Surgical outcomes of total duct excision in the diagnosis and management of nipple discharge.

INTRODUCTION: Total duct excision (TDE) is performed for the diagnosis and management of nipple discharge. The Association of Breast Surgery's recent guidelines recommend considering diagnostic surgery for single-duct, blood-stained or clear nipple discharge, and for symptomatic management. METHODS: We retrospectively reviewed the diagnostic and surgical outcomes of all cases of TDE between January 2013 and November 2019. RESULTS: In total, 259 TDEs were carried out: 219 for nipple discharge, 29 for recurrent mastitis, 3 for screening abnormalities and 8 for breast lumps. Of the nipple discharge group, 121 had blood-stained discharge. Mean patient age was 52 years (range 19-81). Median follow-up time was 45 months (interquartile range 24-63). The following cases were identified on histopathology: 236 benign breast changes, 10 atypical ductal hyperplasia, 4 lobular carcinoma in situ, 2 low-grade ductal carcinoma in situ (DCIS), 3 intermediate-grade DCIS, 2 high-grade DCIS and 2 invasive ductal carcinomas. In total, 3.5% of patients who underwent TDE had a diagnosis of DCIS or invasive carcinoma. Blood-stained discharge was associated with a significant increase in risk of DCIS or carcinoma compared with other nipple discharge colours (p = 0.043). The most common complications of TDE were infection, poor wound healing and haematoma. Nipple discharge recurred in 14.2% of cases. CONCLUSIONS: TDE can be considered for the diagnostics and management of nipple discharge. Blood-stained nipple discharge increases the risk of DCIS or malignancy, but the majority of the time TDE reveals benign breast pathology.

Optimizing Sex Ratios of Hyalella azteca to Reduce Variability in Reproduction and Improve Reproductive Toxicity Test Methods.

Standard toxicological test methods with Hyalella azteca incorporate both lethal and sublethal (growth, reproduction) endpoints, although lethal endpoints are often favored in routine testing. However, sublethal endpoints are important to consider because they are ecologically relevant and are often more sensitive than lethality. It is difficult to achieve robust data for reproduction in H. azteca because high biological variability is associated with reproductive yield, likely due to complex interactions in mate selection, which can add to the variability in brood sizes that females produce. In addition, effects on reproduction often co-occur with effects on growth, making it difficult to differentiate effects on growth from those on reproduction in standard tests initiated with juveniles. The present study characterized the reproductive capacity of H. azteca by investigating the role of sex ratios in reproductive yield. Experiments were initiated in the absence of toxicants with sexually mature (6-8-week-old) individuals that were placed in different female-to-male ratios (1:1, 2:3, 3:2, and 7:3). Reproduction was monitored during weekly static renewals for 7 weeks. The results indicated that a higher female:male ratio (seven females to three males) improved reproductive success and lowered biological variability in reproduction. In addition, the body lengths and weights of newly mature amphipods were used to create a size distribution to aid in the identification of small female amphipods. Based on the results of our study, a novel reproductive toxicity test method is proposed that begins with sexually mature amphipods in a ratio of seven females to three males to minimize reproductive variability in amphipods and to enable a more effective assessment of contaminants using reproduction as a highly sensitive endpoint. However, evaluation of this novel method with toxicants is needed to demonstrate that results are comparable to standard methods. Environ Toxicol Chem 2024;43:712-722. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model

Abstract Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

Resumo A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.

Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model / Potencial terapêutico de células-tronco e melatonina na redução da fibrose hepática induzida por CCl4 no modelo de ratos experimentais

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados ​​como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.

Brolucizumab after failure of aflibercept with photodynamic therapy in polypoidal choroidal vasculopathy: A case report.

We describe one case of polypoidal choroidal vasculopathy with persistent subretinal fluid despite multiple treatment with intravitreal Bevacizumab, Ranibizumab and Aflibercept, as well as Aflibercept associated with photodynamic therapy. The patient reached complete resolution after intravitreal Brolucizumab injection, but experienced recurrence of subretinal fluid 12 weeks after discontinuation. Brolucizumab might be an option in treating subretinal fluid after failure of other anti-VEGF agents associated with photodynamic therapy.

Correlation of Transient Elastography with Liver Iron Concentration and Serum Ferritin Levels in Patients with Transfusion-Dependent Thalassemia Major from Oman.

Aims: In a longitudinal study, we aimed to assess the correlation between ultrasound transient elastography (TE), serum ferritin (SF), liver iron content (LIC) by magnetic resonance imaging (MRI) T2* along with the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis among chronically transfusion-dependent beta-thalassemia (TDT) patients. Methods: The study was conducted at a tertiary health center treating TDT patients. Transient elastography was performed within 3 months of Liver MRI T2* examinations at the radiology department over a median of one-year duration. T-test for independent data or Mann-Whitney U test was used to analyze group differences. Spearman correlation with linear regression analysis was used to evaluate the correlation between TE liver stiffness measurements, Liver MRI T2* values, and SF levels. Results: In this study on 91 patients, the median age (IQR) of the subjects was 33 (9) years, and the median (IQR) body mass index was 23.8 (6.1) kg/m2. Median (IQR) TE by fibroscan, MRI T2*(3T), Liver iron concentration (LIC) by MRI Liver T2*, and SF levels were 6.38 (2.6) kPa, 32.4 (18) milliseconds, 7(9) g/dry wt., and 1881 (2969) ng/mL, respectively. TE measurements correlated with LIC g/dry wt. (rS =0.39, p=0.0001) and with SF level (rS =0.43, P=0.001) but not with MRI T2* values (rS =-0.24; P=0.98). Conclusion: In TDT patients, liver stiffness measured as TE decreased significantly with improved iron overload measured as LIC by MRI and SF levels. However, there was no correlation of TE with the fibrosis-4 (FIB-4) score.

Post-COVID-19 vaccine uveitis: A case series.

OBJECTIVE: With the recent emergence and worldwide distribution of COVID-19 vaccines, many side effects may be underreported and possibly unknown. Cases of vaccine-associated uveitis have been linked to almost all vaccines administered in the past; however, there is scarcity of literature providing insight into post-COVID-19 vaccine-associated uveitis. This case series documents patients presenting with uveitis after administration of the Pfizer and Moderna mRNA vaccines, in hope of advancing our current understanding of potential ocular complications of COVID-19 vaccines. METHODS: Patients with ocular symptoms consistent with uveitis within 14 days after administration of the Pfizer or Moderna COVID-19 vaccines were included in this case series. RESULTS: Eight patients with a mean age of 44.4 years (range, 19-83) were included. Six patients received a Pfizer, and 2 received a Moderna vaccine. Four patients presented after their first dose, 3 after their second dose, and 1 after both doses. The mean onset of ocular symptoms after the vaccine was 5.19 days (range, 1-14), and the mean BCVA was 0.678. Patients were diagnosed with bilateral anterior granulomatous uveitis (case 1), unilateral non-granulomatous anterior uveitis (case 2, 5-8), and bilateral non-granulomatous anterior uveitis (case 3-4). CONCLUSIONS: The pathogenesis of vaccine-induced uveitis is not properly understood; however, the outcomes of this case series will aid in establishing a temporal association between the Pfizer and Moderna COVID-19 vaccines and the onset of uveitis. As the rate of COVID-19 vaccinations increases globally, it is imperative for physicians to be aware of the possible association and presentation of these ocular findings and diagnoses in order to treat patients effectively.

Culturally adapted psychosocial interventions (CaPSI) for early psychosis in a low-resource setting: study protocol for a large multi-center RCT.

BACKGROUND: Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan. METHOD: A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety). CONCLUSIONS: A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP. TRIAL REGISTRATION: NCT05814913.

Achieving optimal clinical outcomes in autologous fat grafting: A systematic review of processing techniques.

BACKGROUND: Autologous fat grafting (AFG) is a versatile technique in reconstructive and cosmetic surgery. Graft processing is a key source of variability resulting in unreliable clinical outcomes, with no consensus on the optimal methodology. This systematic review identifies the evidence base supporting different processing paradigms. METHODS: A systematic literature search was conducted using the PubMed, Scopus and The Cochrane Foundation databases. Studies comparing AFG processing methods and reporting long-term patient outcomes were identified. RESULTS: Twenty-four studies (2413 patients) were identified. Processing techniques evaluated included centrifugation, decantation, washing, filtration, gauze rolling, as well as commercial devices and adipose-derived stem/stromal cell (ASC) enrichment methods. Objective volumetric and subjective patient-reported outcomes were discussed. There was a variable reporting of complications and volume retention rates. Complications were infrequent; palpable cysts (0-20%), surgical-site infections (0-8%) and fat necrosis (0-58.4%) were the most reported. No significant differences in long-term volume retention between techniques were found in AFG in the breast. In head and neck patients, greater volume retention was documented in ASC enrichment (64.8-95%) and commercial devices (41.2%) compared to centrifugation (31.8-76%). CONCLUSIONS: Graft processing through washing and filtration, including when incorporated into commercial devices, results in superior long-term outcomes compared to centrifugation and decantation methods. ASC enrichment methods and commercial devices seem to have superior long-term volume retention in facial fat grafting.

Paediatric tibial shaft fractures: an instructional review for the FRCS exam.

This instructional review presents the literature and guidelines relevant to the classification, management and prognosis of paediatric tibial shaft fractures at a level appropriate for the FRCS exit examination in Trauma and Orthopaedic surgery.

Analysis of perceived risk and satisfaction with telematic follow-up in patients and families of congenital diaphragmatic hernia patients during SARS-CoV-2 pandemia.

BACKGROUND: The impact of COVID-19 in families and patients with congenital diaphragmatic hernia (CDH) is unknown, this situation has generated uncertainty not only in family members but also in the optimal outpatient follow-up. Telehealth has become a fundamental tool for the follow-up during the pandemic. The objective of this survey is to evaluated the impact of SARS-CoV-2 in families and patients with CDH and the satisfaction with telematic follow-up. METHODS: Telephone survey of patient's caregivers with CHD, aged 1-16 years, followed in neonatal surgery outpatients, from January 31, 2020 to November 15, 2020. The ethical clearance for this study was taken from the Clinical Research Ethics Committee of our Research Institute vide letter number VHIR/239283/01.01.2021. RESULTS: 81 surveys of 100 patients with active follow-up were carried out. There were no refusals in any contacted parents. There were 30 contacts (37%), 44.8% at school and 27.6% from cohabiting family members. Four infections (4.9%) were diagnosed, half symptomatic. In 40 patients (49.4%) the follow-up was telematic, with a mean score of 3.1±1.3 out of 5. For future controls, 65% prefer presential follow-up, 25% alternate and 10% telematics. 50.6% reported greater anxiety and 34.6% (28/81) extreme measures of isolation, being more accentuated in the group of 3-6 years (p<0.05). CONCLUSION: The impact of COVID19 in patients with CHD is not greater than in the general pediatric population. Although the incorporation of the telehealth was well valued, most of the caregivers prefer the face-to-face outpatient follow-up.

Effects of selenium supplementation on the growth performance, slaughter characteristics, and blood biochemistry of naked neck chicken.

This study examined how selenium-supplemented diets affected the performance of naked neck chickens. The birds were fed both organic and inorganic selenium at 0.30 ppm, while the control diet did not include any additional selenium. A total of 225 one-day-old naked neck chicks were randomly divided into 3 experimental groups, each of which was replicated 5 times (replicates) and contained 15 birds. This was done using a completely randomized design. The data was collected after growth, meat quality, and blood profile parameters were assessed. The findings showed that the birds fed inorganic selenium in the diet displayed increased (P < 0.05) feed intake followed by those administered organic selenium and the control diet. On the other hand, birds fed organic selenium in the diet showed enhanced body weight gain and better feed conversion ratio (P < 0.05). Similarly, organic selenium supplementation increased (P < 0.05) breast and thigh weight compared to inorganic selenium, but no other metrics, such as dressing percentage, drumstick weight, liver weight, gizzard weight, heart weight, or wing weight, significantly differed between treatments (P > 0.05). When compared to birds fed inorganic Se and control diet, the birds fed organic Se had greater (P < 0.05) blood levels of total protein and globulin. Additionally, it was discovered that organic Se-fed birds had greater (P < 0.05) blood Se concentrations than control and inorganic Se-fed birds. However, no differences between treatments were found in albumin, glucose, cholesterol, triglycerides, or uric acid (P > 0.05). In conclusion, adding Se-enriched yeast, as an organic selenium source, to diets may enhance the poor growth and slaughter characteristics of naked neck chicks without negatively affecting blood chemistry.

Paediatric distal radius fractures: an instructional review for the FRCS examination.

An instructional review of the literature and guidelines relevant for the classification, management and prognosis of paediatric distal radius fractures. Aimed at the knowledge level required for the trauma and orthopaedic FRCS examination.

The dynamics of genome size and GC contents evolution in genus Nicotiana / A dinâmica do tamanho do genoma e a evolução dos conteúdos de GC no gênero Nicotiana

Hybridization and Polyploidization are most common of the phenomenon observed in plants, especially in the genus Nicotiana leading to the duplication of genome. Although genomic changes associated with these events has been studied at various levels but the genome size and GC content variation is less understood because of absence of sufficient genomic data. In this study the flow cytometry technique was used to uncover the genome size and GC contents of 46 Nicotiana species and we compared the genomic changes associated with the hybridization events along evolutionary time scale. The genome size among Nicotiana species varied between 3.28 pg and 11.88 pg whereas GC contents varied between 37.22% and 51.25%. The tetraploid species in genus Nicotiana including section Polydiclae, Repandae, Nicotiana, Rustica and Sauveolentes revealed both up and downsizing in their genome sizes when compared to the sum of genomes of their ancestral species. The genome sizes of three homoploid hybrids were found near their ancestral species. Loss of large genome sequence was observed in the evolutionary more aged species (>10 Myr) as compared to the recently evolved one’s (<0.2 Myr). The GC contents were found homogenous with a mean difference of 2.46% among the Nicotiana species. It is concluded that genome size change appeared in either direction whereas the GC contents were found more homogenous in genus Nicotiana.

A hibridização e a poliploidização são os fenômenos mais comuns observados em plantas, principalmente no gênero Nicotiana, levando à duplicação do genoma. Embora as mudanças genômicas associadas a esses eventos tenham sido estudadas em vários níveis, o tamanho do genoma e a variação do conteúdo de GC são menos compreendidos devido à ausência de dados genômicos suficientes. Neste estudo, a técnica de citometria de fluxo foi usada para descobrir o tamanho do genoma e o conteúdo de GC de 46 espécies de Nicotiana, e comparamos as mudanças genômicas associadas aos eventos de hibridização ao longo da escala de tempo evolutiva. O tamanho do genoma entre as espécies de Nicotiana variou entre 3,28 pg e 11,88 pg, enquanto os conteúdos de GC variaramentre 37,22% e 51,25%. As espécies tetraploides do gênero Nicotiana, incluindo as seções Polydiclae, Repandae, Nicotiana, Rustica e Sauveolentes, revelaram aumento e redução do tamanho do genoma quando comparados à soma dos genomas de suas espécies ancestrais. Os tamanhos do genoma de três híbridos homoploides foram encontrados perto de suas espécies ancestrais. A perda da grande sequência do genoma foi observada nas espécies evolutivas mais velhas (> 10 Myr) em comparação com as que evoluíram recentemente (< 0,2 Myr). Os teores de GC foram homogêneos com diferença média de 2,46% entre as espécies de Nicotiana. Conclui-se que a mudança no tamanho do genoma apareceu em ambas as direções, enquanto os conteúdos de GC foram encontrados mais homogêneos no gênero Nicotiana.

Traditional knowledge about medicinal plant in the remote areas of Wari Tehsil, Dir Upper, Pakistan

Abstract Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitants age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of RFC, UV, ICF, FL, and JI shows that medicinal flora needs to be pharmacologically and phytochemically investigated to prove their efficacy. The documentation of medicinal knowledge is important to preserve this precious old knowledge before it is lost forever, due to technological and environmental changes in the world.

Resumo A medicina tradicional é mais barata e facilmente disponível à população local para cuidar das doenças mais frequentes nas áreas do norte do Paquistão. Nosso estudo teve como objetivo inventariar medicamentos de plantas locais, documentar seus usos e avaliar seu valor de mercado em 2015-2018 durante as temporadas de primavera, verão e inverno. Foram feitas 15 viagens, 5 em cada temporada. Foram realizadas entrevistas semiestruturadas com 165 moradores na faixa etária de 20 a 80 anos, com dados analisados por meio de frequência relativa de citação (RFC), valor de uso (UV), nível de fidelidade (FL), fator de consenso de informantes (CIF), e o índice de Jaccard (JI) para encontrar as espécies utilizadas mais frequentes e conhecidas na área. Um total de 86 espécies pertencentes a 39 famílias de plantas vasculares, 33 gêneros foram documentados como medicamente importantes. A família Asteraceae foi observada como a família dominante entre todas as famílias com 10 espécies, a folha foi a parte mais utilizada e a decocção 36% foi o tipo de preparação mais preferido. A erva foi a forma de vida predominante (67%). O UV máximo (0,92) foi demonstrado pelas espécies de J. adhatoda L., enquanto A. sativum L. mostra RFC máximo (0,58), o maior valor de ICF representado por diarreia e dermatite 0,92, e alto valor de FL é registrado 100%. De acordo com nossas coleções, as espécies selvagens foram 45%, as espécies invasoras 38% e as cultivadas 17% registradas, as espécies dicotiledôneas foram registradas mais 81%. Sete espécies medicinais estão sendo economicamente importantes e exportadas para o mercado local e internacional do mundo, enquanto as espécies de P. integrima L. foram as espécies mais exportadas de acordo com os comerciantes locais. A área investigada é rural e a população local depende das plantas da área para suas necessidades de saúde e outros usos como vegetal, lenha, forragem etc. O resultado atual de RFC, UV, ICF, FL e JI mostra que a flora medicinal precisa ser investigada farmacológica e fitoquimicamente para comprovar sua eficácia. A documentação do conhecimento medicinal é importante para preservar esse precioso conhecimento antigo antes que se perca para sempre, devido às mudanças tecnológicas e ambientais do mundo.

The dynamics of genome size and GC contents evolution in genus Nicotiana

Abstract Hybridization and Polyploidization are most common of the phenomenon observed in plants, especially in the genus Nicotiana leading to the duplication of genome. Although genomic changes associated with these events has been studied at various levels but the genome size and GC content variation is less understood because of absence of sufficient genomic data. In this study the flow cytometry technique was used to uncover the genome size and GC contents of 46 Nicotiana species and we compared the genomic changes associated with the hybridization events along evolutionary time scale. The genome size among Nicotiana species varied between 3.28 pg and 11.88 pg whereas GC contents varied between 37.22% and 51.25%. The tetraploid species in genus Nicotiana including section Polydiclae, Repandae, Nicotiana, Rustica and Sauveolentes revealed both up and downsizing in their genome sizes when compared to the sum of genomes of their ancestral species. The genome sizes of three homoploid hybrids were found near their ancestral species. Loss of large genome sequence was observed in the evolutionary more aged species (>10 Myr) as compared to the recently evolved ones ( 0.2 Myr). The GC contents were found homogenous with a mean difference of 2.46% among the Nicotiana species. It is concluded that genome size change appeared in either direction whereas the GC contents were found more homogenous in genus Nicotiana.

Resumo A hibridização e a poliploidização são os fenômenos mais comuns observados em plantas, principalmente no gênero Nicotiana, levando à duplicação do genoma. Embora as mudanças genômicas associadas a esses eventos tenham sido estudadas em vários níveis, o tamanho do genoma e a variação do conteúdo de GC são menos compreendidos devido à ausência de dados genômicos suficientes. Neste estudo, a técnica de citometria de fluxo foi usada para descobrir o tamanho do genoma e o conteúdo de GC de 46 espécies de Nicotiana, e comparamos as mudanças genômicas associadas aos eventos de hibridização ao longo da escala de tempo evolutiva. O tamanho do genoma entre as espécies de Nicotiana variou entre 3,28 pg e 11,88 pg, enquanto os conteúdos de GC variaram entre 37,22% e 51,25%. As espécies tetraploides do gênero Nicotiana, incluindo as seções Polydiclae, Repandae, Nicotiana, Rustica e Sauveolentes, revelaram aumento e redução do tamanho do genoma quando comparados à soma dos genomas de suas espécies ancestrais. Os tamanhos do genoma de três híbridos homoploides foram encontrados perto de suas espécies ancestrais. A perda da grande sequência do genoma foi observada nas espécies evolutivas mais velhas (> 10 Myr) em comparação com as que evoluíram recentemente ( 0,2 Myr). Os teores de GC foram homogêneos com diferença média de 2,46% entre as espécies de Nicotiana. Conclui-se que a mudança no tamanho do genoma apareceu em ambas as direções, enquanto os conteúdos de GC foram encontrados mais homogêneos no gênero Nicotiana.

The dynamics of genome size and GC contents evolution in genus Nicotiana / A dinâmica do tamanho do genoma e a evolução dos conteúdos de GC no gênero Nicotiana

Abstract Hybridization and Polyploidization are most common of the phenomenon observed in plants, especially in the genus Nicotiana leading to the duplication of genome. Although genomic changes associated with these events has been studied at various levels but the genome size and GC content variation is less understood because of absence of sufficient genomic data. In this study the flow cytometry technique was used to uncover the genome size and GC contents of 46 Nicotiana species and we compared the genomic changes associated with the hybridization events along evolutionary time scale. The genome size among Nicotiana species varied between 3.28 pg and 11.88 pg whereas GC contents varied between 37.22% and 51.25%. The tetraploid species in genus Nicotiana including section Polydiclae, Repandae, Nicotiana, Rustica and Sauveolentes revealed both up and downsizing in their genome sizes when compared to the sum of genomes of their ancestral species. The genome sizes of three homoploid hybrids were found near their ancestral species. Loss of large genome sequence was observed in the evolutionary more aged species (>10 Myr) as compared to the recently evolved one's (<0.2 Myr). The GC contents were found homogenous with a mean difference of 2.46% among the Nicotiana species. It is concluded that genome size change appeared in either direction whereas the GC contents were found more homogenous in genus Nicotiana.

Resumo A hibridização e a poliploidização são os fenômenos mais comuns observados em plantas, principalmente no gênero Nicotiana, levando à duplicação do genoma. Embora as mudanças genômicas associadas a esses eventos tenham sido estudadas em vários níveis, o tamanho do genoma e a variação do conteúdo de GC são menos compreendidos devido à ausência de dados genômicos suficientes. Neste estudo, a técnica de citometria de fluxo foi usada para descobrir o tamanho do genoma e o conteúdo de GC de 46 espécies de Nicotiana, e comparamos as mudanças genômicas associadas aos eventos de hibridização ao longo da escala de tempo evolutiva. O tamanho do genoma entre as espécies de Nicotiana variou entre 3,28 pg e 11,88 pg, enquanto os conteúdos de GC variaram entre 37,22% e 51,25%. As espécies tetraploides do gênero Nicotiana, incluindo as seções Polydiclae, Repandae, Nicotiana, Rustica e Sauveolentes, revelaram aumento e redução do tamanho do genoma quando comparados à soma dos genomas de suas espécies ancestrais. Os tamanhos do genoma de três híbridos homoploides foram encontrados perto de suas espécies ancestrais. A perda da grande sequência do genoma foi observada nas espécies evolutivas mais velhas (> 10 Myr) em comparação com as que evoluíram recentemente (< 0,2 Myr). Os teores de GC foram homogêneos com diferença média de 2,46% entre as espécies de Nicotiana. Conclui-se que a mudança no tamanho do genoma apareceu em ambas as direções, enquanto os conteúdos de GC foram encontrados mais homogêneos no gênero Nicotiana.

Traditional knowledge about medicinal plant in the remote areas of Wari Tehsil, Dir Upper, Pakistan / Conhecimento tradicional sobre plantas medicinais nas áreas remotas de Wari Tehsil, Dir Upper, Paquistão

Abstract Traditional medicine is cheaper and easily available to local people, to care for most frequent diseases in the Northern parts of Pakistan. Our study aimed at inventorying medicine from local plants, documenting their uses, and assessing their market value in 2015-2018 during spring, summer, and winter seasons. A total of 15 trips were made, 5 in each season. Semi-structured interviews with 165 inhabitant's age range between 20-80 years were conducted, analyzed the data is analyzed using Relative frequency of citation(RFC), Use Value(UV), Fidelity Level(FL), Informants consensus factor(ICF), and Jaccard index(JI) to find the most frequent and well-known used species in the area. A total of 86 species belonging to 39 vascular plant families, 33 genera were documented as medicinally important. Family Asteraceae was observed as the dominant family among all the families with 10 species, the leaf was the most used parts and decoction 36% was the most preferred preparation type. Herb was the predominant life form (67%). The maximum UV (0.92) was demonstrated by J. adhatoda L. species, while A. sativum L. shows maximum RFC (0.58), the highest ICF value represented by diarrhea and dermatitis 0.92, and high FL value is recorded 100%. According to our collections, wild species were 45%, invasive species were 38% and cultivated 17% recorded, dicots species were recorded more 81%. Seven 7 medicinal species is being economically important and export to the local and international market of the world, whereas P. integrima L. species were the most exported species according to the local dealers. The investigated area is rural and the local people depend on the area's plants for their health needs, and other uses like a vegetable, fuelwood, fodder, etc. The current result of RFC, UV, ICF, FL, and JI shows that medicinal flora needs to be pharmacologically and phytochemically investigated to prove their efficacy. The documentation of medicinal knowledge is important to preserve this precious old knowledge before it is lost forever, due to technological and environmental changes in the world.

Resumo A medicina tradicional é mais barata e facilmente disponível à população local para cuidar das doenças mais frequentes nas áreas do norte do Paquistão. Nosso estudo teve como objetivo inventariar medicamentos de plantas locais, documentar seus usos e avaliar seu valor de mercado em 2015-2018 durante as temporadas de primavera, verão e inverno. Foram feitas 15 viagens, 5 em cada temporada. Foram realizadas entrevistas semiestruturadas com 165 moradores na faixa etária de 20 a 80 anos, com dados analisados ​​por meio de frequência relativa de citação (RFC), valor de uso (UV), nível de fidelidade (FL), fator de consenso de informantes (CIF), e o índice de Jaccard (JI) para encontrar as espécies utilizadas mais frequentes e conhecidas na área. Um total de 86 espécies pertencentes a 39 famílias de plantas vasculares, 33 gêneros foram documentados como medicamente importantes. A família Asteraceae foi observada como a família dominante entre todas as famílias com 10 espécies, a folha foi a parte mais utilizada e a decocção 36% foi o tipo de preparação mais preferido. A erva foi a forma de vida predominante (67%). O UV máximo (0,92) foi demonstrado pelas espécies de J. adhatoda L., enquanto A. sativum L. mostra RFC máximo (0,58), o maior valor de ICF representado por diarreia e dermatite 0,92, e alto valor de FL é registrado 100%. De acordo com nossas coleções, as espécies selvagens foram 45%, as espécies invasoras 38% e as cultivadas 17% registradas, as espécies dicotiledôneas foram registradas mais 81%. Sete espécies medicinais estão sendo economicamente importantes e exportadas para o mercado local e internacional do mundo, enquanto as espécies de P. integrima L. foram as espécies mais exportadas de acordo com os comerciantes locais. A área investigada é rural e a população local depende das plantas da área para suas necessidades de saúde e outros usos como vegetal, lenha, forragem etc. O resultado atual de RFC, UV, ICF, FL e JI mostra que a flora medicinal precisa ser investigada farmacológica e fitoquimicamente para comprovar sua eficácia. A documentação do conhecimento medicinal é importante para preservar esse precioso conhecimento antigo antes que se perca para sempre, devido às mudanças tecnológicas e ambientais do mundo.

Assessment of skeletal relationships in cleft palate with or without cleft lip: A cone-beam computed tomography study in a pakistani population.

Background: Understanding the different skeletal relationships in orofacial clefts by using cone-beam computed tomography (CBCT) may eventually lead to developing better diagnosis and treatment protocols for facial deformities. Aims: The objective of this study was to investigate the different skeletal relationships in the cleft palate with or without cleft lip (CP ± L), using CBCT scans. This is a retrospective study conducted at the Orthodontics and Oral Radiology department, CMH-Lahore medical college and Institute of dentistry. In the current study, 4,152 CBCT scans (dcm format) were collected from a radiology center in Lahore, Pakistan between February 2015 and February 2018. All CBCT scans were imported to the Romexis Viewer, version 4.4.0 (Planmeca, Finland). Data sorting was performed to identify age, sex, cleft phenotype, unilateral cleft quadrant, sagittal skeletal relationship, and facial soft tissue involvement. Materials and Methods: Statistics were generated, using the Chi-square test. A P value <0.05 was considered statistically significant. Results: We identified 73 cases of CP ± L in the sample. The male-to-female ratio was 1.21:1. Bilateral cleft lip and palate (BCLP) mostly affected males (60%), whereas unilateral cleft lip and palate (UCLP) mainly affected females (57.6%), with a left-side female predominance. The different cleft phenotypes do not show any statistically significant difference regarding skeletal relationships and sex (P > 0.05). Conclusions: Skeletal class III relationships were found to be predominant in both sexes, followed by class II, and class I skeletal relationships. Henceforth, such CP ± L patients should be pre-emptively screened in early life to avoid such skeletal complications.

No significant increase in Guillain-Barré syndrome after COVID-19 vaccination in adults: A vaccine adverse event reporting system study.

OBJECTIVE: To investigate the association between Guillain-Barré syndrome (GBS) and COVID-19 vaccination. BACKGROUND: On July 13, 2021, the US Food and Drug Administration (FDA) released a new warning that Johnson & Johnson COVID-19 vaccine could increase the risk of developing GBS. METHODS: The reporting rate of adult GBS after COVID-19 vaccination, ascertained with Brighton criteria, was compared with the reporting rate after other vaccinations during the same time period, and also compared with the reporting rate during control periods. Statistical methods such as proportion tests, and Pearson's chi-squared test were utilized to identify significant relationships. Self-controlled and case centered analyses were conducted. A machine learning model was utilized to identify the factors associated with a worse outcome defined as emergency room (ER) or doctor visits, hospitalizations, and deaths. RESULTS: The reporting rate of GBS after COVID-19 vaccination was significantly higher than after influenza and other vaccinations (49.7, 0.19, 0.16 per 10 million, p < 0.0001). However, the reporting rate was within the incidence range of GBS in the general population. Using self-controlled and case centered analyses, there was a significant difference in the reporting rate of GBS after COVID-19 vaccination between the risk period and control period (p < 0.0001). There was an estimated 0.7-1.7 per million excess reports of GBS within 6 weeks of COVID-19 vaccination. Machine learning model demonstrated that female gender and age between 18 and 44 are associated with worse outcome. No association was found between the onset interval of GBS and its prognosis. CONCLUSIONS: Although the reporting rate of GBS after COVID-19 vaccination was not statistically different than that of the general population, the increased reporting of GBS within the first 6 weeks after COVID-19 vaccination, more so than with other vaccinations, suggests that some cases of GBS are temporally associated with COVID-19 vaccination. However, there is a reduction in the reporting rate of GBS after other vaccines, compared to reporting rates pre-COVID-19, highlighting limitations inherent in any passive surveillance system. These findings warrant continuous analysis of GBS after COVID-19 vaccination. Further improvement of the machine learning model is needed for clinical use.