Title - Long term outcomes of vitrectomy and ERM peel: Can pre-operative metamorphopsia measured using the D-Chart help improve surgical candidate selection?

PURPOSE: To assess the predictive value of pre-operative metamorphopsia, measured using the D-Chart, in patients undergoing epiretinal membrane (ERM) surgery and how this relates to improvement in quality of life after surgery. METHODS: 17 patients from vitreo-retinal surgery clinics at a tertiary ophthalmology centre were recruited when listed for pars plana vitrectomy (PPV) with ERM peel between September 2019 - February 2020. Pre-operatively patients underwent visual acuity (VA), Visual-Function Index 14 (VF-14) and metamorphopsia (D-Chart-Thomson Software Solutions) assessment and answered a questionnaire regarding cardinal ERM symptoms. Post-operatively patients were re-assessed in the same domains. RESULTS: 13 patients completed the protocol (inclusion rate 76%) with a mean follow-up of 32.1 (± 3.1) months. Mean pre-operative VA of the affected eye was 0.42 logMAR (± 0.25). Mean pre-operative VF-14 score was 81.51 (± 12.8) and mean M-Score of the affected eye was 14.6 (± 12.7). Post-operatively, mean VA of the operated eye was 0.11 logMAR (± 0.11), mean VF-14 score was 97.4 (± 3.8) and mean M-Score was 1.31 (± 2.8). Mean improvement in VA was 0.31 logMAR (p < 0.001), in VF-14 15.9 (p = 0.002), and M-Score -13.3 (p = 0.003). There was a significant association between pre-operative D-Chart score and improvement in VA (r = -0.570, p = 0.042), visual functioning (r = 0.606 p = 0.028) and metamorphopsia (r = 0.916 p < 0.001), with those demonstrating poorer D-Chart scores showing greater improvements. CONCLUSION: Pre- and post-operative visual distortion measured using the D-Chart, correlates with vision related quality of life in patients undergoing epiretinal membrane surgery. Patients with worse pre-operative distortion scores noticed the greatest improvements in distortion and vision related quality of life following surgery. With a mean follow-up time of 32.1 months, this long-term follow-up data further reinforces the efficacy of vitrectomy and ERM peel by demonstrating significant and sustained improvement in visual acuity, metamorphopsia and visual functioning. The authors suggest there is a role for D-Chart assessment pre-operatively to improve selection of patients in ERM surgery.

The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach.

Cancer is the leading cause of mortality and morbidity worldwide, and its cases are rapidly increasing every year. Several factors contribute to the development of tumorigenesis. including radiation, dietary lifestyle, smoking, environmental, and genetic factors. The cell cycle is regulated by a variety of molecular signaling proteins. However, when the proteins involved in the cell cycle regulation are altered, cellular growth and proliferation are significantly affected. Natural products provide an important source of new drug development for a variety of ailments. including cancer. Phytosterols (PSs) are an important class of natural compounds reported for numerous pharmacological activities, including cancer. Various PSs, such as ergosterol, stigmasterol, sitosterol, withaferin A, etc., have been reported for their anti-cancer activities against a variety of cancer by modulating the tumor microenvironment via molecular signaling pathways discussed within the article. These signaling pathways are associated with the production of pro-inflammatory mediators, growth factors, chemokines, and pro-apoptotic and anti-apoptotic genes. These mediators and their upstream signaling are very active within the variety of tumors and by modulating these signalings, thus PS exhibits promising anti-cancer activities. However, further high-quality studies are needed to firmly establish the clinical efficacy as well the safety of the phytosterols.

Suppression of MAPK/NF-kB and activation of Nrf2 signaling by Ajugarin-I in EAE model of multiple sclerosis.

Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin-I (Aju-I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju-I was first confirmed against glutamate-induced HT22 cells and hydrogen peroxide (H2 O2 )-induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju-I post-immunization treatment markedly reduced the EAE-associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju-I. It effectively restored the EAE-associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE-induced inflammation in the CNS by reducing the expression levels of p-38/JNK/NF-κB but increased the expression of IkB-α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap-1. It suppressed EAE-induced apoptosis in the CNS by regulating Bax/Bcl-2 and Caspase-3 expression. Taken together, this study suggests that Aju-I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/NF-κB, Nrf2/Keap-1, and Bcl2/Bax signaling.

HSV-infection-related herpetic anogenital ulcer disease among PLWH in southeastern US: electronic medical record based analysis.

ObjectivesThe southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer disease (HAUD) and assessed its associations with demographic and clinical characteristics, specifically with immunological markers using median, nadir and trajectory CD4 counts. METHODS: Electronic medical records (EMR) of over 7000 people living with HIV (PLWH) attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analysed. IR of HSV-related HAUD were estimated per 10 000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of IR. All IR and trends were stratified by gender and race. Six CD4 trajectory groups were constructed using the group-based trajectory modelling. Multivariable logistic models were conducted to assess the associations of CD4 counts (nadir, median CD4 and newly defined CD4 trajectory), separately with HAUD. RESULTS: Of the 4484 PLWH eligible individuals (3429 men, 1031 women and 24 transgender), we observed 425 patients with HSV-related HAUD. The mean log10viral load was higher in HAUD than HAUD-free groups, whereas the median nadir CD4 count (cells/uL) was higher in the non-cases than the case groups (p<0.05). HAUD were more frequent in women than men. Median CD4 (<200 cell/uL) was associated with HAUD (OR=2.1), but there were no significant associations with nadir CD4. Significant associations with declining and sustained low CD4 counts trajectory patterns were observed with HAUD. CONCLUSIONS: There were significant differences between men and women with incident HAUD among PLWH. EMR-based studies can provide innovative trajectory models that can potentially be helpful in guiding screening and clinical care of HAUD among high-risk PLWH.

Anti-neuropathic pain activity of Ajugarin-I via activation of Nrf2 signaling and inhibition of TRPV1/TRPM8 nociceptors in STZ-induced diabetic neuropathy.

This study aimed to investigate the anti-neuropathic pain activity and its underlying molecular mechanism of Ajugarin-I (Aju-I) in a rat model of diabetic neuropathic pain. The rats were given a single injection of 60 mg/kg of streptozotocin (STZ) intraperitoneally (i.p.) to induce diabetic neuropathic pain. After two weeks, rats were given Aju-I (1 and 5 mg/kg/day) i.p. for four consecutive weeks. The results demonstrated that in diabetic rats, treatment with Aju-I decreased STZ-induced hyperglycemia. It reduced the pain hypersensitivity (mechanical, thermal, and cold nociception) caused by STZ. It effectively restored STZ-associated pathological changes in the pancreas. In the sciatic nerve and spinal cord, it attenuated STZ-associated histopathological alterations and DNA damage. It suppressed oxidative stress by increasing the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2), thioredoxin (Trx), and heme oxygenase (HO-1), but decreasing the immunoreactivity of Kelch-like ECH-associated protein 1 (Keap1). Additionally, TRPV1 (transient receptor potential vanilloid 1) and TRPM8 (transient receptor potential melastatin 8) expression levels were considerably reduced by Aju-I treatment. It enhanced antioxidant levels and suppressed inflammatory cytokines production. Taken together, this research suggests that Aju-I treatment reduces pain behaviors in the STZ model of diabetic neuropathy via modulating Nrf2/Keap-1/HO-1 signaling and TRPV1/TRPM8 nociceptors.

Enhancing the antibacterial efficacy of aluminum foil by nanostructuring its surface using hot water treatment.

Bacterial biofilm has become one of the most frequent health problems as it contributes to persistent chronic infections. Therefore, it is vital to find alternatives to currently used bactericidal agents to prevent bacterial contamination on surfaces effectively and prevent the biofilms formation. Several metallic materials are well known for their antimicrobial activity; this includes copper, copper alloys, silver, gold, titanium, and zinc. On the other hand, some metals, such as aluminum, do not have noteworthy antimicrobial properties. In this study, we demonstrate that the antibacterial activity of household aluminum foil can be enhanced by nanostructuring the foil's surface by a simple hot water treatment (HWT) process. Cultures ofEscherichia coliandStaphylococcus aureuswere grown on nutrient agar while exposed to the samples of treated and untreated Al foils and left for 24 h. Our results indicate that treated Al foil can more effectively inhibit the bacteria growth compared to the regular untreated Al foil. This enhancement in antibacterial property might be due to a combination of chemical and morphological changes that the cell undergoes once it encounters nanofeatures of HWT-Al foil surface.

Anti-neuropathic pain activity of a cationic palladium (II) dithiocarbamate by suppressing the inflammatory mediators in paclitaxel-induced neuropathic pain model.

BACKGROUND: Neuropathic pain is a chronic pain state that negatively impacts the quality of life. Currently, available therapies for the treatment of neuropathic pain often lack efficacy and tolerability. Therefore, the search for novel drugs is crucial to obtain treatments that effectively suppress neuropathic pain. OBJECTIVES: The present study was undertaken to investigate the antinociceptive properties of (1,4-bis-(diphenylphosphino) butane) palladium (II) chloride monohydrate (Compound 1) in a paclitaxel (PTX)-induced neuropathic pain model. METHODS: Initially, behavioral tests such as mechanical and cold allodynia as well as thermal and tail immersion hyperalgesia were performed to investigate the antinociceptive potential of Compound 1 (5 and 10 mg/kg, b.w). RT-PCR was performed to determine the effect of Compound 1 on the mRNA expression level of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF)-α, interleukin (IL)-1ß, and IL-6. In addition, antioxidant protein, nitric oxide (NO), and malondialdehyde (MDA) levels were also determined. RESULTS: The results demonstrated that once-daily dosing of Compound 1 significantly suppressed the PTX-induced behavioral pain responses dose-dependently. The mRNA gene expressions of iNOS, COX-2, and inflammatory cytokines were markedly reduced by Compound 1. Furthermore, it enhanced the level of antioxidant enzymes and lowered the level of MDA and NO production. CONCLUSION: These findings suggest that the antinociceptive potential of Compound 1 in the PTX-induced neuropathic pain model is via suppression of oxidative stress and inflammation. Thus, Compound 1 might be a potential candidate for the therapeutic management of PTX induced neuropathic pain.

Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain.

Vincristine (VCR) is a widely used chemotherapy drug that induced peripheral painful neuropathy. Yet, it still lacks an ideal therapeutic strategy. The transient receptor potential (TRP) channels, purinergic receptor (P2Y), and mitogen-activated protein kinase (MAPK) signaling play a crucial role in the pathogenesis of neuropathic pain. Withametelin (WMT), a potential Phytosteroid isolated from datura innoxa, exhibits remarkable neuroprotective properties. The present investigation was designed to explore the effect of withametelin on VCR-induced neuropathic pain and its underlying molecular mechanism. Initially, the neuroprotective potential of WMT was confirmed against hydrogen peroxide (H2O2)-induced PC12 cells. To develop potential candidates for neuropathic pain treatment, a VCR-induced neuropathic pain model was established. Vincristine (75 µg/kg) was administered intraperitoneally (i.p.) for 10 consecutive days (day 1-10) for the induction of neuropathic pain. Gabapentin (GBP) (60 mg/kg, i.p.) and withametelin (0.1 and 1 mg/kg i.p.) treatments were given after the completion of VCR injection on the 11th day up to 21 days. The results revealed that WMT significantly reduced VCR-induced pain hypersensitivity, including mechanical allodynia, cold allodynia, and thermal hyperalgesia. It reversed the VCR-induced histopathological changes in the brain, spinal cord, and sciatic nerve. It inhibited VCR-induced changes in the biochemical composition of the myelin sheath of the sciatic nerve. It markedly downregulated the expression levels of TRPV1 (transient receptor potential vanilloid 1); TRPM8 (Transient receptor potential melastatin 8); and P2Y nociceptors and MAPKs signaling, including ERK (Extracellular Signal-Regulated Kinase), JNK (c-Jun N-terminal kinase), and p-38 in the spinal cord. It suppressed apoptosis by regulating Bax (Bcl2-associated X-protein), Bcl-2 (B-cell-lymphoma-2), and Caspase-3 expression. It considerably attenuated inflammatory cytokines, oxidative stress, and genotoxicity. This study suggests that WMT treatment suppressed vincristine-induced neuropathic pain by targeting the TRPV1/TRPM8/P2Y nociceptors and MAPK signaling.

Alleviation of Memory Deficit by Bergenin via the Regulation of Reelin and Nrf-2/NF-κB Pathway in Transgenic Mouse Model.

The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against H2O2-induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aß) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aß (1-42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains.

CD4 Trajectory Models and Onset of Non-AIDS-Defining Anal Genital Warts, Precancer, and Cancer in People Living With HIV Infection-1.

BACKGROUND: It is unclear how the characteristics of CD4 counts predict non-AIDS-defining human papillomavirus-related anogenital warts (AGWs) and anal high-grade squamous intraepithelial lesions/cancer (HSIL) in people living with HIV infection-1 (PLWH). We compared the associations between 3 CD4 counts measures and these disease outcomes in the study. METHODS: Retrospective sociobehavioral and clinical data from electronic health records of 4803 PLWH from 2006 to 2018 were included. Three different measurements of CD4 counts-(a) nadir, (b) median, and (c) trajectory-were estimated. Six CD4 trajectory groups were constructed using the group-based trajectory modeling from all patients older than 18 years with ≥3 clinical visits. Univariate and multivariable logistic regression models were used to assess the associations with AGW and HSIL, separately. RESULTS: A total of 408 AGW, 102 anal HSIL (43 HSIL, 59 cancer), 4 penile cancer, and 15 vaginal cancer cases were observed. Median CD4 (<200 cell/µL) was associated with AGW (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.6-3.0]), and anal HSIL (OR, 2.7 [95% CI, 1.5-5.0]; each, P < 0.001). Low nadir CD4 (<200 cell/µL) was associated with AGW (OR, 1.8 [95% CI, 1.3-2.6]) and anal HSIL (OR, 2.4 [95% CI, 1.2-4.7]; each, P ≤ 0.001). Different patterns (declining and sustained low CD4 counts) of CD4 trajectories showed the strongest associations with onset of both AGW (OR, 1.8-3.1) and HSIL (OR, 2.7-6.7). CONCLUSIONS: People living with HIV infection-1 with the same median CD4 could have very different CD4 trajectories, implying different dynamics of immune status. CD4 trajectory could be a better predictor of incident AGW and HSIL among PLWH.

Dedifferentiated Carcinoma of the Endometrium Associated With Low-grade Müllerian Adenosarcoma: A Clinicopathologic Case Report Including the Immunohistochemical and Molecular Profile.

Dedifferentiated carcinoma is defined as undifferentiated carcinoma coexisting with a second component of FIGO grade 1 or 2 endometrioid carcinoma. It is a rare entity with highly aggressive behavior. Dedifferentiated carcinoma combined with another primary uterine tumor is even rarer. We describe a case containing 3 different morphologies comprised of a dedifferentiated carcinoma associated with a low-grade endometrioid carcinoma coexisting with a low-grade Müllerian adenosarcoma. We also used targeted genomic analysis to show all 3 components arise from the same founding clone and identify novel mutations that drive tumor progression.

Comorbidities associated with HPV infection among people living with HIV-1 in the southeastern US: a retrospective clinical cohort study.

BACKGROUND: The southeastern US is an epicenter for incident HIV in the US with high prevalence of human papillomavirus (HPV) co-infections. However, epidemiologies of HPV-associated clinical conditions (CC) among people living with HIV-1 infection (PLWH) are not fully known. METHODS: Electronic medical records (EMR) of PLWH attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analyzed. The retrospective study was nested within the University of Alabama at Birmingham HIV clinical cohort, which has electronically collected over 7000 PLWH's clinical and sociobehavioral data since 1999. Incidence rates of HPV-related CC including anogenital warts, penile, anal, cervical, and vaginal/vulvar low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) were estimated per 10,000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of incident CC. All rates and trends were stratified by gender and race. RESULTS: Of the 4484 PLWH included in the study (3429 men, 1031 women, and 24 transgender), we observed 1038 patients with HPV-related CC. The median nadir CD4 count (cells/uL) was higher in the HPV-condition free group than the case groups (P < 0.0001). Anogenital warts, anal LSIL, HSIL, and cancer were more likely to be diagnosed among HIV-infected men than women. White men presented more frequently with anal LSIL and anal and penile cancers than black men (P < 0.03). White women were also more likely to be diagnosed with cervical HSIL (P = 0.023) and cancer (P = 0.037) than black women. CONCLUSIONS: There were significant differences between gender and race with incidence of HPV-related CC among HIV patients. EMR-based studies provide insights on understudied HPV-related anogenital conditions in PLWH; however, large-scale studies in other regions are needed to generalize current findings and draw public health attention to co-infection induced non-AIDS defining comorbidities among PLWH.

Gene expression signature of atypical breast hyperplasia and regulation by SFRP1.

BACKGROUND: Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4-7%, with the overall risk of developing breast cancer increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERα+) and represent risk indicators and/or precursor lesions to low grade ERα+ tumors. Therefore, molecular profiles of AH lesions offer insights into the earliest changes in the breast epithelium, rendering it susceptible to oncogenic transformation. METHODS: In this study, women were selected who were diagnosed with ductal or lobular AH, but no breast cancer prior to or within the 2-year follow-up. Paired AH and histologically normal benign (HNB) tissues from patients were microdissected. RNA was isolated, amplified linearly, labeled, and hybridized to whole transcriptome microarrays to determine gene expression profiles. Genes that were differentially expressed between AH and HNB were identified using a paired analysis. Gene expression signatures distinguishing AH and HNB were defined using AGNES and PAM methods. Regulation of gene networks was investigated using breast epithelial cell lines, explant cultures of normal breast tissue and mouse tissues. RESULTS: A 99-gene signature discriminated the histologically normal and AH tissues in 81% of the cases. Network analysis identified coordinated alterations in signaling through ERα, epidermal growth factor receptors, and androgen receptor which were associated with the development of both lobular and ductal AH. Decreased expression of SFRP1 was also consistently lower in AH. Knockdown of SFRP1 in 76N-Tert cells resulted altered expression of 13 genes similarly to that observed in AH. An SFRP1-regulated network was also observed in tissues from mice lacking Sfrp1. Re-expression of SFRP1 in MCF7 cells provided further support for the SFRP1-regulated network. Treatment of breast explant cultures with rSFRP1 dampened estrogen-induced progesterone receptor levels. CONCLUSIONS: The alterations in gene expression were observed in both ductal and lobular AH suggesting shared underlying mechanisms predisposing to AH. Loss of SFRP1 expression is a significant regulator of AH transcriptional profiles driving previously unidentified changes affecting responses to estrogen and possibly other pathways. The gene signature and pathways provide insights into alterations contributing to AH breast lesions.

Correction to: Anti-inflammatory, anti-rheumatic and analgesic activities of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS) in rodents.

Unfortunately, Fig. 1 was incorrectly published in the original publication. The corrected Fig. 1 is given as below.

Anti-inflammatory, anti-rheumatic and analgesic activities of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS) in rodents.

Chronic inflammation is pathologically associated with various clinical conditions such as rheumatoid arthritis. Several anti-inflammatory and analgesic drugs currently available in market presents a wide range of problems. Therefore, the current study was aimed to evaluate anti-inflammatory and analgesic activities of newly synthesized compound 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS). Carrageenan and CFA-induced models were developed for evaluation of anti-inflammatory and analgesic activity. Quantitative real-time PCR (qRT-PCR) was performed to determine the mRNA expression levels of inflammatory mediators. Pain behaviours were evaluated by performing Von Frey, Randall Selitto, cold acetone and hot plate test respectively. X-ray imaging and haematoxylin and eosin (H&E) staining were performed for examination of soft tissues of treated mice paw. Additionally, Kodzeila's screen test and weight test were performed for determination of any side effects on motor function and muscle strength. Acute pretreatment of animals with MOPBS (1, 10, 50 and 100 mg/kg, i.p.) produced a significant reduction of paw oedema against carrageenan-induced acute inflammation as well as notable inhibition of mechanical hyperalgesia, allodynia and thermal hyperalgesia. Similarly, in chronic inflammation model, administration of MOPBS (50 mg/kg, i.p.) produced a remarkable reduction of paw oedema. Additionally, MOPBS pretreatment showed a significant inhibition of thermal hyperalgesia, mechanical allodynia, and mechanical hyperalgesia in chronic arthritis model. Several pro-inflammatory mediators such as nitric oxide (NO), vascular endothelial growth factor (VEGF), interleukins (IL-1ß, IL-6) and tumor necrosis factor-α (TNF-α) were inhibited by MOPBS treatment in blood plasma and paw tissues, respectively. MOPBS also enhanced the mRNA expression levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), superoxide dismutase (SOD2) and heme oxygenase (HO-1) and in turn reduced arthritis severity and inflammation. Furthermore, anti-inflammatory data were confirmed by X-rays and histological analysis. MOPBS pretreatment did not produce any apparent toxic effect on gastric, kidney and liver function and on muscle strength and motor function. Hence, the present data suggest that MOPBS might be a candidate for several chronic inflammatory diseases such RA and other auto-immune diseases.

Primary Transitional Cell Carcinoma of the Conjunctiva.

A 77-year-old male presented with a large papillomatous conjunctival lesion on his lower eyelid. Biopsy and extensive systemic investigation revealed this to be a primary conjunctival transitional cell carcinoma. Patient preference and coexisting medical problems dictated conservative management with surgical debulking, topical mitomicin, and radiotherapy. Local control has been maintained for 4 years to date.

Correction of a Forefoot Deformity Caused by a Large, Solitary Metatarsal Osteochondroma in an Adolescent: A Case Report.

Solitary osteochondroma is the most common bone tumor, accounting for 20% to 50% of all benign bony tumors. Osteochondromas are usually found on the metaphysis of the long bones near the physis; the bones of the foot are less commonly involved. We describe a 13-year-old female with a large osteochondroma arising from the fourth metatarsal. Pressure from the tumor on the adjacent metatarsals had deformed her forefoot, creating cosmetic and functional problems. The second and third toes were deviated laterally at the metatarsophalangeal joint, and the fourth and fifth toes were deviated medially. In addition, the fourth and fifth toes were flexed at the proximal interphalangeal joint. We excised the osteochondroma and stabilized the metatarsophalangeal joints. After 3 years, the cosmetic and functional results were satisfactory. The subluxation at the metatarsophalangeal joints had resolved without treatment. Her Revised Foot Function Index score had improved from 141 preoperatively to 95 postoperatively, and her Manchester-Oxford Foot Questionnaire score had improved from 25 to 0. This case is a rare example of a large metatarsal osteochondroma in a growing child in which pressure from the tumor caused secondary forefoot deformities. The management of this case also shows the potential for the forefoot to remodel itself during adolescence, after the tumor has been resected and the joints stabilized.

Isolation and molecular characterization of Salmonella enterica serovar Enteritidis from poultry house and clinical samples during 2010.

A total of 60 Salmonella enterica serovar (ser.) Enteritidis isolates, 28 from poultry houses and 32 from clinical samples, were isolated during 2010. These isolates were subjected to testing and analyzed for antibiotic resistance, virulence genes, plasmids and plasmid replicon types. To assess genetic diversity, pulsed-field gel electrophoresis (PFGE) fingerprinting, using the XbaI restriction enzyme, Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA) and plasmid profiles were performed. All isolates from poultry, and 10 out of 32 clinical isolates were sensitive to ampicillin, chloramphenicol, gentamicin, kanamycin, nalidixic acid, sulfisoxazole, streptomycin, and tetracycline. Twenty-one of thirty-two clinical isolates were resistant to ampicillin and tetracycline, and one isolate was resistant to nalidixic acid. PFGE typing of sixty ser. Enteritidis isolates by XbaI resulted in 10-12 bands and grouped into six clusters each with similarity from 95% to 81%. The MLVA analysis of sixty isolates gave 18 allele profiles with the majority of isolates displayed in three groups, and two clinical isolates found to be new in the PulseNet national MLVA database. All isolates were positive for 12 or more of the 17 virulence genes mostly found in S. enterica (spvB, spiA, pagC, msgA, invA, sipB, prgH, spaN, orgA, tolC, iroN, sitC, IpfC, sifA, sopB, and pefA) and negative for one gene (cdtB). All isolates carried a typical 58 kb plasmid, type Inc/FIIA. Three poultry isolates and one clinical isolate carried small plasmids with 3.8, 6, 7.6 and 11.5 kb. Ten of the clinical isolates carried plasmids, with sizes 36 and 38 kb, types IncL/M and IncN, and one isolate carried an 81 kb plasmid, type IncI. Southern hybridization of a plasmid with an Inc/FIIA gene probe hybridized one large 58 kb plasmid in all isolates. Several large and small plasmids from poultry isolates were not typed by our PCR-based method. These results confirmed that PFGE fingerprinting has limited discriminatory power for ser. Enteritidis in both poultry and clinical sources. However, the plasmid and MLVA allele profiles were a useful and important epidemiology tool to discriminate outbreak strains of ser. Enteritidis from poultry and clinical samples.

Whole-Genome Sequence Analysis of Antibiotic Resistance, Virulence, and Plasmid Dynamics in Multidrug-Resistant E. coli Isolates from Imported Shrimp.

We analyzed antimicrobial resistance and virulence traits in multidrug-resistant (MDR) E. coli isolates obtained from imported shrimp using whole-genome sequences (WGSs). Antibiotic resistance profiles were determined phenotypically. WGSs identified key characteristics, including their multilocus sequence type (MLST), serotype, virulence factors, antibiotic resistance genes, and mobile elements. Most of the isolates exhibited resistance to gentamicin, streptomycin, ampicillin, chloramphenicol, nalidixic acid, ciprofloxacin, tetracycline, and trimethoprim/sulfamethoxazole. Multilocus sequence type (MLST), serotype, average nucleotide identity (ANI), and pangenome analysis showed high genomic similarity among isolates, except for EC15 and ECV01. The EC119 plasmid contained a variety of efflux pump genes, including those encoding the acid resistance transcriptional activators (gadE, gadW, and gadX), resistance-nodulation-division-type efflux pumps (mdtE and mdtF), and a metabolite, H1 symporter (MHS) family major facilitator superfamily transporter (MNZ41_23075). Virulence genes displayed diversity, particularly EC15, whose plasmids carried genes for adherence (faeA and faeC-I), invasion (ipaH and virB), and capsule (caf1A and caf1M). This comprehensive analysis illuminates antimicrobial resistance, virulence, and plasmid dynamics in E. coli from imported shrimp and has profound implications for public health, emphasizing the need for continued surveillance and research into the evolution of these important bacterial pathogens.

Deep learning-based cell segmentation for rapid optical cytopathology of thyroid cancer.

Fluorescence polarization (Fpol) imaging of methylene blue (MB) is a promising quantitative approach to thyroid cancer detection. Clinical translation of MB Fpol technology requires reduction of the data analysis time that can be achieved via deep learning-based automated cell segmentation with a 2D U-Net convolutional neural network. The model was trained and tested using images of pathologically diverse human thyroid cells and evaluated by comparing the number of cells selected, segmented areas, and Fpol values obtained using automated (AU) and manual (MA) data processing methods. Overall, the model segmented 15.8% more cells than the human operator. Differences in AU and MA segmented cell areas varied between - 55.2 and + 31.0%, whereas differences in Fpol values varied from - 20.7 and + 10.7%. No statistically significant differences between AU and MA derived Fpol data were observed. The largest differences in Fpol values correlated with greatest discrepancies in AU versus MA segmented cell areas. Time required for auto-processing was reduced to 10 s versus one hour required for MA data processing. Implementation of the automated cell analysis makes quantitative fluorescence polarization-based diagnosis clinically feasible.