Adult-Onset Still's Disease Misdiagnosed as Acute Fibrinous and Organizing Pneumonia: A Case Report and Literature Review

Adult-onset Stil's disease(AOSD)is a rare condition that lies between autoinflammatory syndrome and autoimmune disease.The main clinical manifestations include fever,chills,rash,joint swelling and pain,peripheral blood leukocytosis,splenomegaly,etc.It is a systemic disease affecting between 1 and 34 people per million.The average age of onset is 35 years old,with a slightly higher prevalence rate in women.Since AOSD lacks early specific symptoms and signs,non-specialist doctors have limited understanding of the disease,and patients are prone to clinical misdiagnosis,mistreatment,and delayed disease progression.This paper reports a patient whose AOSD was misdiagnosed as acute fibrinous and organizing pneumonia.

Impacts of exercise interventions on different diseases and organ functions in mice

Background'. In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This reviewsummarizes the exercise interventions used in studies involving mice as they are related to special diseases or physiological status. To furtherunderstand the effects of exercise interventions in treating or preventing diseases, it is important to establish a template for exercise interventionsthat can be used in future exercise-related studies.Methods'. PubMed was used as the data resource for articles. To identify studies related to the effectiveness of exercise interventions for treatingvarious diseases and organ functions in mice, we used the following search language: (exercise [Title] OR training [Title] OR physical activity[Title]) AND (mice [title/abstract] OR mouse [title/abstract] OR mus [title/abstract]). To limit the range of search results, we included 2 filters:one that limited publication dates to "in 10 years,^ and one that sorted the results as "best match^^. Then we grouped the commonly used exercisemethods according to their similarities and differences. We then evaluated the effectiveness of the exercise interventions for their impact on diseasesand organ functions in 8 different systems.Results'. A total of 331 articles were included in the analysis procedure. The articles were then segmented into 8 systems for which the exerciseinterventions were used in targeting and treating disorders: motor system (60 studies), metabolic system (45 studies), cardio-cerebral vascularsystem (58 studies), nervous system (74 studies), immune system (32 studies), respiratory system (7 studies), digestive system (1 study), and thesystem related to the development of cancer (54 studies). The methods of exercise interventions mainly involved the use of treadmills, voluntarywheel-running, forced wheel-running, swimming, and resistance training. It was found that regardless of the specific exercise method used, mostof them demonstrated positive effects on various systemic diseases and organ functions. Most diseases were remitted with exercise regardless ofthe exercise method used, although some diseases showed the best remission effects when a specific method was used.Conclusion-. Our review strongly suggests that exercise intervention is a cornerstone in disease prevention and treatment in mice. Because exerciseinterventions in humans typically focus on chronic diseases, national fitness, and body weight loss, and typically have low intervention com・pliance rates, it is important to use mice models to investigate the molecular mechanisms underlying the health benefits from exerciseinterventions in humans.

Infrequent organ involvement in immunoglobulin G4-related prostate disease: A case report

BACKGROUND Immunoglobulin G4-related prostate disease(IgG4-RPD)characterized by a high count of IgG4-positive plasma cells has distinctive serological and radiological findings.Here we report a case of a patient who was successfully treated for IgG4-RPD,which manifested as frequent micturition,dysuric,and systemic lymphadenopathy.CASE SUMMARY The patient was a 33-year-old man who was referred to our hospital because of urinary tract symptoms that had persisted for 4 years.A physical examination revealed systemic lymphadenopathy and blood tests showed hyperglobulinemia with an IgG level of 18.90 g/L and an IgG4 level of 18.40 g/L.Computed tomography(CT)revealed bilateral lacrimal gland,right parotid gland and prostatic enlargement.Based on these findings,IgG4-RD was suspected,and further pathological examination and follow-up results showed expected results.Finally,the patient was diagnosed with IgG4-RPD based on clinical symptoms,pathological examination,therapeutic effects,and follow-up results.He received 50 mg oral prednisolone(the dose was gradually reduced and a low dose was used for long-term maintenance)in combination with cyclophosphamide 1.0 g via an intravenous drip for 6 mo.One year after the treatment was initiated,he was free of urinary or other complaints and his serum IgG4 level normalized.CONCLUSION In IgG4-RPD with severe urinary tract symptoms,radiological findings should be carefully examined.IgG4-RPD prognosis is good because the disease responds well to glucocorticoids.Furthermore,it is urgent for clinicians and pathologists to improve their understanding of IgG4-RPD.

Bioengineered functional humanized livers： An emerging supportive modality to bridge the gap of organ transplantation for management of end-stage liver diseases

End stage liver diseases （ESLD） represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients li-mits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolu-tionized the feld of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be con-sidered as better site for transplanting humanized bio-engineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for inve-stigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs thr-ough intra-omental transplantation of ex vivo genera-ted bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients

BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.

Risk of infectious diseases and cutaneous tumours in solid organ recipients: A meta-analysis of literature

AIM: To compare the risk of cutaneous infections and tumours in kidney transplant recipients with data recently published about this topic.METHODS: In the present work, we evaluated the incidence of bacterial, fungal and viral cutaneous infectious diseases and the development of skin cancers in a cohort of 436 patients who underwent a renal transplantation. The median age at transplantation of our patients was 50 years and the median duration of the immunosuppression was of 7.2 years. Data obtainedfrom our cohort were compared with those obtained by a systematic review of the literature of the last 20 years about the same topic.RESULTS: Infectious diseases were the most frequent dermatological disorders that were diagnosed after transplantation, affecting about the 16.5% of patients. Herpes virus reactivation occurs in about the 35% of patients and is more common within 6 mo from transplantation, whereas when the immunosuppression is reduced, skin infections are mainly represented by Human Papilloma Virus infections and localized mycosis, such as pityriasis versicolor and superficial candidiasis. Bacterial infections were relatively rare and occur mainly in the first months after transplantation. The cumulative risk to develop skin cancer enhance significantly over the time, as consequence of longterm immunosuppressive regiments. Endogenous and exogenous risk factors, as well as the schedule of immunosuppression can play a role and justify the different incidence of skin cancer in the various series. CONCLUSION: Skin infections and cancer, commonly diagnosed in transplanted patients, impact on survival and life-quality, justifying the realization of follow-up programs for the early diagnosis and treatment.

Root and Foot Rot Diseases of Winter Wheat Grown in Conventional and Organic Systems

The object of the study was fungous diseases occurring on roots, leave sheaths and stem base of winter wheat in the two opposing cropping systems (organic and conventional). The observations were made in vegetation periods (2007-2009) in the fields of winter wheat in northern Poland. Every year on each plot of compared farming systems root rot occurred (Fusarium spp., Gaeumannomyces graminis and other fungi). For the period of 3 years the degree of disease injury on the roots of winter wheat grown in the conventional system in the vegetation period increased, while in the organic one remained on pretty the same level. On average a lot more affected roots, especially in the flowering stage, occurred on the winter wheat grown in the conventional system. Fusarium foot rot (Fusarium spp.) developed on the wheat during the entire vegetation period. It was the most dangerous root and foot rot disease (the highest indexes of injury). The mean degree of disease injury on leave sheath was on pretty the same level in the two farming systems, although in investigated vegetation periods differed a lot, whereas at the bases of stems the pathogen was on the higher level on the wheat in the conventional system. Also eyespot (Tapesia yallude) developed in the entire vegetation period of the winter wheat, but its intensity was much lower than in case of fusarium foot rot. Leave sheaths of the wheat grown in the conventional system were slightly stronger affected than those grown in the organic system. In the flowering stage the intensity of the disease in both farming systems became equal, while in the wax maturity it was considerably higher in the conventional system. Sharp eyespot (Rhizoctonia spp.) appeared relatively late and occurred only in two years of investigation. The intensiveness of the disease was definitely higher on the organic plots. Among the affected roots, taken in the stem elongation stage, from the organic system 28 cultures of fungi were isolated, and from the conventional one 24 colonies. Cereals pathogenic fungi amounted 35.8% of isolates obtained from the organic system and as many as 66.7% from the conventional system. Among the affected roots, taken in the flowering stage, from the organic system 68 cultures of fungi were isolated in all, and from the conventional one 25 colonies. Cereals pathogenic fungi amounted 38.2% of isolates obtained from the organic system and 56.0% from the conventional system. Among the affected stem bases, taken in the wax maturity stage, from the organic system 56 cultures of fungi were isolated in all, and from the conventional one 52 colonies. Cereals pathogenic fungi amounted 48.4% of isolates obtained from the organic system and 53.6% from the conventional system. In the case of all root and foot rot diseases of wheat grown in the organic system, an advantageous influence of greater biodiversity and number of various fungi species living in root proximity was noticed as opposed to the conventional system.

Chinese Scientists Working on Diseases of Cultured Organisms in Seawater

Considerable research efforts are being made in China to understand the pathogeny of major marine cultured organisms and their resistance to diseases, which has been listed in the national development program for major basic research projects. The program, also called "973," is in effect a national plan focused on the leading basic

On the Comprehensive Prevention and Control Technology of the Reproductive Organ Disease of Breeding Geese under the Anti-season Breeding Mode

Reproductive organ disease of geese is an endemic and multiple infectious disease in large-scale breeding of breeding geese, especially in anti-season production, which brings a great economic loss to goose production. To make effective prevention and control of reproductive organ disease of breeding geese under the anti-season breeding mode, the characteristics of control principles of infectious diseases of the poultry and the occurrence and prevalence of reproductive organ disease must be combined, so as to carry out scientific prevention and control.At the same time, according to the climate characteristics of summer, the feeding and management of breeding geese and water quality control should also be done well, and many corresponding measures should also be taken, thus obtaining better effect.

Gap junction-mediated cell-to-cell communication in oral development and oral diseases: a concise review of research progress

Homoeostasis depends on the close connection and intimate molecular exchange between extracellular, intracellular and intercellular networks. Intercellular communication is largely mediated by gap junctions(GJs), a type of specialized membrane contact composed of variable number of channels that enable direct communication between cells by allowing small molecules to pass directly into the cytoplasm of neighbouring cells. Although considerable evidence indicates that gap junctions contribute to the functions of many organs, such as the bone, intestine, kidney, heart, brain and nerve, less is known about their role in oral development and disease. In this review, the current progress in understanding the background of connexins and the functions of gap junctions in oral development and diseases is discussed. The homoeostasis of tooth and periodontal tissues, normal tooth and maxillofacial development, saliva secretion and the integrity of the oral mucosa depend on the proper function of gap junctions.Knowledge of this pattern of cell–cell communication is required for a better understanding of oral diseases. With the everincreasing understanding of connexins in oral diseases, therapeutic strategies could be developed to target these membrane channels in various oral diseases and maxillofacial dysplasia.

Inflammatory bowel diseases: Current problems and future tasks

Current knowledge on inflammatory bowel disease(IBD)is mainly endorsed by controlled trials and epidemiologic studies. Yet,we seldom look at the messages from real-world practice. Among a patient population followed since2008,we looked at an unselected sample of 64 IBD patients [26 Crohn's disease(CD) and 38 ulcerative colitis(UC)] who had been seen as out-patients in the last year.Inducing remission,mesalamines(86% for UC/69% for CD/33%-16% as MMX formulation) prevailed as prescrip-tions; steroids(55%/19% for UC/CD) ranked second.Prescription of third-party drugs(antibiotics,NSAIDs,biologics) and adherence,were issues in the maintenance.34% of CD,and 23% of UC patients showed accompany-ing immunologic diseases: CD-associated familiar psoriasis(4:9) ranked first. Main Message. The association between IBD(CD mainly) and psoriasis,now found in our practice,matches current basic science gathering IBD together with psoriasis(and perhaps chronic respiratory disease) under the comprehensive term "barrier organ disease" wherein an epithelial surface with sensor system srules contacts between outer antigens and a reactive underneath tissue,with the balance between inflammation and quiescence kept at any time by mucosal permeability.IBD is thus viewed as a polyfactorial/polygenic/syndromic disorder,embedded into a galaxy of immune conditions offering multiple points of attack. This mindset of splitting the IBDs into pathogenic categories may allow overcoming the uniformly targeting of a single cytokine by biological drugs,in favor of demarcating the boundaries between different disease-subtype-specific indications,and paving the way to future personalized strategies.

Role of CARD15,DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases

AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.

Adult-onset Still's disease evolving with multiple organ failure and death:A case report and review of the literature

BACKGROUND Adult-onset Still’s disease(AOSD)is a rare systemic inflammatory disease,which is characterized by daily fever and arthritis,with an evanescent rash and neutrophilic leukocytosis.To date,there has been no definite laboratory or imaging test available for diagnosing AOSD;the diagnosis is one of exclusion,which can be very challenging.In particular,AOSD patients may experience different complications affecting their clinical picture,management,and prognosis.The treatment of AOSD remains largely empirical and involves therapeutic agents.CASE SUMMARY We report the case of a 36-year-old woman who presented with fever,red rash,arthralgia,and sore throat.Her serum ferritin level and white blood cell count were markedly elevated,and the first diagnosis 22 years prior was"juvenile rheumatoid arthritis of systemic type".The patient was treated with prednisone,sulfasalazine,methotrexate,and leflunomide.After remission of her symptoms,the patient stopped taking the medications,and the disease recurred.Ultimately,the patient was diagnosed with adult-onset Still's disease.Relapse occurred several times due to self-medication withdrawal,and an interleukin-6 antagonist(tocilizumab/Actemra)was administered to control the disease.Recently,she was hospitalized because an incision did not heal,and the patient suddenly developed high fever and diarrhea during hospitalization.The patient's disease progressed violently and quickly developed into macrophage activation syndrome,disseminated intravascular coagulation,shock,and multiple organ failure.The patient had sudden cardiac arrest,and she died despite emergency rescue efforts.CONCLUSION AOSD patients need regular follow-up in the long-term treatment process,and must press formulary standard medication,and do not voluntarily withdraw or reduce the dose.Otherwise it may cause disease back-and-forth or serious lifethreatening complications.Meanwhile,strict management of trauma,infections,tumors,and other diseases may contribute to improved outcomes in patients with complications.

Determining the environmental and atmospheric effects of coronavirus disease 2019(COVID-19)quarantining by studying the total aerosol optical depth,black carbon,organic matter,and sulfate in Blida City of Algeria

Background:To study,estimate and discuss the variations of the aerosol optical depth(AOD),black carbon,sulfate and organic matter,in the atmosphere in Blida City of Algeria,which was greatly affected by COVID-19 pandemic.Methods:We analyzed the effects of changes in the total AOD,black carbon,sulfate,and organic matter in the atmosphere(λ=550 nm)in the same period of 2019 and 2020,following the COVID-19 epidemic in Blida City,which was the most-affected city in Algeria.Results:The quarantine that was enacted to limit the spread of COVID-19 resulted in side effects that were identifiable in the total AOD and in some of its atmospheric components.Comparing these variables in 2019 and 2020(in the months during the quarantine)revealed that in April,the BCAOD values were much lower in 2020than in 2019.Conclusion:Based on the effects of the emerging COVID-19,the research listed the changes received from the AOD,and is considered as a comparative study and represents a significant side effect of the quarantine that was mainly designed to limit COVID-19.

Kidney disease in non-kidney solid organ transplantation

Kidney disease after non-kidney solid organ transplantation(NKSOT)is a common post-transplant complication associated with deleterious outcomes.Kidney disease,both acute kidney injury and chronic kidney disease(CKD)alike,emanates from multifactorial,summative pre-,peri-and post-transplant events.Several factors leading to kidney disease are shared amongst solid organ transplantation in addition to distinct mechanisms unique to individual transplant types.The aim of this review is to summarize the current literature describing kidney disease in NKSOT.We conducted a narrative review of pertinent studies on the subject,limiting our search to full text studies in the English language.Kidney disease after NKSOT is prevalent,particularly in intestinal and lung transplantation.Management strategies in the peri-operative and post-transplant periods including proteinuria management,calcineurin-inhibitor minimization/sparing approaches,and nephrology referral can counteract CKD progression and/or aid in subsequent kidney after solid organ transplantation.Kidney disease after NKSOT is an important consideration in organ allocation practices,ethics of transplantation.Kidney disease after SOT is an incipient condition demanding further inquiry.While some truths have been revealed about this chronic disease,as we have aimed to describe in this review,continued multidisciplinary efforts are needed more than ever to combat this threat to patient and allograft survival.

Bioadhesive ultrasound for long-term continuous imaging of diverse organs

Continuous imaging of internal organs over days could provide crucial information about health and diseases and enable insights into developmental biology.We report a bioadhesive ultrasound(BAUS)device that consists of a thin and rigid ultrasound probe robustly adhered to the skin via a couplant made of a soft,tough,antidehydrating,and bioadhesive hydrogel-elastomer hybrid.The BAUS device provides 48 hours of continuous imaging of diverse internal organs,including blood vessels,muscle,heart,gastrointestinal tract,diaphragm,and lung.The BAUS device could enable diagnostic and monitoring tools for various diseases.

Role of interaction between selenium and organic matters on causes of Kaschin-Beck disease

Influences of organic matters of soil and water on speciation and biological utilization of selenium are discussed. Humic acid is found to be the main pool of selenium in soil and affects the bio-availability of the element in soil-plant system. Fulvic acid from drinking water inhibits the absorption of selenium taken from diet. The relationship between high content of organic matters of water and selenium deficiency on the causes of KBD could be reflected in the limited synthesis of glutathione peroxidase, which is generally stimulated by fulvic acid from drinking water.

Research on organic matters in the drinking water of Kaschin-Beck disease area

Organic matters in drinking water of Kaschin-Beck disease areas were extracted. Then analyses and characterization were performed by means of multiply chemical and physical methods. The results did not show the obvious difference in the frame structure of humic substances and the structure of rmcromolecular compounds in the drinking water of disease and non-disease areas, but the difference in the contents of some micromolecular compounds and radicals. The investigation also includes the preliminary research on the photoreaction of drinking water from disease and non-disease areas and the accumulation of natural organic matter in the bone of tested animals.

A STUDY ON RELATIONSHIP BETWEEN ORGANIC SUBSTANCES IN WATER AND PREVALENCE OF KASHIN BECK DISEASE

This study is to acquire the relationship between organic substances in water and prevalence of Kashin Beck disease (KBD). We sampled in three endemic areas and their corresponding neighboring non endemic areas, determined the contents of organic substances and examined the children. The results showed that:①humus type B exited only in endemic areas; ②the content of humus type B is proportional to the state of the illness. KBD may be related to the humus type B in drinking water.

Clinical Features and Organ System Dysfunction in Coronavirus Disease 2019 in China

Objectives: To enhance understanding of COVID-19 in clinical characteristics, related organ system dysfunctions and therapies. Methods: We enrolled patients with COVID-19 admitted to two Chinese hospitals from 19 January 2020 to 15 March 2020 and collected demographic and clinical data. Results: We retrospectively enrolled 130 patients: 7 mild, 103 moderate, and 20 severe cases. Severe patients were older than mild/moderate patients (60.1 vs 52.9 years;P = 0.028) and had more comorbidities (85.0% vs 52.7%;p = 0.006). 116 patients (89.2%) were 2019-noval coronavirus RNA-positive with a median detectable time of 10 days. Obvious absorbed of pneumonia in chest imaging occurred in 20 days. The most common symptoms were fever (n = 87, 66.9%), cough (n = 74, 56.9%), fatigue (n = 73, 56.2%), and chest tightness (n = 54, 41.5%). The incidence of liver, kidney, heart, and coagulation dysfunction was 38.4%, 24.5%, 30.1%, and 24.6%, respectively. The most frequently used antiviral therapies were arbidol (n = 64, 49.2%), oseltamivir (n = 73, 56.2%), and Lianhua Qingwen (n = 73, 56.2%). All patients recovered being hospitalized with a median duration of 15 days. Conclusions: Middle-aged and elderly with comorbidities are more likely to be infected with COVID-19 and develop severe symptoms. The lung, liver, heart, kidney, and coagulation system all may sustain injury, especially in severe cases.