A physical mechanism underlying the torque generation of the bacterial flagellar motor.

This study proposes a physical mechanism underlying the torque generation of a bacterial flagellar motor (BFM), in which the torque for the rotation of the rotor can be generated from impulsive forces resulting from collisions between the randomly moving stator and rotor. The torque required for the rotation of the rotor may be generated through two coexisting mechanisms: mechanism (A), in which the stator collides with the rotor, whose rotation axis fluctuates asymmetrically, generating a torque in the direction of the rod, and mechanism (B), in which physical collisions between the stator and the asymmetric [Formula: see text]and [Formula: see text] generate the torque in the direction of the rod. Mechanism (A) might be related the bidirectional rotation and the tumbling of the motion of the cell. Mechanism (B) might be related to occurrence of the steps in the time traces of the rotational angle, backward stepping or switching of the rotational direction, and the knee-shaped [Formula: see text]-[Formula: see text] relation. The above-mentioned characteristics of the rotation of BFM are reproduced in a model device designed to confirm the applicability of the proposed concept to real BFM. Moreover, a prediction of the disappearance of the knee-shaped [Formula: see text]-[Formula: see text] relation of the actual BFM at a high temperature is proposed.

Nanotwin orientation on history-dependent stress decay in Cu nanopillar under constant strain.

Cu with nanotwin (NT) possesses great electrical, mechanical, and thermal properties and has potential for electronic applications. Various studies have reported the effect of NT orientation on Cu mechanical properties. However, its effect on Cu stress-relaxation behavior has not been clarified, particularly in nano-scale. In this study, Cu nanopillars with various orientations were examined by a picoindenter under constant strain and observed byin situTEM. The angles between the twin plane and the loading direction in the examined nanopillars were 0°, 60°, to 90°, and a benchmark pillar of single-crystal Cu without NT was examined. The stress drops were respectively 10%, 80%, 4%, and 50%. Owing to the interaction by NT, the dislocation behavior in nanopillars was different from that in bulk or in thin film samples. Especially, the rapid slip path of dislocations to go to the free surface of the nanopillar induced a dislocation-free zone in the 0° nanopillar, which led to work-softening. On the contrary, a high dislocation density was observed in the 90° nanopillar, which was generated by dislocation interaction and obstruction of dislocation slip by twin planes, and it led to work-hardening. The findings reveal the NT orientation in Cu nanopillars affected stress relaxation significantly.

Performance and reading time of lung nodule identification on multidetector CT with or without an artificial intelligence-powered computer-aided detection system.

AIM: To compare the performance and reading time of different readers using automatic artificial intelligence (AI)-powered computer-aided detection (CAD) to detect lung nodules in different reading modes. MATERIALS AND METHODS: One hundred and fifty multidetector computed tomography (CT) datasets containing 340 nodules ≤10 mm in diameter were collected retrospectively. A CAD with vessel-suppressed function was used to interpret the images. Three junior and three senior readers were assigned to read (1) CT images without CAD, (2) second-read using CAD in which CAD was applied only after initial unassisted assessment, and (3) a concurrent read with CAD in which CAD was applied at the start of assessment. Diagnostic performances and reading times were compared using analysis of variance. RESULTS: For all readers, the mean sensitivity improved from 64% (95% confidence interval [CI]: 62%, 66%) for the without-CAD mode to 82% (95% CI: 80%, 84%) for the second-reading mode and to 80% (95% CI: 79%, 82%) for the concurrent-reading mode (p<0.001). There was no significant difference between the two modes in terms of the mean sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for both junior and senior readers and all readers (p>0.05). The reading time of all readers was significantly shorter for the concurrent-reading mode (124 ± 25 seconds) compared to without CAD (156 ± 34 seconds; p<0.001) and the second-reading mode (197 ± 46 seconds; p<0.001). CONCLUSION: In CAD for lung nodules at CT, the second-reading mode and concurrent-reading mode may improve detection performance for all readers in both screening and clinical routine practice. Concurrent use of CAD is more efficient for both junior and senior readers.

Fabrication and characteristics of highly [Formula: see text]-oriented nanotwinned Au films.

Fine grained and nanotwinned Au has many excellent properties and is widely used in electronic devices. We have fabricated [Formula: see text] preferred-oriented Au thin films by DC plating at 5 mA/cm2. Microstructure analysis of the films show a unique fine grain structure with a twin formation. Hardness tests performed on electroplated [Formula: see text] Au films show a hardness 47% greater than random and untwinned Au. We then achieved direct bonding between two Au [Formula: see text] surfaces operating at 200 °C for an hour in a vacuum oven. The highly-oriented [Formula: see text] nanotwinned Au films could be an ideal material in many gold products.

Mechanical mechanism for the translocation of hexameric and nonstructural helicases: Dependence on physical parameters.

Three recently observed facts of the translocation of actual hexameric and nonstructural (NS) helicases are related to the various physical quantities and are in accordance with the recently proposed mechanical mechanism: a) the translocation of hexameric helicases might be led by either the N-terminal domain (NTD) or C-terminal domain (CTD) depending on which domain has a smaller central pore, b) the translocation speed (vt) of the ring-shaped helicases and NS helicases decreased with decreasing applied tension, and c) a large difference in the vt of the NS helicase was observed for the helicase translocating on DNA and RNA. These findings are the effects of the physical quantities of the helicase/nuclei acid strands on the translocation of helicases and are difficult to explain with biochemical models. We predict that a similar behavior as described in b) and c) is also shown by hexameric helicases. The validity of the mechanical mechanism is demonstrated in simulation experiments.

Helicobacter pylori infection and the risk of colorectal cancer: a nationwide population-based cohort study.

BACKGROUND: The role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings. AIMS: This study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study. METHODS: A total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan's National Health Insurance Research Database. The Kaplan-Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC. RESULTS: The cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P < 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of CRC (adjusted HR 1.87; 95% CI 1.37-2.57). In addition, the HR of CRC appeared to increase with increasing frequency of clinical visits for H. pylori infection. CONCLUSIONS: Our study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies.

Observations of metastable states of the free swelling knots and directional motion of tensioned knots in vibrated bead chains.

The free swelling of knots and the directional motion of knots under tension were studied in vertically vibrated bead chains. A metastable state of swelling was observed in the strongly vibrated two-end-free bead chains, as predicted by Grosberg and Rabin (Phys. Rev. Lett. 99, 217801 (2007)). Knots in the two-end-fixed chains were found to move directionally. The direction of motion could be changed by flipping the knot over. The velocity of motion depended on the tension in the bead chain. The effects of tension on the motion of knots were studied in one-end-fixed chains. The directional reptation might have been influenced by the random motion of the leading arc of the knot. The knots might move in a forced-reptation manner under the interaction with a simulated translocase.

'Transformed rights' sexual health programme evaluation for the parents and service workers of adults with an intellectual disability.

BACKGROUND: To promote sexual health in adults with an intellectual disability (ID) in Taiwan, sexual health programmes were provided to adults with ID, their parents and service workers. This study evaluates the impact of these programmes that involved the parents and service workers. METHODS: Intervention and participatory research paradigms were applied to develop, implement and evaluate programmes that address the challenges that relate to the sexual rights of adults with ID. Additionally, the programmes fostered open dialogue among the participants concerning the sexual health of people with ID. In total, 57 parents and 164 service workers were involved in the programmes. A quasi-experimental design and standardised questionnaires (Attitudes to Sexuality Questionnaire - Individuals with an Intellectual Disability), as well as in-depth interviews, were used to collect both quantitative and qualitative data on the programmes' effectiveness and participants' experiences between April 2012 and July 2015. RESULTS: The findings revealed that after the programmes were implemented, attitudes towards the sexual rights of people with ID were significantly more positive among both the parents and service workers. Participation in the sexual health programmes facilitated constructive dialogue by revealing hidden concerns and by transforming the perspectives of the parents and service workers from viewing sexuality as a social problem to understanding the sexual rights of adults with ID. CONCLUSIONS: Both the quantitative and qualitative results demonstrate that the programmes had a positive impact on the parents and service workers in terms of their attitudes towards the sexual rights of people with ID. Open dialogue and reciprocal interaction strategies caused transformations in the perspectives of parents and service workers on sexual health.

Stroke in Parkinson's disease.

BACKGROUND: The association between Parkinson's disease (PD) and stroke remains completely understood. AIM: We aimed to investigate stroke risk and post-stroke outcomes in patients with PD. DESIGN: The retrospective cohort study included 1303 patients aged ≥ 40 years with new-diagnosed PD and 5212 non-PD adults were selected by frequency matching with age and sex in 2000-05. Both two groups were followed up until the end of 2013. Another nested stroke cohort study of 17 678 patients with stroke hospitalization in 2002-09 was conducted to compare the admission outcome in patients with and without PD history. METHODS: We collected patients' characteristics and medical conditions in the present two studies from claims data of Taiwan's National Health Insurance. Incidences and risks of stroke in people with and without PD during the follow-up period were calculated by adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in the Cox proportional hazard model. Complications and mortality during the stroke admission associated with PD were analysed by calculating adjusted odds ratios (ORs) and 95% CIs in the logistic regressions. RESULTS: Incidences of stroke for people with and without PD were 19.8 and 9.93 per 1000 person-years, respectively, with corresponding HR of 1.96 (95% CI 1.67-2.30). History of PD was associated with post-stroke gastrointestinal bleeding (OR 1.25, 95% CI 1.05-1.49), epilepsy (OR 1.64, 95% CI 1.32-2.04), pneumonia (OR 1.34, 95% CI 1.20-1.49), urinary tract infection (OR 1.33, 95% CI 1.21-1.45) and mortality (OR 1.35, 95% CI 1.13-1.62). CONCLUSION: PD increases stroke risk and influences post-stroke outcomes.

Overexpression of AdeABC efflux pump associated with tigecycline resistance in clinical Acinetobacter nosocomialis isolates.

OBJECTIVES: Tigecycline non-susceptible Acinetobacter nosocomialis (TNAN) has been discovered in clinical isolates. The resistance-nodulation-cell division (RND)-type efflux system plays a major role in tigecycline non-susceptible Acinetobacter baumannii, but the mechanism in A. nosocomialis remains unknown. Our aim was to analyse the contribution of efflux-based tigecycline resistance in clinical A. nosocomialis isolates collected from multiple medical centres in Taiwan. METHODS: A total of 57 A. nosocomialis isolates, including 46 TNAN and 11 tigecycline-susceptible A. nosocomialis (TSAN) isolates, were analysed. Of these, 46 TNAN isolates were clustered to ST410 (43 isolates) and ST68 (three isolates) by multi-locus sequence typing. RESULTS: The relationship between the RND efflux pump and tigecycline resistance was indirectly verified by successfully reducing tigecycline resistance with NMP, an efflux pump inhibitor. The three RND efflux systems (AdeABC, AdeIJK and AdeFGH) were detected in all clinical isolates. The transcript level of adeB gene increased significantly and was correlated with tigecycline resistance. Moreover, the AdeRS two-component system was further classified into four different types of AdeRS patterns considering the amino acid sequence. Further analysis showed that tigecycline resistance was related to the transcript level of adeB gene and the AdeRS pattern. CONCLUSION: This study showed that the dissemination of TNAN isolates in Taiwan is attributable mainly to the spread of ST410. The AdeABC efflux pump appeared to play an important role in the tigecycline resistance of A. nosocomialis.

Monitoring Taiwanese bovine arboviruses and non-arboviruses using a vector-based approach.

In current sampling approaches, there exists a divergence between the surveillance of arthropod-borne and that of non-arthropod-borne viruses. It is commonly held that the collection of vector specimens applies only to arbovirus surveillance and that the surveillance of non-arboviruses must rely on traditional methods that involve the sampling of blood, faeces or saliva, or other examinations. The vector-based approach is a sampling method that has the ability to survey both arboviruses and non-arboviruses by distinguishing engorged vector specimens from entire vector samples. Accordingly, five arboviruses and three non-arboviruses were detected in a study using a vector-based approach conducted during 2012-2015. Hence, this report provides the first description of the Taiwanese vector species for the bovine arboviruses detected. The present investigations demonstrate that the vector-based approach applies not only to the surveillance of arboviruses, but also has potential as a possible tool for monitoring non-arboviruses on livestock farms in the future.

Significance and positive predictive values of mammographic findings in the Asia-Pacific region: a single-centre study in Taiwan.

AIM: To report positive predictive values (PPVs) of mammographic findings (MFs) of a screening cohort in Taiwan with a view to providing radiologists around the world with adequate information for assessing MFs before recommending biopsy for Asian women. MATERIALS AND METHODS: Between January 2014 and June 2017, 18,449 women received screening mammography at Tri-Service General Hospital (TSGH). Of these women, 1,622 exhibited specific MFs, namely mass (n=518), microcalcification (n=668), focal asymmetry (FA; n=462), and architectural distortion (AD; n=117). The distribution and PPVs of each MF were calculated after stratification based on cancer type, age, and breast density. RESULTS: The age group with the highest proportion of women was 50-59 years (48.1%), and most women presented with dense breasts (68.6%). The most common MF in the recalled women was microcalcification (41.2%) and the least common was AD (7.2%). AD was the most predictive MF for overall breast cancers, invasive carcinomas, and carcinomas in situ. Microcalcification was the second most predictive MF among recalled women for predicting overall breast cancers; however, it was less predictive than mass and FA in women who received a biopsy recommendation or underwent biopsy. CONCLUSION: AD can indicate the likelihood of breast cancer development in Asian women with abnormal screening results. Benign breast diseases are more likely to occur in women recommended for or receiving breast biopsy owing to microcalcification than to mass or FA.

Survival outcome of weak estrogen/progesterone receptor expression in HER2 negative breast cancer is similar to triple negative breast cancer.

BACKGROUND: Recent publications have suggested that human epidermal growth factor receptor 2 (HER2)-negative breast cancers with "weak" estrogen receptor (ER)/progesterone receptor (PR) expression levels by immunohistochemical (IHC) analysis were considered as the triple-negative (TN) subtype. This study aimed to evaluate the overall survival (OS), disease-free survival rates (DFS), and disease-specific survival (DSS) based on ER and PR expression levels into one of three groups, ER and PR <1%, ER and PR 1%-20%, and ER or PR >20% by hormone therapy. METHODS: Medical records of 3353 breast cancer patients treated from 2006 to 2013 were retrospectively reviewed. Tumor characteristics, type of treatment, OS, DFS and DSS were evaluated among the three patient groups. RESULTS: Regarding OS, there were significant differences according to the received hormone therapy in the different groups: ER and PR <1% (P = 0.972), ER and PR 1%-20% (P = 0.264), and ER or PR >20% (P = 0.014). Regarding DFS and DSS, there were also significant differences in the different groups: ER and PR <1% (P = 0.611, 0.766), ER and PR 1%-20% (P = 0.847, 0.629), and ER or PR >20% (P = 0.031, 0.002). CONCLUSIONS: In HER2 negative breast cancer patient with hormone therapy, ER and PR expression level of 1%-20% has similar survival outcome to the ER and PR expression level of <1% by IHC analysis.

Comparison of self-determination of students with disabilities: multivariate and discriminant function analyses.

BACKGROUND: Self-determined behaviour is composed of multiple, interrelated component elements, and yet little empirical study has researched the self-determination components other than choice making and goal setting. Also, few theoretical relationships have been drawn between the component elements of self-determined behaviour and the impact of disability category. Therefore, this study examined profiles of the combination of three self-report measures of component elements of self-determined behaviour (autonomous functioning, problem solving and internal locus of control) between two groups (ID and learning disabilities/emotional disorders). METHOD: We analysed data from 96 middle school and high school students ages 13 through 22 years who completed three self-report instruments of the Autonomy - section 1 of The Arc's Self-determination Scale, the Problem Solving Survey and the Nowicki-Strickland Locus of Control Scale. A multivariate analysis of covariance was conducted to investigate the differences between the two groups after controlling for the developmental effects of age. A discriminant function analysis examined whether membership of the two groups could be predicted from the three component elements. RESULTS: Results showed that each group had different profiles within the combined three component elements of self-determination but groups were not different on any single measure of component elements of self-determined behaviour exclusively. The combination of three variables was useful in confirming the membership of two dichotomous groups. CONCLUSIONS: Score differences on the three component behaviour imply that the two groups have different instructional needs and therefore require differentiated instructional approaches. The three measures of the component elements of self-determined behaviour collectively separate the two groups, suggesting that the component elements should be considered in a combination as opposed to being treated as individual elements in the context of discussing self-determined behaviour.

Torque generation through the random movement of an asymmetric rotor: A potential rotational mechanism of the γ subunit of F(1)-ATPase.

The rotation of the γ subunit of F(1)-ATPase is stochastic, processive, unidirectional, reversible through an external torque, and stepwise with a slow rotation. We propose a mechanism that can explain these properties of the rotary molecular motor, and that can determine the direction of rotation. The asymmetric structures of the γ subunit, both at the tip of the shaft (C and N termini) and at the part (ε subunit) protruding from the α(3)ß(3) subunits, are critical. The torque required for stochastic rotation is generated from the impulsive reactive force due to the random collisions between the γ subunit and the quasihexagonal α(3)ß(3) subunits. The rotation is the result of the random motion of the confined asymmetric γ subunit. The steps originate from the chemical reactions of the γ subunit and physical interaction between the γ subunit and the flexible protrusions of the α(3)ß(3) subunits. An external torque as well as a configurational modification in the γ subunit (the central rotor) can reverse the rotational direction. We demonstrate the applicability of the mechanism to a macroscopic simulation system, which has the essential ingredients of the F(1)-ATPase structure, by reproducing the dynamic properties of the rotation.

Synthesis of nanostructures in nanowires using sequential catalyst reactions.

Nanowire growth by the vapour-liquid-solid (VLS) process enables a high level of control over nanowire composition, diameter, growth direction, branching and kinking, periodic twinning, and crystal structure. The tremendous impact of VLS-grown nanowires is due to this structural versatility, generating applications ranging from solid-state lighting and single-photon sources to thermoelectric devices. Here, we show that the morphology of these nanostructures can be further tailored by using the liquid droplets that catalyse nanowire growth as a 'mixing bowl', in which growth materials are sequentially supplied to nucleate new phases. Growing within the liquid, these phases adopt the shape of faceted nanocrystals that are then incorporated into the nanowires by further growth. We demonstrate this concept by epitaxially incorporating metal-silicide nanocrystals into Si nanowires with defect-free interfaces, and discuss how this process can be generalized to create complex nanowire-based heterostructures.

The correlation between lipoprotein ratios and hearing outcome in idiopathic sudden sensorineural hearing loss patients.

OBJECTIVE: Recent reports have identified hypercholesterolaemia as a significant risk factor for idiopathic sudden sensorineural hearing loss (ISSNHL). Therefore, we investigated whether lipid profiles and lipoprotein ratios are correlated with the prognosis of hearing recovery in ISSNHL patients. DESIGN: A retrospective cohort study. MAIN OUTCOME MEASURES: Patients with ISSNHL were classified into four groups (complete, partial, slight and no recovery) according to their degree of hearing recovery using Siegel's criteria and the Sudden Deafness Research Group (SDRG) criteria developed by the Japanese Ministry of Welfare. All patients' lipid profiles were analysed, including total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol and triglycerides. We calculated the ratios of TC/HDL-C and LDL-C/HDL-C and used statistical methods to evaluate correlations between lipid profiles and lipoprotein ratios and ISSNHL prognosis. RESULTS: Hearing recovery was observed in 103 (62.0%) of 166 cases using Siegel's criteria and in 114 (68.7%) of 166 cases using SDRG's criteria. Among the three recovery groups (i.e. excluding the no recovery group), the ratio of LDL-C/HDL-C was found to be associated with recovery outcome by showing the ratio on an upward trend from complete recovery to slight recovery group, and the difference is statistically significant (P = 0.016 by Siegel's criteria, P = 0.041 by SDRG's criteria). Multiple linear regression analysis further revealed a significantly higher LDL-C/HDL-C ratio in slight hearing recovery group compared with complete recovery group (P = 0.007 by Siegel's criteria, P = 0.031 by SDRG's criteria). CONCLUSION: We suggested that lipoprotein ratio of LDL-C/HDL-C may be a prognostic factor for hearing recovery in ISSNHL patients. Further studies should be conducted to determine whether hearing outcomes in ISSNHL can be improved by changing patients' lipid profiles via antilipidemic treatment.

Risk and adverse outcomes of fractures in patients with Parkinson's disease: two nationwide studies.

UNLABELLED: The association between Parkinson's disease and fracture was not completely understood. This nationwide study investigated increased risk of fracture in patients with Parkinson's disease. In the nested cohort study, Parkinson's disease was associated with pneumonia, septicemia, stroke, urinary tract infection, and mortality after fracture admission. INTRODUCTION: Falls are a common complication in people with Parkinson's disease (PD). This study evaluated fracture risk and post-fracture outcomes in patients with PD. METHODS: We identified 1,423 adults aged 40 years and older newly diagnosed with PD using the Taiwan National Health Insurance Research Database from 2000 to 2003. Comparison cohort consisted of 5,692 adults without PD randomly selected from the same dataset, frequency matched in age and sex. Followed-up events of fracture from January 1, 2000, until December 31, 2008, were ascertained from medical claims. Adjusted hazard ratios (HR) and 95 % confidence interval (CI) of fracture associated with PD were evaluated. Another nested cohort study of 397,766 hospitalized fracture patients analyzed for adjusted odds ratios (ORs) and 95 % CIs of adverse events after fracture among patients with and without PD between 2004 and 2010. RESULTS: The incidences of fracture for people with and without PD were 39.5 and 23.9 per 1,000 person-years, respectively (p < 0.0001). Compared with control, the adjusted HR of fracture was 2.25 (95 % CI 1.97-2.58) for PD patients. Previous PD was associated with risks of pneumonia (OR 1.44, 95 % CI 1.36-1.52), septicemia (OR 1.41, 95 % CI 1.33-1.49), stroke (OR 1.40, 95 % CI 1.32-1.50), urinary tract infection (OR 1.53, 95 % CI 1.46-1.61), and mortality (OR 1.25, 95 % CI 1.15-1.35) after fracture. CONCLUSIONS: PD was associated with higher risk of fracture. Patients with PD had more complications and mortality after fracture. Fracture prevention and attention to post-fracture adverse events are needed for this susceptible population.

The recommended dose of ertapenem poses a potential risk for central nervous system toxicity in haemodialysis patients - case reports and literature reviews.

WHAT IS KNOWN AND OBJECTIVE: Dosage adjustment of 500 mg ertapenem daily is recommended for patients with advanced kidney disease. 30% of ertapenem is cleared by a session of haemodialysis (HD). However, because most published carbapenems studies have excluded patients on dialysis, little is known about the dosing of ertapenem to avoid central nervous system (CNS) toxicity in regular HD patients. We report of four patients who developed CNS toxicity in such patients. CASE SUMMARY: The 4 HD patients developed unexplained CNS toxicity manifested as seizures, hallucination and cognitive dysfunction after receiving 3-7 consecutive recommended doses of ertapenem. Their symptoms of CNS toxicity were completely resolved within 8 days after discontinuation of ertapenem. In one of our presented cases, we demonstrated the very high level of plasma ertapenem accumulating with several consecutive doses. Cognitive function gradually recovered in line with a corresponding decline in blood level of ertapenem. WHAT IS NEW AND CONCLUSIONS: This is the first report of ertapenem-associated CNS toxicity in patients on regular HD and utilizing the plasma ertapenem concentration to demonstrate the causal relationship. The recommended dosage of 500 mg ertapenem daily may be still too high in regular HD patients, especially in Asians, owing to their relatively small body size. An increased awareness of ertapenem-associated CNS toxicity would avoid unnecessary examinations, hospitalization, and potentially catastrophic complications.