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We investigated the simultaneous influence of expectation and experience on metacontrol, which we define as the instantiation of context-specific control states. These states could entail heightened control states in preparation for frequent task switching or lowered control states for task repetition. Specifically, we examined whether "expectations" regarding future control demands prompt proactive metacontrol, while "experiences" with items associated with specific control demands facilitate reactive metacontrol. In Experiment 1, we utilized EEG with a high temporal resolution to differentiate between brain activities associated with proactive and reactive metacontrol. We successfully observed cue-locked and image-locked ERP patterns associated with proactive and reactive metacontrol, respectively, supporting concurrent instantiation of two metacontrol modes. In Experiment 2, we focused on individual differences to investigate the modulatory role of working memory capacity (WMC) in the concurrent instantiation of two metacontrol modes. Our findings revealed that individuals with higher WMC exhibited enhanced proactive metacontrol, indicated by smaller response time variability (RTV). Additionally, individuals with higher WMC showed a lower tendency to rely on reactive metacontrol, indicated by a smaller item-specific switch probability (ISSP) effect. In conclusion, our results suggest that proactive and reactive metacontrol can coexist, but their interplay is influenced by individuals' WMC. Higher WMC promotes the use of proactive metacontrol while attenuating reliance on reactive metacontrol. This study provides insights into the interplay between proactive and reactive metacontrol and highlights the impact of WMC on their concurrent instantiation.
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Electroencefalografía , Potenciales Evocados , Memoria a Corto Plazo , Humanos , Memoria a Corto Plazo/fisiología , Masculino , Femenino , Adulto Joven , Electroencefalografía/métodos , Adulto , Potenciales Evocados/fisiología , Encéfalo/fisiología , Tiempo de Reacción/fisiología , Función Ejecutiva/fisiología , Adolescente , Individualidad , Anticipación Psicológica/fisiologíaRESUMEN
In this study, a stimulated-echo (STE) method was employed to robustify the cerebral vessel size estimation near air-tissue, bone-tissue interfaces, and large vessels. The proposed solution is to replace the relaxation rate change from gradient-echo (GRE) with that from STE with long diffusion time after the injection of an intravascular contrast agent, superparamagnetic iron oxide nanoparticles. The corresponding diffusion length of STE is shorter than the length over which the unwanted macroscopic field inhomogeneities but is still longer than the correlation length of the fields induced by small vessels. Therefore, the unwanted field inhomogeneities are refocused, while preserving microscopic susceptibility contrast from cerebral vessels. The mean vessel diameter (dimensionless) derived from the diffusion-time-varying STE method was compared to the mean vessel diameter obtained by a conventional spin-echo (SE) and GRE combination based on Monte-Carlo proton diffusion simulations and in vivo rat experiments at 7 âT. The in vivo mean vessel diameter from the MRI experiments was directly compared to available reference mouse brain vasculature obtained by a knife-edge scanning microscope (KESM), which is considered to be the gold standard. Monte-Carlo simulation revealed that SE and GRE-based MR relaxation rate changes (ΔR2 and ΔR2∗, respectively) can be enhanced using single STE-based MR relaxation rate change (ΔRSTE) by regulating diffusion time, especially for small vessels. The in vivo mean vessel diameter from the STE method demonstrated a closer agreement with that from the KESM compared to the combined SE and GRE method, especially in the olfactory bulb and cortex. This study demonstrates that STE relaxation rate changes can be used as consistent measures for assessing small cerebral microvasculature, where macroscopic field inhomogeneity is severe and signal contamination from adjacent large vessels is significant.
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Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Microvasos/diagnóstico por imagen , Animales , Simulación por Computador , Estudios de Factibilidad , Humanos , Ratones , Ratas WistarRESUMEN
This study was designed to test the interaction between amyloid-ß and tau proteins as a determinant of metabolic decline in preclinical Alzheimer's disease (AD). We assessed 120 cognitively normal individuals with [18F]florbetapir positron emission tomography (PET) and cerebrospinal fluid (CSF) measurements at baseline, as well as [18F]fluorodeoxyglucose ([18F]FDG) PET at baseline and at 24 months. A voxel-based interaction model was built to test the associations between continuous measurements of CSF biomarkers, [18F]florbetapir and [18F]FDG standardized uptake value ratios (SUVR). We found that the synergistic interaction between [18F]florbetapir SUVR and CSF phosphorylated tau (p-tau) measurements, rather than the sum of their independent effects, was associated with a 24-month metabolic decline in basal and mesial temporal, orbitofrontal, and anterior and posterior cingulate cortices (P<0.001). In contrast, interactions using CSF amyloid-ß1-42 and total tau biomarkers did not associate with metabolic decline over a time frame of 24 months. The interaction found in this study further support the framework that amyloid-ß and hyperphosphorylated tau aggregates synergistically interact to cause downstream AD neurodegeneration. In fact, the regions displaying the metabolic decline reported here were confined to brain networks affected early by amyloid-ß plaques and neurofibrillary tangles. Preventive clinical trials may benefit from using a combination of amyloid-ß PET and p-tau biomarkers to enrich study populations of cognitively normal subjects with a high probability of disease progression in studies, using [18F]FDG as a biomarker of efficacy.
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Péptidos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/metabolismo , Cognición/fisiología , Femenino , Fluorodesoxiglucosa F18/metabolismo , Humanos , Estudios Longitudinales , Masculino , Tomografía de Emisión de Positrones/métodos , Proteínas tau/líquido cefalorraquídeoRESUMEN
A tropical gray leaf spot (GLS)-resistant line, YML 32, was crossed to a temperate GLS-susceptible line, Ye 478, to produce an F2:3 population for the identification of quantitative trait loci (QTL) associated with resistance to GLS. The population was evaluated for GLS disease resistance and flowering time at two locations in Yunnan province. Seven QTL using GLS disease scores and six QTL using flowering time were identified on chromosomes 2, 3, 4, 5, and 8 in the YML 32 × Ye 478 maize population. All QTL, except one identified on chromosome 2 using flowering time, were overlapped with the QTL for GLS disease scores. The results indicated that QTL for flowering time in this population strongly corresponded to QTL for GLS resistance. Among the QTL, qRgls.yaas-8-1/qFt.yaas-8 with the largest genetic effect accounted for 17.9 to 18.1 and 11.0 to 21.42% of variations for GLS disease scores and flowering time, respectively, and these should be very useful for improving resistance to GLS, especially in subtropical maize breeding programs. The QTL effects for resistance to GLS were predominantly additive in nature, with a dominance effect having been found for two QTL on the basis of joint segregation genetic analysis and QTL analysis.
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The new allele B*59:09 showed two nucleotide differences with B*59:01:01:01 in exon 3.
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Alelos , Antígenos HLA-B/genética , Polimorfismo de Nucleótido Simple , Secuencia de Bases , Trasplante de Células Madre de Sangre del Cordón Umbilical , Exones , Femenino , Genotipo , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , República de Corea , Análisis de Secuencia de ADN , Donantes de TejidosRESUMEN
The novel alleles DRB1*12:03:03 and DRB1*13:143 differ from DRB1*12:03:02 and DRB1*13:02:01 by one nucleotide in exon 2, respectively.
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Alelos , Cadenas HLA-DRB1/genética , Exones , Humanos , Datos de Secuencia MolecularRESUMEN
We report the experimental demonstration of a passively mode-locked Er-doped fiber ring laser operating at the 337th harmonic (1.80 GHz) of the cavity. The laser makes use of highly efficient Raman-like optoacoustic interactions between the guided light and gigahertz acoustic resonances trapped in the micron-sized solid glass core of a photonic crystal fiber. At sufficient pump power levels the laser output locks to a repetition rate corresponding to the acoustic frequency. A stable optical pulse train with a side-mode suppression ratio higher than 45 dB was obtained at low pump powers (~60 mW).
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Human leucocyte antigen (HLA) alleles and haplotypes differ significantly among different ethnic groups, and high-resolution typing methods allow for the detection of a wider spectrum of HLA variations. In this study, HLA-A, -B and -DRB1 genotypes were analysed in 4128 cord blood units obtained from Korean women using the sequence-based typing method. A total of 44 HLA-A, 67 HLA-B and 48 HLA-DRB1 most probable alleles were identified. Of these, high-frequency alleles found at a frequency of ≥5% were 6 HLA-A (A*02:01, A*02:06, A*11:01, A*24:02, A*31:01, A*33:03), 5 HLA-B (B*15:01, B*44:03, B*51:01, B*54:01, B*58:01) and 7 HLA-DRB1 (DRB1*01:01, DRB1*04:05, DRB1*07:01, DRB1*08:03, DRB1*09:01, DRB1*13:02, DRB1*15:01) alleles. At each locus, A*02, B*15 and DRB1*04 generic groups were most diverse at allelic level, consisting of 8, 11 and 10 different alleles, respectively. Two- and three-locus haplotypes estimated by the maximum likelihood method revealed 73 A-B, 74 B-DRB1 and 42 A-B-DRB1 haplotypes with frequencies of ≥0.3%. A total of 193 A-B-DRB1 haplotypes found at a frequency of ≥0.1% were presented, and the six most common haplotypes were A*33:03-B*44:03-DRB1*13:02 (4.6%), A*33:03-B*58:01-DRB1*13:02 (3.0%), A*24:02-B*07:02-DRB1*01:01 (2.7%), A*33:03-B*44:03-DRB1*07:01 (2.5%), A*30:01-B*13:02-DRB1*07:01 (2.2%) and A*24:02-B*52:01-DRB1*15:02 (2.1%). Compared with previous smaller scale studies, this study further delineated the allelic and haplotypic diversity in Koreans including low-frequency alleles and haplotypes. Information obtained in this study will be useful for the search for unrelated bone marrow donors and for anthropologic and disease association studies.
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Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadenas HLA-DRB1/genética , Polimorfismo Genético , Alelos , Pueblo Asiatico/genética , Femenino , Sangre Fetal/metabolismo , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Reacción en Cadena de la Polimerasa , República de Corea , Análisis de Secuencia de ADNRESUMEN
Background: Comorbidities may influence the levels of blood-based biomarkers for Alzheimer's disease (AD). We investigated whether differences in risk factors or comorbid conditions might explain the discordance between clinical diagnosis and biomarker classifications in a multi-ethnic cohort of elderly individuals. Aims: To evaluate the relationship of medical conditions and other characteristics, including body mass index (BMI), vascular risk factors, and head injury, with cognitive impairment and blood-based biomarkers of AD, phosphorylated tau (P-tau 181, P-tau 217), in a multi-ethnic cohort. Methods: Three-hundred individuals, aged 65 and older, were selected from a prospective community-based cohort for equal representation among three racial/ethnic groups: non-Hispanic White, Hispanic/Latino and African American/Black. Participants were classified into four groups based on absence (Asym) or presence (Sym) of cognitive impairment and low (NEG) or high (POS) P-tau 217 or P-tau 181 levels, determined previously in the same cohort: (Asym/NEG, Asym/POS, Sym/NEG, Sym/POS). We examined differences in individual characteristics across the four groups. We performed post-hoc analysis examining the differences across biomarker and cognitive status. Results: P-tau 217 or P-tau 181 positive individuals had lower BMI than P-tau negative participants, regardless of symptom status. Symptomatic and asymptomatic participants did not differ in terms of BMI. BMI was not a mediator of the effect of P-tau 217 or P-tau 181 on dementia. Frequencies of other risk factors did not differ between the four groups of individuals. Conclusions: Participants with higher levels of P-tau 217 or P-tau 181 consistent with AD had lower BMI regardless of whether the individual was symptomatic. These findings suggest that weight loss may change with AD biomarker levels before onset of cognitive decline. They do not support BMI as a confounding variable. Further longitudinal studies could explore the relationship of risk factors with clinical diagnoses and biomarkers.
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The novel allele A*02:328 showed one nucleotide difference with A*02:06:01 in exon 3 resulting in an amino acid change at codon 120 from Gly to Arg.
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Alelos , Sangre Fetal , Antígenos HLA-A/genética , Pueblo Asiatico/genética , Secuencia de Bases , Femenino , Genotipo , Humanos , Datos de Secuencia Molecular , República de Corea , Alineación de Secuencia , Terminología como Asunto , Organización Mundial de la SaludRESUMEN
The new allele, HLA-A*33:25, differs from A*33:03:01 by one nucleotide substitution in exon 4 (c.778G>A) which results in an amino acid change at codon 236 [GCAâACA (Ala>Thr)] in ß2-microglobulin-binding domain.
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Pueblo Asiatico , Antígenos HLA-A/genética , Adulto , Alelos , Sustitución de Aminoácidos , Secuencia de Bases , Trasplante de Médula Ósea , Trasplante de Células Madre de Sangre del Cordón Umbilical , Exones , Femenino , Frecuencia de los Genes , Antígenos HLA-A/inmunología , Haplotipos , Prueba de Histocompatibilidad , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación Puntual , Reacción en Cadena de la Polimerasa , Estructura Terciaria de Proteína , Sistema de Registros , República de Corea , Análisis de Secuencia de ADNRESUMEN
The novel allele B*40:179 showed one nucleotide difference with B*40:01:01 in exon 4.
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Antígenos HLA-B/genética , Polimorfismo de Nucleótido Simple , Alelos , Pueblo Asiatico , Secuencia de Bases , Exones , Femenino , Sangre Fetal , Antígenos HLA-B/inmunología , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Embarazo , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
A novel kind of nanostructured optical fiber, displaying an extremely high and optically broadband optomechanical nonlinearity, is presented. It comprises two closely spaced ultrathin glass membranes (webs) suspended in air and attached to the inner walls of a glass fiber capillary. Light guided in this dual-web structure can exert attractive or repulsive pressure on the webs, causing them to be pushed together or pulled apart. The elastic deflection of the webs is, in turn, coupled to the electromagnetic field distribution and results in a change in the effective refractive index within the fiber. Employing a pump-probe technique in an interferometric setup, optomechanically induced refractive index changes more than 10^{4} times larger than the Kerr effect are detected. Theoretical estimates of the optomechanical nonlinearity agree well with the experimental results. The dual-web fiber combines the sensitivity of a microoptomechanical device with the versatility of an optical fiber and could trigger new developments in the fields of nonlinear optics, optical metrology, and sensing.
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Interferometría/métodos , Modelos Teóricos , Nanoestructuras/química , Fibras Ópticas , Interferometría/instrumentación , Microscopía Electrónica de Rastreo , Dinámicas no Lineales , Dióxido de Silicio/químicaRESUMEN
Virulent Escherichia coli strains have commonly been associated with diarrheal illness in humans and animals. Typical enteropathogenic Escherichia coli (EPEC) with intimin gene (eaeA) and E. coli adherence factor plasmid, or atypical EPEC with only eaeA have been implicated in human cases. In the present study, we investigated the prevalence of virulence-associated genes including eaeA in the E. coli strains isolated from cloacal specimens of 184 chicken flocks in 7 provinces in Korea between 2009 and 2010. When 7 virulence genes (VT1, VT2, LT, and ST for enterotoxigenic E. coli; eaeA and bfpA for enteropathogenic E. coli; and aggR for enteroaggregative E. coli) were screened by multiplex PCR, a total of 30 E. coli strains carrying only the eaeA gene were detected from 184 flocks that were identified as atypical enteropathogenic Escherichia coli (aEPEC). The aEPEC strains were analyzed by eae subtyping, phylogenetic grouping PCR, and serotyping. Twelve (40%) of 30 aEPEC strains possessed an eae-ß subtype, followed by θ (30%), ε (16.7%), and ß1 (13.3%). Eight (26.7%) of 30 aEPEC strains were designated into the phylogenetic group A. Two (6.7%) and 3 (10%) aEPEC strains were classified into the phylogenetic group B2 and D, respectively. A total of 15 (50%) aEPEC strains were serotyped to groups O24, O25, O26, O71, O80, O103, and O157, and the remaining strains were nontypeable. In analyzing the genetic diversity among the 30 aEPEC isolates by the pulsed-field gel electrophoresis method with XbaI-digestion, the pulsed-field gel electrophoresis profiling produced 20 different patterns, but isolates within the same group did not show clear geographic or breed relationships. Our data indicate that healthy chickens may constitute an important natural reservoir of aEPEC strains, and suggest that transmission to humans could not be excluded.
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Adhesinas Bacterianas/metabolismo , Infecciones por Escherichia coli/veterinaria , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Enfermedades de las Aves de Corral/microbiología , Adhesinas Bacterianas/genética , Animales , Reservorios de Enfermedades , Escherichia coli/patogenicidad , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/genética , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica/fisiología , Enfermedades de las Aves de Corral/epidemiología , Prevalencia , República de Corea/epidemiología , Serotipificación , VirulenciaRESUMEN
The aims of this study were to determine if the chicken embryo lethality assay and the presence of 9 virulence-associated genes of Escherichia coli were correlated and to discover which virulence genes contributed most to embryo lethality. We examined 58 E. coli strains isolated from visceral organs of chickens with colibacillosis for the presence of 9 virulence genes (fimC, tsh, fyuA, irp2, iucD, cvi/cva, iss, astA, and vat) by PCR. The gene FimC (type I fimbriae) was detected with the highest prevalence in 93.1% of the isolates, followed by iucD (67.24%), iss (58.62%), tsh (34.48%), cvi/cva (34.48%), fyuA (32.76%), astA (31.0%), irp2 (27.59%), and vat (17.24%). The embryo mortality ranged from 5 to 100%; however, most of the isolates were moderately or highly virulent. High positive correlations were observed between the presence of virulence genes and chicken embryo lethality. In addition, presence of the iucD (aerobactin) gene was the trait that best contributed to embryo mortality by using the multivariate model. These results suggest that expression frequency of these 9 virulence genes is associated with embryo mortality, and the gene that best predicted embryo mortality was iucD.
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Embrión de Pollo/microbiología , Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Escherichia coli/patogenicidad , Regulación Bacteriana de la Expresión Génica/fisiología , Animales , Proteínas de Escherichia coli/genética , Serotipificación , VirulenciaRESUMEN
A side-scattering technique for investigating the inner microstructure of photonic crystal fibers (PCFs) is reported. Multiple scattering is reduced by filling the hollow PCF channels with index-matching fluid. The scattered signal is measured for fixed angles of incidence and detection while the fiber is rotated. A pattern of peaks, unique to each PCF, whether solid or hollow core, correlates closely with the symmetry planes of the PCF structure. As an example of the technique, the twist profile of a structural rocking filter is directly measured.
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Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi's disease, is a benign and self-limiting lymphadenopathy that typically affects young Asian females. It presents with lymphadenopathy, usually cervical, accompanied by fever, chills and leukopenia. Although the association between systemic lupus erythematosus (SLE) and HNL is rare, the number of reports of HNL in SLE patients is increasing. We present nine cases of HNL in patients with SLE. Among the seven patients with diverse skin manifestations, three had skin manifestations that were histologically compatible with SLE. A review of previous reports in the literature showed that cutaneous involvement was commonly found in HNL in association with SLE. In the patients who had simultaneous onset of both diseases, lupus flare-ups were commonly observed. We suggest that HNL in SLE patients is associated with cutaneous manifestations. This report contributes to our understanding of the relationship between these diseases.
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Linfadenitis Necrotizante Histiocítica/patología , Lupus Eritematoso Sistémico/patología , Piel/patología , Adolescente , Adulto , Pueblo Asiatico , Comorbilidad , Femenino , Linfadenitis Necrotizante Histiocítica/epidemiología , Linfadenitis Necrotizante Histiocítica/fisiopatología , Humanos , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
The present study reports on layer chickens with colibacillosis in 2 commercial egg-producing farms (referred to as farm A and farm B, which were managed by the same owner and were about 1 km apart) in the middle region of the Korean peninsula. The 2 flocks were infected at the initiation of egg laying. They were characterized by no previous clinical signs but sudden mortality (2.7-4.0%), with severe lesions of septicemia and fibrinous polyserositis. Escherichia coli was isolated from the lesions of the infected birds. Serotyping tests identified isolates that belonged to somatic groups O1 (12/17), O46 (2/17), O78 (1/17), and O84 (1/17) or that were unidentified (1/17). Thirteen of 17 E. coli isolates (76.4%) obtained from 11 birds in the 2 flocks showed similar pulsed-field gel electrophoresis patterns that were arbitrarily designated as pattern A. The isolates had high frequencies of putative virulence genes including 100% [fimC (type 1 fimbriae), iucD (aerobactin synthesis), and iss (increased serum survival)], 94.1% [cva/cvi (structural genes of colicin V operon) and vat (vacuolating autotransporter toxin)], 88.2% [irp2, iron-repressible protein (yersinia bactin) synthesis, and fyuA, ferric yersinia uptake], and 82.3% [tsh (temperature-sensitive hemagglutinin)]; astA (encoding a heat-stable cytotoxin associated with enteroaggregative E. coli) was not associated with the enteric disorder. These data suggest that all chickens with colibacillosis on farms A and B were likely infected by E. coli strains that are highly pathogenic in avian species.
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Pollos , Infecciones por Escherichia coli/veterinaria , Escherichia coli/clasificación , Enfermedades de las Aves de Corral/microbiología , Animales , Electroforesis en Gel de Campo Pulsado/veterinaria , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Femenino , Reacción en Cadena de la Polimerasa/veterinaria , Enfermedades de las Aves de Corral/epidemiología , República de Corea/epidemiología , SerotipificaciónRESUMEN
Focal myositis is a rare disease defined by an isolated inflammatory pseudotumour usually restricted to one skeletal muscle. Approximately, 250 cases of focal myositis have been described in the literature, and two recent large cohorts have been used to help in the diagnosis. Isolated gastrocnemius myositis, a rare immune-mediated condition, is a diagnostic entity used by internal medicine clinician in the gastrocnemius myalgia syndrome associated with Crohn's disease (CD). However, focal myositis and isolated gastrocnemius myositis with Crohn's disease share clinical, haematological, pathological, and radiological similarities. We present a case of unilateral focal myositis of the gastrocnemius muscle in a patient with no underlying diseases, including Crohn's disease. At clinical evaluation, we encountered a challenge in differentiating between focal myositis and the isolated gastrocnemius myositis of Crohn's due to similarities in clinical manifestation. We attempt to clarify focal myositis and isolated gastrocnemius myositis through our case report and a review of literature.
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Lumbar decompressive laminectomy is a standard treatment for degenerative lumbar spinal stenosis, but in some cases, can lead to iatrogenic spondylolysis and delayed segmental instability. Iatrogenic spondylolysis occurs in most cases in pars interarticularis, but rare cases have also been reported, pediculolysis in pedicle and laminolysis in lamina. Minimally invasive spine surgery (MIS) is known to have a low risk of developing these iatrogenic spondylolyses, and unilateral biportal endoscopy is the MIS that has been drawing attention. We present a case of a 72-year-old female who was diagnosed with L4-5 unstable non-isthmic spondylolisthesis and severe right central disc extrusion 10 weeks after UBE assisted unilateral laminotomy for bilateral decompression (ULBD) at the consecutive segments of L3-4 and L4-5. Pre-operative imaging studies revealed severe central stenosis without spondylolisthesis at L3-L4 and L4-L5 along with L4-L5 facet tropism. She was managed by anterior lumbar interbody fusion and cement augmented pedicle screw fixation, which resulted in the complete resolution of her clinical and neurologic symptoms.