Peripapillary Optical Coherence Tomography Angiography in Alzheimer's Disease, Mild Cognitive Impairment, and Normal Cognition.

OBJECTIVE: This study aimed to identify peripapillary microvascular changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). PATIENTS AND METHODS: In this prospective study, 66 eyes of 36 subjects with AD, 119 eyes of 63 with MCI, and 513 eyes of 265 controls with normal cognition were enrolled. Peripapillary capillary perfusion density (CPD), capillary flux index (CFI), and retinal nerve fiber layer (RNFL) thickness were determined. RESULTS: Average CPD differed significantly between all three groups (P = 0.001), being significantly greater in AD vs controls (0.446 ± 0.015 vs 0.439 ± 0.017, P = 0.001) and MCI vs controls (0.443 ± 0.020 vs 0.439 ± 0.017, P = 0.007) but not AD vs MCI (P = 0.69). CFI and average RNFL thickness did not significantly differ among groups (all P > 0.05). CONCLUSION: Peripapillary CPD is increased in eyes with AD or MCI compared to controls despite similar RNFL thickness. [Ophthalmic Surg Lasers Imaging Retina 2024;55:78-84.].

Design and Fabrication of a Fiber Bragg Grating Shape Sensor for Shape Reconstruction of a Continuum Manipulator.

Continuum dexterous manipulators (CDMs) are suitable for performing tasks in a constrained environment due to their high dexterity and maneuverability. Despite the inherent advantages of CDMs in minimally invasive surgery, real-time control of CDMs' shape during nonconstant curvature bending is still challenging. This study presents a novel approach for the design and fabrication of a large deflection fiber Bragg grating (FBG) shape sensor embedded within the lumens inside the walls of a CDM with a large instrument channel. The shape sensor consisted of two fibers, each with three FBG nodes. A shape-sensing model was introduced to reconstruct the centerline of the CDM based on FBG wavelengths. Different experiments, including shape sensor tests and CDM shape reconstruction tests, were conducted to assess the overall accuracy of the shape-sensing. The FBG sensor evaluation results revealed the linear curvature-wavelength relationship with the large curvature detection of 0.045 mm and a high wavelength shift of up to 5.50 nm at a 90° bending angle in both the bending directions. The CDM's shape reconstruction experiments in a free environment demonstrated the shape-tracking accuracy of 0.216 ± 0.126 mm for positive/negative deflections. Also, the CDM shape reconstruction error for three cases of bending with obstacles was observed to be 0.436 ± 0.370 mm for the proximal case, 0.485 ± 0.418 mm for the middle case, and 0.312 ± 0.261 mm for the distal case. This study indicates the adequate performance of the FBG sensor and the effectiveness of the model for tracking the shape of the large-deflection CDM with nonconstant-curvature bending for minimally invasive orthopedic applications.

Fluoroscopic Navigation for a Surgical Robotic System Including a Continuum Manipulator.

We present an image-based navigation solution for a surgical robotic system with a Continuum Manipulator (CM). Our navigation system uses only fluoroscopic images from a mobile C-arm to estimate the CM shape and pose with respect to the bone anatomy. The CM pose and shape estimation is achieved using image intensity-based 2D/3D registration. A learning-based framework is used to automatically detect the CM in X-ray images, identifying landmark features that are used to initialize and regularize image registration. We also propose a modified hand-eye calibration method that numerically optimizes the hand-eye matrix during image registration. The proposed navigation system for CM positioning was tested in simulation and cadaveric studies. In simulation, the proposed registration achieved a mean error of 1.10±0.72 mm between the CM tip and a target entry point on the femur. In cadaveric experiments, the mean CM tip position error was 2.86±0.80 mm after registration and repositioning of the CM. The results suggest that our proposed fluoroscopic navigation is feasible to guide the CM in orthopedic applications.

Characteristics of Branch Retinal Vein Occlusion in African American Patients.

BACKGROUND AND OBJECTIVES: To describe the presentation, management, and clinical outcomes of branch retinal vein occlusion (BRVO) in African American patients compared to patients of other racial or ethnic backgrounds. PATIENTS AND METHODS: This retrospective cohort study included eyes diagnosed with BRVO and macular edema at a tertiary referral center. Presenting features, treatment, and outcomes were compared based on racial or ethnic backgrounds. RESULTS: The study included 285 eyes: 21.8% African American, 78.2% other. African American patients were more likely to have comorbid diabetes (P = .012), open-angle glaucoma (P < .001), and to present with subretinal fluid (P = .049); multivariate analysis showed race and ethnicity alone may not fully explain presenting subretinal fluid (odds ratio = 2.807; 95% CI, 0.997 to 7.903; P = .051). There was no difference in other comparisons of clinical outcomes or treatment burden, including visual acuity, duration, or treatment method. CONCLUSIONS: Despite significant differences at presentation, the management and outcomes of BRVO did not differ significantly between African American patients and patients of other racial and ethnic backgrounds. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:492-497.].

An Active Steering Hand-held Robotic System for Minimally Invasive Orthopaedic Surgery Using a Continuum Manipulator.

This paper presents the development and experimental evaluation of an active steering hand-held robotic system for milling and curved drilling in minimally invasive orthopaedic interventions. The system comprises a cable-driven continuum dexterous manipulator (CDM), an actuation unit with a handpiece, and a flexible, rotary cutting tool. Compared to conventional rigid drills, the proposed system enhances dexterity and reach in confined spaces in surgery, while providing direct control to the surgeon with sufficient stability while cutting/milling hard tissue. Of note, for cases that require precise motion, the system is able to be mounted on a positioning robot for additional controllability. A proportional-derivative (PD) controller for regulating drive cable tension is proposed for the stable steering of the CDM during cutting operations. The robotic system is characterized and tested with various tool rotational speeds and cable tensions, demonstrating successful cutting of three-dimensional and curvilinear tool paths in simulated cancellous bone and bone phantom. Material removal rates (MRRs) of up to 571 mm3/s are achieved for stable cutting, demonstrating great improvement over previous related works.

Initial Presentation of Cutibacterium (Formerly Propionibacterium) acnes Endophthalmitis Twenty-One Years After Cataract Surgery.

The authors report a case of an 81-year-old female who presented with sudden onset of light perception vision and intraocular inflammation. After several months of continuing symptoms despite antibiotics, an aqueous tap culture grew Cutibacterium acnes. The patient had cataract surgery 21 years prior, and had no intervening trauma, intraocular procedure, or endogenous source. The presumed diagnosis was C. acnes endophthalmitis with significantly delayed onset. Capsulectomy and intraocular lens removal resolved the patient's symptoms. In rare cases, C. acnes endophthalmitis may present as recurrent inflammation despite an extremely remote history of cataract surgery, mimicking a virulent, acute-onset endophthalmitis despite antibiotic administration. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:44-46.].

Identification and editing of a hybrid lethality gene expands the range of interspecific hybridization potential in Nicotiana.

KEY MESSAGE: Identification and inactivation of hybrid lethality genes can be used to expand the available gene pool for improvement of a cultivated crop species. Hybrid lethality is one genetic mechanism that contributes to reproductive isolation in plants and serves as a barrier to use of diverse germplasm for improvement of cultivated species. A classic example is the seedling lethality exhibited by progeny from the Nicotiana tabacum × N. africana interspecific cross. In order to increase the body of knowledge on mechanisms of hybrid lethality in plants, and to potentially develop tools to circumvent them, we utilized a transposon tagging strategy to identify a candidate gene involved in the control of this reaction. N. tabacum gene Nt6549g30 was identified to code for a class of coiled-coil nucleotide-binding site-leucine-rich repeat (CC-NBS-LRR) proteins, the largest class of plant defense proteins. Gene editing, along with other experiments, was used to verify that Nt6549g30 is the gene at the N. tabacum Hybrid Lethality 1 (NtHL1) locus controlling the hybrid lethality reaction in crosses with N. africana. Gene editing of Nt6549g30 was also used to reverse interspecific seedling lethality in crosses between N. tabacum and eight of nine additional tested species from section Suaveolentes. Results further implicate the role of disease resistance-like genes in the evolution of plant species and demonstrate the possibility of expanding the gene pool for a crop species through gene editing.

Characterization of Phn15.1, a Newly Identified Phytophthora nicotianae Resistance QTL in Nicotiana tabacum.

Phytophthora nicotianae is an oomycete that causes black shank, one of the most economically important diseases affecting tobacco production worldwide. Identification and introgression of novel genetic variability affecting partial genetic resistance to this pathogen is important because of the increased durability of partial resistance over time as compared with genes conferring immunity. A previous mapping study identified a quantitative trait locus (QTL), hereafter designated as Phn15.1, with a major effect on P. nicotianae resistance in tobacco. In this research, we describe significantly improved resistance of nearly isogenic lines (NILs) of flue-cured tobacco carrying the introgressed Phn15.1 region derived from highly resistant cigar tobacco cultivar Beinhart 1000. The Phn15.1 region appeared to act in an additive or partially dominant manner to positively affect resistance. To more finely resolve the position of the gene or genes underlying the Phn15.1 effect, the QTL was mapped with an increased number of molecular markers (single-nucleotide polymorphisms) identified to reside within the region. Development and evaluation of subNILs containing varying amounts of Beinhart 1000-derived Phn15.1-associated genetic material permitted the localization of the QTL to a genetic interval of approximately 2.7 centimorgans. Importantly, we were able to disassociate the Beinhart 1000 Phn15.1 resistance alleles from a functional NtCPS2 allele(s) which contributes to the accumulation of a diterpene leaf surface exudate considered undesirable for flue-cured and burley tobacco. Information from this research should be of value for marker-assisted introgression of Beinhart 1000-derived partial black shank resistance into flue-cured and burley tobacco breeding programs.

Serum Mac-2-binding protein glycosylation isomer and risk of hepatocellular carcinoma in entecavir-treated chronic hepatitis B patients.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) can still develop in chronic hepatitis B (CHB) patients receiving antiviral treatment. Serum Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis. We investigated its role on incidence of HCC in entecavir (ETV)-treated CHB patients. METHODS: We identified HCC cases diagnosed at ≥ 1 year of ETV treatment. CHB patients without HCC (matched for age, gender, baseline hepatitis B virus-DNA, and duration of ETV treatment) were identified in approximately 1:2 ratio (HCC: non-HCC) for comparison. Serum samples were retrieved at baseline (initiation of ETV), 3, and 5 years of ETV for serum M2BPGi measurement (expressed in cut-off index [COI]). RESULTS: One hundred HCC cases were matched with 185 CHB patients without HCC (median age 56.7 years, 78.9% male, baseline hepatitis B virus-DNA 5.6 logIU/mL, and median follow-up 7.1 years). Median time from ETV initiation to incident HCC was 3.9 years. Serum M2BPGi levels were significantly higher in HCC cases compared with controls at baseline and year 3 (1.25 vs 0.98 [P = 0.004], 0.89 vs 0.74 [P = 0.018] COI, respectively). Multivariate analysis showed that baseline M2BPGi was the only independent factor associated with incident HCC (odds ratio 1.241, 95% confidence interval 1.039-1.482, P = 0.017). Using a cut-off value of 1.15 COI, the sensitivity, specificity, positive predictive value, and negative predictive value of baseline serum M2BPGi in cirrhotic patients to predict incident HCC were 90%, 53.8%, 69.6%, and 82.1%, respectively. CONCLUSIONS: Baseline and 3-year serum M2BPGi may be useful to identify high risk patients on antiviral treatment for subsequent HCC development.

The positive effect of a dedicated adolescent and young adult fertility program on the rates of documentation of therapy-associated infertility risk and fertility preservation options.

PURPOSE: Minimal data exist regarding documentation of therapy-associated infertility risk (IR) and fertility preservation (FP) options during the initial oncology consultation prior to systemic therapy. This study investigated factors affecting IR/FP documentation and assessed the effect of implementation of an Adolescent and Young Adult (AYA) program on documentation rates. METHODS: A retrospective review of charts of patients receiving gonadotoxic therapy was undertaken for documentation of IR/FP pre- and post-implementation of an AYA program. Change in documentation rates was assessed using univariate and multiple logistic regression. RESULTS: A total of 173 charts were reviewed. On univariate analysis, IR/FP documentation was less likely if patients had metastatic disease (P < 0.01, P < 0.01), by tumor type (P < 0.01, P < 0.01), received less intensive chemotherapy (P = 0.03, P = 0.06), were older (P = 0.14, P < 0.01), had more children (P < 0.01, P < 0.01), or lacked AYA program involvement (P < 0.01, P < 0.01). FP discussion was more common in males (P = 0.02). On multivariable analysis, more children (P = 0.01, P = 0.03), older age (P < 0.01, P < 0.01), tumor type (P < 0.01, P = 0.01), stage (P = 0.02, NS), relationship (P = 0.03, NS), and lack of AYA involvement (P < 0.01, P < 0.01) were associated with lower rates of IR/FP documentation. Following AYA program implementation, IR/FP rates increased from 56% (CI 46-65%) to 85% (CI 74-92%, P < 0.01) and 54% (CI 45-64%) to 86% (CI 75-93%, P < 0.01), respectively. The effect of AYA program implementation on IR/FP documentation was most noticeable in leukemia, lymphoma, and breast groups (P < 0.01). CONCLUSIONS: Implementing an AYA consultation service at an adult cancer institution had a positive effect on the rates of IR/FP documentation. Specific programming can improve service delivery to AYA cancer patients, and fertility counseling should be integrated for patients undergoing gonadotoxic therapy.

Early Secreted Antigenic Target of 6-kDa of Mycobacterium tuberculosis Stimulates IL-6 Production by Macrophages through Activation of STAT3.

As early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis (Mtb) is an essential virulence factor and macrophages are critical for tuberculosis infection and immunity, we studied ESAT-6 stimulated IL-6 production by macrophages. ESAT-6 stimulated significantly higher IL-6 secretion by murine bone marrow derived macrophages (BMDM) compared to culture filtrate protein 10 kDa (CFP10) and antigen 85A. Polymyxin B, an LPS blocker, did not affect ESAT-6 stimulated macrophage IL-6 production. ESAT-6 but not Pam3CSK4 induced IL-6 by TLR2 knockout BMDM. ESAT-6 induced phosphorylation and DNA binding of STAT3 and this was blocked by STAT3 inhibitors but not by rapamycin. STAT3 inhibitors suppressed ESAT-6-induced IL-6 transcription and secretion without affecting cell viability. This was confirmed by silencing STAT3 in macrophages. Blocking neither IL-6Rα/IL-6 nor IL-10 affected ESAT-6-induced STAT3 activation and IL-6 production. Infection of BMDM and human macrophages with Mtb with esat-6 deletion induced diminished STAT3 activation and reduced IL-6 production compared to wild type and esat-6 complemented Mtb strains. Administration of ESAT-6 but not CFP10 induced STAT3 phosphorylation and IL-6 expression in the mouse lungs, consistent with expression of ESAT-6, IL-6 and phosphorylated-STAT3 in Mtb-infected mouse lungs. We conclude that ESAT-6 stimulates macrophage IL-6 production through STAT3 activation.

The Tobacco Trichome Exudate Z-abienol and Its Relationship With Plant Resistance to Phytophthora nicotianae.

In previous research, we discovered a favorable quantitative trait locus (QTL) in cigar tobacco cultivar 'Beinhart 1000' designated as Phn15.1, which provides a high level of partial resistance to the black shank disease caused by Phytophthora nicotianae. A very close genetic association was also found between Phn15.1 and the ability to biosynthesize Z-abienol, a labdanoid diterpene exuded by the trichomes onto above-ground plant parts, and that imparts flavor and aroma characteristics to Oriental and some cigar tobacco types. Because accumulation of Z-abienol is considered to be undesirable for cultivars of other tobacco types, we herein describe a series of experiments to gain insight on whether this close association is due to genetic linkage or pleiotropy. First, in an in vitro bioassay, we observed Z-abienol and related diterpenes to inhibit hyphal growth of P. nicotianae at concentrations between 0.01 and 100 ppm. Secondly, we field-tested transgenic versions of Beinhart 1000 carrying RNAi constructs for downregulating NtCPS2 or NtABS, two genes involved in the biosynthesis of Z-abienol. Thirdly, we also field tested a recombinant inbred line population segregating for a truncation mutation in NtCPS2 leading to an interrupted Z-abienol pathway. We observed no correlation between field resistance to P. nicotianae and the ability to accumulate Z-abienol in either the transgenic materials or the mapping population. Results suggest that, although Z-abienol may affect P. nicotianae when applied at high concentrations in in vitro assays, the compound has little effect on black shank disease development under natural field conditions. Thus, it should be possible to disassociate Phn15.1-mediated black shank resistance identified in cigar tobacco cultivar Beinhart 1000 from the ability to accumulate Z-abienol, an undesirable secondary metabolite for burley and flue-cured tobacco cultivars.

Impact of IL28B and PNPLA3 polymorphisms on treatment outcomes in patients infected with genotype 6 hepatitis C virus.

BACKGROUND/AIMS: Interleukin-28B (IL28B) and patatin-like phospholipase domain containing 3 (PNPLA3) gene polymorphisms are associated with hepatitis C virus (HCV) clearance and fatty liver, respectively. We aimed to test if their polymorphisms are associated with virologic responses in Chinese chronic hepatitis C (CHC) patients. METHODS: This was a retrospective-prospective cohort study. Consecutive patients infected by genotype 1 and 6 HCV received antiviral therapy were included. Host IL-28B rs12979860/rs8099917 and PNPLA3 rs738409 genotype were tested. The primary outcome was sustained virologic response (sustained virologic response [SVR]: undetectable HCV RNA 24 weeks post-treatment). RESULTS: From 305 patients had positive antibody to HCV, 52 and 31 patients infected by genotype 1 and 6 HCV, respectively were recruited. Mean age was 58 ± 11 years; 70% were male. Mean baseline HCV RNA was 6.8 ± 2.7 log IU/ml. The SVR for patients infected by genotype 1 and 6 HCV was 67.3% and 90.3%, respectively. The proportions of IL28B genotypes were 78%, 21%, and 1% for TT/TG/GG at rs8099917, and 81%, 18%, and 1% for CC/TC/TT at rs12979860, respectively. The proportions of PNPLA3 rs738409 genotypes were 16%, 36%, and 48% for GG/GC/CC. IL28B genotype was significantly associated with SVR in patients infected by genotype 1 but not genotype 6 HCV, with 80% versus 38% of patients infected by genotype 1 achieved SVR carried TT versus TG/GG at rs8099917, respectively (P=0.003). PNPLA3 genotype was not associated with SVR. CONCLUSIONS: IL28B gene with rs8099917 T allele as an independent predictor of SVR in Chinese CHC patients infected by genotype 1 but not genotype 6 HCV.

Predictive factors for intraoperative balloon dilation in semirigid ureteroscopic lithotripsy.

PURPOSE: To analyze preoperative predictive factors for intraoperative balloon dilation in semirigid ureteroscopic lithotripsy. PATIENTS AND METHODS: We retrospectively reviewed data from 397 consecutive semirigid ureteroscopic lithotripsies performed in 389 patients with ureteral stones at our institution during the calendar year 2010. Preoperative patient-related variables (age, sex, body mass index, history of urinary tract infection, previous stent placement, and time from initial presentation to intervention) and stone-related variables (laterality, numbers, location, width, and degree of hydronephrosis) were collected. Univariate analysis and multivariate logistic regression were performed to examine the statistical association between these variables and the use of intraoperative balloon ureteral dilation. RESULTS: Intraoperative balloon dilation was performed in 109 (27.5%) procedures. Univariate analysis identified increasing stone width (P<0.001) and lack of previous stent placement (P<0.001) as preoperative predictors of intraoperative balloon dilation. Stone width (P<0.001, odds ratio [OR] 1.274, 95% confidence interval [CI] 1.147-1.415) and lack of previous stent placement (P<0.001, OR 0.025, CI 0.006-0.105) remained independently associated with intraoperative balloon dilation in multivariate logistic regression. CONCLUSIONS: To our knowledge, our study is the first to statistically analyze the potential predictive factors for intraoperative balloon dilation in semirigid ureteroscopic lithotripsy. Larger stone width was significantly associated with intraoperative balloon dilation, whereas the presence of an indwelling ureteral stent, for at least 1 week, nearly eliminated the need for balloon dilation in subsequent ureteroscopic lithotripsy.

Interferon-inducible protein 16: insight into the interaction with tumor suppressor p53.

IFI16 is a member of the interferon-inducible HIN-200 family of nuclear proteins. It has been implicated in transcriptional regulation by modulating protein-protein interactions with p53 tumor suppressor protein and other transcription factors. However, the mechanisms of interaction remain unknown. Here, we report the crystal structures of both HIN-A and HIN-B domains of IFI16 determined at 2.0 and 2.35 Å resolution, respectively. Each HIN domain comprises a pair of tightly packed OB-fold subdomains that appear to act as a single unit. We show that both HIN domains of IFI16 are capable of enhancing p53-DNA complex formation and transcriptional activation via distinctive means. HIN-A domain binds to the basic C terminus of p53, whereas the HIN-B domain binds to the core DNA-binding region of p53. Both interactions are compatible with the DNA-bound state of p53 and together contribute to the effect of full-length IFI16 on p53-DNA complex formation and transcriptional activation.