Monodigital Double Cross-Finger Flaps-A Novel Approach for Coverage of Large Volar Defects.

INTRODUCTION: A single cross-finger flap can only address digital defects of a limited size, and larger defects often require distant flaps such as abdominal or groin flaps that are cumbersome to perform and sometimes bulky. Two cross-finger flaps harvested from the same donor digit could offer a simple and effective solution for many such defects. In this study, we describe the technique of monodigital double cross-finger flaps and its clinical applicability, with evaluation of donor and recipient site morbidity. METHODS AND MATERIALS: A total of 10 subjects with large volar defects were included in the study. The demographic data, etiology, defect size, flap donor, and recipient sites were tabulated prior to surgery. Each subject was assessed for postoperative complications at the donor and recipient site and followed up for 6-12 months to document any flap or donor site morbidities. RESULTS: The subjects included 9 males and 1 female subjects, with an average age of 35.6 years (21-67 years). Most patients had posttraumatic defects, with 3 cases of full thickness burns and one with postsurgical tissue necrosis. All defects were volar, with 4 on the little finger, 3, 2, and 1 in the ring, index and middle fingers, respectively. No major postoperative complications were noted in any case. All flaps survived well with good contour, and donor fingers achieved near-normal range of flexion with only minimal restriction (10-15°) at the distal interphalangeal joint that did not result in any overall functional disability. CONCLUSIONS: Monodigital double cross-finger flap technique offers a simple and effective solution for reconstruction of large digital defects that are not amenable for closure by a classical cross-finger flap, and is a good alternative for other procedures, providing supple soft tissue coverage and no significant morbidity at the donor digit provided that there is preservation of a small skin bridge across the proximal interphalangeal joint.

Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones.

High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and poor prognosis. Here, we use spatial transcriptomics to identify HGSOC subclones and study their association with infiltrating cell populations. Visium spatial transcriptomics reveals multiple tumour subclones with different copy number alterations present within individual tumour sections. These subclones differentially express various ligands and receptors and are predicted to differentially associate with different stromal and immune cell populations. In one sample, CosMx single molecule imaging reveals subclones differentially associating with immune cell populations, fibroblasts, and endothelial cells. Cell-to-cell communication analysis identifies subclone-specific signalling to stromal and immune cells and multiple subclone-specific autocrine loops. Our study highlights the high degree of subclonal heterogeneity in HGSOC and suggests that subclone-specific ligand and receptor expression patterns likely modulate how HGSOC cells interact with their local microenvironment.

Volatile Oil Containing Plants as Phytopharmaceuticals to Treat Psoriasis: A Review.

INTRODUCTION: Psoriasis is a chronic skin condition caused by an autoimmune response that accelerates the life cycle of skin cells, resulting in the characteristic symptoms of scaling, inflammation, and itching. METHODS: Palliative treatment options for psoriasis often prioritize the use of volatile oils. These oils contain monoterpenes, sesquiterpenes, and phenylpropanoids that are intricately linked to the molecular cascades involved in the pathogenesis and symptoms of psoriasis. To evaluate the antipsoriatic efficacy of volatile oils and their components, we conducted a systematic review of scientific studies. Our literature search encompassed various online databases, including PubMed, BIREME, SCIELO, Open Grey, Scopus, and ScienceDirect. The selected studies included experimental in vitro/in vivo assessments as well as clinical studies that examined the potential of volatile oils and their extracts as antipsoriatic agents. We excluded conference proceedings, case reports, editorials, and abstracts. Ultimately, we identified and evaluated a total of 12 studies for inclusion in our analysis. RESULTS: The data collected, compiled, and analyzed strongly support the interaction between volatile oils and their constituents with the key molecular pathways involved in the pathogenesis of psoriasis and the development of its symptoms. Volatile oils play a significant role in the palliative treatment of psoriasis, while their chemical constituents have the potential to reduce the symptoms and recurrence of this condition. CONCLUSION: The current review highlights that the constituents found in volatile oils offer distinct chemical frameworks that can be regarded as promising starting points for the exploration and development of innovative antipsoriatic agents.

Chemical composition and biological activities of Lonicera caprifolium L. (Caprifoliaceae) essential oil.

This work aimed to investigate the chemical composition, antioxidant activity, antinociceptive effect, and wound healing activity of the Lonicera caprifolium L. flower essential oil (LCEO). Linalool (16.42%), d-limonene (9.99%), and α-cadinol (10.65%) were the most prevalent components of the LCEO. The LCEO revealed moderate DPPH and ABTS radical-scavenging activity. LCEO exhibited potent antinociceptive activity in acetic acid-induced writhing and hot plate-induced pain model; LCEO reduced 73.88 ± 2.78% of writhing and significantly increased pain withdrawal latency in the mice, respectively. The LCEO also presented a potent wound healing effect, with 98.08 ± 1.37% wound closure on the 12th day of treatment. The results of the study demonstrate antioxidant and wound healing potential with antinociceptive effect. To the best of our knowledge, this is the first report on the bioactivities of L. caprifolium L. essential oil.

Nutritional Composition, Mineral Profiling, In Vitro Antioxidant, Antibacterial and Enzyme Inhibitory Properties of Selected Indian Guava Cultivars Leaf Extract.

Psidium guajava L. is a small evergreen tree known for its magnificent medicinal and nutritional value. This study aimed to evaluate the nutritional profile and in vitro pharmacological potentialities of the different leaf extracts of four cultivars of Psidium guajava namely Surka chitti, Allahabad safeda, Karela, and Lucknow-49. The standard procedures of the Association of Official Analytical Chemists (AOAC) were followed to carry out the nutritional analysis and all of the cultivars recorded the presence of elements at a nominal range. The highest presence of phenols (125.77 mg GAE/g) and flavonoids (92.38 mg QE/g) in the methanolic leaf extract of the Karela cultivar was recorded. A wide range of minerals such as sodium, phosphorus, magnesium, zinc, and boron were recorded with a higher percentage in the Karela cultivar of Psidium guajava. In the enzyme inhibitory assays, Allahabad safeda showed potential inhibition with an IC50 of 113.31 ± 1.07, 98.2 ± 0.66 and 95.73 ± 0.39 µg/mL in α-amylase, α-glucosidase, and tyrosinase inhibition assays, respectively. The strong antioxidant effect was established by Lucknow-49 (IC50 of 74.43 ± 1.86 µg/mL) and Allahabad safeda (IC50 of 78.93 ± 0.46 µg/mL) for ABTS and DPPH assays, respectively. The ethyl acetate and methanolic leaf extracts of the Allahabad safeda cultivar showed better inhibition against Pseudomonas aeruginosa with an MIC of 14.84 and 28.69 µg/mL, respectively. A decent mean zone of inhibition was recorded in methanolic leaf extract that ranged from 21-25 mm in diameter against the tested bacterial strains (Proteus vulgaris, Bacillus subtilis, and P. aeruginosa). This is the first scientific report on the comparative and comprehensive analysis of indigenous guava cultivars to evidently shortlist the elite cultivars with enriched dietary nutrition and biological activities.

Evidence-based opioid prescribing guidelines after lung resection: a prospective, multicenter analysis.

Background: Opioid prescribing guidelines have significantly decreased overprescribing and post-discharge use after cardiac surgery; however, limited recommendations exist for general thoracic surgery patients, a similarly high-risk population. We examined opioid prescribing and patient-reported use to develop evidence-based, opioid prescribing guidelines after lung cancer resection. Methods: This prospective, statewide, quality improvement study was conducted between January 2020 to March 2021 and included patients undergoing surgical resection of a primary lung cancer across 11 institutions. Patient-reported outcomes at 1-month follow-up were linked with clinical data and Society of Thoracic Surgery (STS) database records to characterize prescribing patterns and post-discharge use. The primary outcome was quantity of opioid used after discharge; secondary outcomes included quantity of opioid prescribed at discharge and patient-reported pain scores. Opioid quantities are reported in number of 5-mg oxycodone tablets (mean ± standard deviation). Results: Of the 602 patients identified, 429 met inclusion criteria. Questionnaire response rate was 65.0%. At discharge, 83.4% of patients were provided a prescription for opioids of mean size 20.5±13.1 pills, while patients reported using 8.2±13.0 pills after discharge (P<0.001), including 43.7% who used none. Those not taking opioids on the calendar day prior to discharge (32.4%) used fewer pills (4.4±8.1 vs. 11.7±14.9, P<0.001). Refill rate was 21.5% for patients provided a prescription at discharge, while 12.5% of patients not prescribed opioids at discharge required a new prescription before follow-up. Pain scores were 2.4±2.5 for incision site and 3.0±2.8 for overall pain (scale 0-10). Conclusions: Patient-reported post-discharge opioid use, surgical approach, and in-hospital opioid use before discharge should be used to inform prescribing recommendations after lung resection.

Phytochemical profile, antioxidant, cytotoxic and anti-inflammatory activities of stem bark extract and fractions of Ailanthus excelsa Roxb.: In vitro, in vivo and in silico approaches.

This study aimed to assess the phytochemical composition, in vitro antioxidant, cytotoxicity, and in vivo anti-inflammatory activities of the methanolic extract of Ailanthus excelsa (Simaroubaceae) stem bark and its fractions. Quantitative phytochemical analysis revealed that methanolic extract and all fractions contained a high level of flavonoids (20.40-22.91 mg/g QE), phenolics (1.72-7.41 mg/g GAE), saponins (33.28-51.87 mg/g DE), and alkaloids (0.21-0.33 mg/g AE). The antioxidant potential was evaluated in vitro using a range of assays, i.e., DPPH•, ABTS radical scavenging ability, and total antioxidant capacity. The chloroform and ethyl acetate fractions showed stronger antioxidant activity than the methanol extract. In vitro cytotoxic activity was investigated in three human tumor cell lines (A-549, MCF7 and HepG2) using the SRB assay. In addition, the in vivo anti-inflammatory effect was assessed by carrageenan-induced paw edema in rats. The chloroform fraction showed a more pronounced effect by effectively controlling the growth with the lowest GI50 and TGI concentrations. The human lung cancer cell line (A-549) was found to be more sensitive to the chloroform fraction. Furthermore, the chloroform fraction exhibited significant anti-inflammatory activity at a dose of 200 mg/kg in the latter phase of inflammation. Besides, methanol extract and ethyl acetate fraction revealed a significant cytotoxic and anti-inflammatory effects. The chloroform fraction of stem bark showed a strong anti-inflammatory effect in experimental animals and significant COX-2 inhibitory potential in the in vitro experiments. GC-MS analysis of chloroform fraction identified the phytochemicals like caftaric acid, 3,4-dihydroxy phenylacetic acid, arachidonic acid, cinnamic acid, 3-hydroxyphenylvaleric acid, caffeic acid, hexadeconoic acid, and oleanolic acid. The in-silico results suggest that identified compounds have better affinity towards the selected targets, viz. the BAX protein (PDB ID: 1F16), p53-binding protein Mdm-2 (PDB ID: 1YCR), and topoisomerase II (PDB ID: 1QZR). Amongst all, caftaric acid exhibited the best binding affinity for all three targets. Thus, it can be concluded that caftaric acid in combination with other phenolic compounds, might be responsible for the studied activity. Additional in vivo and in vitro studies are required to establish their exact molecular mechanisms and consider them as lead molecules in developing of valuable drugs for treating oxidative stress-induced disorders, cancers, and inflammations.

A longitudinal study of antibody responses to selected host antigens in rheumatic fever and rheumatic heart disease.

Introduction. Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD).Gap Statement. Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process.Aim. To determine the antibody responses over time in patients and healthy controls against host tissue proteins - cardiac myosin and peptides from its S2 subfragment, tropomyosin, laminin and keratin.Methodology. We used enzyme-linked immunosorbent assays (ELISA) to determine antibody responses in: (1) healthy controls; (2) patients with streptococcal pharyngitis; (3) patients with ARF with carditis and (4) patients with RHD on penicillin prophylaxis.Results. We observed significantly higher antibody responses against extracellular proteins - laminin and keratin in pharyngitis group, patients with ARF and patients with RHD when compared to healthy controls. The antibody responses against intracellular proteins - cardiac myosin and tropomyosin were elevated only in the group of patients with ARF with active carditis. While the reactivity to S2 peptides S2-1-3, 8-11, 14, 16-18, 21-22 and 32 was higher in patients with ARF, the reactivity in the RHD group was high only against S2-1, 9, 11, 12 when compared to healthy controls. The reactivity against S2 peptides reduced as the disease condition stabilized in the ARF group whereas the reactivity remained unaltered in the RHD group. By contrast antibodies against laminin and keratin persisted in patients with RHD.Conclusion. Our findings of antibody responses against host proteins support the multistep hypothesis in the development of rheumatic carditis. The differential kinetics of serum antibody responses against S2 peptides may have potential use as markers of ongoing cardiac damage that can be used to monitor patients with ARF/RHD.

Population structure and genetic diversity of invasive Fall Armyworm after 2 years of introduction in India.

Fall Armyworm (FAW), Spodoptera frugiperda, is a polyphagous pest capable of feeding over 80 plant species and was indigenous to the Western Hemisphere. Within a span of 4 years, FAW has established itself throughout most of the regions in Africa and Asia causing significant losses in maize production. Owing to its revamped distribution range, it would be prudent to analyze the ensuing genetic changes and study the emerging phylogeographic patterns across the world. In this regard, we would like to provide a current snapshot of genetic diversity of FAW in India 2 years after the initial introduction and compare it with the worldwide diversity in order to trace the origins and evolutionary trajectories of FAW in India. We have investigated around 190 FAW samples from different regions in India for strain identity and polymorphism analysis on the basis of partial mitochondrial cytochrome oxidase I (COI) gene sequences. Apart from the ancestral rice and corn strain haplotype, our study demonstrates the presence of 14 more haplotypes unique to India at a haplotype diversity of 0.356. We were also able to record inter-strain hybrid haplotypes of rice and corn strains in India. Regional heterogeneity within Indian populations seems to be quite low representative of extensive migration of FAW within India. Distribution analysis of pairwise differences and rejection of neutrality tests suggest that the FAW population in India might be undergoing expansion. Our data is consistent with the findings suggesting a recent and common origin for invasive FAW populations in Asia and Africa, and does not indicate multiple introductions to India. This study reports the highest genetic diversity for Indian FAW populations to date and will be useful to track the subsequent evolution of FAW in India. The findings would have important ramifications for FAW behavior and composition throughout the world.

A novel pharmacological approach of herbal mediated cerium oxide and silver nanoparticles with improved biomedical activity in comparison with Lawsonia inermis.

Diabetes mellitus is one of the threatening, non-communicable and chronic ailments worldwide since ancient times to the current stage of human existence. The utilization of nanoparticles as a medicine in the treatment of diabetes is an attractive proposition. In the present study, herbal mediated cerium oxide nanoparticles (HMCeO2 NPs), herbal mediated silver nanoparticles (HMAg NPs) and Lawsonia intermix extract (LIE) was evaluated for them for in-vivo hypoglycemic effect and compared the potency. The resulting HMCeO2 NPs, HMAg NPs and Lawsonia inermis have been characterized by different analytical equipments such as X-ray Diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Particle size analyzer (PSA), Field emission scanning electron microscope (FESEM) and High resolution transmission electron microscope (HRTEM). The synthesized NPs and Lawsonia inermis extract were assessed for toxicity by using acute oral toxicity using female albino mice (s) model by following OECD-425 guidelines. In in-vivo hypoglycemic animal model, the male wistar rats with weight varying between 180-200 gms were grouped as: normal control: did not receive any treatment, diabetic control (saline): received a single intraperitoneal dose of Streptozotocin (40 mg/kg), standard: received a single daily oral dose of 50 mg/kg body weight, HMCeO2 NPs: received single daily oral dose of 100 mg/kg, 200 mg/kg, HMAg NPs: received a single daily oral dose of 100 mg/kg, 200 mg/kg, and Lawsonia inermis: received a single daily oral dose of 100 mg/kg, 200 mg/kg. The herbal mediated NPs were considered safe as they have not shown toxic effects. From the current study results, it may conclude that, due to the advanced biological and pharmacological characters, the HMAg NPs depicted more potent hypoglycemic activity than that of LIE and CeO2 NPs.

Risk of persistent or recurrent cervical neoplasia in patients with 'pure' adenocarcinoma-in-situ (AIS) or mixed AIS and high-grade cervical squamous neoplasia (cervical intra-epithelial neoplasia grades 2 and 3 (CIN 2/3)): a population-based study.

OBJECTIVE: To compare outcomes of patients with pure adenocarcinoma-in-situ (AIS) and mixed AIS/CIN 2/3 lesions including the incidence of AIS persistence, recurrence and progression to adenocarcinoma. DESIGN: Retrospective cohort study. SETTING: Statewide population in Western Australia. POPULATION: Women diagnosed with AIS between 2001 and 2012. METHODS: We conducted a retrospective, population-based cohort study. MAIN OUTCOME MEASURES: De-identified linked data were utilised to ascertain the association between patient age at excisional treatment, margin status, lesion type, lesion size, and risk of persistent AIS (defined as the presence of AIS <12 months from treatment), recurrent AIS (≥12 months post-treatment), and adenocarcinoma. RESULTS: 636 patients were eligible for analysis. The mean age was 32.3 years and median follow-up interval was 2.5 years. Within the study cohort, 266 patients (41.8%) had pure AIS and 370 (58.2%) had mixed AIS/CIN 2/3. Overall, 47 patients (7.4%) had AIS persistence/recurrence and 12 (1.9%) had adenocarcinoma. Factors associated with persistence/recurrence were pure AIS (hazard ratio (HR) 2.3; 95%CI 1.28-3.94; P = 0.005), age >30 years (HR 2.1; 95%CI 1.16-3.81; P = 0.015), positive endocervical margins (HR 5.8; 95%CI 3.05-10.92; P = <0.001) and AIS lesions >8 mm (HR 2.5; 95%CI 1.00-6.20; P = 0.049). A histologically positive AIS ectocervical margin was not associated with persistence/recurrence. CONCLUSION: In this study, pure AIS was associated with greater risk of persistence/recurrence than was mixed AIS/CIN 2/3. AIS lesions >8 mm and positive endocervical margins were significant predictors for persistent or recurrent disease. TWEETABLE ABSTRACT: Pure cervical adenocarcinoma-in-situ (AIS) may have greater risk of recurrence than AIS co-existing with CIN 2/3.

Evaluation of analgesic and anti-inflammatory activity of Bridelia retusa (Spreng) bark.

Several species of Bridelia have been used in the condition of pain & arthritis in Indian folk medicine. Present study revealed the preliminary phytochemical investigation and evaluation of analgesic, anti-inflammatory and anti-arthritic activity as well as underlying mechanism of bark of Bridelia retusa Spreng. (Euphorbiaceae). The bark was subjected to extraction using pet.ether, ethyl acetate and acetone. All the extracts were significantly inhibit abdominal writhings response and licking time in late phase of formalin test. Extracts could also significantly inhibit mean paw edema of rats induced by carrageenan & histamine at dose of 200 & 400 mg/kg, i.p. Test materials also showed significant dose dependent reduction in cotton pellet granuloma & acetic acid induced vascular permeability at 400 mg/kg. Oral administration of B. retusa fractions in CFA induced arthritic rats, physical, biochemical and hematological parameters observed in arthritic animals were altered significantly to near normal condition. The maximum paw edema inhibition at day 21 was observed at 400 mg/kg. It also proved significant protection against protein denaturation & RBC membrane damage. The GC-MS analysis of EA extract revealed the presence of ß-sitosterol, stigmasterol, lupeol and friedelin (Pentacyclic triterpenoid). Therefore present study has demonstrated the analgesic; anti-inflammatory and anti-arthritic activities of B. retusa bark and suggested that the molecular membrane might be associated with inhibition of biochemical and hematological parameters. Overall bioactive profile of B. retusa used phytomedicine in future for inflammatory conditions.

Synergistic effects of coralyne and paclitaxel on cell migration and proliferation of breast cancer cells lines.

Breast cancer is one of the most frequently diagnosed cancer in woman. Triple-negative breast cancer (TNBC) is most aggressive form of breast cancer. There is a growing interest in the use of natural products in combinational chemotherapy to improve the effectiveness in combating proliferation of cancer cells. Here, we hypothesized that coralyne in combination with paclitaxel may exhibit synergistic effect on inhibition of proliferation, migration and induction of apoptosis in MCF-7 and MDA-MB-231 breast cancer cell lines. MTT and BrdU incorporation assays were performed to study the effect of drugs alone and in combination on cell cytotoxicity and proliferation of the breast cancer cell lines, respectively. Adhesion and wound healing assays were performed to study the cell and extracellular matrix interactions. In addition, expression of proliferation marker ki-67 and apoptotic markers Bax and Bcl-2 was determined to study the effect of coralyne in combination with paclitaxel by reverse transcriptase PCR and confirmed by Western blot. The results indicated the synergism between coralyne and paclitaxel on proliferation and migration of breast cancer cell lines. This study also showed that combinational drug treatment decreased the expression of ki-67 and there was an increase in pro apoptotic factor Bax with decreased in expression of anti-apoptotic factor Bcl-2 in breast cancer cell lines with negligible effect on normal breast cell line. Overall, our data described the promising therapeutic potential of coralyne in combination with paclitaxel in treating breast cancer at lower effective dose.

Frontline treatment of epithelial ovarian cancer.

This is a contemporaneous review of the frontline treatment of epithelial ovarian cancer (EOC), specifically on the importance of optimal surgical cytoreductive surgery, the pivotal role of platinum-based adjuvant chemotherapy (which encompasses intraperitoneal and dose-dense regimens) and the emergence of neo-adjuvant chemotherapy. Additionally, the benefit of concurrent and maintenance bevacizumab in the suboptimally debullked stage III and stage IV EOC setting is also reviewed. The article also discusses the increasing importance of prognostic and predictive molecular biomarkers in the future management of EOC.

Foamy gland changes in gastric-type endocervical neoplasia.

Foamy gland (FG) change is a distinctive morphological alteration most widely recognised in adenocarcinomas of the prostate and pancreas, and characterised by cells showing prominent cytoplasmic microvacuolation often with deceptively bland nuclear appearances. To our knowledge, FG alteration has not been described in endocervical neoplasia. We report four patients with gastric-type endocervical neoplasms (3 invasive and 1 in situ) in which FG change was present in 30-80% of the tumour cells. The mean age was 56.5 years (range 45-66 years) and three patients, one of whom also had post-coital bleeding, had atypical glandular cells detected on cervical cytology. Three cases showed a pure gastric phenotype and benign gastric-type changes including pyloric metaplasia, tunnel clusters and/or lobular endocervical glandular hyperplasia were also present. These cases were MUC6 positive and p16 negative on immunohistochemistry while HPV was not detected. One adenocarcinoma showed a mixed histological pattern including usual-type endocervical carcinoma and gastric-type adenocarcinoma: only the latter component expressed MUC6 and this case was p16 and HPV18 positive. This report expands the morphological spectrum exhibited by gastric-type endocervical lesions and the range of anatomical sites in which neoplasms with FG features may be encountered.

Antibodies to group A streptococcal virulence factors, SIC and DRS, increase predilection to GAS pyoderma.

BACKGROUND: Streptococcus pyogenes (group A streptococcus; GAS) is an etiological agent for pharyngitis, pyoderma, and invasive infections in humans. Pharyngitis and pyoderma may lead to serious immune sequelae such as rheumatic heart disease and post-streptococcal glomerulonephritis (PSGN). Streptococcal Inhibitor of Complement (SIC) and its orthologue, distantly related to SIC (DRS), are virulence factors expressed by only four of more than 100 M types of GAS. These four types (M1, M57, M12 and M55) are among the M types, which are associated with PSGN. In several populations PSGN has been shown to be a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). Previous studies showed SIC or DRS antibody-prevalence was associated with PSGN, and seroprevalence of SIC antibodies is significantly high among CKD and ESRD patients in Mumbai. METHODS: Streptococcal isolates recovered from GAS pyoderma cases were typed. Seropositivity for SIC and DRS antibodies in subjects with pyoderma, PSGN pediatric cases, age matched healthy controls and non-GAS pyoderma cases were determined. RESULTS: We confirm in this study an association between seroprevalence to SIC and DRS antibodies, and PSGN in Mumbai population despite low point prevalence of M1, M12, M55 and M57. In addition we extended the study to GAS-pyoderma and non-GAS pyoderma cases. To our surprise, we found a positive association between the seroprevalence to SIC and DRS antibodies, and GAS-pyoderma owing to infection with diverse M types. The mechanism of increased predisposition to pyoderma owing to infection by diverse GAS among SIC or DRS antibody-positive population is not clear. Nonetheless, our findings could be explained by a phenomenon akin to antibody-dependent enhancement (ADE). CONCLUSIONS: This is the first report showing a small number of GAS M types conferring predisposition to pyoderma by diverse types. Implications of this ADE-like phenomenon are discussed in the light of evolutionary advantage to GAS, vaccine design and control of renal diseases.

Olfactory cues increase avoidance behavior and induce Fos expression in the amygdala, hippocampus and prefrontal cortex of socially defeated mice.

Genes and proteins of the Fos family are used as markers of neuronal activity and can be modulated by stress. This study investigated whether social defeat (SD) or exposure to an olfactory cue associated with the SD experience activated Fos and FosB/DeltaFosB (ΔFosB) expression in brain regions implicated in the development of post-traumatic stress disorder. Mice exposed to acute SD showed more Fos positive cells in the basolateral amygdala (BLA), CA1 of the hippocampus and the medial prefrontal cortex (mPFC) 1h after SD, and had greater expression of the more persistent FosB/ΔFosB protein in the BLA 24 h after SD compared to controls. Mice exposed to an olfactory cue 24 h or 7 days after SD had higher levels of Fos expression in all three regions 1h after exposure to the cue, and displayed increased avoidance behavior compared to controls. While the avoidance response dissipated with time (less at 7 day vs 24 h after social defeat), Fos expression in the mPFC and CA1 in response to an olfactory cue was greater at 7 days relative to 24 h after social defeat. The results suggest additional processing of the cue-stress association and may provide further support for a role of the mPFC in fear inhibition. These findings may have implications for brain regions and circuitry involved in the avoidance of cues associated with a stressful event that may lead to context-dependent adaptive or maladaptive behavior.

Pre-emptive, early, and delayed alendronate treatment in a rat model of knee osteoarthritis: effect on subchondral trabecular bone microarchitecture and cartilage degradation of the tibia, bone/cartilage turnover, and joint discomfort.

OBJECTIVE: Bisphosphonates are considered potential disease modifying osteoarthritis (OA) agents. The present study investigated the efficacy of pre-emptive, early, and delayed alendronate (ALN) treatment initiation on subchondral trabecular bone and cartilage in low-dose monosodium iodoacetate (MIA)-induced knee OA in rats. METHODS: Male rats received pre-emptive (n = 12, day 0-end of week 2), early (n = 12, end of week 2-end of week 6), or delayed (n = 12, end of week 6-end of week 10) ALN treatment (30 µg/kg/week). Pre-emptive ALN-treated rats were scanned using in vivo micro-computed tomography (micro-CT) after 2 weeks and then sacrificed, early ALN-treated rats were scanned after 2 and 6 weeks and sacrificed, and the delayed ALN-treated rats were scanned after 2, 6, and 10 weeks of OA induction and sacrificed. After sacrifice, bone histomorphometry and histology of the tibia and biomarker analyses were undertaken. Changes in hind limb weight-bearing were assessed from day -1 until day 14. RESULTS: MIA-induced pathological features similar to progressive human OA in the cartilage and subchondral bone. Pre-emptive ALN treatment preserved subchondral trabecular bone microarchitecture, prevented bone loss, decreased bone turnover and joint discomfort. Pre-emptive ALN treatment had moderate effects on cartilage degradation. Early and delayed ALN treatments prevented loss of trabeculae and decreased bone turnover, but had no significant effect on cartilage degradation. CONCLUSION: ALN prevented increased bone turnover and preserved the structural integrity of subchondral bone in experimental OA. The time point of treatment initiation is crucial for treating OA. Treating both the subchondral bone and cartilage in OA would be clinically more beneficial.

Ten-core versus 16-core transrectal ultrasonography guided prostate biopsy for detection of prostatic carcinoma: a prospective comparative study in Indian population.

PURPOSE: To compare the cancer detection rate in patients with raised serum prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE) results between the 10-core and the 16-core biopsy techniques in an Indian population. METHODS: Between November 2010 and November 2012, 95 men aged >50 years who presented to the Urology Department with lower urinary tract symptoms, elevated serum PSA, and/or abnormal DRE findings underwent transrectal ultrasonography (TRUS)-guided prostate biopsy. A total of 53 patients underwent 10-core biopsy and 42 patients underwent 16-core biopsy. RESULTS: Of the 53 men in the 10-core group, 8 had cancer, whereas in the 16-core biopsy group, 23 of 42 men had cancer. Detection of prostate cancer was significantly higher in patients who underwent 16-core biopsy than in those who underwent 10-core biopsy (P<0.001). Among the 95 men, 44 men had abnormal DRE findings (46.3%), of whom 23 showed cancer (52.27%). Of 51 men with normal DRE findings and elevated PSA, 8 men had malignancy with a cancer detection rate of 15.68%. Among 20 men with PSA between 4.1 and 10 ng/mL, 2 (10%) had cancer. In 31 men with PSA between 10.1 and 20 ng/mL, 3 cancers (9.67%) were detected, and in 44 men with PSA >20 ng/mL, 26 cancers were detected (59.09%). CONCLUSIONS: The cancer detection rate with 16-core TRUS-guided biopsy is significantly higher than that with 10-core biopsy (54.76% vs. 15.09%, P<0.001). In patients with both normal and abnormal DRE findings, 16-core biopsy has a better detection rate than the 10-core biopsy protocol. With increasing PSA, there is a high rate of detection of prostate cancer in both 10-core and 16-core biopsy patients.