolving blood clots, improve liver function and treat complication. A 51-year-old female patient presented with complaints of pain in right side of abdomen, loss of appetite, abdominal heaviness, abdominal distension, nausea and swelling at bilateral lower leg for one month. Ultrasonography of the abdomen revealed cirrhosis of the liver, thrombosis of the right, middle, and left hepatic veins, along with features of BCS with gross ascites. She is known case of Budd-Chiari syndrome along with gross ascites. The patient was treated with Deepana (which simulates the digestion) and Pachana (enhancing digestion) Koshthashodhana (mild purgation) followed by Vardhamana pippalirasayana(administration of Pippali in a increasing dose and then tapering the dose) and Shamana chikitsa (pacifying treatment)). Pathya-apathya (wholesome diet and regimen) were advised in line with the management of Jalodara for three months. After three-months treatment there was changes in liver profile (SGPT reduced from 250 to 47, SGOT from 328 to 68, alkaline phosphate 272 to 134mg/dl). The assessment of quality of life using the Chronic Liver Disease Questionnaire (CLDQ) indicated improvement in quality of life. This suggests that Ayurvedic treatment can give symptomatic relief and help to prevent it further complication and also improve the overall quality of life.

In this study, the exposure to polychlorinated biphenyls (PCBs) through fish consumption was assessed in Türkiye. The concentrations of total 41 PCBs and six indicator (i6) PCBs ranged 4.5-45.7; 1.0-32.1 ngg-1 wet weight (ww) in 21 edible fish species supplied from Izmir markets in 2022 and i6 PCBs are less than the maximum value allowed by the EU and the Turkish Food Codex. Cultured seabass and sea bream have significantly higher PCB levels than wild-caught fish. The most prevalent PCB congeners in all samples were 6Cl PCBs, which were followed by 5Cl PCBs. High chlorinated congeners (chlorine > 5) accounted for 74-90% of the ∑PCBs. The majority of the total seven indicator (i7) PCBs accounted for PCB153 and 138. PCBs 206 and 209 were the most prevalent congeners among the total PCB levels in mussel samples. According to the United States of America's Environmental Protection Agency's (US EPA) recommended oral reference dose and the Agency for Toxic Substances and Disease Registry's minimal risk level, consuming 20 g per day for a person of 21 fish species does not pose a health risk to human health. Based on 50th and 95th percentile PCBs concentrations, the hazard ratios for cancer were more than one, suggesting these PCB concentrations may cause a lifetime risk of cancer for consumers to more than one in a million.

A term baby presented with cholestatic jaundice since birth. She was diagnosed as gestational alloimmune liver disease-neonatal haemochromatosis (GALD-NH) on evaluation. The baby received intravenous immunoglobulin (IVIG) and recovered gradually from the illness. She was also diagnosed with alpha thalassaemia during the course of evaluation, confirmed by genetic testing. NH is a very rare disorder that results in fetal loss or neonatal death due to liver failure. NH is now known to be a phenotypic expression of GALD. Worldwide, NH is seen in less than one in a million pregnancies. The mortality rate of GALD has traditionally been around 80% with almost all babies needing liver transplantation, with advent of maternal and neonatal IVIG treatment, this has reduced significantly. There is no reported case of GALD-NH treated successfully with IVIG from India. Here, we report an interesting case of GALD-NH with alpha thalassaemia.

The odds of being struck by lightning are one in a million, however lightning strike accounts for 24,000 annual fatalities worldwide (Jensen et al, 2023). Due to its rarity, guidelines for the management of burns acquired by lightning strike are scarce. Current standard of treatment is to treat burns acquired as one would treat electrical burns (Stander & Wallace, 2011). We present a case series of three patients that were struck by lightning and contrast their outcomes to patients with electrical burns. We attempt to provide general recommendations for lightning burns. We conducted retrospective chart review of patients presenting between 2015- 2022 for electrical and lightning burns. SPSS V28 was used for statistical analysis. Lightning burn patients were matched to electric burn patients by age, gender, Total Burn Surface Area (TBSA), and comorbidities. Descriptive statistical analysis was conducted between the three groups due to discrepancies in sample size. We report three lightning burn cases: 2 adult males with 1-1.5% TBSA second-degree burns and 1 pediatric case with 4% TBSA. The pediatric case had a more complex hospital course: longer stay (15 vs 4-5 days), ICU stay (13 vs 2 days), and required ventilation but no surgery. In adults aged 19-29, electrical burns patients had longer hospital stays (6.38 vs 5.00 days), similar ICU stays (2.25 vs 2 days), and lower initial CPK (1624.29 vs 3506.00) than lightning burn patients. In those 50+ with TBSA < 5% and hypertension, electrical burns patients had longer stays (6.75 vs 4 days), longer ICU stays (3.25 vs 2.00 days), and lower initial CPK levels (435.5 vs 648.00). CPK normalization took longer for electric burns (29.5 vs 6 hours). In younger patients, lightning burns had lower initial myoglobin (569.30 vs 759.01) but faster normalization (8.5 vs 15.92 hours), while in older patients, myoglobin trends favored lightning burns (6 vs 3.25 hours). Pediatric patients with TBSA < 5% had shorter stays (3.83 vs 15.00 days), ICU stays (0.83 vs 13 days), lower initial CPK (508.25 vs 17393.00), lower myoglobin (91.50 vs 10000.00), and quicker CPK normalization (10.00 vs 14.00) in electric burns compared to lightning burns. Electric burns and lightning burns present similarly in adults. Although initial CPK levels are elevated in lightning burn patients, time taken for CPK to trend down was less than electric burn patients. More research is needed on lightning burn management in a pediatric population. Lightning burns can be managed similarly to electric burns. Providers ought to expect an increased length of stay in patients who sustain electric burns as well as an extended recovery time for muscular injury.

Colorectal Carcinoma (CRC) has recently been on the rise among children, bearing a prevalence of 1-2 children/adolescents per million people. Here, we present a rare case of CRC in a 14-year-old male, emphasizing the need for development of better screening techniques to diagnose CRC earlier and with adequate time for intervention. A 14-year-old male visited our hospital with constipation, intermittent per rectal bleed and dull-aching pain abdomen for 2&#xa0;months. On per rectal examination, a hard mass was identified, approximately 3&#xa0;cm above the anal verge. Contrast-enhanced CT (Chest and Abdomen) and MRI Pelvis identified a circumferential thickening in the rectum predominantly involving the anterior rectal wall with effacement of fat planes with the Urinary Bladder without infiltrating it. Colonoscopic biopsy identified Signet Ring Adenocarcinoma. A multi-disciplinary decision was taken to treat him with neoadjuvant chemotherapy and radiotherapy (NACT-RT). MRI Pelvis, post-NACT-RT, showed that the previously- effaced fat plane was now clear and an Abdominoperineal Resection (APR) with permanent end- descending-colostomy was done. Histopathology report of the specimen identified a poorly undifferentiated mucin-secreting adenocarcinoma. At presentation, the patient could have been either planned for extensive surgery or NACT-RT. The choice of NACT-RT was justified in our patient and was advantageous as extensive surgery was prevented. We implore vigilance in cases of rectal masses due to the rising incidence of CRC among children. We also advocate that there must be no hesitation in subjecting adolescents to Chemotherapy and/or radiotherapy, as the benefits significantly outweigh the risks of with-holding.

Oro-facial digital(OFD) syndrome is a rare anomaly which is often missed out as just cleft lip and palate.It is an X-linked dominant condition with lethality in males. It however results from the pleotropic effect of a morphogenetic impairment affecting almost invariably the mouth, face and digits and it also includes lower IQ and mental retardation. 14 different variations of these syndrome can be seen with the majority of cases of type 1 and 2 based on characteristic clinical manifestations. Present case report describes a 9 year old girl patient who was mis-diagnosed with partial cleft palate and was later diagnosed as orofacial digital syndrome based on the clinical and oral features. Not much literature is present regarding this topic and with no relevent family history makes this case a one in a million case of OFD. Therefore, this case report is a complete insight on Oro-facial digital syndrome.

Intraoperative fluoroscopy use is essential during spinal fusion procedures. The amount of radiation dose should always be minimized. This study aimed to determine the feasibility of halving the frame rate from 12.5 to 6.25 frames per second (fps) and to quantify the reduction in the risk of developing radiation-induced cancer. This pilot study included 34 consecutive patients operated for open lumbar posterolateral fusion (PLF) with or without transforaminal lumbar interbody fusion (TLIF). C-arm modes were changed from half-dose (12.5 frames per second (fps), group I) to quarter-dose (6.25&#xa0;fps, group II). Age, body mass index, surgical procedure, number of treated levels, and complications were collected. Kerma area product (KAP), cumulative air kerma (CAK), and fluoroscopy time were compared. Effective dose and radiation-induced cancer risk were estimated. Eighteen and 16 patients were, respectively, included in group I and II. Demographic, surgical data, and fluoroscopy time were similar in both groups. However, CAK, KAP, and effective dose were significantly lower in group II, respectively, 0.56 versus 0.41&#xa0;mGy (p&#x2009;=&#x2009;0.03), 0.09 versus 0.06&#xa0;Gy&#xa0;cm2 (p&#x2009;=&#x2009;0.04), and 0.03 versus 0.02&#xa0;mSv (p&#x2009;=&#x2009;0.04). Radiation-induced cancer risk decreased by 47.7% from 1.49&#x2009;&#xd7;&#x2009;10-6 to 7.77&#x2009;&#xd7;&#x2009;10-7 after optimization. No complications were recorded in either group. This study demonstrates the feasibility of setting 6.25&#xa0;fps for TLIF with and without PLF. By halving the fps, radiation-induced cancer risk could be almost divided by two, without compromising surgical outcome. Finally, after optimization, the risk of developing radiation-induced cancer was less than one in a million.

To analyse communication about the natural course of self-limiting illnesses, as part of shared decision-making (SDM), in general practice consultations. Natural history communication and SDM (using Observing Patient Involvement in Decision-Making (OPTION-12) and Assessing Communication about Evidence and Patient Preferences (ACEPP) items) were rated by two raters using transcripts from the UK 'One in a Million' database. Of 55 eligible consultations, a 'wait and see' option was mentioned in 27 consultations (49&#xa0;%), using varying terminology, with a general recovery timeframe provided in 21. Mean OPTION-12 score (of 100) was 25.2 (SD=7.4), indicating a low level of SDM. Mean ACEPP score (out of 5) was 1.2 (SD=0.5), indicating minimal communication about the options' benefits and harms. Recovery likelihood was quantified in only two consultations, while harms were quantified in none. Communication about the natural history of self-limiting illnesses was generally limited. The 'wait and see' approach, along with its benefits and harms, was typically not explicitly presented as an option for patients to consider. Improving clinicians' awareness of the importance of and skills for communicating the natural history of self-limiting illnesses, as part of SDM, may facilitate informed decision-making in managing these conditions.