Targeting S6K/NFκB/SQSTM1/Polθ signaling to suppress radiation resistance in prostate cancer.

In this study we have identified POLθ-S6K-p62 as a novel druggable regulator of radiation response in prostate cancer. Despite significant advances in delivery, radiotherapy continues to negatively affect treatment outcomes and quality of life due to resistance and late toxic effects to the surrounding normal tissues such as bladder and rectum. It is essential to develop new and effective strategies to achieve better control of tumor. We found that ribosomal protein S6K (RPS6KB1) is elevated in human prostate tumors, and contributes to resistance to radiation. As a downstream effector of mTOR signaling, S6K is known to be involved in growth regulation. However, the impact of S6K signaling on radiation response has not been fully explored. Here we show that loss of S6K led to formation of smaller tumors with less metastatic ability in mice. Mechanistically we found that S6K depletion reduced NFκB and SQSTM1 (p62) reporter activity and DNA polymerase θ (POLθ) that is involved in alternate end-joining repair. We further show that the natural compound berberine interacts with S6K in a in a hitherto unreported novel mode and that pharmacological inhibition of S6K with berberine reduces Polθ and downregulates p62 transcriptional activity via NFκB. Loss of S6K or pre-treatment with berberine improved response to radiation in prostate cancer cells and prevented radiation-mediated resurgence of PSA in animals implanted with prostate cancer cells. Notably, silencing POLQ in S6K overexpressing cells enhanced response to radiation suggesting S6K sensitizes prostate cancer cells to radiation via POLQ. Additionally, inhibition of autophagy with CQ potentiated growth inhibition induced by berberine plus radiation. These observations suggest that pharmacological inhibition of S6K with berberine not only downregulates NFκB/p62 signaling to disrupt autophagic flux but also decreases Polθ. Therefore, combination treatment with radiation and berberine inhibits autophagy and alternate end-joining DNA repair, two processes associated with radioresistance leading to increased radiation sensitivity.

Genetic variations and phylogenetic relationship of genus Uromastyx from Punjab Pakistan

Abstract During the present study, specimens were collected from selected sites of Cholistan desert and Kalabagh Game Reserve, Punjab province, Pakistan. Each captured specimen was tagged with voucher number and morphometric measurements were taken. The average snout to vent length was 172.559±1.40 mm and average weight was 92.1±1.30 g. The DNA of Uromastyx hardwickii was amplified and sequenced using 16S rRNA primer set. The obtained DNA sequence has shown reliable and clear species identification. After trimming ambiguous bases, the obtained 16S rRNA fragment was 520 bp while 16S rRNA fragments aligned with closely matched sequence from NCBI comprised of 510 bp. Closely matched sequences of genus Uromastyx were retrieved from NCBI in blast searches. Neighbour-joining tree of genus Uromastyx was constructed based on p-distance using MEGA X. The mean intraspecific variation was 0.095±0.01 while intraspecific variation was ranging from 0-1%. Similarly, interspecific variation of Uromastyx hardwikii with Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti was 0-12%, 0-19%, 0-19%, 0-20%, 12-19% respectively. The newly produced DNA was submitted to NCBI and accession number was obtained (MW052563.1). Results of current study provided information about the molecular and morphological identification of Genus Uromastyx. In our recommendation, comprehensive molecular based identification of Pakistans reptiles is required to report any new or subspecies from country.

Resumo Durante o presente estudo, os espécimes foram coletados em locais selecionados do deserto do Cholistan e da Reserva de Caça de Kalabagh, província de Punjab, Paquistão. Cada espécime capturado foi etiquetado com o número do comprovante e medidas morfométricas foram realizadas. O comprimento médio do focinho à cloaca foi de 172,559 ± 1,40 mm, e o peso médio foi de 92,1 ± 1,30 g. O DNA de Uromastyx hardwickii foi amplificado e sequenciado usando o conjunto de primer 16S rRNA. A sequência de DNA obtida mostrou identificação de espécies confiável e clara. Após o corte de bases ambíguas, o fragmento de rRNA 16S obtido tinha 520 pb, enquanto os fragmentos de rRNA 16S alinhados com a sequência próxima do NCBI composta por 510 pb. Sequências semelhantes do gênero Uromastyx foram recuperadas do NCBI em pesquisas de explosão. A árvore de união de vizinhos do gênero Uromastyx foi construída com base na distância-p usando MEGA X. A variação intraespecífica média foi de 0,095 ± 0,01, enquanto a variação intraespecífica foi de 0-1%. Da mesma forma, a variação interespecífica de Uromastyx hardwikii com Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti foi de 0-12%, 0-19%, 0-19%, 0-20%, 12-19%, respectivamente. O DNA recém-produzido foi submetido ao NCBI e o número de acesso foi obtido (MW052563.1). Os resultados do estudo atual forneceram informações sobre a identificação molecular e morfológica do Gênero Uromastyx. Em nossa recomendação, a identificação de base molecular abrangente de répteis do Paquistão é necessária para relatar qualquer nova ou subespécie do país.

Prevalence of parasites in selected captive bird species

Abstract Blood and fecal samples of chukar partridge (Alectoris chukar), albino pheasant (Phasianus colchicus), silver pheasant (Lophura nycthemera), rose-ringed parakeet (Psittacula krameri) and turkeys (Meleagris gallopavo) were analyzed to check parasitic prevalence. To record parasites these five avian species were placed kept in separate cages at Avian Conservation and Research Center, Department of Wildlife an Ecology, University of Veterinary and Animal Sciences, Lahore, Pakistan. 100 fecal and 100 blood samples for each bird species were inspected to analyze internal parasites. During present study, 17 species of endoparasites 14 from fecal samples and three from blood were examined. Two species of ectoparasites i.e. mite Dermanyssus gallinae 42% and fowl ticks Args persicus 41%were studied. Blood parasites included Plasmodium juxtanucleare 50%, Leucoctoyzoon simond having parasitic prevalence 40%, and Aegyptinella pullorum having parasitic prevalence of 40%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Allodpa suctoria 2%. Syngamus trachea with parasitic prevalence of 60%, Capillaria annulata 37.5%, Ascardia galli 24%, Capillaria anatis 40% and Heterakis gallinarum 28.3%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 50% and Prosthogonimus macrorchis 21% were also documented from fecal avian samples . Single cestode species Raillietina echinobothrida having parasitic prevalence of 72% and 3 protozoan species i.e. Eimeria maxima having parasitic prevalence of 21%, Giardia lamblia 41% and Histomonas meleagridis 18% were documented during corpological analysis. In our recommendation, proper sanitation, medication and vaccination of birds enclousres are suggested to avoid parasites.

RESUMO Amostras de sangue e fezes de perdiz chukar (Alectoris chukar), faisão-albino (Phasianus colchicus), faisão-prateado (Lophura nycthemera), periquito-de-rosa (Psittacula krameri) e perus (Meleagris gallopavo) foram analisadas para verificar a prevalência de parasitas. Para registrar os parasitas, essas cinco espécies de aves foram colocadas em gaiolas separadas no Centro de Conservação e Pesquisa de Aves, Departamento de Vida Selvagem e Ecologia, Universidade de Veterinária e Ciências Animais, Lahore, Paquistão. Cem amostras fecais e 100 amostras de sangue para cada espécie de ave foram inspecionadas para analisar os parasitas internos. Durante o presente estudo, foram examinadas 17 espécies de endoparasitas, 14 de amostras fecais e 3 de sangue. Foram estudadas duas espécies de ectoparasitas, ou seja, o ácaro Dermanyssus gallinae 42% e o carrapato aviário Args persicus 41%. Os parasitas sanguíneos incluíram Plasmodium juxtanucleare 50%, Leucoctoyzoon simond com prevalência parasitária de 40% e Aegyptinella pullorum com prevalência parasitária de 40%. As espécies parasitas registradas em amostras fecais incluíram 6 espécies de nematoides viz. Allodpa suctoria 2%, Syngamus traqueia com prevalência parasitária de 60%, Capillaria annulata 37,5%, Ascardia galli 24%, Capillaria anatis 40% e Heterakis gallinarum 28,3%. Da mesma forma, duas espécies de trematódeos viz. Prosthogonimus ovatus com prevalência parasitária de 50% e Prosthogonimus macrorchis 21% também foram documentados em amostras fecais de aves. Espécies de cestoide único Raillietina echinobothrida com prevalência parasitária de 72% e 3 espécies de protozoários, isto é, Eimeria maxima com prevalência parasitária de 21%, Giardia lamblia 41% e Histomonas meleagridis 18% foram documentadas durante a análise corpológica. Em nossa recomendação, o saneamento adequado, medicação e vacinação de invólucros de pássaros são sugeridos para evitar parasitas.

Emergence and control of an outbreak of PVL-positive MRSA in a UK-based maternity setting.

This paper aims to describe the investigation and control of an outbreak of USA300 ST8 Panton-Valentine leucocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA), confirmed by whole genome sequencing (WGS), within a maternity and neonatal setting in the UK. The identification of two linked PVL-MRSA cases led to an outbreak investigation. A lookback exercise conducted using the infection control surveillance database, typing of saved MRSA isolates, enhanced patient screening, and staff screening were used to identify further cases. Environmental screening was also performed. Genetic relatedness between isolates was assessed by WGS. During the outbreak, 18 cases were identified between 11th July 2021 and 22nd December 2022: 10 cases were infections and eight cases were colonizations. A healthcare worker (HCW) tested positive for colonization with the same strain, and environmental swabbing identified contaminated information technology equipment in the hospital. The outbreak was brought to an end by exclusion of the colonized HCW from work, and infection prevention and control measures. Since the end of the outbreak, cases of PVL-MRSA with similar molecular profiles have been found in the community. It is likely that the HCW played a role in the transmission of PVL-MRSA. Their exclusion from work and decolonization were key to preventing further cases. WGS was valuable in identifying and linking cases. The identification of community cases of PVL-MRSA with similar molecular profiles confirms transmission of the organism outside of healthcare settings.

Prevalence of parasites in selected captive bird species / Prevalência de parasitas em espécies de pássaros em cativeiro selecionados

Abstract Blood and fecal samples of chukar partridge (Alectoris chukar), albino pheasant (Phasianus colchicus), silver pheasant (Lophura nycthemera), rose-ringed parakeet (Psittacula krameri) and turkeys (Meleagris gallopavo) were analyzed to check parasitic prevalence. To record parasites these five avian species were placed kept in separate cages at Avian Conservation and Research Center, Department of Wildlife an Ecology, University of Veterinary and Animal Sciences, Lahore, Pakistan. 100 fecal and 100 blood samples for each bird species were inspected to analyze internal parasites. During present study, 17 species of endoparasites 14 from fecal samples and three from blood were examined. Two species of ectoparasites i.e. mite Dermanyssus gallinae 42% and fowl ticks Args persicus 41%were studied. Blood parasites included Plasmodium juxtanucleare 50%, Leucoctoyzoon simond having parasitic prevalence 40%, and Aegyptinella pullorum having parasitic prevalence of 40%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Allodpa suctoria 2%. Syngamus trachea with parasitic prevalence of 60%, Capillaria annulata 37.5%, Ascardia galli 24%, Capillaria anatis 40% and Heterakis gallinarum 28.3%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 50% and Prosthogonimus macrorchis 21% were also documented from fecal avian samples . Single cestode species Raillietina echinobothrida having parasitic prevalence of 72% and 3 protozoan species i.e. Eimeria maxima having parasitic prevalence of 21%, Giardia lamblia 41% and Histomonas meleagridis 18% were documented during corpological analysis. In our recommendation, proper sanitation, medication and vaccination of bird's enclousres are suggested to avoid parasites.

RESUMO Amostras de sangue e fezes de perdiz chukar (Alectoris chukar), faisão-albino (Phasianus colchicus), faisão-prateado (Lophura nycthemera), periquito-de-rosa (Psittacula krameri) e perus (Meleagris gallopavo) foram analisadas para verificar a prevalência de parasitas. Para registrar os parasitas, essas cinco espécies de aves foram colocadas em gaiolas separadas no Centro de Conservação e Pesquisa de Aves, Departamento de Vida Selvagem e Ecologia, Universidade de Veterinária e Ciências Animais, Lahore, Paquistão. Cem amostras fecais e 100 amostras de sangue para cada espécie de ave foram inspecionadas para analisar os parasitas internos. Durante o presente estudo, foram examinadas 17 espécies de endoparasitas, 14 de amostras fecais e 3 de sangue. Foram estudadas duas espécies de ectoparasitas, ou seja, o ácaro Dermanyssus gallinae 42% e o carrapato aviário Args persicus 41%. Os parasitas sanguíneos incluíram Plasmodium juxtanucleare 50%, Leucoctoyzoon simond com prevalência parasitária de 40% e Aegyptinella pullorum com prevalência parasitária de 40%. As espécies parasitas registradas em amostras fecais incluíram 6 espécies de nematoides viz. Allodpa suctoria 2%, Syngamus traqueia com prevalência parasitária de 60%, Capillaria annulata 37,5%, Ascardia galli 24%, Capillaria anatis 40% e Heterakis gallinarum 28,3%. Da mesma forma, duas espécies de trematódeos viz. Prosthogonimus ovatus com prevalência parasitária de 50% e Prosthogonimus macrorchis 21% também foram documentados em amostras fecais de aves. Espécies de cestoide único Raillietina echinobothrida com prevalência parasitária de 72% e 3 espécies de protozoários, isto é, Eimeria maxima com prevalência parasitária de 21%, Giardia lamblia 41% e Histomonas meleagridis 18% foram documentadas durante a análise corpológica. Em nossa recomendação, o saneamento adequado, medicação e vacinação de invólucros de pássaros são sugeridos para evitar parasitas.

Genetic variations and phylogenetic relationship of genus Uromastyx from Punjab Pakistan / Variações genéticas e relação filgenética do gênero Uromastyx de Punjab, Paquistão

Abstract During the present study, specimens were collected from selected sites of Cholistan desert and Kalabagh Game Reserve, Punjab province, Pakistan. Each captured specimen was tagged with voucher number and morphometric measurements were taken. The average snout to vent length was 172.559±1.40 mm and average weight was 92.1±1.30 g. The DNA of Uromastyx hardwickii was amplified and sequenced using 16S rRNA primer set. The obtained DNA sequence has shown reliable and clear species identification. After trimming ambiguous bases, the obtained 16S rRNA fragment was 520 bp while 16S rRNA fragments aligned with closely matched sequence from NCBI comprised of 510 bp. Closely matched sequences of genus Uromastyx were retrieved from NCBI in blast searches. Neighbour-joining tree of genus Uromastyx was constructed based on p-distance using MEGA X. The mean intraspecific variation was 0.095±0.01 while intraspecific variation was ranging from 0-1%. Similarly, interspecific variation of Uromastyx hardwikii with Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti was 0-12%, 0-19%, 0-19%, 0-20%, 12-19% respectively. The newly produced DNA was submitted to NCBI and accession number was obtained (MW052563.1). Results of current study provided information about the molecular and morphological identification of Genus Uromastyx. In our recommendation, comprehensive molecular based identification of Pakistan's reptiles is required to report any new or subspecies from country.

Resumo Durante o presente estudo, os espécimes foram coletados em locais selecionados do deserto do Cholistan e da Reserva de Caça de Kalabagh, província de Punjab, Paquistão. Cada espécime capturado foi etiquetado com o número do comprovante e medidas morfométricas foram realizadas. O comprimento médio do focinho à cloaca foi de 172,559 ± 1,40 mm, e o peso médio foi de 92,1 ± 1,30 g. O DNA de Uromastyx hardwickii foi amplificado e sequenciado usando o conjunto de primer 16S rRNA. A sequência de DNA obtida mostrou identificação de espécies confiável e clara. Após o corte de bases ambíguas, o fragmento de rRNA 16S obtido tinha 520 pb, enquanto os fragmentos de rRNA 16S alinhados com a sequência próxima do NCBI composta por 510 pb. Sequências semelhantes do gênero Uromastyx foram recuperadas do NCBI em pesquisas de explosão. A árvore de união de vizinhos do gênero Uromastyx foi construída com base na distância-p usando MEGA X. A variação intraespecífica média foi de 0,095 ± 0,01, enquanto a variação intraespecífica foi de 0-1%. Da mesma forma, a variação interespecífica de Uromastyx hardwikii com Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti foi de 0-12%, 0-19%, 0-19%, 0-20%, 12-19%, respectivamente. O DNA recém-produzido foi submetido ao NCBI e o número de acesso foi obtido (MW052563.1). Os resultados do estudo atual forneceram informações sobre a identificação molecular e morfológica do Gênero Uromastyx. Em nossa recomendação, a identificação de base molecular abrangente de répteis do Paquistão é necessária para relatar qualquer nova ou subespécie do país.

Secure and Stable Wireless Communication for an Ingestible Device.

Wireless communication enables an ingestible device to send sensor information and support external on-demand operation while in the gastrointestinal (GI) tract. However, it is challenging to maintain stable wireless communication with an ingestible device that travels inside the dynamic GI environment as this environment easily detunes the antenna and decreases the antenna gain. In this paper, we propose an air-gap based antenna solution to stabilize the antenna gain inside this dynamic environment. By surrounding a chip antenna with 1 ~ 2 mms of air, the antenna is isolated from the environment, recovering its antenna gain and the received signal strength by 12 dB or more according to our in vitro and in vivo evaluation in swine. The air gap makes margin for the high path loss, enabling stable wireless communication at 2.4 GHz that allows users to easily access their ingestible devices by using mobile devices with Bluetooth Low Energy (BLE). On the other hand, the data sent or received over the wireless medium is vulnerable to being eavesdropped on by nearby devices other than authorized users. Therefore, we also propose a lightweight security protocol. The proposed protocol is implemented in low energy without compromising the security level thanks to the base protocol of symmetric challenge-response and Speck, the cipher that is optimized for software implementation.

Studies on parasitic prevalence in pet birds from Punjab, Pakistan / Estudos de prevalência parasítica em pássaros de estimação de Punjab, Paquistão

During this one year study, blood and fecal samples of doves (Zenaida asiatica), ducks (Anas platyrhynchos), pigeons (Columba livia), partridges (Alectoris chukar), turkeys (Meleagris gallopavo) and goose (Chen caerulescens) were collected to assess the parasitic prevalence in these birds. The birds were kept at Avian Conservation and Research Center, Department of Wildlife and Ecology, University of Veterinary and Animal Sciences, Lahore. All these avian species were kept in separate cages and their entire body was inspected on regularly basis to record external parasites. For internal parasites, 100 blood and 100 fecal samples for each species were analyzed. During present study, two species of ectoparasites i.e. fowl ticks (Args persicus) and mite (Dermanyssus gallinae) while 17 species of endoparasites; three from blood and 14 from fecal samples were identified. Prevalence of blood parasites was Plasmodium juxtanucleare 29.3%, Aegyptinella pullorum 15% and Leucoctoyzoon simond 13%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Syngamus trachea with parasitic prevalence of 50%, Capillaria anatis 40%, Capillaria annulata 37.5%, Heterakis gallinarum 28.3%, Ascardia galli 24% and Allodpa suctoria 2%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 12.1% and Prosthogonimus macrorchis 9.1% were also recorded from fecal samples of the birds. Single cestode species Raillietina echinobothrida having parasitic prevalence of 27% and 3 protozoan species i.e. Eimeria maxima having prevalence 20.1%, Histomonas meleagridis 8% and Giardia lamblia 5.3% were recorded. In our recommendation, proper medication and sanitation of the bird's houses and cages is recommended to avoid parasites.

Durante este estudo de um ano, amostras de sangue e fezes de pombos (Zenaida asiatica), patos (Anas platyrhynchos), pombos (Columba livia), perdizes (Alectoris chukar), perus (Meleagris gallopavo) e ganso (Chen caerulescens) foram coletados para avaliar a prevalência de parasitas nessas aves. As aves foram mantidas no Centro de Conservação e Pesquisa de Aves, Departamento de Vida Selvagem e Ecologia, Universidade de Veterinária e Ciências Animais, Lahore. Todas essas espécies de aves foram mantidas em gaiolas separadas e todo o seu corpo foi inspecionado regularmente para registrar parasitas externos. Para parasitas internos, foram analisadas 100 amostras de sangue e 100 amostras fecais de cada espécie. Durante o presente estudo, duas espécies de ectoparasitas, ou seja, carrapatos de aves (Args persicus) e ácaros (Dermanyssus gallinae), enquanto 17 espécies de endoparasitas, três de sangue e 14 de amostras fecais, foram identificadas. Os parasitas sanguíneos prevalentes foram Plasmodium juxtanucleare, 29,3%, Aegyptinella pullorum, 15%, e Leucoctoyzoon simond, 13%. As espécies parasitas registradas em amostras fecais incluíram 6 espécies de nematoides viz. Syngamus traqueia com prevalência parasitária de 50%, Capillaria anatis, 40%, Capillaria annulata, 37,5%, Heterakis gallinarum, 28,3%, Ascardia galli, 24% e Allodpa suctoria, 2%. Da mesma forma, duas espécies de trematódeos viz. Prosthogonimus ovatus com prevalência parasitária de 12,1% e Prosthogonimus macrorchis, 9,1%, também foram registrados nas amostras fecais das aves. Espécies de cestoide único Raillietina echinobothrida com prevalência parasitária de 27% e 3 espécies de protozoários, ou seja, Eimeria maxima tendo prevalência de 20,1%, Histomonas meleagridis, 8%, e Giardia lamblia, 5,3%, foram registradas. Em nossa recomendação, são indicados medicação adequada e saneamento das casas e gaiolas dos pássaros para evitar parasitas.

Studies on parasitic prevalence in pet birds from Punjab, Pakistan

Abstract During this one year study, blood and fecal samples of doves (Zenaida asiatica), ducks (Anas platyrhynchos), pigeons (Columba livia), partridges (Alectoris chukar), turkeys (Meleagris gallopavo) and goose (Chen caerulescens) were collected to assess the parasitic prevalence in these birds. The birds were kept at Avian Conservation and Research Center, Department of Wildlife and Ecology, University of Veterinary and Animal Sciences, Lahore. All these avian species were kept in separate cages and their entire body was inspected on regularly basis to record external parasites. For internal parasites, 100 blood and 100 fecal samples for each species were analyzed. During present study, two species of ectoparasites i.e. fowl ticks (Args persicus) and mite (Dermanyssus gallinae) while 17 species of endoparasites; three from blood and 14 from fecal samples were identified. Prevalence of blood parasites was Plasmodium juxtanucleare 29.3%, Aegyptinella pullorum 15% and Leucoctoyzoon simond 13%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Syngamus trachea with parasitic prevalence of 50%, Capillaria anatis 40%, Capillaria annulata 37.5%, Heterakis gallinarum 28.3%, Ascardia galli 24% and Allodpa suctoria 2%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 12.1% and Prosthogonimus macrorchis 9.1% were also recorded from fecal samples of the birds. Single cestode species Raillietina echinobothrida having parasitic prevalence of 27% and 3 protozoan species i.e. Eimeria maxima having prevalence 20.1%, Histomonas meleagridis 8% and Giardia lamblia 5.3% were recorded. In our recommendation, proper medication and sanitation of the birds houses and cages is recommended to avoid parasites.

Resumo Durante este estudo de um ano, amostras de sangue e fezes de pombos (Zenaida asiatica), patos (Anas platyrhynchos), pombos (Columba livia), perdizes (Alectoris chukar), perus (Meleagris gallopavo) e ganso (Chen caerulescens) foram coletados para avaliar a prevalência de parasitas nessas aves. As aves foram mantidas no Centro de Conservação e Pesquisa de Aves, Departamento de Vida Selvagem e Ecologia, Universidade de Veterinária e Ciências Animais, Lahore. Todas essas espécies de aves foram mantidas em gaiolas separadas e todo o seu corpo foi inspecionado regularmente para registrar parasitas externos. Para parasitas internos, foram analisadas 100 amostras de sangue e 100 amostras fecais de cada espécie. Durante o presente estudo, duas espécies de ectoparasitas, ou seja, carrapatos de aves (Args persicus) e ácaros (Dermanyssus gallinae), enquanto 17 espécies de endoparasitas, três de sangue e 14 de amostras fecais, foram identificadas. Os parasitas sanguíneos prevalentes foram Plasmodium juxtanucleare, 29,3%, Aegyptinella pullorum, 15%, e Leucoctoyzoon simond, 13%. As espécies parasitas registradas em amostras fecais incluíram 6 espécies de nematoides viz. Syngamus traqueia com prevalência parasitária de 50%, Capillaria anatis, 40%, Capillaria annulata, 37,5%, Heterakis gallinarum, 28,3%, Ascardia galli, 24% e Allodpa suctoria, 2%. Da mesma forma, duas espécies de trematódeos viz. Prosthogonimus ovatus com prevalência parasitária de 12,1% e Prosthogonimus macrorchis, 9,1%, também foram registrados nas amostras fecais das aves. Espécies de cestoide único Raillietina echinobothrida com prevalência parasitária de 27% e 3 espécies de protozoários, ou seja, Eimeria maxima tendo prevalência de 20,1%, Histomonas meleagridis, 8%, e Giardia lamblia, 5,3%, foram registradas. Em nossa recomendação, são indicados medicação adequada e saneamento das casas e gaiolas dos pássaros para evitar parasitas.

Prevalence of parasites in selected captive bird species.

Blood and fecal samples of chukar partridge (Alectoris chukar), albino pheasant (Phasianus colchicus), silver pheasant (Lophura nycthemera), rose-ringed parakeet (Psittacula krameri) and turkeys (Meleagris gallopavo) were analyzed to check parasitic prevalence. To record parasites these five avian species were placed kept in separate cages at Avian Conservation and Research Center, Department of Wildlife an Ecology, University of Veterinary and Animal Sciences, Lahore, Pakistan. 100 fecal and 100 blood samples for each bird species were inspected to analyze internal parasites. During present study, 17 species of endoparasites 14 from fecal samples and three from blood were examined. Two species of ectoparasites i.e. mite Dermanyssus gallinae 42% and fowl ticks Args persicus 41%were studied. Blood parasites included Plasmodium juxtanucleare 50%, Leucoctoyzoon simond having parasitic prevalence 40%, and Aegyptinella pullorum having parasitic prevalence of 40%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Allodpa suctoria 2%. Syngamus trachea with parasitic prevalence of 60%, Capillaria annulata 37.5%, Ascardia galli 24%, Capillaria anatis 40% and Heterakis gallinarum 28.3%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 50% and Prosthogonimus macrorchis 21% were also documented from fecal avian samples . Single cestode species Raillietina echinobothrida having parasitic prevalence of 72% and 3 protozoan species i.e. Eimeria maxima having parasitic prevalence of 21%, Giardia lamblia 41% and Histomonas meleagridis 18% were documented during corpological analysis. In our recommendation, proper sanitation, medication and vaccination of bird's enclousres are suggested to avoid parasites.

Genetic variations and phylogenetic relationship of genus Uromastyx from Punjab Pakistan.

During the present study, specimens were collected from selected sites of Cholistan desert and Kalabagh Game Reserve, Punjab province, Pakistan. Each captured specimen was tagged with voucher number and morphometric measurements were taken. The average snout to vent length was 172.559±1.40 mm and average weight was 92.1±1.30 g. The DNA of Uromastyx hardwickii was amplified and sequenced using 16S rRNA primer set. The obtained DNA sequence has shown reliable and clear species identification. After trimming ambiguous bases, the obtained 16S rRNA fragment was 520 bp while 16S rRNA fragments aligned with closely matched sequence from NCBI comprised of 510 bp. Closely matched sequences of genus Uromastyx were retrieved from NCBI in blast searches. Neighbour-joining tree of genus Uromastyx was constructed based on p-distance using MEGA X. The mean intraspecific variation was 0.095±0.01 while intraspecific variation was ranging from 0-1%. Similarly, interspecific variation of Uromastyx hardwikii with Saara asmussi, Uromastyx alfredschmidti, Uromastyx geyri, Uromastyx thomasi, Uromastyx alfredschmidti was 0-12%, 0-19%, 0-19%, 0-20%, 12-19% respectively. The newly produced DNA was submitted to NCBI and accession number was obtained (MW052563.1). Results of current study provided information about the molecular and morphological identification of Genus Uromastyx. In our recommendation, comprehensive molecular based identification of Pakistan's reptiles is required to report any new or subspecies from country.

Genomic Signatures in HPV-Associated Tumors.

Papillomaviruses dysregulate the G1/S cell cycle transition in order to promote DNA synthesis in S phase, which is a requirement for viral replication. The human papillomaviruses (HPV) E6 and E7 oncoproteins mediate degradation of the cell cycle regulators p53 and Rb, which are two of the most universally disrupted tumor-suppressor genes in all of cancer. The G1/S checkpoint is activated in normal cells to allow sufficient time for DNA repair in G1 before proceeding to replicate DNA and risk propagating unrepaired errors. The TP53 pathway suppresses a variety of such errors, including translocation, copy number alterations, and aneuploidy, which are thus found in HPV-associated tumors similarly to HPV-negative tumors with other mechanisms of TP53 disruption. However, E6 and E7 maintain a variety of other virus-host interactions that directly disrupt a growing list of other DNA repair and chromatin remodeling factors, implying HPV-specific repair deficiencies. In addition, HPV-associated squamous cell carcinomas tumors clinically respond differently to DNA damaging agents compared to their HPV negative counterparts. The focus of this review is to integrate three categories of observations: (1) pre-clinical understanding as to the effect of HPV on DNA repair, (2) genomic signatures of DNA repair in HPV-associated tumor genomes, and (3) clinical responses of HPV-associated tumors to DNA damaging agents. The goals are to try to explain why HPV-associated tumors respond so well to DNA damaging agents, identify missing pieces, and suggest clinical strategies could be used to further improve treatment of these cancers.

Studies on parasitic prevalence in pet birds from Punjab, Pakistan.

During this one year study, blood and fecal samples of doves (Zenaida asiatica), ducks (Anas platyrhynchos), pigeons (Columba livia), partridges (Alectoris chukar), turkeys (Meleagris gallopavo) and goose (Chen caerulescens) were collected to assess the parasitic prevalence in these birds. The birds were kept at Avian Conservation and Research Center, Department of Wildlife and Ecology, University of Veterinary and Animal Sciences, Lahore. All these avian species were kept in separate cages and their entire body was inspected on regularly basis to record external parasites. For internal parasites, 100 blood and 100 fecal samples for each species were analyzed. During present study, two species of ectoparasites i.e. fowl ticks (Args persicus) and mite (Dermanyssus gallinae) while 17 species of endoparasites; three from blood and 14 from fecal samples were identified. Prevalence of blood parasites was Plasmodium juxtanucleare 29.3%, Aegyptinella pullorum 15% and Leucoctoyzoon simond 13%. Parasitic species recorded from fecal samples included 6 species of nematodes viz. Syngamus trachea with parasitic prevalence of 50%, Capillaria anatis 40%, Capillaria annulata 37.5%, Heterakis gallinarum 28.3%, Ascardia galli 24% and Allodpa suctoria 2%. Similarly, two species of trematodes viz. Prosthogonimus ovatus having parasitic prevalence of 12.1% and Prosthogonimus macrorchis 9.1% were also recorded from fecal samples of the birds. Single cestode species Raillietina echinobothrida having parasitic prevalence of 27% and 3 protozoan species i.e. Eimeria maxima having prevalence 20.1%, Histomonas meleagridis 8% and Giardia lamblia 5.3% were recorded. In our recommendation, proper medication and sanitation of the bird's houses and cages is recommended to avoid parasites.

We Need to Know: A Call for Interdisciplinary Education on COVID-19.

COVID-19 disrupted numerous disciplines which led to widespread misinformation on the virus. Thirteen students from across the USA designed a web-based conference, or "webinar," to minimize the misinformation among student populations. Professionals presented the current and possible future impacts of COVID-19 in their respective fields. Pre- and post-conference surveys were administered to the attendees to gauge the impact of the conference. Survey results demonstrated increased knowledge and a lower degree of feeling overwhelmed by COVID-19 information overall, indicating a niche use for webinars during the COVID-19 pandemic and beyond.

Measuring nonhomologous end-joining, homologous recombination and alternative end-joining simultaneously at an endogenous locus in any transfectable human cell.

Double strand break (DSB) repair primarily occurs through 3 pathways: non-homologous end-joining (NHEJ), alternative end-joining (Alt-EJ), and homologous recombination (HR). Typical methods to measure pathway usage include integrated cassette reporter assays or visualization of DNA damage induced nuclear foci. It is now well understood that repair of Cas9-induced breaks also involves NHEJ, Alt-EJ, and HR pathways, providing a new format to measure pathway usage. Here, we have developed a simple Cas9-based system with validated repair outcomes that accurately represent each pathway and then converted it to a droplet digital PCR (ddPCR) readout, thus obviating the need for Next Generation Sequencing and bioinformatic analysis with the goal to make Cas9-based system accessible to more laboratories. The assay system has reproduced several important insights. First, absence of the key Alt-EJ factor Pol θ only abrogates ∼50% of total Alt-EJ. Second, single-strand templated repair (SSTR) requires BRCA1 and MRE11 activity, but not BRCA2, establishing that SSTR commonly used in genome editing is not conventional HR. Third, BRCA1 promotes Alt-EJ usage at two-ended DSBs in contrast to BRCA2. This assay can be used in any system, which permits Cas9 delivery and, importantly, allows rapid genotype-to-phenotype correlation in isogenic cell line pairs.

A large outbreak of measles in the West Midlands, England, 2017-2018: descriptive epidemiology, control measures and lessons learnt.

In November 2017, eight confirmed measles cases were reported to Public Health England from a hospital in the West Midlands. A multidisciplinary Incident Management Team (IMT) was established to determine the extent of the problem and coordinate an outbreak response. Between 1 November 2017 and 4 June 2018, a total of 116 confirmed and 21 likely measles cases were linked to this outbreak; just under half (43%) were aged over 15 years of age. Fifty-five of the confirmed cases were hospitalised (48%) and no deaths were reported. At the start of the outbreak, cases were mostly individuals of Romanian origin; the outbreak subsequently spread to the wider population. Over the 8-month response, the IMT conducted the following control measures: extensive contact tracing, immediate provision of post-exposure prophylaxis, community engagement amongst specific high-risk groups, MMR awareness raising including catch-up campaigns and enhanced vaccination services at selected GP surgeries. Key challenges to the effective control measures included language difficulties limiting community engagement; delays in diagnosis, notification and appropriate isolation of cases; limited resources for contact tracing across multiple high-risk settings (including GPs and hospitals) and lack of timely data on vaccine coverage in sub-groups of the population to guide public health action.

Human papillomavirus 16 promotes microhomology-mediated end-joining.

Squamous cell carcinomas (SCCs) arising from aerodigestive or anogenital epithelium that are associated with the human papillomavirus (HPV) are far more readily cured with radiation therapy than HPV-negative SCCs. The mechanism behind this increased radiosensitivity has been proposed to be secondary to defects in DNA repair, although the specific repair pathways that are disrupted have not been elucidated. To gain insight into this important biomarker of radiosensitivity, we first examined genomic patterns reflective of defects in DNA double-strand break repair, comparing HPV-associated and HPV-negative head and neck cancers (HNSCC). Compared to HPV-negative HNSCC genomes, HPV+ cases demonstrated a marked increase in the proportion of deletions with flanking microhomology, a signature associated with a backup, error-prone double-strand break repair pathway known as microhomology-mediated end-joining (MMEJ). Then, using 3 different methodologies to comprehensively profile double-strand break repair pathways in isogenic paired cell lines, we demonstrate that the HPV16 E7 oncoprotein suppresses canonical nonhomologous end-joining (NHEJ) and promotes error-prone MMEJ, providing a mechanistic rationale for the clinical radiosensitivity of these cancers.

Suppression of ribosomal protein RPS6KB1 by Nexrutine increases sensitivity of prostate tumors to radiation.

Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations.

Outbreak of Salmonella enteritidis PT14b gastroenteritis at a restaurant in England: the use of molecular typing to achieve a successful prosecution.

OBJECTIVES: To describe an outbreak of Salmonella enteritidis phage type (PT) 14b in people who had eaten at a restaurant, and the investigation and subsequent prosecution of the food business operator (FBO). STUDY DESIGN: The local health protection team and environmental health department formed an outbreak control team to investigate the outbreak. METHODS: Epidemiological, microbiological, and environmental investigations were undertaken. Epidemiological investigations involved case finding and interviews. Microbiological investigation: stool samples from the suspected cases and environmental samples from the implicated food business were investigated. Salmonella isolates obtained were subjected to multiple locus variable-number tandem repeat analysis (MLVA) profiling and whole genome sequencing. In addition, adenosine triphosphate (ATP) hygiene swab tests were used to verify the quality of cleaning procedures and data loggers were used to determine the water temperature of the mechanical dishwasher. RESULTS: Fifteen cases of illness where the causative agent was shown to be S. enteritidis PT14b were identified, all of whom had eaten at the same restaurant. S. enteritidis PT14b was also identified from three of the 11 food and environmental samples taken at the restaurant and found to have the same MLVA profile as the cases. A case for prosecution was built and the FBO was successfully prosecuted in July 2015. CONCLUSIONS: This investigation highlighted that the use of molecular typing as part of thorough epidemiological, microbiological, and environmental investigations can present a robust case for prosecution against restaurants which pose a risk to public health.

Association between post-craniotomy Propionibacterium acnes infection and dural implants: a case-control study.

BACKGROUND: In 2011, 15 deep-seated Propionibacterium acnes infections were identified in patients following craniotomies in a hospital in the UK. AIM: To describe the outbreak and report findings from the investigation undertaken in order to identify the source and risk factors and inform control measures. METHODS: Data were obtained from hospital clinical records and included patient and surgical variables. Cases were defined as patients with microbiologically confirmed deep or organ space surgical site infection (SSI) caused by P. acnes following craniotomy undertaken in 2011. Four controls per case were randomly selected from patients who had a craniotomy in 2011 but who did not develop any SSI. The relationship between infection and putative exposures was examined using multivariate regression techniques. Infection prevention procedures and the theatre environment were reviewed to assess compliance with existing standards. FINDINGS: Fifteen cases and 65 controls were recruited. Odds of infection were higher for those who had a dural implant inserted during their operation [adjusted odds ratio (aOR): 14.6; 95% confidence interval (CI): 0.95-∞] and for those who had alcohol/Betadine®/chlorhexidine mix as a disinfectant (aOR: 7.9; 95% CI: 0.8-∞). Environmental investigations suggested that theatre ventilation systems delivered air exchange rates below the recommended standard. CONCLUSION: There was a positive association between using dural implants and P. acnes infection. Infection may have been facilitated by inefficient use of skin disinfectant and environmental factors. Recommendations included ongoing surveillance, the use of chlorhexidine skin disinfectant, ensuring adequate air exchanges and appropriate use of doors in theatre to minimize air turbulence.