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PARP10 is a mono-ADP-ribosyltransferase with multiple cellular functions, including proliferation, apoptosis, metabolism and DNA repair. PARP10 is overexpressed in a significant proportion of tumors, particularly breast and ovarian cancers. Identifying genetic susceptibilities based on PARP10 expression levels is thus potentially relevant for finding new targets for precision oncology. Here, we performed a series of CRISPR genome-wide loss-of-function screens in isogenic control and PARP10-overexpressing or PARP10-knockout cell lines, to identify genetic determinants of PARP10-mediated cellular survival. We found that PARP10-overexpressing cells rely on multiple DNA repair genes for survival, including ATM, the master regulator of the DNA damage checkpoint. Moreover, we show that PARP10 impacts the recruitment of ATM to nascent DNA upon replication stress. Finally, we identify the CDK2-Cyclin E1 complex as essential for proliferation of PARP10-knockout cells. Our work identifies a network of functionally relevant PARP10 synthetic interactions, and reveals a set of factors which can potentially be targeted in personalized cancer therapy.

Silvia Busquets,1,2 Marta Castillejo,1 Queralt Jové,1 Baptiste Jude,3 Patricia Mejías,1 Francisco J López-Soriano,1,2 Josep M Argilés1,2 1Cancer Research Group, Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; 2Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain; 3Laboratoire de Physiologie - EA 4324 ORPHY, IBSAM, Université de Bretagne Occidentale, Brest, FranceCorrespondence: Silvia BusquetsCancer Research Group, Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 643, Barcelona, 08028, SpainTel +34-934021002Fax +34-934021559Email silviabusquets@ub.eduBackground: During cancer cachexia, both skeletal muscle and adipose tissue losses take place. The use of β 2-agonists, formoterol in particular, has proven to be very successful in the treatment of the syndrome in pre-clinical models. The object of the present research was to study the effects of a combination of formoterol and dantrolene, an inhibitor of the ryanodine receptor 1 (RyR1), on body weight loss and cachexia in tumour-bearing animals.Methods: Rats were separated into two groups: controls (C) and tumour bearing (TB). TB group was further subdivided into four groups: untreated (saline as a vehicle), treated with Formoterol (TF) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with Dantrolene (TD) (5 mg/kg body weight in saline, subcutaneous (s.c.), daily), and double-treated treated (TFD) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and Dantrolene (5 mg/kg body weight, subcutaneous (s.c.), daily). 7 days after tumour transplantation, muscle weight, grip force, and total physical activity were specified in all experimental groups.Results: While formoterol had, as in previous studies, a very positive effect in reducing muscle weight loss, dantrolene had no effects, neither on skeletal muscle nor on any of the parameters studied. Finally, the combined treatment (formoterol and dantrolene) did not result in any significant benefit on the action of the β 2-agonist.Conclusion: It is concluded that, in the preclinical cachectic model used, no synergy exists between β 2-agonist treatment and the blockade of sarcoplasmic-calcium flow.Keywords: cancer cachexia, skeletal muscle, dantrolene, formoterol, calcium, ryanodine receptor 1

Background: Malnutrition is an important clinical outcome amongst HIV patients in developing countries and in Uganda, there is scarcity of information on its prevalence and risk factors amongst HIV adult patients. Methods: A cross-sectional study amongst 253 HIV patients in Bushenyi district assessed their nutritional status using the body mass index (BMI) and mid-upper arm circumference (MUAC), and a questionnaire was used to identify major risk factors. Results: The mean age of the study participants was 38.74 ± 0.80 yrs, while females and males were 52.2% and 47.8% respectively. Prevalence of malnutrition was 10.28% (95% CI: 6.82 – 14.69) in the study. Major socio-economic factors associated with malnutrition were being female, unemployed, dependent and with many family members. Patients with op- portunistic infections, low adherence to HAART, and stage of HIV/AIDS had a higher risk of malnutrition. Discussion: In rural communities, a majority of malnourished patients are elderly and these were identified as priority groups for HIV outreach campaigns. The current policy of prioritizing children and women is outdated due to changing disease dynamics, thus showing a need to revise extension service provision in rural communities. Conclusion: Malnutrition is a threat in HIV adult patients in rural communities of Uganda. Keywords: Malnutrition; HIV adult patients; Bushenyi district; Uganda.

Supply chain management strategies will help the prawn and crab growers mitigate and adapt to the impact of various disruptions such as typhoons, water-borne diseases, and climate change. The study was conducted to determine the production and disruptions and prawn and crab basis for supply chain management strategies of the growers. The study employed a descriptive research design using quantitative data. The study used secondary data for performance and disaster history. A content analysis was used in processing the data. The researchers validated the findings and results of the study, and a random interview was conducted. Findings revealed that disruptions affect the production of prawn and crab, growers have their fishing technique and management practices, supply chain management strategies were not prioritized for value-adding and technology accessibility. A supply chain management strategy may be employed to operate and produce prawns and crabs in the Province of Capiz to achieve profitability and sustainability. It should be noted that the data is from 2011 to 2017. The data coverage is the Province of Capiz and focuses on the volume and value of prawns and crab (tiger prawn, endeavor prawn, and mud crab). Supply Chain Management (SCM) of the growers in the Province of Capiz is not given priority in improving its competitive performance of the entire network through the application of an integrated approach to the planning and control of material, information, and cash streams. Also, it has less priority on the practice of the business in breaking changes in sustainable fishing practices to improve business performance. No network is present in the province solely on the same industry of production of prawns and crabs. It is expected that the proposed SCM strategies are all contextualized based on the present needs of the growers. These strategies can be used to become proactive and agile in decision-making and facing possible disruptions.

Introduction and importance Seromucinous hamartoma is a rare benign glandular proliferation arising from the respiratory epithelium, which was originally described by Baillie and Batsakis in 1974. Since this time, case reports started to be published on SH, as a middle aged and elderly disease, here we report a case of a pediatric patient who found to have SH. Presentation of the case 2-year-old girl, brought by her parent with a complain of a mass at the right medial canthal area for one year. Clinical discussion As this pediatric patient presented with long standing history of right medial canthal area, we made out differential diagnosis list, with keeping congenital midline nasal masses such as nasal glioma, dermoid, and encephalocele at the top of our differentials, followed by inflammatory disease and lacreimal system disease. After bedside clinical assessment and imaging, patient underwent endoscopic sinus surgery for surgical excision, histopathology analysis came as Seromucinous hamartoma. Postoperative course was unremarkable, patient is disease- free for 18 months, till her most recent follow up. With no additional treatment or recurrence. Conclusion This case report indicates that seromucinous hamartoma should always be considered in the differential diagnosis of pediatric sinonasal disease. According to the literature review we did; this is the first case reported in such an age group., Highlights • Sinonasal Hamartomas were originally described in Baillie and Batsakis in 1974, in patient who presented with polypoidal mass at the posterior vomer. • Seromucinous hamartoma (SH) is rare benign glandular proliferation of the sinonasal tract as classified by WHO. • SH is middle and advanced aged disease, posterior septum in the most common site. Females are slightly higher than males. They are usually asymptomatic. However, if they develop symptoms, they present with nasal obstruction or epistaxis. • Diagnosis made by clinical examination including nasal endoscopy, imaging and histopathological analysis. Treatment is simple surgical excision, either external approach or by endoscopic sinus surgery, recurrence is rare, however reported in the literature

Background Improved Water, Sanitation and Hygiene (WASH) in Healthcare facilities (HCFs) is of significant public health importance. It is associated with a reduction in the transmission of healthcare acquired infections (HAIs), increased trust and uptake of healthcare services, cost saving from infections averted, increased efficiency and improved staff morale. Despite these benefits, there is limited evidence on availability of WASH services in HCFs in the Greater Kampala Metropolitan Area (GKMA). This study assessed the availability and status of WASH services within HCFs in the GKMA in order to inform policy and WASH programming. Methods A cross-sectional study was conducted in 60 HCFs. Availability of WASH services in the study HCFs was assessed using a validated WASH Conditions (WASHCon) tool comprising of structured interviews, HCF observations and microbial water quality analysis. Data were analysed using Stata 14 software and R software. Results Overall, 84.5% (49/58) and 12.1% (7/58) of HCFs had limited and basic WASH service respectively. About 48.3% (28/58) had limited water service, 84.5% (49/58) had limited sanitation service, 50.0% (29/58) had limited environmental cleanliness service, 56.9% (33/58) had limited hand hygiene service, and 51.7% (30/58) had limited waste management service. About 94.4% of public HCFs had limited WASH service compared to only 68.2% of private not for profit facilities. More health centre IIIs, 92.5% and health centre IVs (85.7%) had limited WASH service compared to hospitals (54.5%). Conclusions Our findings indicate that provision of water, sanitation, hand hygiene, environmental cleanliness, and health care waste management services within HCFs is largely hindered by structural and performance limitations. In spite of these limitations, it is evident that environmental cleanliness and treatment of infectious waste can be attained with better oversight and dedicated personnel. Attaining universal WASH coverage in HCFs will require deliberate and strategic investments across the different domains.

Background: Improved Water, Sanitation and Hygiene (WASH) in Healthcare facilities (HCFs) is of significant public health importance. It is associated with a reduction in the transmission of healthcare acquired infections (HAIs), increased trust and uptake of healthcare services, cost saving from infections averted, increased efficiency and improved staff morale. Despite these benefits, there is limited evidence on availability of WASH services in HCFs in the Greater Kampala Metropolitan Area (GKMA). This study assessed the availability of WASH services within HCFs in the GKMA in order to inform policy and WASH programming.Methods: A cross-sectional study was conducted in 60 HCFs. Availability of WASH services in the study HCFs was assessed using a validated WASH Conditions (WASHCon) tool comprising of structured interviews, HCF observations and microbial water quality analysis. Data were analysed using Stata 14 software and R software. Results: Overall, 84.5% (49/58) and 12.1% (7/58) of HCFs had limited and basic WASH service respectively. About 48.3% (28/58) had limited water service, 84.5% (49/58) had limited sanitation service, 50.0% (29/58) had limited environmental cleanliness service, 56.9% (33/58) had limited hand hygiene service, and 51.7% (30/58) had limited waste management service. About 94.4% of public HCFs had limited WASH service compared to only 68.2% of private not for profit facilities. More health centre IIIs, 92.5% and health centre IVs (85.7%) had limited WASH service compared to hospitals (54.5%).Conclusions: Our findings indicate that provision of water, sanitation, hand hygiene, environmental cleanliness, and health care waste management services within HCFs are largely hindered by structural and performance limitations. In spite of these limitations, it is evident that environmental cleanliness and treatment of infectious waste can be attained with better oversight and dedicated personnel. Attaining universal WASH coverage in HCFs will require deliberate and strategic investments across the different domains.

Background: Improved Water, Sanitation and Hygiene (WASH) services in Health Care Facilities (HCFs) is of significant public health importance. It is associated with a reduction in the transmission of hospital acquired infections (HAIs), increased trust and uptake of healthcare services, cost saving from infections averted, increased efficiency and improved staff morale. Despite these benefits, there is limited evidence on the status of WASH in HCFs in the Greater Kampala Metropolitan Area (GKMA). This study assessed the status of WASH within HCFs in the GKMA in order to inform policy and WASH programming.Methods: A cross-sectional study was conducted in 60 HCFs. The status of WASH in the study facilities was assessed using a validated WASH Conditions (WASHCon) tool comprising of structured interviews, HCF observations and microbial water quality analysis. Data were analysed using Stata 14 software and R software. The relationships between WASH status and HCF characteristics were assessed using Fishers’ exact tests.Results: Overall, 84.5% (49/58) and 12.1% (7/58) of HCFs had limited and basic WASH status respectively. About 48.3% (28/58) had a limited water supply status, 84.5% (49/58) had limited sanitation status, 50.0% (29/58) had limited environmental cleanliness status, 56.9% (33/58) had limited hand hygiene status and 51.7% (30/58) had limited waste management status. Overall, there were significant differences in water supply status by ownership of the HCF and level of HCF. There was a significant statistical difference in WASH status between public and private not for profit facilities (p = 0.021). A significant difference was also observed in WASH status between hospitals and lower levels HCFs (p = 0.004). Conclusion: Majority of the HCFs in the GKMA had limited access to all WASH service domains i.e. water supply, sanitation, hand hygiene, environmental cleanliness and healthcare waste management. We recommend deliberate increased investments in WASH for healthcare services, especially for sanitation and hand hygiene provisions which were in the poorest state. Improvements in WASH conditions will not only minimize the risk of transmission of HAIs but also associated costs.

Additional file 1. Definitions of WASH status indicators (domains)