(2-Methylbutyryl)shikonin Naturally Occurring Shikonin Derivative Ameliorates the α-MSH-Induced Melanogenesis via ERK1/2 and p38 MAP Kinase-Mediated Down-Regulation of the MITF Transcription Factor.

Cutaneous pigmentation is an important phenotypic trait whose regulation, despite recent advances, has yet to be completely elucidated. Melanogenesis, a physiological process of melanin production, is imperative for organism survival as it provides protection against the environmental insults that majorly involve sunlight-induced skin photodamage. However, immoderate melanin synthesis can cause pigmentation disorders associated with a psychosocial impact. In this study, the hypopigmentation effect of (2-methylbutyryl)shikonin, a natural product present in the root extract of Lithospermum erythrorhizon, and the underlying mechanisms responsible for the inhibition of melanin synthesis in α-MSH-stimulated B16F10 cells and C57BL/6J mice was studied. Non-cytotoxic concentrations of (2-methylbutyryl)shikonin significantly repressed cellular tyrosinase activity and melanin synthesis in both in vitro and in vivo models (C57BL/6J mice). (2-Methylbutyryl)shikonin remarkably abolished the protein expression of MITF, tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2, thereby blocking the production of pigment melanin via modulating the phosphorylation status of MAPK proteins, viz., ERK1/2 and p38. In addition, specific inhibition of ERK1/2 attenuated the inhibitory effects of (2-methylbutyryl)shikonin on melanin synthesis, whereas selective inhibition of p38 augmented the inhibitory effect of BSHK on melanin synthesis. Moreover, topical application of (2-methylbutyryl)shikonin on C57BL/6J mouse tails remarkably induced tail depigmentation. In conclusion, with these findings, we, for the first time, report the hypopigmentation effect of (2-methylbutyryl)shikonin via inhibition of cellular tyrosinase enzyme activity, subsequently ameliorating the melanin production, thereby indicating that (2-methylbutyryl)shikonin is a potential natural therapy for hyperpigmentation disorders.

A clinico-radiological review of chronic non-bacterial osteomyelitis in paediatrics, adolescents, and adults: demystifying a forgotten differential.

Chronic non-bacterial osteomyelitis (CNO), also known as non-bacterial osteitis, is a chronic autoinflammatory disease of unknown aetiology that primarily occurs in the paediatric population, although rare cases of adult-onset disease also exist. CNO has non-specific clinical and radiological presentations, and the affected population often present with bone pain of insidious onset secondary to sterile bony inflammation that can be associated with swelling, focal tenderness, and warmth at the affected sites. The pattern of bony involvement appears to be dependent on the age of onset, with adults frequently having axial skeletal lesions and children and adolescents often being affected in the appendicular skeletal sites. CNO is a diagnosis of exclusion, and imaging is heavily relied on to identify and characterise the bony lesions in addition to exclude diseases that can mimic CNO. Magnetic resonance imaging is often the reference standard with biochemical and histopathological findings being complementary. Although combining imaging methods can be used to facilitate the diagnosis, a single technique could be adequate depending on the clinical picture. Given the relatively rare incidence of CNO, limited awareness of the disease among care providers, and its similarity in clinical and radiological presentation to various bony diseases, there are often long delays in diagnosis, with adults being unfavourably affected compared to paediatrics and adolescents. This review of CNO will describe the condition, overview its clinical presentation, highlight the radiological features, and emphasise clinical pearls that can aid in diagnosis and ruling out the mimics.

Long-Term Outcomes of Autologous Hematopoietic Stem Cell Transplant (HSCT) for Multiple Myeloma: While New Horizons Emerge, It Is Still Only a Silver Lining for Resource-Constrained Settings.

Background Significant hurdles impede the optimal implementation of hematopoietic stem cell transplantation (HSCT) in low-middle income countries (LMICs). Herein, we highlight the challenges faced in LMICs while performing HSCT and report the long-term outcomes of patients with newly diagnosed multiple myeloma (MM) who underwent autologous HSCT (AHSCT) at our center. Besides, we provide a comprehensive review of studies reporting long-term outcomes of AHSCT in MM from the Indian subcontinent. Methodology This study was conducted at the State Cancer Institute, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India. Case records of all patients with MM who received AHSCT from December 2010 to July 2018 were reviewed retrospectively. A non-systematic literature search was performed using PubMed and Google Scholar databases. Data regarding clinicopathological parameters and long-term follow-up were extracted from relevant studies and for patients included in our study. Results At our center, 47 patients (median age 52.0 years) with MM underwent AHSCT. Majority of patients had stage III disease (ISS) and median time to transplant was 11.5 months. The five-year progression free survival (PFS) and overall survival (OS) were 59.1% and 81.2%, respectively. Studies from the Indian subcontinent have observed a five-year OS of ~50% to ~85%. However, a greater variability in the five-year PFS has been reported, ranging from ~20% to ~75%. The median time to transplant has ranged from seven to 17 months (indicating time delays) with median CD34 cell counts of 2.7-6.3×106 cells/kg (lower than developed countries). Conclusions Despite significant resource limitations in LMICs, AHSCT is increasingly been performed in MM with encouraging long-term outcomes.

Inhibition of melanogenesis by 3-(1'-methyltetrahydropyridinyl)-2,4-6-trihydroxy acetophenone via suppressing the activity of cAMP response element-binding protein (CREB) and nuclear exclusion of CREB-regulated transcription coactivator 1 (CRTC1).

Exposure to Ultraviolet radiation or α-melanocyte-stimulating hormone (α-MSH) stimulates the Cyclic Adenosine Monophosphate/Protein Kinase A signalling pathway, which leads to the synthesis and deposition of melanin granules in the epidermis. Skin pigmentation is the major physiological defence against inimical effects of sunlight. However, excessive melanin production and accumulation can cause various skin hyperpigmentation disorders. The present study involved the identification of 3-(1'-methyltetrahydropyridinyl)-2,4-6-trihydroxy acetophenone (IIIM-8) as an inhibitor of melanogenesis, IIIM-8 significantly inhibited pigment production both in vitro and in vivo without incurring any cytotoxicity in Human Adult Epidermal Melanocytes (HAEM). IIIM-8 repressed melanin synthesis and secretion both at basal levels and in α-MSH stimulated cultured HAEM cells by decreasing the levels of Cyclic Adenosine Monophosphate (cAMP) and inhibiting the phosphorylation of cAMP response element-binding (CREB) protein, coupled with restoring the phosphorylation of CREB-regulated transcription coactivator 1 (CRTC1) and its nuclear exclusion in HAEM cells. This impeding effect correlates with diminished expression of master melanogenic proteins including microphthalmia-associated transcription factor (MITF), Tyrosinase (TYR), Tyrosinase related protein 1 (TRP1), and Tyrosinase related protein 2 (TRP2). Additionally, topical application of IIIM-8 induced tail depigmentation in C57BL/6J mice. Furthermore, IIIM-8 efficiently mitigated the effect of ultraviolet-B radiation on melanin synthesis in the auricles of C57BL/6J mice. This study demonstrates that IIIM-8 is an active anti-melanogenic agent against ultraviolet radiation-induced melanogenesis and other hyperpigmentation disorders.

Molecular basis of skin photoaging and therapeutic interventions by plant-derived natural product ingredients: A comprehensive review.

Skin areas exposed to ultraviolet radiation (UV) from sunlight are more prone to photoaging than unexposed areas evidenced by several signs which include skin dryness, irregular pigmentation, lentigines, hyperpigmentation, wrinkling, and decreased elasticity. Plant-based natural product ingredients with therapeutic potential against skin photoaging are gaining more attention. This article aims the reviewing the research work done in exploring the cellular and molecular mechanisms involved in UV-induced skin photoaging, followed by summarizing the mechanistic insights involved in its therapeutics by natural product-based ingredients. In the mechanistic section of the convoluted procedure of photoaging, we described the effect of UV radiation (UVR) on different cellular macromolecules (direct damage) and subsequently, the deleterious consequences of UVR-generated reactive oxygen species (indirect damage) and signaling pathways activated or inhibited by UV induced ROS generation in various cellular pathologies of skin photoaging like inflammation, extracellular matrix degradation, apoptosis, mitochondrial dysfunction, and immune suppression. We also discussed the effect of UV radiation on the adipose tissue, and transient receptor potential cation channel V of photoaging skin. In the past few decades, mechanistic studies performed in this area have deciphered various therapeutic targets, opening avenues for different available therapeutic options against this pathological condition. So the remaining portion of the review deals with various natural product-based therapeutic agents available against skin photodamage.

Therapeutic and cosmeceutical role of glycosylated natural products in dermatology.

Natural products (NPs) remain the primary source of pharmacologically active candidates for drug discovery. Since time immemorial, NPs have attracted considerable attention because of their beneficial skin effects. Moreover, there has been a great interest in using such products for the cosmetics industry in the past few decades, bridging the gap between modern and traditional medicine. Terpenoids, Steroids, and Flavonoids having glycosidic attachment have proven biological effects with a positive impact on human health. NPs derived glycosides are mainly found in fruits, vegetables, and plants, and most of them have a special reverence in traditional and modern medicine for disease prevention and treatment. A literature review was performed using scientific journals, Google scholar, Scifinder, PubMED, and Google patents. These scientific articles, documents, and patents establish the significance of glycosidic NPs in the areas of dermatology. Considering the human inclination to the usage of NPs rather than synthetic or inorganic drugs (especially in the area of skin care), in the present review we have discussed the worth of NP glycosides in beauty care and skin-related therapeutics and the mechanistic pathways involved.

Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats.

BACKGROUND: Ageing is the primary risk factor for Parkinson's disease. Progressive motor and coordination decline that occurs with ageing has been linked to nigrostriatal dysfunction. Few studies have investigated the efficacy of mesenchymal stem cells in ameliorating the structural and functional alterations in the ageing nigrostriatal system. This study is the first to evaluate the effects of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose- induced rat model of nigrostriatal ageing. MATERIALS AND METHODS: BMMSCs were intravenously injected once every 2 weeks for 8 weeks. The transplanted cells survived, migrated to the brain, and differentiated into dopaminergic neurones and astrocytes. RESULTS: BMMSC transplantation improved locomotor activity, restored dopaminergic system function, preserved atrophic dopaminergic neurones in the substantia nigra, exerted antioxidative effects, and restored neurotrophic factors. CONCLUSIONS: Our findings demonstrate the efficacy of BMMSC injection in a nigrostriatal ageing rat model, and suggest that these cells may provide an effective therapeutic approach for the ageing nigrostriatal system.

Trigonelline, a plant derived alkaloid prevents ultraviolet-B-induced oxidative DNA damage in primary human dermal fibroblasts and BALB/c mice via modulation of phosphoinositide 3-kinase-Akt-Nrf2 signalling axis.

BACKGROUND: DNA is the main target for UV-B-irradiation-induced skin photodamage and accounts for 90 % of all the non-melanoma skin cancers. PURPOSE: In this study, we explored the mechanistic basis of photoprotective effect of Trigonelline, a naturally occurring alkaloid from the Trigonella foenum-graecum, against UV-B-induced oxidative DNA Damage Response using Primary Human Dermal Fibroblasts (HDFs) and BALB/C mice as models of skin photodamage. METHODS: Primary HDFs were subjected to UV-B exposure (10 mJ/cm2) with or without TG for 24 h. Effect of UV-B exposure and TG treatment was evaluated by analyzing the cell survival, cellular morphology, oxidative stress & DNA damage response markers by performing biochemical studies, florescent microscopy & protein expression studies. In in-vivo study, TG pre-treated BALB/c mice were -irradiated with 180 mJ/cm2 of UV-B dose thrice a week on alternative days for four months, followed by topical application of different concentrations of TG. The photodamage caused by UV-B exposure and its ameleoriation by topical treatment of TG was studied by physical and morphological appearance and analyzing the oxidative stress & DNA damage response markers from skin. RESULTS: We found that TG significantly alleviates UV-B-induced cell death effects in HDFs. TG protects HDF cells and BALB/c mice from UV-B-induced DNA damage by regulating the expression profile of key protein markers of DNA damage which include P53, ATM, ATR, ϒH2AX, Chk1 and Chk2. We found that TG offers geno-protection to UV-B-irradiated HDFs by alleviating CPD induction, reducing the number of TUNEL positive cells and by decreasing the expression levels of DNA damage marker protein ϒH2AX in immunocytochemistry. Further, we found that TG prevents the UVB induced oxidative stress by activating the PI3K-AKT-Nrf2 signalling pathway. On employing PI3K inhibitor, LY294002, we found the expression of ϒH2AX and p-P53 is significantly increased compared to UV-B treated only, indicating that TG mediates the geno-protection against UV-B irradiation via PI3K-AKT-Nrf2 signalling pathway. CONCLUSION: Current study presents for the first time the photo-protective role of TG against UV-B-induced oxidative DNA damage and provides its mechanistic insights also and provide strong evidence for TG to be carried forward as a potential remedial and cosmeceutical agent against UV-B-induced skin photodamage disorders.

Molecular detection of Mycoplasma gallisepticum in different poultry breeds of Abbottabad and Rawalpindi, Pakistan / Detecção molecular de Mycoplasma gallisepticum em diferentes raças de aves de Abbottabad e Rawalpindi, Paquistão

The poultry sector in Pakistan is contributing mainly in bridging gap between demand and supply for protein. Mycoplasma gallisepticum is an emerging bacterium causing serious problems in poultry industry of Pakistan. A cross-sectional study was conducted to evaluate the M. gallisepticum load in poultry populated regions of Pakistan. Total 600 serum and 600 swab samples were collected, 200 from each broiler, layers and breeders poultry in Rawalpindi and Abbottabad districts. Serum samples were analyzed through ELISA for seroprevalence. Swabs were cultured on Frey’s medium followed by PCR and partial mgc2 gene sequencing. Results of seroprevalence of M. gallisepticum showed that layers (75%, n=150) are more positive as compared to breeders (70%, n=140) and broilers (50%, n=100). Typical colonies of the M. gallisepticum were observed in breeder (26.5%), followed by layer (21%) and broilers (9%). A total of 37.1% (n=42) samples were identified positive through PCR out of total 113 cultured based positive samples. A total of six M. gallisepticum isolates of current study showed 98-99 percent similarity with previously reported isolates on the basis of mgc2 gene partial sequencing. The M. gallisepticum was found highly prevalent in different poultry breads. Results of this study would add into basic data and provide a direction for livestock sector to strengthen a control strategy for mycoplasmosis in poultry farms.

O setor avícola do Paquistão está contribuindo principalmente para preencher a lacuna entre a demanda e a oferta de proteína. Mycoplasma gallisepticum é uma bactéria emergente que causa sérios problemas na indústria avícola do Paquistão. Um estudo transversal foi conduzido para avaliar a carga de M. gallisepticum em regiões de avicultura do Paquistão. Um total de 600 amostras de soro e 600 amostras de esfregaço foi coletado, 200 de cada frango de corte, poedeiras e aves reprodutoras nos distritos de Rawalpindi e Abbottabad. Amostras de soro foram analisadas por ELISA para soroprevalência. As zaragatoas foram cultivadas em meio Frey, seguido de PCR e sequenciação parcial do gene mgc2. Os resultados da soroprevalência de M. gallisepticum mostraram que as poedeiras (75%, n = 150) são mais positivas em comparação com matrizes (70%, n = 140) e frangos de corte (50%, n = 100). Colônias típicas de M. gallisepticum foram observadas em reprodutoras (26,5%), seguidas de poedeiras (21%) e frangos de corte (9%). Um total de 37,1% (n = 42) das amostras foi identificado como positivas por PCR de um total de 113 amostras positivas baseadas em cultura. Um total de seis isolados de M. gallisepticum do estudo atual mostrou 98-99% de similaridade com isolados relatados anteriormente com base no sequenciamento parcial do gene mgc2. O M. gallisepticum foi encontrado com alta prevalência em diferentes pães de aves. Os resultados deste estudo acrescentariam dados básicos e forneceriam orientação para o setor pecuário fortalecer uma estratégia de controle da micoplasmose em granjas avícolas.

Molecular detection of Mycoplasma gallisepticum in different poultry breeds of Abbottabad and Rawalpindi, Pakistan

Abstract The poultry sector in Pakistan is contributing mainly in bridging gap between demand and supply for protein. Mycoplasma gallisepticum is an emerging bacterium causing serious problems in poultry industry of Pakistan. A cross-sectional study was conducted to evaluate the M. gallisepticum load in poultry populated regions of Pakistan. Total 600 serum and 600 swab samples were collected, 200 from each broiler, layers and breeders poultry in Rawalpindi and Abbottabad districts. Serum samples were analyzed through ELISA for seroprevalence. Swabs were cultured on Freys medium followed by PCR and partial mgc2 gene sequencing. Results of seroprevalence of M. gallisepticum showed that layers (75%, n=150) are more positive as compared to breeders (70%, n=140) and broilers (50%, n=100). Typical colonies of the M. gallisepticum were observed in breeder (26.5%), followed by layer (21%) and broilers (9%). A total of 37.1% (n=42) samples were identified positive through PCR out of total 113 cultured based positive samples. A total of six M. gallisepticum isolates of current study showed 98-99 percent similarity with previously reported isolates on the basis of mgc2 gene partial sequencing. The M. gallisepticum was found highly prevalent in different poultry breads. Results of this study would add into basic data and provide a direction for livestock sector to strengthen a control strategy for mycoplasmosis in poultry farms.

Resumo O setor avícola do Paquistão está contribuindo principalmente para preencher a lacuna entre a demanda e a oferta de proteína. Mycoplasma gallisepticum é uma bactéria emergente que causa sérios problemas na indústria avícola do Paquistão. Um estudo transversal foi conduzido para avaliar a carga de M. gallisepticum em regiões de avicultura do Paquistão. Um total de 600 amostras de soro e 600 amostras de esfregaço foi coletado, 200 de cada frango de corte, poedeiras e aves reprodutoras nos distritos de Rawalpindi e Abbottabad. Amostras de soro foram analisadas por ELISA para soroprevalência. As zaragatoas foram cultivadas em meio Frey, seguido de PCR e sequenciação parcial do gene mgc2. Os resultados da soroprevalência de M. gallisepticum mostraram que as poedeiras (75%, n = 150) são mais positivas em comparação com matrizes (70%, n = 140) e frangos de corte (50%, n = 100). Colônias típicas de M. gallisepticum foram observadas em reprodutoras (26,5%), seguidas de poedeiras (21%) e frangos de corte (9%). Um total de 37,1% (n = 42) das amostras foi identificado como positivas por PCR de um total de 113 amostras positivas baseadas em cultura. Um total de seis isolados de M. gallisepticum do estudo atual mostrou 98-99% de similaridade com isolados relatados anteriormente com base no sequenciamento parcial do gene mgc2. O M. gallisepticum foi encontrado com alta prevalência em diferentes pães de aves. Os resultados deste estudo acrescentariam dados básicos e forneceriam orientação para o setor pecuário fortalecer uma estratégia de controle da micoplasmose em granjas avícolas.

Molecular detection of Mycoplasma gallisepticum in different poultry breeds of Abbottabad and Rawalpindi, Pakistan / Detecção molecular de Mycoplasma gallisepticum em diferentes raças de aves de Abbottabad e Rawalpindi, Paquistão

Abstract The poultry sector in Pakistan is contributing mainly in bridging gap between demand and supply for protein. Mycoplasma gallisepticum is an emerging bacterium causing serious problems in poultry industry of Pakistan. A cross-sectional study was conducted to evaluate the M. gallisepticum load in poultry populated regions of Pakistan. Total 600 serum and 600 swab samples were collected, 200 from each broiler, layers and breeders poultry in Rawalpindi and Abbottabad districts. Serum samples were analyzed through ELISA for seroprevalence. Swabs were cultured on Frey's medium followed by PCR and partial mgc2 gene sequencing. Results of seroprevalence of M. gallisepticum showed that layers (75%, n=150) are more positive as compared to breeders (70%, n=140) and broilers (50%, n=100). Typical colonies of the M. gallisepticum were observed in breeder (26.5%), followed by layer (21%) and broilers (9%). A total of 37.1% (n=42) samples were identified positive through PCR out of total 113 cultured based positive samples. A total of six M. gallisepticum isolates of current study showed 98-99 percent similarity with previously reported isolates on the basis of mgc2 gene partial sequencing. The M. gallisepticum was found highly prevalent in different poultry breads. Results of this study would add into basic data and provide a direction for livestock sector to strengthen a control strategy for mycoplasmosis in poultry farms.

Resumo O setor avícola do Paquistão está contribuindo principalmente para preencher a lacuna entre a demanda e a oferta de proteína. Mycoplasma gallisepticum é uma bactéria emergente que causa sérios problemas na indústria avícola do Paquistão. Um estudo transversal foi conduzido para avaliar a carga de M. gallisepticum em regiões de avicultura do Paquistão. Um total de 600 amostras de soro e 600 amostras de esfregaço foi coletado, 200 de cada frango de corte, poedeiras e aves reprodutoras nos distritos de Rawalpindi e Abbottabad. Amostras de soro foram analisadas por ELISA para soroprevalência. As zaragatoas foram cultivadas em meio Frey, seguido de PCR e sequenciação parcial do gene mgc2. Os resultados da soroprevalência de M. gallisepticum mostraram que as poedeiras (75%, n = 150) são mais positivas em comparação com matrizes (70%, n = 140) e frangos de corte (50%, n = 100). Colônias típicas de M. gallisepticum foram observadas em reprodutoras (26,5%), seguidas de poedeiras (21%) e frangos de corte (9%). Um total de 37,1% (n = 42) das amostras foi identificado como positivas por PCR de um total de 113 amostras positivas baseadas em cultura. Um total de seis isolados de M. gallisepticum do estudo atual mostrou 98-99% de similaridade com isolados relatados anteriormente com base no sequenciamento parcial do gene mgc2. O M. gallisepticum foi encontrado com alta prevalência em diferentes pães de aves. Os resultados deste estudo acrescentariam dados básicos e forneceriam orientação para o setor pecuário fortalecer uma estratégia de controle da micoplasmose em granjas avícolas.

Physical education teachers' attitudes toward inclusion of students with disabilities in Saudi Arabia.

The attitudes of physical education (PE) teachers toward inclusion are critical to the successful provision of inclusive teaching for students with disabilities. Therefore, the purpose of this study was to investigate the attitudes of Saudi Arabian PE teachers toward the inclusion of students with disabilities in PE classes and the effect of sociodemographic variables (e.g., gender and length of teaching experience) on their attitudes toward inclusion. A total of 1,314 PE teachers (M age = 41.09, SD = 9.40, females = 42.8%) completed the Arabic version of the Sentiments, Attitudes, and Concerns about Inclusive Education-Revised Scale (SACIE-R). Analyses found that, in general, PE teachers had moderately positive attitudes toward the inclusion of students with disabilities in PE lessons. A significant difference was found between the two genders in their attitudes toward inclusion. Specifically, female PE teachers demonstrated more positive attitudes toward inclusion than males. Multiple linear regression analysis, meanwhile, showed that the length of teaching experience and the experience of teaching a student with a disability were significant predictors of participants' attitudes toward inclusion. Our findings highlighted the importance of reconsidering the quality of PE teachers' experiences and interactions with students with disabilities as a means to improving their attitudes, which in turn would translate into successful inclusion.

Synthesis and anti-melanoma effect of 3-O-prenyl glycyrrhetinic acid against B16F10 cells via induction of endoplasmic reticulum stress-mediated autophagy through ERK/AKT signaling pathway.

Melanoma is an aggressive form of cancer with poor prognosis and survival rates and limited therapeutic options. Here, we report the anti-melanoma effect of 3-O-prenyl glycyrrhetinic acid (NPC-402), a derivative of glycyrrhtinic acid, from a reputed medicinal plant Glycyrrhiza glabra against B16F10 cells. We studied the cytotoxic effect of NPC-402 on melanoma cells and investigated the role of mitogen-activated protein (MAP) kinase, AKT axis, and endoplasmic reticulum (ER) stress/unfolded protein response (UPR)-mediated autophagy as the involved signaling cascade by studying specific marker proteins. In this study, 4-phenylbutyric acid (4PBA, a chemical chaperone) and small interference RNA (siRNA) knockdown of C/EBP Homologous Protein (CHOP)/growth arrest- and DNA damage-inducible gene 153(GAD153) blocked NPC-402-mediated autophagy induction, thus confirming the role of ER stress and autophagy in melanoma cell death. NPC-402 induced oxidative stress and apoptosis in melanoma cells, which were effectively mitigated by treatment with N-acetylcysteine (NAC). In vivo studies showed that intraperitoneal (i.p.) injection of NPC-402 at 10 mg/kg (5 days in 1 week) significantly retarded angiogenesis in the Matrigel plug assay and reduced the tumor size and tumor weight without causing any significant toxic manifestation in C57BL/6J mice. We conclude that NPC-402 has a high potential to be developed as a chemotherapeutic drug against melanoma.

Antimicrobial stewardship using electronic prescribing systems in hospital settings: a scoping review of interventions and outcome measures.

Objectives: To identify interventions implemented in hospital electronic prescribing systems and the outcome measures used to monitor their impact. Methods: We systematically searched CINAHL, EMBASE, Google Scholar and Medline using keywords in three strands: (i) population: hospital inpatient or emergency department; (ii) intervention: electronic prescribing functionality; and (iii) outcome: antimicrobial stewardship. The interventions were grouped into six themes: alerts, order sets, restriction of access, mandated documentation, embedded guidelines and automatic prescription stop. The outcome measures were organized into those that measure the quality or quantity of prescribing or clinical decision support (CDS) activity. The impact of each intervention reported was grouped into a positive, negative or no change. Results: A total of 28 studies were eligible for inclusion. There were 28 different interventions grouped into the six themes. Alerts visible to the practitioner in the electronic health record (EHR) were most frequently implemented (n = 11/28). Twenty different outcome measures were identified, divided into quality (n = 13/20) and quantity outcomes (n = 4/20) and CDS activity (n = 3/20). One-third of outcomes reported across the 28 studies showed positive change (34.4%, n = 42/122) and 61.4% (n = 75/122) showed no change. Conclusions: The most frequently implemented interventions were alerts, the majority of which were to influence behaviour or decision-making of the practitioner within the EHR. Quality outcomes were most frequently selected by researchers. The review supports previous research that larger well-designed randomized studies are needed to investigate the impact of interventions on AMS and outcome measures to be standardized.

Genetic structure of Arabian Peninsula dromedary camels revealed three geographic groups.

Dromedary camels (Camelus dromedarius) are widespread in the desert and semi-desert areas of Africa, the Arabian Peninsula, some parts of southwest Asia and Australia. In the Arabian Peninsula, these well-adapted species have been classified based on their ecology into Desert camels, found mainly in the north and center of the Peninsula, Mountain camels, distributed along the west and south of the Peninsula, and Beach camels, populating the west to southwest of the Peninsula. Here, we aimed to investigate the genetic relationship between 386 camels corresponding to 12 dromedary populations from different geographical locations and ecology in the Arabian Peninsula with the genotyping of 17 microsatellite loci. No significant deviation was observed in heterozygosity, allelic richness, Fis (inbreeding coefficient) among the studied populations had a mean value of 0.5849, 4.808 and 0.04, respectively. A mean Fst (fixation index) value of 0.0304 was calculated for the various populations with the highest value obtained between racing Omani and Awarik camel populations (0.079). Both the neighbor-joining phylogenetic tree and the STRUCTURE analysis divided the populations into three different groups corresponding to their Arabian Peninsula geographic location (North, Central and West, South-West, and South-East of the Arabian Peninsula), rather than their ecological classification, with a high level of genetic admixture and gene flow among them. Investigating the genetic relationship of dromedary populations in the Arabian Peninsula can be considered as the first milestone to conserve this well-adapted species. The results obtained here need to be further validated using whole genome sequencing data.

Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.

OBJECTIVES: At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI). STUDY DESIGN: We undertook an ecological study using routinely available national data. METHODS: We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure. RESULTS: Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity. CONCLUSIONS: These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.

Complex differences in infection rates between ethnic groups in Scotland: a retrospective, national census-linked cohort study of 1.65 million cases.

BACKGROUND: Ethnicity can influence susceptibility to infection, as COVID-19 has shown. Few countries have systematically investigated ethnic variations in infection. METHODS: We linked the Scotland 2001 Census, including ethnic group, to national databases of hospitalizations/deaths and serological diagnoses of bloodborne viruses for 2001-2013. We calculated age-adjusted rate ratios (RRs) in 12 ethnic groups for all infections combined, 15 infection categories, and human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses. RESULTS: We analysed over 1.65 million infection-related hospitalisations/deaths. Compared with White Scottish, RRs for all infections combined were 0.8 or lower for Other White British, Other White and Chinese males and females, and 1.2-1.4 for Pakistani and African males and females. Adjustment for socioeconomic status or birthplace had little effect. RRs for specific infection categories followed similar patterns with striking exceptions. For HIV, RRs were 136 in African females and 14 in males; for HBV, 125 in Chinese females and 59 in males, 55 in African females and 24 in males; and for HCV, 2.3-3.1 in Pakistanis and Africans. CONCLUSIONS: Ethnic differences were found in overall rates and many infection categories, suggesting multiple causative pathways. We recommend census linkage as a powerful method for studying the disproportionate impact of COVID-19.

Frizzled receptors in melanomagenesis: From molecular interactions to target identification.

Frizzled (FZD) proteins are receptors for the WNT family ligands. Inherited human diseases and genetic experiments using knockout mice have revealed a central role of FZDs in multiple aspects of embryonic development and tissue homeostasis. Misregulated FZD signaling has also been found in many cancers. Recent studies on three out of the ten mammalian FZDs in melanoma have shown that they promote tumor cell proliferation and invasion, via the activation of the canonical WNT/ß-catenin or non-canonical PCP signaling pathway. In this concise review, we summarize our current knowledge of individual FZDs in melanoma, discuss the involvement of both the canonical and non-canonical pathways, and describe ongoing efforts to target the FZD receptors for melanoma treatment.

Food habits of indian crested porcupine (Hystrix indica) (Kerr 1792), in district Bagh, Azad Jammu and Kashmir / Hábitos alimentares do porco-espinho de crista indiano (Hystrix indica) (Kerr 1972) nos distritos de Bagh, Azad Jammu e Caxemira

The Indian Crested Porcupine (Hystrix indica) is classified as an agricultural pest species. It feeds on plants and crops; hence, it is responsible for massive financial losses worldwide. The current study was conducted to assess the diet composition of Indian Crested Porcupine in District Bagh, Azad Jammu and Kashmir (AJ&K). Thus, fecal samples were collected and examined from different sampling sites. Reference slides of the material collected from the study area were prepared for identification of dietary components in fecal pellets. A total of 80 fecal samples were collected and processed. Percent relative frequencies (P.R.F.) were calculated for each plant species recovered from pellets. Data revealed that Indian Crested Porcupine consumed 31 plant species in its diet, among them Zea mays (34.31±7.76) was the most frequently selected species followed by Rumex obtusifolius (15.32±2.57) and Melia azedarach (12.83±4.79). The study revealed that the greatest diversity of (n=20) plant species were consumed in summer season while minimum (n=13) species were used during winter. Among the parts of plants, stem was highly consumed in spring (57.2%) as compared to seed in fall (36.7%) while spikes and leaf were the least recovered parts from the fecal matter. The Berger-Parker diversity index showed highly diversified food (10.92) in the summer time of the year as compared to the autumn season (2.95). This study provides a baseline for the diet preference of this pest in the study area. Based on current findings, a detailed investigation on damage assessment, exploration, habitat use and management of Indian Crested Porcupine in AJ&K has been recommended.

O porco-espinho de crista indiano (Hystrix indica) é classificado como uma espécie de praga agrícola. Alimenta-se de plantas e colheitas; portanto, é responsável por enormes perdas financeiras em todo o mundo. O estudo atual foi realizado para avaliar a composição da dieta do porco-espinho de crista indiano nos distritos de Bagh, Azad Jammu e Caxemira (AJ&K). Assim, amostras fecais foram coletadas e examinadas em diferentes locais de amostragem. Lâminas de referência do material coletado na área de estudo foram preparadas para identificação dos componentes da dieta em pellets fecais. Um total de 80 amostras fecais foi coletado e processado. As frequências relativas percentuais (P.R.F.) foram calculadas para cada espécie de planta recuperada de pelotas. Os dados revelaram que o porco-espinho indiano consumiu 31 espécies de plantas em sua dieta, entre elas Zea mays (34,31 ± 7,76) foi a espécie mais selecionada, seguida por Rumex obtusifolius (15,32 ± 2,57) e Melia azedarach (12,83 ± 4,79). O estudo revelou que a maior diversidade de (n = 20) espécies de plantas foi consumida no verão, enquanto o mínimo (n = 13) espécies foi utilizado durante o inverno. Entre as partes das plantas, o caule foi muito consumido na primavera (57,2%) em relação à semente no outono (36,7%), enquanto a espiga e a folha foram as partes menos recuperadas da matéria fecal., O índice de diversidade de Berger-Parker mostrou alimentos altamente diversificados (10,92) no verão do ano em comparação com o outono (2,95). Este estudo fornece uma linha de base para a preferência alimentar dessa praga na área de estudo. Com base nas descobertas atuais, uma investigação detalhada sobre avaliação de danos, exploração, uso de habitat e gerenciamento de porco-espinho de crista indiano em AJ&K foi recomendada.

Food habits of indian crested porcupine (Hystrix indica) (Kerr 1792), in district Bagh, Azad Jammu and Kashmir

Abstract The Indian Crested Porcupine (Hystrix indica) is classified as an agricultural pest species. It feeds on plants and crops; hence, it is responsible for massive financial losses worldwide. The current study was conducted to assess the diet composition of Indian Crested Porcupine in District Bagh, Azad Jammu and Kashmir (AJ&K). Thus, fecal samples were collected and examined from different sampling sites. Reference slides of the material collected from the study area were prepared for identification of dietary components in fecal pellets. A total of 80 fecal samples were collected and processed. Percent relative frequencies (P.R.F.) were calculated for each plant species recovered from pellets. Data revealed that Indian Crested Porcupine consumed 31 plant species in its diet, among them Zea mays (34.31±7.76) was the most frequently selected species followed by Rumex obtusifolius (15.32±2.57) and Melia azedarach (12.83±4.79). The study revealed that the greatest diversity of (n=20) plant species were consumed in summer season while minimum (n=13) species were used during winter. Among the parts of plants, stem was highly consumed in spring (57.2%) as compared to seed in fall (36.7%) while spikes and leaf were the least recovered parts from the fecal matter. The Berger-Parker diversity index showed highly diversified food (10.92) in the summer time of the year as compared to the autumn season (2.95). This study provides a baseline for the diet preference of this pest in the study area. Based on current findings, a detailed investigation on damage assessment, exploration, habitat use and management of Indian Crested Porcupine in AJ&K has been recommended.

Resumo O porco-espinho de crista indiano (Hystrix indica) é classificado como uma espécie de praga agrícola. Alimenta-se de plantas e colheitas; portanto, é responsável por enormes perdas financeiras em todo o mundo. O estudo atual foi realizado para avaliar a composição da dieta do porco-espinho de crista indiano nos distritos de Bagh, Azad Jammu e Caxemira (AJ&K). Assim, amostras fecais foram coletadas e examinadas em diferentes locais de amostragem. Lâminas de referência do material coletado na área de estudo foram preparadas para identificação dos componentes da dieta em pellets fecais. Um total de 80 amostras fecais foi coletado e processado. As frequências relativas percentuais (P.R.F.) foram calculadas para cada espécie de planta recuperada de pelotas. Os dados revelaram que o porco-espinho indiano consumiu 31 espécies de plantas em sua dieta, entre elas Zea mays (34,31 ± 7,76) foi a espécie mais selecionada, seguida por Rumex obtusifolius (15,32 ± 2,57) e Melia azedarach (12,83 ± 4,79). O estudo revelou que a maior diversidade de (n = 20) espécies de plantas foi consumida no verão, enquanto o mínimo (n = 13) espécies foi utilizado durante o inverno. Entre as partes das plantas, o caule foi muito consumido na primavera (57,2%) em relação à semente no outono (36,7%), enquanto a espiga e a folha foram as partes menos recuperadas da matéria fecal., O índice de diversidade de Berger-Parker mostrou alimentos altamente diversificados (10,92) no verão do ano em comparação com o outono (2,95). Este estudo fornece uma linha de base para a preferência alimentar dessa praga na área de estudo. Com base nas descobertas atuais, uma investigação detalhada sobre avaliação de danos, exploração, uso de habitat e gerenciamento de porco-espinho de crista indiano em AJ&K foi recomendada.