Predictors of Locoregional Recurrence in Oral Squamous Cell Carcinoma

Introduction: Lip and oral cavity cancer is the third and fifth most frequent cancer for men & women respectively in Bangladesh. Locoregional recurrence after primary surgery is common for oral cancer due to aggressive local invasion and metastasis. The objective of this study was to analyze the predictors of locoregional failure in a tertiary center hospital. Materials and Methods: A prospective cohort study was designed to analyze the presence of recurrences of OSCC patients after surgery. The purposive sampling technique was used to include patients in the study. Excision of the primary tumor was done with neck dissection followed by reconstruction with local or regional flap. The variables considered were demographic information, site, TNM stage at diagnosis, margin status, lymph node metastasis, perineural invasion, recurrence, and the adjuvant therapy used for disease control. Patients were followed up by hospital revisits or phone calls and necessary information was collected through a standardized data collection sheet. Results: A total of 39 patients were included for data analysis. The male to female ratio was 1:2 and the most common primary site was mandibular alveolar mucosa (31%). Nearly 90% of patients were admitted with stage ׀׀׀ or ׀ᴠ lesions and tumor margin was positive in 21% of cases. Lymph node metastasis and perineural invasion were identified in 64% and 23% of cases respectively. Recurrence developed in 14 patients (36%) during the average follow-up of 13 months. Recurrences were more common in females (42%) and Postoperative histopathology showed a positive margin, perineural invasion, and N3 neck node. Univariate logistic regression analysis for locoregional recurrence showed no significant association between the variables and recurrence. Patients with clinically palpable lymph node, grade 2 lesion, presence of perineural invasion, presence of co-morbidity, patients who did not receive any adjuvant therapy, and patients who had metastatic neck node showed an increased odds ratio (OR>1). Conclusion: The clinicopathologic and treatment-related factors of recurrence in OSCC were explored in this study. Although no significant association was identified between the variables and recurrence of lesions, a high recurrence rate was observed in a shorter span of the follow-up period

Large-Scale Social and Behavior Change Communication Interventions Have Sustained Impacts on Infant and Young Child Feeding Knowledge and Practices: Results of a 2-Year Follow-up Study in Bangladesh

Background: Sustained improvements in infant and young child feeding (IYCF) require continued implementation of effective interventions. From 2010-2014, Alive & Thrive (A&T) provided intensive interpersonal counseling (IPC), community mobilization (CM), and mass media (MM) in Bangladesh, demonstrating impact on IYCF practices. Since 2014, implementation has been continued and scaled up by national partners with support from other donors and with modifications such as added focus on maternal nutrition and reduced program intensity. Objective: We assessed changes in intervention exposure and IYCF knowledge and practices in the intensive (IPC + CM + MM) compared with nonintensive areas (standard nutrition counseling + less intensive CM and MM) 2 y after termination of initial external donor support. Methods: We used a cluster-randomized design with repeated cross-sectional surveys at baseline (2010, n = 2188), endline (2014, n = 2001), and follow-up (2016, n = 2400) in the same communities, among households with children 0-23.9 mo of age. Within-group differences over time and differences between groups in changes were tested. Results: In intensive areas, exposure to IPC decreased slightly between endline and follow-up (88.9% to 77.2%); exposure to CM activities decreased significantly (29.3% to 3.6%); and MM exposure was mostly unchanged (28.1-69.1% across 7 TV spots). Exposure to interventions did not expand in nonintensive areas. Most IYCF indicators in intensive areas declined from endline to follow-up, but remained higher than at baseline. Large differential improvements of 12-17 percentage points in intensive, compared with nonintensive areas, between baseline and follow-up remained for early initiation of and exclusive breastfeeding, timely introduction of foods, and consumption of iron-rich foods. Differential impact in breastfeeding knowledge remained between baseline and follow-up; complementary feeding knowledge increased similarly in both groups. Conclusions: Continued IPC exposure and sustained impacts on IYCF knowledge and practices in intensive areas indicated lasting benefits from A&T\u27s interventions as they underwent major scale-up with reduced intensity. This trial was registered at clinicaltrials.gov as NCT02740842

Integrating Nutrition Interventions Into an Existing Maternal, Neonatal, and Child Health Program Increased Maternal Dietary Diversity, Micronutrient Intake, and Exclusive Breastfeeding Practices in Bangladesh: Results of a Cluster-Randomized Program Evaluation

Maternal undernutrition is a major concern globally, contributing to poor birth outcomes. Limited evidence exists on delivering multiple interventions for maternal nutrition simultaneously. Alive & Thrive addressed this gap by integrating nutrition-focused interpersonal counseling, community mobilization, distribution of free micronutrient supplements, and weight-gain monitoring through an existing Maternal, Neonatal, and Child Health (MNCH) program in Bangladesh. We evaluated the effect of providing nutrition-focused MNCH compared with standard MNCH (antenatal care with standard nutrition counseling) on coverage of nutrition interventions, maternal dietary diversity, micronutrient supplement intake, and early breastfeeding practices. We used a cluster-randomized design with cross-sectional surveys at baseline (2015) and endline (2016) ( ∼ 300 and 1000 pregnant or recently delivered women, respectively, per survey round). We derived difference-in-difference effect estimates, adjusted for geographic clustering and infant age and sex. Coverage of interpersonal counseling was high; \u3e90% of women in the nutrition-focused MNCH group were visited at home by health workers for maternal nutrition and breastfeeding counseling. The coverage of community mobilization activities was ∼50%. Improvements were significantly greater in the nutrition-focused MNCH group than in the standard MNCH group for consumption of iron and folic acid [effect: 9.8 percentage points (pp); 46 tablets] and calcium supplements (effect: 12.8 pp; 50 tablets). Significant impacts were observed for the number of food groups consumed (effect: 1.6 food groups), percentage of women who consumed ≥5 food groups/d (effect: 30.0 pp), and daily intakes of several micronutrients. A significant impact was also observed for exclusive breastfeeding (EBF; effect: 31 pp) but not for early initiation of breastfeeding. Addressing nutrition during pregnancy by delivering interpersonal counseling and community mobilization, providing free supplements, and ensuring weight-gain monitoring through an existing MNCH program improved maternal dietary diversity, micronutrient supplement consumption, and EBF practices. This trial was registered at clinicaltrials.gov as NCT02745249

LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures

Effect of Non-linear Co-efficient of a hexagonal PCF depending on effective area

A photonic crystal fiber (PCF) is an optical fiber that gets the waveguide characteristics from an array of very small and tightly separated air holes that run the length of the fiber rather than from a spatially changing glass structure. These air holes can be created by stacking capillary and/or solid tubes and implanting those into a bigger tube, or even by utilizing a preform containing holes. PCFs have a wide range of characteristics. One of these is the non-linear co-efficient. This property is influenced by factors such as effective area, pitch size, and so on. The overall goal of this study is to develop and improve the optical characteristics of PCFs and to design a hexagonal PCF for wideband near-zero dispersion-flattened features for dispersion managed applications. The non-linear co-efficient of the hexagonal PCF with respect to effective area is also calculated here

Integrating Nutrition Interventions into an Existing Maternal, Neonatal, and Child Health Program Increased Maternal Dietary Diversity, Micronutrient Intake, and Exclusive Breastfeeding Practices in Bangladesh: Results of a Cluster-Randomized Program Evaluation

Maternal undernutrition is a major concern globally, contributing to poor birth outcomes. Limited evidence exists on delivering multiple interventions for maternal nutrition simultaneously. Alive & Thrive addressed this gap by integrating nutrition-focused interpersonal counseling, community mobilization, distribution of free micronutrient supplements, and weight-gain monitoring through an existing Maternal, Neonatal, and Child Health (MNCH) program in Bangladesh. We evaluated the effect of providing nutrition-focused MNCH compared with standard MNCH (antenatal care with standard nutrition counseling) on coverage of nutrition interventions, maternal dietary diversity, micronutrient supplement intake, and early breastfeeding practices. We used a cluster-randomized design with cross-sectional surveys at baseline (2015) and endline (2016) ( ∼ 300 and 1000 pregnant or recently delivered women, respectively, per survey round). We derived difference-in-difference effect estimates, adjusted for geographic clustering and infant age and sex. Coverage of interpersonal counseling was high; \u3e90% of women in the nutrition-focused MNCH group were visited at home by health workers for maternal nutrition and breastfeeding counseling. The coverage of community mobilization activities was ∼50%. Improvements were significantly greater in the nutrition-focused MNCH group than in the standard MNCH group for consumption of iron and folic acid [effect: 9.8 percentage points (pp); 46 tablets] and calcium supplements (effect: 12.8 pp; 50 tablets). Significant impacts were observed for the number of food groups consumed (effect: 1.6 food groups), percentage of women who consumed ≥5 food groups/d (effect: 30.0 pp), and daily intakes of several micronutrients. A significant impact was also observed for exclusive breastfeeding (EBF; effect: 31 pp) but not for early initiation of breastfeeding. Addressing nutrition during pregnancy by delivering interpersonal counseling and community mobilization, providing free supplements, and ensuring weight-gain monitoring through an existing MNCH program improved maternal dietary diversity, micronutrient supplement consumption, and EBF practices. This trial was registered at clinicaltrials.gov as NCT02745249

Distinct and Atypical Intrinsic and Extrinsic Cell Death Pathways between Photoreceptor Cell Types upon Specific Ablation of <i>Ranbp2</i> in Cone Photoreceptors

<div><p>Non-autonomous cell-death is a cardinal feature of the disintegration of neural networks in neurodegenerative diseases, but the molecular bases of this process are poorly understood. The neural retina comprises a mosaic of rod and cone photoreceptors. Cone and rod photoreceptors degenerate upon rod-specific expression of heterogeneous mutations in functionally distinct genes, whereas cone-specific mutations are thought to cause only cone demise. Here we show that conditional ablation in cone photoreceptors of <i>Ran-binding protein-2</i> (<i>Ranbp2</i>), a cell context-dependent pleiotropic protein linked to neuroprotection, familial necrotic encephalopathies, acute transverse myelitis and tumor-suppression, promotes early electrophysiological deficits, subcellular erosive destruction and non-apoptotic death of cones, whereas rod photoreceptors undergo cone-dependent non-autonomous apoptosis. Cone-specific <i>Ranbp2</i> ablation causes the temporal activation of a cone-intrinsic molecular cascade highlighted by the early activation of metalloproteinase 11/stromelysin-3 and up-regulation of <i>Crx</i> and <i>CoREST</i>, followed by the down-modulation of cone-specific phototransduction genes, transient up-regulation of regulatory/survival genes and activation of caspase-7 without apoptosis. Conversely, PARP1⁺-apoptotic rods develop upon sequential activation of caspase-9 and caspase-3 and loss of membrane permeability. Rod photoreceptor demise ceases upon cone degeneration. These findings reveal novel roles of <i>Ranbp2</i> in the modulation of intrinsic and extrinsic cell death mechanisms and pathways. They also unveil a novel spatiotemporal paradigm of progression of neurodegeneration upon cell-specific genetic damage whereby a cone to rod non-autonomous death pathway with intrinsically distinct cell-type death manifestations is triggered by cell-specific loss of <i>Ranbp2</i>. Finally, this study casts new light onto cell-death mechanisms that may be shared by human dystrophies with distinct retinal spatial signatures as well as with other etiologically distinct neurodegenerative disorders.</p></div

Temporal and morphological profile of degeneration of cone photoreceptors in <i>Ranbp2^−/−</i> mice.

<p>(<b>A–H</b>′″) Immunohistochemistry of retinal sections of <i>HRGP-cre:Ranbp2^+/−</i> (<i>Ranbp2^+/−</i>) and <i>HRGP-cre:Ranbp2^−/−</i> (<i>Ranbp2^−/−</i>) mice at P9 (<b>A–B</b>′″), P13 (<b>C–D</b>′″) P20 (<b>E–F</b>′″) and P27 (<b>G–H</b>′″) of age with the antibodies against Cre recombinase and cone arrestin (Arr4) showing rapid loss of cone photoreceptors in <i>RanBP2^−/−</i>. Cre co-localized with Arr4 only in DAPI-stained cell bodies of cone cells throughout all ages regardless of genotype. Arrowheads in indicate Cre⁺ nuclei retracted to the proximal ONL (outer nuclear layer) in <i>Ranbp2^−/−</i> at P13, P20 and P27 of age, respectively. Arrows point to prominent swellings of synaptic pedicles of cone photoreceptors in <i>Ranbp2^−/−</i> at P20 of age. Scale bars = 25 µm.</p

Cre-mediated ablation of <i>Ranbp2</i> selectively in cone photoreceptors.

<p>(<b>A</b>) Schematic diagram for targeted <i>Ranbp2</i> allele upon HGRP-driven Cre excision of exon 2 and production of the recombinant mRNA of <i>Ranbp2.</i> Pr1 and Pr2 are specific to fused exons 1 and 3, and exon 5, respectively, and were used to monitor the functional excision of <i>Ranbp2^Flox</i> allele. (<b>B</b>) Schematic diagram of a constitutively targeted <i>Ranbp2</i> allele upon insertion of a promoterless bicistronic (β-geo-PLAP) cassette with a splicing acceptor site (SA) between exons 1 and 2. (<b>C</b>) RT-PCR of recombinant <i>Ranbp2</i> mRNA without exon 2 using Pr1 and Pr2 primers. Excision of exon 2 (<b><i>Δ</i></b>E2) was detectable in <i>HRGP-cre:Ranbp2^−/−</i> (−/−) but not wild-type (+/+) mice at P7 of age, a day after expression of <i>Cre</i> recombinase. (<b>D</b>) Co-expression (a″″–c″″) of Arr4 (a′), M-opsin (b′), S-opsin (c′), Cre (a″–c″) and PNA (a′″–c′″) in cone photoreceptor neurons of the superior (dorsal, a–b″″) or inferior (ventral, c–c″″) regions of the retina of <i>HRGP-cre:Ranbp2^+/−</i> mice at P15. Sections were counterstained with DAPI (a–c). Legends: HGRP, L/M opsin promoter; Arr4, cone arrestin 4; PNA, Peanut Agglutinin. Scale bars = 25 µm.</p

Temporal profiles of changes in gene expression by ablation of <i>Ranbp2</i> in cone photoreceptors.

<p>(<b>A–G</b>) qRT-PCR of cone-specific (<b>A, B</b>), pan-photoreceptor (<b>C</b>), cone survival (<b>D</b>) and cone transcription factors (<b>E</b>), <i>col6α3</i> and <i>col1α1</i> (<b>F</b>), and <i>Gfap</i> and <i>Hif1α</i> transcripts (<b>G</b>). There is a decrease of cone-specific transcripts beginning at P13 (<b>A, B</b>), whereas pan-photoreceptor (<b>C</b>) and cone survival genes (<b>D</b>) begin transient up-regulations at the same age. The expression of cone survival genes peaks at P20 (<b>D</b>). (<b>E</b>) The transcription factors, <i>Crx</i> and <i>CoREST</i> (<i>Rcor1</i>), are the first nuclear factors whose changes of their transcriptional levels coincides with the genetic ablation of <i>Ranbp2</i> at P7. These events are followed by the up-regulations at P20 of the transcription factors, <i>Nrp1</i>, <i>Trß2</i> and <i>Otx2</i> (<b>E</b>). The up-regulations of transcripts encoding the substrate of MMP11, <i>col6α3</i>, begins at P9 and peaks at P20 (<b>F</b>), whereas those for the hypoxia marker, <i>Hif1α</i>, and inflammatory marker, <i>Gfap</i>, begin at P9 and P20, respectively (<b>G</b>). Legends: Data shown represent the mean ± SD, <i>n = </i>3–4; *, <i>p</i><0.05; **, <i>p</i><0.01; ***, <i>p</i><0.001; refer to table S1 for gene designations/symbols.</p