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To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel β-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU).
Design:
Retrospective, multicenter, cohort.
Setting:
Ten hospitals in the southeastern United States.
Methods:
GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel β-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel β-lactams.
Results:
The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 (P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel β-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden.
Conclusions:
The overall prevalence of GNB with DTR and the use of novel β-lactams remain low. However, the uptrend in the use of novel β-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR.
Tuberous sclerosis complex (TSC) is a rare genetic disorder that commonly leads to drug-resistant epilepsy in affected patients. This study aimed to determine whether the underlying genetic mutation (TSC1 vs. TSC2) predicts seizure outcomes following surgical treatments for epilepsy.
Methods:
We retrospectively assessed TSC patients using the TSC Natural History Database core registry. Data review focused on outcomes in patients treated with surgical resection or vagus nerve stimulation.
Results:
A total of 42 patients with a TSC1 mutation, and 145 patients with a TSC2 mutation, were identified. We observed a distinct clinical phenotype: children with TSC2 mutations tended to be diagnosed with TSC at a younger age than those with a TSC1 mutation (p < 0.001), were more likely to have infantile spasms (p < 0.001), and to get to surgery at a later age (p = 0.003). Among this TSC2 cohort, seizure control following resective epilepsy surgery was achieved in less than half (47%) the study sample. In contrast, patients with TSC1 mutations tended to have more favorable postsurgical outcomes; seizure control was achieved in 66% of this group.
Conclusion:
TSC2 mutations result in a more severe epilepsy phenotype that is also less responsive to resective surgery. It is important to consider this distinct clinical disposition when counseling families preoperatively with respect to seizure freedom. Larger samples are required to better characterize the independent effects of genetic mutation, infantile spasms, and duration of epilepsy as they relate to seizure control following resective or neuromodulatory epilepsy surgery.
Subcutaneous immunotherapy is an effective and safe treatment for allergic rhinitis and allergic asthma. Different symptom scores are used to evaluate the efficacy of subcutaneous immunotherapy in clinical trials.
Method
A total of 58 allergic rhinitis patients sensitised to house dust mites, with or without mild asthma, were included. Symptom score, medication score, visual analogue scale score and quality of life were assessed before and after 6, 12 and 24 months of subcutaneous immunotherapy.
Results
After two years of subcutaneous immunotherapy, asthma symptom scores nearly reached zero, whereas the scores remained higher for nasal symptoms. The changes in asthma symptom scores were markedly different (p < 0.05) and occurred faster than the changes in nasal symptom scores when compared between monosensitised and polysensitised groups. Significant reductions in visual analogue scale score and medication score were demonstrated after subcutaneous immunotherapy.
Conclusion
Two-year subcutaneous immunotherapy with house dust mite vaccine is an effective treatment for both monosensitised and polysensitised allergic patients. The changes in asthma symptom scores were markedly different and occurred quicker than the changes in nasal symptom scores in Chinese house dust mite allergic patients.
South-east Asian apple snails, Pila spp., have been declining since the introduction of globally invasive, confamilial South American Pomacea spp., yet Pila ecology remains poorly studied, with most occurrence records unconfirmed. Pila scutata, a previously widespread species, presumed native to the Malay peninsula and assessed as Least Concern in the IUCN Red List, was formerly harvested for food, and may have experienced anthropogenic translocations. We surveyed the Malay peninsula (specifically Peninsular Malaysia and Singapore) to investigate the current distribution and genetic diversity of P. scutata. Six populations were found in Singapore, but only one in Peninsular Malaysia. Mitochondrial COI and 16S sequencing revealed that the Malaysian population shared a single haplotype of both genes with the Singapore populations (500 km distant). This low genetic diversity could stem from a recent anthropogenic introduction, which brings into question the true native range of P. scutata and, coupled with poorly resolved taxonomy of the genus, necessitates a reassessment of its IUCN Red List status. Introduced populations pose a dilemma, and the lack of genetic diversity is of concern in light of Pila decline throughout South-east Asia. Our results highlight that conservation management of P. scutata and its congeners must therefore be better informed by greater taxonomic resolution and more comprehensive investigations of their ecology, both in native and introduced ranges.
Active drag reduction of an Ahmed body with a slant angle of $25^{\circ }$, corresponding to the high-drag regime, has been experimentally investigated at Reynolds number $Re=1.7\times 10^{5}$, based on the square root of the model cross-sectional area. Four individual actuations, produced by steady blowing, are applied separately around the edges of the rear window and vertical base, producing a drag reduction of up to 6–14 %. However, the combination of the individual actuations results in a drag reduction 29 %, higher than any previous drag reductions achieved experimentally and very close to the target (30 %) set by automotive industries. Extensive flow measurements are performed, with and without control, using force balance, pressure scanner, hot-wire, flow visualization and particle image velocimetry techniques. A marked change in the flow structure is captured in the wake of the body under control, including the flow separation bubbles, over the rear window or behind the vertical base, and the pair of C-pillar vortices at the two side edges of the rear window. The change is linked to the pressure rise on the slanted surface and the base. The mechanisms behind the effective control are proposed. The control efficiency is also estimated.
Plant height and lodging resistance can affect rice yield significantly, but these traits have always conflicted in crop cultivation and breeding. The current study aimed to establish a rapid and accurate plant type evaluation mechanism to provide a basis for breeding tall but lodging-resistant super rice varieties. A comprehensive approach integrating plant anatomy and histochemistry was used to investigate variations in flexural strength (a material property, defined as the stress in a material just before it yields in a flexure test) of the rice stem and the lodging index of 15 rice accessions at different growth stages to understand trends in these parameters and the potential factors influencing them. Rice stem anatomical structure was observed and the lignin content the cell wall was determined at different developmental stages. Three rice lodging evaluation models were established using correlation analysis, multivariate regression and artificial radial basis function (RBF) neural network analysis, and the results were compared to identify the most suitable model for predicting optimal rice plant types. Among the three evaluation methods, the mean residual and relative prediction errors were lowest using the RBF network, indicating that it was highly accurate and robust and could be used to establish a mathematical model of the morphological characteristics and lodging resistance of rice to identify optimal varieties.
To investigate lung function in Chinese patients suffering from chronic rhinosinusitis with nasal polyps and examine its association with histopathological features.
Methods:
The lung function of 99 patients with nasal polyps was measured. Haematoxylin and eosin and immunohistochemistry staining were performed to evaluate any inflammatory cells and epithelial tissue remodelling.
Results:
Predicted maximal expiratory flow rate at 25 per cent vital capacity was reduced (p < 0.05) in epithelial hyperplasia, and predicted maximal expiratory flow rate at 50 per cent vital capacity was reduced (p < 0.05) in goblet cell hyperplasia. Both peripheral blood eosinophilia and tissue eosinophilia nasal polyps manifested significantly reduced: forced expiratory volume in 1 second/forced vital capacity ratio, predicted maximal expiratory flow rate at 25, 50 and 75 per cent of vital capacity, and predicted maximal mid-expiratory flow. Peripheral blood eosinophils were negatively correlated with predicted maximal expiratory flow rate at 25 and 50 per cent of vital capacity, and predicted maximal mid-expiratory flow. Eosinophils in tissue were negatively correlated with all lung function parameters investigated except predicted forced vital capacity.
Conclusion:
Clinicians should be aware of lung function decline in nasal polyps patients, especially in those with tissue eosinophilia.
Patients with bipolar disorder (BD) frequently exhibit impulsive behaviors independent of their mood state, and trait impulsivity is increasingly recognized as a crucial BD biomarker. This study aimed to investigate structural correlates of trait impulsivity measured using the Barratt Impulsiveness Scale (BIS) in healthy controls (HCs) and patients with BD.
Method
We recruited 59 patients diagnosed with BD I or BD II (35.3 ± 8.5 years) and 56 age- and sex-matched HCs (33.9 ± 7.4 years). Participants underwent structural magnetic resonance imaging and clinical evaluations, and their BIS scores were evaluated. An automated surface-based method (FreeSurfer) was used to measure cortical thickness and generate thickness maps for each participant. Brain-wise regression analysis of the association between cortical thickness and BIS scores was performed separately for BD and HC groups by using a general linear model.
Results
Patients with BD obtained significantly higher BIS scores than HCs. In HCs, higher BIS scores were associated with a thinner cortex in the left inferior, middle and medial frontal cortices. By contrast, in BD patients, higher BIS scores were associated with a thicker cortex in the right insula. Patients with BD showed a thinner cortex than HCs in all these four structures.
Conclusions
The findings indicate that the left prefrontal cortex plays a cardinal role in trait impulsivity of healthy individuals. Patients with BD have a different structural correlate of trait impulsivity in the right insula. However, the use of various psychotropics in patients with BD may limit our interpretation of BD findings.
At the end of 2013, China reported a countrywide outbreak of measles. From January to May 2014, we investigated the clinical and immunological features of the cases of the outbreak admitted to our hospital. In this study, all 112 inpatients with clinically diagnosed measles were recruited from the 302 Military Hospital of China. The virus was isolated from throat swabs from these patients, and cytokine profiles were examined. By detecting the measles virus of 30 of the 112 patients, we found that this measles outbreak was of the H1 genotype, which is the major strain in China. The rates of complications, specifically pneumonia and liver injury, differed significantly in patients aged <8 months, 8 months to 18 years, and >18 years: pneumonia was more common in children, while liver injury was more common in adults. Pneumonia was a significant independent risk factor affecting measles duration. Compared to healthy subjects, measles patients had fewer CD4+IL-17+, CD4+IFN-γ+, and CD8+IFN-γ+ cells in both the acute and recovery phases. In contrast, measles patients in the acute phase had more CD8+IL-22+ cells than those in recovery or healthy subjects. We recommend that future studies focus on the age-related distribution of pneumonia and liver injury as measles-related complications as well as the association between immunological markers and measles prognosis.
Trichogramma chilonis Ishii (Hymenoptera: Trichogrammatidae) is an important natural enemy of many species of lepidopterous pests and a widely used biological control agent. Detailed knowledge about its mate choice and host discrimination behavior is lacking. In this study, we studied the mate choice and host discrimination behavior of T. chilonis in experimental arenas through video tracking. Males’ mate recognition capacity was realized by perceiving the sex pheromone of females. When offered two females of different species, male could distinguish the conspecific female from Trichogrammatoidea bactrae Nagaraja (Hymenoptera: Trichogrammatidae), a species that has overlapping hosts with T. chilonis. When placed with two females of different mating status, male preferred mating with the virgin female to the mated female. T. chilonis females could distinguish unparasitized host eggs from parasitized ones (parasitized by conspecific females or heterospecific females). They preferred to stay on and lay eggs in unparasitized host eggs. When T. chilonis females were only provided with parasitized host eggs (parasitized by T. chilonis and T. bactrae females), conspecific superparasitism occurred more often than heterospecific superparasitism. Furthermore, the host egg discrimination ability of T. chilonis females was mainly achieved through antennal perception.
Conventional identification of Paragonimus species and their natural definitive hosts is based on the morphological features of adult parasites isolated from the lungs of wild mammalian hosts. However, wild animals are protected by strict regulations and sampling is not always possible. Recently, molecular techniques have been developed to identify the internal transcribed spacer (ITS) sequences of Paragonimus eggs in faeces/sputum of human patients. Also, mammalian hosts can be identified using the D-loop sequence of mitochondrial DNA in faecal samples. In this study, we used molecular techniques on faeces from wild animals collected in Da Krong Nature Reserve, Quang Tri province, central Vietnam, where Paragonimus metacercariae are highly prevalent in mountain crabs, to identify Paragonimus species and their natural definitive hosts. The results indicated that wild cats, Prionailurus bengalensis, were infected with at least three different Paragonimus species, P. westermani, P. skrjabini and P. heterotremus. Because all of these species can infect humans in Asian countries, human paragonimiasis should be considered in this area.
Necrophoric behaviour is critical sanitation behaviour in social insects. However, little is known about the necrophoric responses of workers towards different developmental stages in a colony as well as its underlying mechanism. Here, we show that Solenopsis invicta workers display distinct necrophoric responses to corpses of workers and pupae. Corpses of workers killed by freezing (dead for <1 h) were carried to a refuse pile, but pupal corpses would take at least 1 day to elicit workers’ necrophoric response. Metarhizium anisopliae-infected pupal corpses accelerated the necrophoric behaviour of resident workers, with 47.5% of unaffected corpses and 73.8% infected corpses discarded by 1 day post-treatment). We found that fungus-infected pupal corpses had a higher concentration of fatty acids (palmitic acid, oleic acid and linoleic acid) on their surface. We experimentally confirmed that linoleic and oleic acids would elicit a necrophoric response in workers. The appearance of linoleic and oleic acids appeared to be chemical signals involved in recognition of pupal corpses, and M. anisopliae infection could promote the accumulation of fatty acids on surface of pupal corpses resulting in accelerated necrophoric responses of workers.
Objective: While acute disc-herniation radiculopathy frequently resolves without clinical sequelae, some patients experience long-term sensory or motor dysfunction. This study examined chronic sensitivity of the rodent hindpaw after resolution of an acute inflammatory neuropathy. Methods: C57BL/6 mice underwent mid-thigh sciatic nerve exposure, with sham animals exposed and experimental animals injured by placement of littermate tail nucleus pulposus (NP). Animals were evaluated for mechanical allodynia (Von Frey), thermal sensitivity (heat withdrawal and acetone latency), and gait stability (RotaRod), until the acute nociceptive phenotype resolved. Thereafter, animals were injected with intraplantar subthreshold capsaicin or vehicle followed by the same testing. At sacrifice, sciatic nerves were assessed for macrophage infiltration by immunohistochemistry, and dorsal root ganglion (DRG) explants were assessed for capsaicin sensitivity using cobalt staining. Results: NP-treated animals were allodynic after subthreshold capsaicin delivery compared with sham-operated controls and NP-treated animals delivered vehicle only. Early intraneural macrophage infiltration at one week dissipated by this three week timepoint. DRGs derived from NP-treated animals exhibited greater cobalt staining upon capsaicin exposure compared with shams. Conclusion: Non-compressive disc herniation creates long-term sensitization in the sciatic nerve distribution. This persists despite resolution of acute intraneural macrophage migration, and the demonstrated role of TRPV1 provides insight into the transformation of acute inflammatory pain into chronic neuropathic pain.
Keratitis is an ocular emergency that can lead to severe visual disability and requires prompt diagnosis and treatment. Sequelae can vary in severity from little or no visual loss to corneal scarring, perforation, endophthalmitis, and loss of the eye. Although the corneal surface is awash with microorganisms of the normal flora, an intact corneal epithelium and ocular defense mechanism serve to prevent infection in the normal eye. Although some organisms such as Neisseria gonorrhoeae, Neisseria meningitidis, Corynebacterium diptheriae, Listeria, and Shigella can penetrate an intact epithelium, all others require damage to the epithelial layer to invade the cornea. Several risk factors predispose the cornea to infection. Dry eyes from Sjogren syndrome, Stevens–Johnson syndrome, or vitamin A deficiency can result in bacterial keratitis. Prolonged corneal exposure from ectropion, lagophthalmos, or proptosis can lead to secondary infection. Entropion and trichiasis resulting in epithelial defects put the cornea at risk. Neurotropic keratopathy from cranial neuropathy, prior herpes simplex, or zoster infections predispose to secondary infections. Some systemic conditions such as chronic alcoholism, severe malnutrition, immunosuppressive drug use, immunodeficiency syndromes, and malignancy can impair immune defenses and allow infection by unusual organisms. Prior ocular surgery such as penetrating keratoplasty or refractive procedures is also a risk factor. Trauma is a common predisposing factor of bacterial keratitis, especially for patients at the extremes of age and in developing countries. Injury to the corneal surface and stroma allows invasion of normal flora as well as organisms harbored by foreign bodies.
Contact lens wear is the most common established risk factor for bacterial keratitis in developed countries. All types of contact lenses have been linked to infection, with extended-wear soft lenses conferring greater risk than daily wear hard or soft lenses. Corneal changes from contact lens use include an induced hypoxic and hypercapnic state promoting epithelial cell derangement and allowing bacterial invasion. Contact lenses also induce dry eye and corneal hypesthesia. Overnight rigid gas-permeable lens use for orthokeratology has also been associated with bacterial keratitis, but with a disproportionately high incidence of Acanthamoeba keratitis.
Conjunctivitis is a nonspecific term used to describe inflammation of the ocular surface and conjunctiva from either infectious or noninfectious causes. Infectious conjunctivitis is most commonly due to exogenous inoculation of the mucous membranes lining the surface of the eye and eyelid, resulting in an activation of a local inflammatory response. The vast majority of cases are acute but it may also present as chronic or recurrent. Although most cases of acute infectious conjunctivitis are self-limited and result in few long-term sequelae, appropriate evaluation and therapy are indicated with specific presentations.
Clinical features
The hallmark of conjunctivitis is injection or hyperemia of the conjunctival vessels, resulting in a red eye as well as tearing and/or mucopurulent discharge. Conjunctivitis may also result in complaints of irritation, foreign-body sensation, mattering or crusting of the eyelids, and mild visual blurring primarily due to alterations of the tear layer. The local inflammatory response may manifest as conjunctival lymphoid follicles or vascular papillae, eyelid edema, and/or preauricular adenopathy. Complaints of severe eye pain, photophobia, significant visual loss, or referred pain should alert the examiner to the possibility of other, more ominous, etiologies. Similarly, loss of normal corneal clarity, either diffuse or focal, proptosis, pupillary abnormalities, conjunctival scarring, or restriction of eye movement are criteria for a detailed ophthalmic evaluation (Table 11.1).
The enteric pathogens causing diarrhoea impair children's health severely. This study retrospectively analysed 1577 pathogens isolated from inpatients and outpatients in six hospitals located in Northern (Inner Mongolia), Northeastern (Hebei), Eastern (Shanghai and Jiangsu), Southern (Hainan) and Central (Hubei) China between 2008 and 2013. Of the 1577 enteric pathogens, Salmonella presented with the highest frequency (36·0%), followed by diarrhoeagenic Escherichia coli (23·7%), Staphylococcus aureus (15·0%), Shigella (13·1%), and Aeromonas (4·6%). The predominant pathogens varied in different regions of China, with Salmonella most prevalent in Shanghai and Hainan, diarrhoeagenic E. coli most prevalent in Inner Mongolia, Jiangsu and Hubei, and Shigella most prevalent in Hebei. Enteric pathogens were more frequently isolated in males (56·9%) than in females (43·1%). The highest proportion of all enteric pathogens was found in infants (67·6%) with a peak in summer and autumn (68·5%). Antimicrobial susceptibility assay demonstrated that Shigella was more resistant to ampicillin, ceftriaxone and sulfamethoxazole than Salmonella. Of the top two serotypes in Salmonella, Typhimurium was more resistant to ciprofloxacin, sulfamethoxazole and chloramphenicol than Enteritidis (P < 0·001). Meanwhile, the resistance rates of Shigella flexneri against ampicillin/sulbactam, ciprofloxacin, and chloramphenicol were significantly higher than those of Shigella sonnei (P < 0·001). Multidrug resistance was apparent in 58·2% of Shigella and 45·9% of Salmonella, and this phenomenon was more pronounced in S. flexneri.
While rabies is a significant public health concern in China, the epidemiology of animal rabies in the north and northwest border provinces remains unknown. From February 2013 to March 2014, seven outbreaks of domestic animal rabies caused by wild carnivores in Xinjiang (XJ) and Inner Mongolia (IM) Autonomous Regions, China were reported and diagnosed in brain samples of infected animals by the fluorescent antibody test (FAT) and RT–PCR. Ten field rabies viruses were obtained. Sequence comparison and phylogenetic analysis based on the complete N gene (1353 bp) amplified directly from the original brain tissues showed that these ten strains were steppe-type viruses, closely related to strains reported in Russia and Mongolia. None had been identified previously in China. The viruses from XJ and IM clustered separately into two lineages showing their different geographical distribution. This study emphasizes the importance of wildlife surveillance and of cross-departmental cooperation in the control of transboundary rabies transmission.
Lifecourse trajectories of clinical or anthropological attributes are useful for identifying how our early-life experiences influence later-life morbidity and mortality. Researchers often use growth mixture models (GMMs) to estimate such phenomena. It is common to place constrains on the random part of the GMM to improve parsimony or to aid convergence, but this can lead to an autoregressive structure that distorts the nature of the mixtures and subsequent model interpretation. This is especially true if changes in the outcome within individuals are gradual compared with the magnitude of differences between individuals. This is not widely appreciated, nor is its impact well understood. Using repeat measures of body mass index (BMI) for 1528 US adolescents, we estimated GMMs that required variance–covariance constraints to attain convergence. We contrasted constrained models with and without an autocorrelation structure to assess the impact this had on the ideal number of latent classes, their size and composition. We also contrasted model options using simulations. When the GMM variance–covariance structure was constrained, a within-class autocorrelation structure emerged. When not modelled explicitly, this led to poorer model fit and models that differed substantially in the ideal number of latent classes, as well as class size and composition. Failure to carefully consider the random structure of data within a GMM framework may lead to erroneous model inferences, especially for outcomes with greater within-person than between-person homogeneity, such as BMI. It is crucial to reflect on the underlying data generation processes when building such models.
A series solution based on the mild-slope equation is produced in this study of wave scattering produced by a circular cylindrical island mounted on an axi-symmetrical shoal. The solution is presumed to be a Fourier cosine expansion with variable coefficients in the radial direction on account of the symmetric scattering field, which translates the original 2-D boundary-value problem to a 1-D one in which an ordinary differential equation is in effect treated. Approximations to the coefficients of the governing equation with the Taylor expansions enable the use of the Frobenius method, and consequently the solution is obtained in a combined Fourier and power series. For verification, the present method is mainly compared with Zhu and Zhang's [1] analytical solution of the linearised shallow water equation for a conical shoal, and with a different analytical solution of the mild-slope equation developed by Liu et al. [2] for a paraboloidal shoal. Fine agreements are achieved. The present method is then used to investigate the variation pattern of the wave run-up when the shoal profile varies from conical to paraboloidal, and some interesting phenomena are observed.