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Parathyroid carcinoma (PC) is a very rare endocrine cancer with aggressive behavior, a high metastatic potential, and a poor prognosis. Surgical resection of affected gland(s) and other involved structures is the elective therapy. Pre-operative and intra-operative differential diagnosis with benign parathyroid adenoma remains a challenge. The lack of a clear pre-operative diagnosis does not allow one, in many cases, to choose the correct surgical approach to malignant PC, increasing persistence, the recurrence rate, and the risk of metastases. An initial wrong diagnosis of parathyroid adenoma, with a minimally invasive parathyroidectomy, is associated with over 50% occurrence of metastases after surgery. Genetic testing could help in identifying patients at risk of congenital PC (i.e., CDC73 gene) and in driving the choice of neck surgery extension. Targeted effective treatments, other than surgery, for advanced and metastatic PC are needed. The pathogenesis of malignant parathyroid carcinogenesis is still largely unknown. In the last few years, advanced molecular techniques allowed researchers to identify various genetic abnormalities and epigenetic features characterizing PC, which could be crucial for selecting molecular targets and developing novel targeted therapeutic agents. We reviewed current findings in PC genetics, epigenetics, and proteomics and state-of-the-art therapies.

Osteoporosis (OP) is the most common skeletal disease, caused by a lack of balance between osteoclast and osteoblast activity. This results in erosion overriding the deposition of new bone matrix, consequently leading to low-quality bone and an increased risk of incurring fragility fractures. Dual energy X-ray absorptiometry is the gold standard for the diagnosis of OP, while anti-osteoporotic drugs are the gold standard for its treatment. However, due to limitations to their use, researchers have turned to epigenetics as a substantial source of molecules that could potentially be used as diagnostic, prognostic, and therapeutic biomarkers for OP. In particular, long non-coding RNAs (lncRNAs) possess special biological properties that could open new horizons in the field of personalized medicine. This mini review seeks to offer an overview of the studies carried out in the last year on the different lncRNAs that could be involved in the pathogenesis of OP and that could pave the way for the development of innovative therapeutic strategies for this disease.

n recent years the endocannabinoid system (ES) has been recognized to play an important role in the regulation of several physiological processes, including pain perception, appetite control, and motor function development. This system has recently been recognized to be present in bone and joint tissues, playing a role in the regulation of bone and joint physiology. The ES seems to play its role mainly by acting on its receptors and thanks to the demonstrated ability of bone cells to synthesize the principal endocannabinoids (i.e., anandamide and 2-arachidonoylglycerol), which can act on bone remodeling and metabolism. Cannabinoids have also been shown to be produced within synovial tissues, and recent studies have shown that cannabinoid receptor ligands are effective in the treatment of inflammatory arthritis. In recent years synthetic endocannabinoid-like compounds and phytocannabinoids, which are the principal components of Cannabis sativa, have also started to be studied as molecules that could play a role not only in bone physiology, but also in the pathogenesis of osteoporosis, the most common bone disease, and in the inflammatory processes underlying osteoarthritis. Accumulating evidence that cannabinoids and their receptors play an important role in bone metabolism and in the regulation of the immune response is now starting to show us the true future therapeutic potential of cannabinoids, and of the phytocannabinoids contained in Cannabis sativa, in the treatment of bone loss and joint diseases. Here we summarize the role of the cannabinoids and their receptors in bone metabolism, osteoporosis, and joint disease.

Osteoporosis is related to dysfunction of the crosstalk between osteoblasts and osteoclasts, the cells involved in the formation and resorption of bone, respectively. Oxidative stress and inflammation are involved in the pathogenesis of osteoporosis. Because of their antioxidant and anti-inflammatory properties, natural compounds such as polyphenols extensively present in fruit, vegetables, wine, tea, extra virgin olive oil, and berries, play an important protective role in disorders of bone metabolism, including osteoporosis. A diet rich in polyphenol-rich fruit and vegetables can reduce bone mineral density loss, decreasing the risk of fracture and preserving lifestyle quality. The aim of the present review is to highlight the principal mechanisms involved in the role played by the main dietary polyphenols in the prevention and/or treatment of osteoporosis.

Objective: To evaluate the long-term effectiveness, safety, and tolerability of erenumab in a real-world migraine population, looking for putative predictors of responsiveness. Background: Erenumab proved to be effective, safe, and well tolerated in the prevention of episodic migraine (EM) and chronic migraine (CM) in long-term extension studies of double-blind, placebo-controlled trials in patients with no more than two (EM) or three (CM) prior preventive treatment failures. Methods: A 48-week, multicenter, longitudinal cohort real-life study was conducted at 15headache centers across eight Italian regions between December 20, 2018 and July 31, 2020. We considered all consecutive patients with high-frequency episodic migraine (HFEM) or CM aged 18–65years. Each patient was treated with erenumab 70mg, administered monthly. The dose was switched to 140mg in nonresponders and in responders who had become nonresponders for at least 4weeks. Change in monthly migraine days (MMDs) or monthly headache days (MHDs) at Weeks 45–48 compared with baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake, achievement of a ≥50%, ≥75%, or 100% reduction in migraine or headache days, and any change in the Visual Analogue Scale (VAS) and Headache Impact Test-6 scores (HIT-6) during the same time interval. Results: A total of 242 patients with migraine received at least one dose of erenumab 70mg and were considered for safety analysis, whereas 221 received a monthly erenumab dose for ≥48weeks and were included in the effectiveness and safety analysis set. All patients had previously been treated unsuccessfully with ≥3migraine-preventive medication classes. From baseline to Weeks 45–48, erenumab treatment reduced MMD by 4.3±5.3(mean±SD) in patients with HFEM, and MHD by 12.8±8.9 (mean±SD) in subjects with CM. VAS and HIT-6scores were decreased by 1.8±1.9 (mean±SD) and 12.3±11 (mean±SD) in HFEM, and by 3.0±2.2 (mean±SD) and 13.1±11.2 (mean±SD) in CM. Median monthly analgesic intake passed from 11.0 (interquartile range [IQR] 10.0–13.0) to 5 (IQR 2.0–8.0) in HFEM and from 20.0 (IQR 15.0–30.0) to 6.0 (IQR 3.8–10.0) in CM. The ≥50% responders were 56.1% (32/57) in HFEM and 75.6% (124/164) in CM; ≥75% responders were 31.6% (18/57) and 44.5% (73/164); and 100% responders were 8.8% (5/57) and 1.2% (2/164), respectively. At Week 48, 83.6% (137/164) of patients with CM had reverted to EM. Erenumab was safe and well tolerated. Responsiveness to erenumab was positively associated with cutaneous allodynia (OR: 5.44, 95% CI: 1.52–19.41; p=0.009) in HFEM. In patients with CM, ≥50% responsiveness was positively associated with male sex (OR: 2.99, 95% CI: 1.03–8.7; p=0.044) and baseline migraine frequency (OR: 1.12, 95% CI: 1.05–1.20; p=0.001) and negatively associated with psychiatric comorbidities (OR: 0.37, 95% CI: 0.15–0.87; p=0.023) and prior treatment failures (OR: 0.77, 95% CI: 0.64–0.92; p=0.004). Conclusions: Long-term (48-week) erenumab treatment provides sustained effectiveness, safety, and tolerability in real-life patients with HFEM or CM with ≥3 prior preventive treatment failures. The dose of 140mg was required in most patients along the study and should be taken into consideration as the starting dose. Allodynia (in HFEM), male sex, and baseline migraine frequency (in CM) might represent positive responsiveness predictors. Conversely, psychiatric comorbidities and multiple prior preventive treatment failures could be negative predictors in patients with CM.

Diabetes is now one of the most prevalent diseases in the world. Over the next twenty years, the number of affected individuals could reach 693 million. Diabetes is a group of chronic carbohydrate metabolism disorders responsible for increased blood glucose levels. It has several effects on the human body, and over the years can even become disabling, greatly impacting the patient’s quality of life. The most common therapy is based on daily and chronic administration of exogenous insulin, but this is associated with a series of dangerous and potentially fatal complications. Unsurprisingly therefore, over time, studies have explored various alternatives for the treatment of diabetes, not involving the use of insulin, primarily transplantation of the whole pancreas and of the islets of Langerhans. However, neither of these solutions can be applied on a large scale, mainly due to the lack of donors. In recent years, a viable alternative to insulin and to transplantation has emerged through exploration of the use of pluripotent stem cells and their properties. In this review we analyze the state of the art in this field, and the advantages and disadvantages of cell therapies used for reconstruction of the functional unit of the pancreas, the islets of Langerhans.

The pituitary gland is defined as a highly “plastic” gland, capable of adapting to the changing needs of the body over the course of a lifetime. In 1969, the first putative pituitary stem cells were isolated, defined as chromophobe cells because of their inability to secrete/incorporate hormones. Since then, studies have improved and have confirmed the presumed existence of a side population characterized by SOX2 expression in both the anterior and marginal pituitary lobes. From the numerous studies conducted to unravel the biological significance of these stem populations, it is currently believed that these cells, at least in the adult basal gland, are highly quiescent; however, their functions are still not well understood. This review reports the major advances achieved in recent years towards developing protocols for the isolation of pituitary stem cells from healthy tissue and pituitary adenomas, as well as the first studies on their use in regenerative medicine.

Background and purpose A rapid response to preventive therapy is of pivotal importance in severely disabled patients with chronic migraine (CM) and diverse preventive treatment failures. This prospective, observational, multicenter real-life study aimed at investigating the effectiveness of galcanezumab in the first 3 months of treatment of CM patients at 14 Italian headache centers. Methods All consecutive adult patients with CM diagnosis with the clinical indication for galcanezumab were considered. We collected patients' baseline characteristics, monthly headache days, monthly painkiller intake, migraine clinical characteristics, and disability scale scores during a 1-month run-in period (baseline) and the first 3 months of therapy. Possible predictive factors of treatment were considered. Results A total of 156 patients (82.4% female, aged 47.3 +/- 12.3 years) were enrolled. The 65 (41.7%) patients with a consecutive >= 50% response rate (RR) in the 3 months of therapy presented a lower body mass index (p = 0.004) and more frequently presented unilateral migraine pain (p = 0.002) and good response to triptans (p = 0.003). Persistent conversion from CM to episodic migraine was observed in 55.8% (87/156) of patients. They more frequently presented a good response to triptans (p = 0.003) and unilateral pain (p = 0.046). At baseline, 131 of 156 (83.9%) patients presented medication overuse (MO). Of these, 61.8% (81/131) no longer displayed MO consistently during the 3 months. These patients were more frequently responders to triptans (p = 0.002) and less frequently suffered from gastrointestinal comorbidity (p = 0.007). Conclusions Unilateral pain, good response to triptans, and normal weight may be associated with a persistent positive response in the first 3 months of therapy with galcanezumab in CM patients.

Penelitian ini bertujuan untuk menganalisis pengaruh likuiditas dan pertumbuhan penjualan terhadap kebijakan hutang perusahaan pertambangan. Dalam penelitian ini, kebijakan hutang diukur menggunakan debt to equity ratio (DER). Sampel dalam penelitian ini berjumlah 10 sampel yang diperoleh dari 49 perusahaan pertambangan selama 5 tahun dengan menggunakan metode purposive sampling. Jumlah data observasi sebanyak 50 data. Teknik analisis data yang digunakan dalam penelitian ini adalah analisis regresi linier berganda dengan menggunakan program SPSS untuk mengolah data. Data penelitian ini adalah data sekunder berupa laporan keuangan tahunan perusahaan pertambangan yang terdaftar di Bursa Efek Indonesia periode 2015 – 2019. Hasil penelitian menunjukkan bahwa likuiditas tidak memiliki pengaruh terhadap kebijakan hutang dan pertumbuhan penjualan memiliki pengaruh terhadap kebijakan hutang.

Penelitian ini dilakukan di Restoran Sisingamangaraja Sites Semarang dengan tujuan untuk menganalisa dan menjelaskan pengaruh kompensasi dan lingkungan kerja terhadap kinerja karyawan. Data penelitian ini diperoleh melalui kuesioner. Sampel yang digunakan dalam penelitian ini yaitu 75 responden. Hasil penelitian diharapkan dapat memberikan informasi yang berguna bagi pihak manajemen maupun karyawan. Data yang digunakan menggunakan analisis deskriptif dan analisis statistik kuantitatif. Analisis kuantitatif menggunakan analisis regresi berganda untuk mengetahui pengaruh variabel independen terhadap variabel dependen, uji hipotesis dan sebelumnya diuji dengan uji validitas dan uji reliabilitas. Hasil analisis regresi menunjukan bahwa adanya pengaruh kompensasi dan lingkungan kerja terhadap kinerja karyawan. Maka hasil uji analisis regresi berganda menunjukan nilai F yang signifikan dengan nilai korelasi determinasi R2 square ssebesar 0,383. Hal ini menunjukkan bahwa untuk meningkatkan kinerja karyawan perlu adanya kompensasi dan lingkungan kerja yang baik

Bone health is ensured by coordinated work between osteoclasts and osteoblasts. When this balance is lacking, skeletal diseases, including osteoporosis (OP), arise. The latter is caused by an increase in erosion and a decrease in bone matrix deposition, resulting in low-quality bone that tends to have a higher risk of fracture. To date, despite the use of sophisticated software to diagnose OP, and the use of several drugs to mitigate the effects of this pathology, there are still limitations that drive the scientific community to search for new biomarkers. In recent years, epigenetics has attracted the attention of many researchers as a possible mechanism involved in the onset and progression of OP. In particular they have focused on circular RNAs (circRNAs), a particular class of non-coding RNAs. Precisely because of their properties, these molecules could open up new possibilities in the field of precision medicine. In conclusion, therefore, the aim of this review is to offer an overview on circRNAs, which could potentially become, in the future, useful diagnostic, prognostic and therapeutic biomarkers in OP routine clinical practice.

Il palcoscenico del XXI secolo ci ha restituito fino ad ora quattro crisi con effetti cumulativi e impatti fortemente negativi sul tessuto socioeconomico del Paese: prima la crisi finanziaria degli anni 2007-2009; poi quella economica del 2011-2012, caratterizzata dal susseguirsi di politiche economiche restrittive per evitare il default dello Stato; quindi, l’epidemia da SARS-COV2 nel 2020 il cui impatto sull’economia è stato devastante e non concluso; e, infine, più recentemente la forte crisi energetica dovuta al conflitto ucraino-russo. Nei precedenti Rapporti SVIMEZ (2020 e 2021) si è evidenziato come il quadro prolungato delle crisi economiche aumenti l’aggressività delle mafie; inoltre, le diverse condizioni di emergenza rappresentano per esse una sorta di “tempesta perfetta” per assoggettare, non necessariamente nella forma predatoria, settori dell’economia, generando nuovi domini. La dinamicità nei mercati illegali è accompagnata, infatti, da una intensa attività imprenditoriale in quelli legali, caratterizzata da investimenti idonei ad occultare i proventi derivanti dalle attività criminali, con forme di riciclaggio che si traducono in acquisizioni di immobili, capannoni, imprese, cogestione delle stesse, collocazione di prestanomi nell’attività produttiva. Avendo già tracciato il carattere ambivalente dell’attività estorsiva nei precedenti Rapporti SVIMEZ (Svimez, 2020: 242-243), è parso opportuno approfondire alla luce di un’aggiornata ricerca comparativa - che ha considerato territori della Campania e del Veneto (Aurilia, Di Gennaro et alii, 2022) - la possibilità di affiancare alla già esistente legislazione antimafia di natura preventiva, una ulteriore iniziativa che rendesse più efficaci le misure di contrasto all’attività estorsiva mediante l’adozione di un modello previsionale machine learning basato sulla costruzione di alert selettivi capaci di interpretare il risk assessmentterritoriale e settoriale economico per svolgere una funzione di assistenza e supporto alle forze dell’ordine (Campedelli, 2022). L’uso dell’Artificial Intelligence (AI) nella ricerca e produzione di modelli predittivi di analisi dei fenomeni criminali è ormai una necessità avvertita dai dipartimenti delle polizie in diversi paesi esteri e la sua applicazione tende a migliorare la prevenzione della criminalità proprio integrando criminologia ambientale, geographic profiling e predicting policing (Wortley e Mazerolle, 2011; Rossmo 1995, 2014; Perry et alii, 2013).

Hipertensi disebut sebagai silent killer karena penderita sering tidak menyadari maupun tidak memiliki masalah kesehatan sebagai tanda awal penyakit hipertensi. Indeks massa tubuh (IMT) secara signifikan menjembatani jalur antara jumlah konsumsi makanan dengan tekanan darah seseorang. Penelitian ini bertujuan untuk mengetahui korelasi indeks massa tubuh dengan tekanan darah pada karyawan dan mahasiswi Politeknik Kudus. Penelitian ini merupakan jenis penelitian Observasional menggunakan data sekunder Posbindu mencakup data nama, antropometri (TB, BB), data tekanan darah, dan riwayat penyakit. Sehingga untuk melengkapi data dasar responden peneliti menggunakan tambahan kuesioner untuk menggali data. Sampel adalah mahasiswa dan karyawan Politeknik Kudus dengan teknik purposive sampling. Analisis data menggunakan uji korelasi Pearson dan kekuatan hubungan (r). Hasil uji Pearson menunjukkan nilai p

The number of vehicles in Bandung City continues to increase every year in line with the growth of motorized vehicle repair shops, thereby increasing the generation of hazardous waste from automotive shop activities. Based on Indonesia’s Governmental Decree 101 of 2014, vehicle maintenance and repair activities are one of the businesses that produce hazardous waste. This study focused on licensed and unlicensed automotive shops in Bandung City using stratified sampling methods by determining waste generation and composition, evaluating existing management systems, followed by developing management system alternatives. In determining the generation and composition of hazardous waste from automotive shop activities, a sampling of 42 unlicensed automotive shops and 11 unlicensed automotive shops in 3 areas of Bandung City was conducted. Sampling results of hazardous waste generation are 1.83 kg/vehicle/day for motorcycle automotive shops and 6.90 kg/vehicle/day for car automotive shops. The largest composition of hazardous waste produced in licensed shops is used oil with a proportion of 29.60 % and metal scrap component with a proportion of 35.83 % for unlicensed automotive shops. The projection results of hazardous waste generation in 2021 are around 774.26 tonnes/day. If the hazardous waste generated is not properly managed it can pose a risk to human health and the environment. An integrated management system for hazardous waste consists of packaging activity, storage activity, collection, transportation, and recycling activity.

Italian Migraine Registry (I-GRAINE) is a multicenter (n = 38), prospective, observational, non-interventional study aimed at providing big data on migraine to ensure proper clinical disease management, according to scientific, and sustainability criteria. We enrolled consecutive patients affected by episodic or chronic migraine according to the systematic random method. Information on sociodemographic characteristics, lifestyle, migraine features, patient's journey, and healthcare resource use were gathered using face-to-face interviews.On the date of 31 December 2021, we enrolled 231 patients at 12 headache centers. Most of them were women (84.4%), with high migraine frequency (9.6 +/- 6.9 days/month) and severe disability (MIDAS score: 43.0 +/- 40.8; HIT-6 score: 60.4 +/- 10.6). Only a minority of patients (38.1%) had previously visited a headache center.A clear-cut difference emerged in the proportion of responders to nonspecific acute treatments (43.5-66.7%) compared to triptans (76.3%) and in responders to unspecific prophylaxis (5.4-35%) compared to anti-CGRP monoclonal antibodies (69.2-78.6%). Most patients underwent >= 1 specialist visit (66.9%) or diagnostic investigation (77.4%) over the last 3 years-mostly subsidized by our national health system-inappropriate in 64.9% and 25% of the cases, respectively.The I-GRAINE registry is expected to provide a large and exponentially increasing collection of clinical, biological, and epidemiologic information and will contribute to moving migraine out of the shadow cone of marginalization, which has been often relegated up to now.

Anjing dan kucing merupakan hewan yang hidup berdampingan dengan manusia sebagai hewan peliharaan. Infeksi parasit cacing merupakan masalah yang umum pada hewan peliharaan namun data tentang prevalensi kejadian kecacingan di Indonesia masih sedikit. Penelitian ini bertujuan untuk mengetahui prevalensi dan faktor risiko kecacingan pada anjing dan kucing serta tindakan preventif untuk mencegah infeksi parasit cacing. Pengambilan data dilakukan dengan merekap rekam medik yang ada di klinik Smilevet Kelapa Gading pada Januari 2020 – Januari 2021. Seluruh data rekam medik di klinik Smilevet Kelapa Gading periode Januari 2020 – Januari 2021 berjumlah 2.259 yang terdiri atas 976 pasien anjing dan 1.283 pasien kucing. Total kasus kecacingan pada anjing dan kucing berjumlah 18 kasus. Data dianalisis secara deskriptif kuantitatif. Prevalensi kecacingan pada anjing dan kucing di klinik Smilevet Kelapa Gading pada Januari 2020 – Januari 2021 kurang dari 1%. Spesies cacing yang teridentifikasi pada pasien kucing adalah Toxocara cati. Faktor risiko kejadian kecacingan pada anjing dan kucing dipengaruhi oleh jenis kelamin, breed, dan umur. Antelmintika yang banyak digunakan memiliki zat aktif febantel, praziquantel, dan pirantel embonate. Pemberian antelmintika secara rutin menjadi tindakan preventif untuk mencegah kejadian kecacingan pada anjing dan kucing Kata kunci: anjing, antelmintik, helmithiasis, kucing, faktor risiko

O presente artigo traz reflexões e considerações acerca da retomada segura das atividades presenciais em creches e pré-escolas, a partir de uma pesquisa junto à profissionais da Educação Infantil, elucidando ainda os principais receios dos educadores infantis com a volta das atividades presenciais no contexto da pandemia Covid-19. Apresentamos ainda, algumas publicações e discussões de estudiosos da área sobre as ações a serem pensadas e planejadas com relação ao retorno das atividades presenciais nas instituições de Educação Infantil, assim como os documentos oficiais e as legislações vigentes. Como resultado compreendemos que é necessário refletir, discutir e repensar as ações pedagógicas como eram antes da pandemia, durante a pandemia e como será em um retorno seguro das atividades presenciais, uma vez que se trata de um atendimento oferecido à crianças de zero a cinco anos, tendo como premissa a criança como centro do planejamento educacional, visando o seu desenvolvimento integral. Consideramos que para haver o retorno adequado é preciso um planejamento cuidadoso e responsável, pautado em prerrogativas que considerem os direitos da criança, sem perder de vista as conquistas históricas da Educação Infantil, em especial as políticas públicas voltadas ao atendimento direcionado a primeira infância.

For the newborns needing respiratory support at 36 weeks postmenstrual age, regardless of the type of ventilation used, it is critical to take into account the mechanics properties of both airways and lungs affected by severe bronchopulmonary dysplasia (sBPD). Ventilator strategies, settings, and weaning must change dramatically after sBPD is established, but to date there is almost no high-quality evidence base supporting a specific approach to guide the optimal ventilator management and weaning in patients with sBPD. Weaning from invasive mechanical ventilation, management of the immediately postextubation period, and weaning from noninvasive ventilation in patients with sBPD are the topics covered in this chapter.

Background To verify the long-term (24-week) efficacy, safety, and tolerability of fremanezumab in real-life patients with high-frequency episodic migraine (HFEM: ≥8 days/month) or chronic migraine (CM: ≥15 days/month), and multiple preventive treatment failures. Methods This is a prospective, cohort, real-life study at 28 headache centers on consecutive patients affected by HFEM or CM with multiple preventive treatment failures who were prescribed subcutaneous fremanezumab (225 mg monthly/675 mg quarterly) for ≥ 24 weeks. Primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM at weeks 21–24 compared to baseline. Secondary endpoints encompassed changes in monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS, HIT-6 and MIDAS scores at the same time interval. Changes in MMDs/MHDs, monthly analgesic medications, ≥ 50%, ≥ 75%, and 100% responder rates, and variation in NRS and HIT-6 scores at week 4 were also monitored. Results 410 patients who had received ≥ 1 dose of fremanezumab were considered for safety analysis while 148 patients treated for ≥ 24 weeks were included in the efficacy analysis. At weeks 21–24, fremanezumab significantly (p

Objective: To assess the effectiveness, safety, and tolerability of erenumab in a real-life migraine population, while trying to identify responsiveness predictors. Background: Erenumab is a fully human Ig-2 monoclonal antibody blocking the calcitonin gene-related peptide receptor, indicated for migraine prophylaxis. Phase II and III trials demonstrated that erenumab is effective, safe, and well tolerated in the prevention of episodic and chronic migraine (CM), showing an early onset of action. Methods: This is a multicenter, prospective, cohort, and real-life study. We considered for enrolment all consecutive patients aged 18–65 affected by high-frequency episodic migraine (HFEM) or CM, with or without medication overuse, visited at nine Italian Headache Centers from December 20, 2018 to September 30, 2019. Each patient was treated with erenumab 70mg, administered subcutaneously every 4weeks. Treatment duration was planned to last from 6 to 12months, depending on the patient's response. The primary endpoint was the change in monthly migraine days (MMDs) at weeks 9–12 compared to baseline. Secondary endpoints included changes in monthly analgesics intake, ≥50%, ≥75%, and 100% responder rates and any variation in the Visual Analog Scale (VAS) and Headache Impact Test scores (HIT). Results: In total, 372 migraine patients were treated with at least one dose of erenumab 70mg. At weeks 9–12, erenumab decreased MMDs by 4.5±4.1days (mean±SD) in patients with HFEM and by 9.3±9.1 (mean±SD) days in those with CM compared to baseline. At weeks 9–12 VAS score was reduced by 1.9±1.9 (mean±SD), HIT score by 10.7±8.8 (mean±SD), and median monthly analgesics intake passed from 12.0 (interquartile range [IQR] 10.0–14.0) to 5.0 (IQR 3.0–7.0) in HFEM. In CM patients, VAS was reduced by 1.7±2.0 (mean±SD), HIT by 9.7±10.4 (mean±SD), and median monthly analgesics intake passed from 20.0 (IQR 15.0–30.0) to 8.0 (IQR 5.0–15.0). At week 12, ≥50% responders were 60/101 (59.4%) for HFEM and 146/263 (55.5%) for CM, ≥75% responders were 17/101 (16.8%) and 59/263 (22.4%) and 100% responders 1/101 (1.0%) and 3/263 (1.1%), respectively. Erenumab responsiveness in HFEM was positively associated with unilateral pain localization (OR: 3.03, 95% CI: 1.24–7.40; p=0.015), whereas in CM responsiveness was positively associated with and baseline migraine frequency (OR: 1.06, 95% CI:1.02–1.11; p=0.031), dopaminergic symptoms (OR: 2.01, 95% CI: 1.14–3.52; p=0.015), and negatively associated with psychiatric comorbidities (OR: 0.43, 95% CI: 0.20–0.93; p=0.003). Conclusions: Erenumab 70mg is effective, safe, and well tolerated in real life. Easily obtainable clinical features might be of help in predicting patient's responsiveness.

Objectives: The COVID-19 pandemic and the consequent lockdown came as a storm disrupting people’s everyday life. This study aimed at observing whether the COVID-19 related lockdown influenced migraine frequency and disability in migraine patients on therapy with monoclonal antibodies inhibiting the CGRP pathway. Methods: In this longitudinal observational cohort study, 147 consecutive patients receiving monthly administration of erenumab or galcanezumab were enrolled in four Italian headache centers. All patients filled a questionnaire concerning working and household settings, recent flu symptoms or COVID-19 diagnosis, and family loss due to COVID-19 infection. Monthly migraine days (MMDs), monthly painkiller intake (MPI), and HIT-6 disability relative to the first month of lockdown imposition (T-lock) and the month before (T-free) were also collected. Results: From T-free to T-lock, the cohort displayed a reduction in MMDs (from 10.5 ± 7.6 to 9.8 ± 7.6, p =.024) and HIT-6 scores (from 59.3 ± 8.3 men reduced MPI more frequently than women (p =.005). Conclusions: Our study observed that the lockdown impact to 57.8 ± 8.8, p=.009), while MPI resulted unchanged (from 11.6 ± 11.5 to 11.1 ± 11.7; p =.114). MMDs, MPI, and HIT-6 variations from T-free to T-lock did not differ according to work settings or household. Patients beyond the first 3 months of therapy presented less often a reduction in MMDs (p =.006) and on everyday life did not affect the migraine load in patients receiving monoclonal antibodies inhibiting the CGRP pathway. Patients in the first months of therapy experienced a greater improvement according to drug pharmacokinetics, while women more frequently needed rescue medications, possibly indicating presenteeism or cephalalgophobia.

Down syndrome is a neurodevelopmental disorder frequently characterized by other developmental defects, such as congenital heart disease. Analysis of gene expression profiles of hearts from trisomic fetuses have shown upregulation of extracellular matrix (ECM) genes. The aim of this work was to identify genes on chromosome 21 potentially responsible for the upregulation of ECM genes and to pinpoint any functional consequences of this upregulation. By gene set enrichment analysis of public data sets, we identified the transcription factor RUNX1, which maps to chromosome 21, as a possible candidate for regulation of ECM genes. We assessed that approximately 80% of ECM genes overexpressed in trisomic hearts have consensus sequences for RUNX1 in their promoters. We found that in human fetal fibroblasts with chromosome 21 trisomy there is increased expression of both RUNX1 and several ECM genes, whether located on chromosome 21 or not. SiRNA silencing of RUNX1 reduced the expression of 11 of the 14 ECM genes analyzed. In addition, collagen IV, an ECM protein secreted in high concentrations in the culture media of trisomic fibroblasts, was modulated by RUNX1 silencing. Attenuated expression of RUNX1 increased the migratory capacity of trisomic fibroblasts, which are characterized by a reduced migratory capacity compared to euploid controls.

Based on empirical research focused on the phenomenon of corruption in Italy. The purpose of the contribution is to show the different models that are made of corruption pacts according to the actors who regulate them. The basis of the judicial documents was provided by the National Anti-Mafia Directorate (DNAA), the Court of Auditors, and a sample of Courts of Appeal from different jurisdictional districts. The information collected offers an account of the influence that the various mafias have on public policies and the ability to circumvent current legislation. The contribution underlines the existing interpretative limits and why they do not explain to what extent great and small corruption are related.

Based on empirical research focused on the phenomenon of corruption in Italy. The purpose of the contribution is to show the different models that are made of corruption pacts according to the actors who regulate them. The basis of the judicial documents was provided by the National Anti-Mafia Directorate (DNAA), the Court of Auditors, and a sample of Courts of Appeal from different jurisdictional districts. The information collected offers an account of the influence that the various mafias have on public policies and the ability to circumvent current legislation. The contribution underlines the existing interpretative limits and why they do not explain to what extent great and small corruption are related.

Tujuan penelitian ini adalah untuk mengetahui pengaruh kepuasan kerja, kemampuan kerja, motivasi terhadap kinerja karyawan tetap di Hotel Graha Santika Semarang. Metode penelitian ini menggunakan metode eksplanatori, pengambilan sampel sebanyak 60 karyawan tetap Hotel Graha Santika Semarang yang diambil dengan menggunakan purposive sampling, khususnya untuk karyawan tetap Hotel Graha Santika Semarang, Pengungkapan data menggunakan instrumen berupa angket yang telah diuji validitas dan reliabilitasnya. Pengujian hipotesis menggunakan uji t, uji F dan koefisien determinasi dari hasil penelitian menunjukkan bahwa variabel kepuasan kerja, kemampuan kerja dan motivasi berpengaruh secara parsial maupun simultan terhadap kinerja karyawan tetap pada Hotel Graha Santika Semarang. Persamaan regresi yang diperoleh adalah Y = 0.455X1 + 0.365X2 + 0.234X3. Dari hasil koefisien determinasi bahwa kepuasan kerja (X1), kemampuan kerja (X2) dan motivasi (X3) telah mampu menjelaskan 68,9% berpengaruh terhadap kinerja, sedangkan 31,1% kinerja karyawan dipengaruhi oleh faktor lain di luar penelitian.

Human needs for clean water can be obtained from various sources, one of those is springs. The spring is the main water source for the people in Redinkidul Hamlet. The dependence of the community on springs shows that there is a need for conservation of spring recharge areas. The purpose of this study was to determine the ability of recharge areas to absorb water and provide conservation direction for spring recharge areas. The research method used is survey and mapping methods to obtain data on existing conditions in the field, scoring and overlay methods to determine the condition of the recharge area based on the results obtained. The scoring parameter refers to Permen PU No. 2 of 2013. The results obtained show that the spring recharge area zone has a moderate class with a score of 11-13. The highest score obtained is on the parameters of land use and rainfall. Based on these results, the proposed conservation directives are in the form of technical conservation directions in the form of bund terraces and spring support buildings. This conservation is needed so that the potential of the spring is maintained.

Indonesia memiliki wilayah perairan yang sangat luas dan terdapat wilayah yang merupakan pertemuan lempengan bumi. Hal ini dapat memungkinkan terjadinya bencana alam tsunami. Penelitian ini bertujuan untuk mengetahui daerah mana saja yang memiliki resiko kerusakan lahan paling tinggi dan yang paling rendah. Data yang digunakan pada penelitian ini adalah citra satelit yang diambil dari tahun 2014-2021 dengan cakupan wilayah di Kabupaten Kulon Progo yang terdiri dari 12 kecamatan. Penelitian ini menggunakan indeks vegetasi UI, NDBI, IBI, EBBI. Dengan algoritma ANN mendapatkan hasil yang cukup akurat dengan tingkat akurasi sebesar 94.50 %. Prediksi menyatakan bahwa wilayah yang memiliki resiko kerusakan tinggi akibat tsunami yaitu desa Jingkaran, Sindutan, Palihan, Glagah, Karangwuluh, Janten, Temon Kulon, Kedundang, Sogan, Kalidengen, Ngestiharjo, Depok, Kanoman, Panjatan, Wahyuharjo, Pandowan, Nomporejo, dan Kranggan Indonesia has a very large water area and there is the territory that is the confluence of the earth's slabs. It can allowing the occurrence of tsunami natural disasters. The study aims to find out which areas have risks the highest and the lowest land damage. The data used in this study were satellite images taken from 2014-2021 with coverage area in Kulon Progo Regency which consists of 12 sub-districts. This study used indexes vegetation UI, NDBI, IBI, EBBI. With an ANN algorithm get results which is quite accurate with an accuracy rate of 94.50%. Predictions states that the area has a high risk of damage due to the tsunami, namely the villages of Jingkaran, Sindutan, Palihan, Glagah, Karangwuluh, Janten, Temon Kulon, Kedundang, Sogan, Kalidengen, Ngestiharjo, Depok, Kanoman, Panjatan, Wahyuharjo, Pandowan, Nomporejo, and, Kranggan.

Background and objectives The identification of predictors of response to antiCGRP mAbs could favor tailored therapies and personalized treatment plans. This study is aimed at investigating predictors of ≥ 50%, ≥ 75% and 100% response at 24 weeks in patients with high-frequency episodic (HFEM: 8–14 days/month) or chronic migraine (CM). Methods This is a large, multicenter, cohort, real-life study. We considered all consecutive adult patients affected by HFEM or CM who were prescribed antiCGRP mAbs for ≥ 24 weeks in 20 headache centers. Patients were interviewed face-to-face using a shared semi-structured questionnaire carefully exploring socio-demographic and clinical characteristics. Patients received subcutaneous erenumab (70 mg or140 mg, monthly), galcanezumab (120 mg monthly, following a 240 mg loading dose), or fremanezumab (225 mg, monthly or 675 mg, quarterly) according to drug market availability, physician’s choice, or patient’s preference. The primary endpoint of the study was the assessment of ≥ 50% response predictors at 24 weeks. Secondary endpoints included ≥ 75% and 100% response predictors at 24 weeks. Results Eight hundred sixty-four migraine patients had been treated with antiCGRP mAbs for ≥ 24 weeks (erenumab: 639 pts; galcanezumab: 173 pts; fremanezumab: 55 pts). The ≥50% response (primary endpoint) in HFEM was positively associated with unilateral pain (UP) + unilateral cranial autonomic symptoms (UAs) (OR:4.23, 95%CI:1.57–11.4; p = 0.004), while in CM was positively associated with UAs (OR:1.49, 95%CI:1.05–2.11; p = 0.026), UP + UAs (OR:1.90, 95%CI:1.15–3.16; p = 0.012), UP + allodynia (OR:1.71, 95%CI:1.04–2.83; p = 0.034), and negatively associated with obesity (OR:0.21, 95%CI:0.07–0.64; p = 0.006). The 75% response (secondary endpoint) was positively associated with UP + UAs in HFEM (OR:3.44, 95%CI:1.42–8.31; p = 0.006) and with UP + UAs (OR:1.78, 95%CI:1.14–2.80; p = 0.012) and UP + allodynia (OR:1.92, 95%CI:1.22–3.06; p = 0.005) in CM. No predictor of 100% response emerged in patients with HFEM or CM. Conclusions A critical evaluation of headache characteristics indicating peripheral or central sensitization may help in predicting responsiveness to antiCGRP mAbs in HFEM and CM. A more precise pain profiling may represent a steppingstone for a mechanism-based approach and personalized treatment of migraine with compounds targeting specific molecular mechanisms.

Based on the survey results found 7 out of 10 mothers who have babies aged 0-1 years want to massage the baby. This is because the mother considers baby massage to be an alternative treatment that can make a healthy baby, the mother's willingness to do baby massage can be influenced by traditions or culture that existed and adopted by the community passed down from generation to generation so that it has become a tradition and culture in the village community the.The research design used in this study is correlation analytic with cross sectional approach. The number of samples in this study were 40 mothers who had babies aged 0-1 years in April-May 2018.Based on statistical tests with the Chi Square test obtained Chi Square count (4.388)> Chi Square table (3.841) and p value = 0.036 (

Background Dopaminergic symptoms may be extremely pronounced in some migraine patients during the attack, representing a major source of disability. Objectives We aimed to carefully characterize the clinical picture of migraine patients with dopaminergic symptoms in a large patients’ population as a putative migraine endophenotype, allowing more precise disease management, treatment and outcome prediction. Methods We screened 1148 consecutive tertiary care episodic and chronic migraine patients with face-to-face interviews collecting thorough data on lifestyle, socio-demographic factors, and clinical migraine features. Results We identified 374 patients with migraine with dopaminergic symptoms (32.6%). The most frequent dopaminergic symptom was yawning followed by somnolence, nausea, vomiting, fatigue, mood changes and diuresis. Migraine patients with dopaminergic symptoms had longer attack duration (OR: 1.82; 95% CI: 1.41–2.36, p Conclusions Migraine patients with dopaminergic symptoms are characterized by a full-blown, more disabling migraine. Dopaminergic system modulation should be carefully considered in individuals with migraine with dopaminergic symptoms for both acute and preventative treatments in future ad hoc designed studies.

To investigate in real-life the conversion from chronic migraine (CM) to episodic migraine (EM), specifically to EM with High-Frequency (HFEM: 8-14 monthly migraine days, MMDs), Medium-Frequency (MFEM, 4-7 MMDs), and Low-Frequency EM (LFEM, 0-3 MMDs), and its persistence during 1 year of treatment with galcanezumab.Consecutive CM patients treated with galcanezumab completing 1 year of observation were enrolled. We collected data on MMDs, pain intensity (Numeric Rating Scale, NRS score), and monthly acute medication intake (MAMI) from baseline (V1) to the 12-month visit (V12).Of the 155 enrolled patients, 116 (around 75%) reverted to EM at every visit and 81 (52.3%) for the entire 1-year treatment. Patients with older onset age (p = 0.010) and fewer baseline MMDs (p = 0.005) reverted more frequently to EM. At V12, 83 participants (53.5%) presented MFEM or LFEM. Patients reverted to MFEM or LFEM for 7 months (25th 1, 75th 11). The medication overuse discontinuation rate at V12 was 82.8% and occurred for 11 months (25th 8, 75th 12). From baseline to V12, the MAMI decreased by 17 symptomatic drugs (p 0.000001) while the NRS score reduced by almost 2 points (p 0.000001). A consistent transition to EM for the entire treatment year was observed in 81 (52.3%) patients.The 1-year GARLIT experience suggests that more than half of CM patients treated with galcanezumab persistently reverted to EM in real life.ClinicalTrials.gov NCT04803513.

Polyethylene terephthalate (PET) is a thermoplastic material that is widely used in many application fields, such as packaging, construction and household products. Due to the relevant contribution of PET to global yearly solid waste, the recycling of such material has become an important issue. Disposed PET does not maintain the mechanical properties of virgin material, as exposure to water and other substances can cause multiple chain scissions, with subsequent degradation of the viscoelastic properties. For this reason, chain extension is needed to improve the final properties of the recycled product. Chain extension is generally performed through reactive extrusion. As the latter involves structural modification and flow of PET molecules, rheology is a relevant asset for understanding the process and tailoring the mechanical properties of the final products. This paper briefly reviews relevant rheological studies associated with the recycling of polyethylene terephthalate through the reactive extrusion process.

Vitamin D deficiency is a constantly growing health problem worldwide. Adults affected with hypovitaminosis D could experience negative consequences on their musculoskeletal system and extra-skeletal health. In fact, an optimal vitamin D status is essential to ensure the correct bone, calcium, and phosphate homeostasis. To improve vitamin D status, it is important to not only increase the intake of food fortified with vitamin D, but also to administer vitamin D supplementation when required. Vitamin D3 (cholecalciferol) is the most widely used supplement. In recent years, the administration of calcifediol (25(OH)D3), the direct precursor of the biologically active form of vitamin D3, as oral vitamin D supplementation has progressively grown. Here, we report the potential medical benefits of some peculiar biological actions of calcifediol, discussing the possible specific clinical scenarios in which the oral intake of calcifediol could be most effective to restore the correct serum levels of 25(OH)D3. In summary, the aim of this review is to provide insights into calcifediol-related rapid non-genomic responses and the possible use of this vitamin D metabolite as a supplement for the treatment of people with a higher risk of hypovitaminosis D.

Extremely preterm infants frequently require some form of respiratory assistance to facilitate the cardiopulmonary transition that occurs in the first hours of life. Current resuscitation guidelines identify as a primary determinant of overall newborn survival the establishment, immediately after birth, of adequate lung inflation and ventilation to ensure an adequate functional residual capacity. Any respiratory support provided, however, is an important contributing factor to the development of bronchopulmonary dysplasia. The risks correlated to invasive ventilatory techniques increase inversely with gestational age. Preterm infants are born at an early stage of lung development and are more susceptible to lung injury deriving from mechanical ventilation. Any approach aiming to reduce the global burden of preterm lung disease must implement lung-protective ventilation strategies that begin from the newborn’s first breaths in the delivery room. Neonatologists today must be able to manage both invasive and noninvasive forms of respiratory assistance to treat a spectrum of lung diseases ranging from acute to chronic conditions. We searched PubMed for articles on preterm infant respiratory assistance. Our narrative review provides an evidence-based overview on the respiratory management of preterm infants, especially in the acute phase of neonatal respiratory distress syndrome, starting from the delivery room and continuing in the neonatal intensive care unit, including a section regarding exogenous surfactant therapy.

Simple Summary Down Syndrome, which is due to the presence of three copies of chromosome 21, always presents with mental retardation, possibly caused by defects in the development of neurons. In recent years, it has been shown that cells and tissues in Down syndrome manifest alterations in the function of mitochondria, the organelles that provide energy to cells. We hypothesized that mitochondrial dysfunction might contribute to the defect in neuronal cell development. To test this hypothesis, we generated a model of stem cells that, upon specific treatments, are capable of giving rise to neuronal cells, as evidenced by the synthesis of specific proteins. We observed that stem cells derived from Down syndrome individuals, after 21 days of growth in an artificial system, had an abnormal tendency to develop as glial cells, compared with control cells. As early as day 7 of culture, the trisomic cells also exhibited defects in mitochondrial function, such as anomalies in their calcium level, oxygen free radicals, oxygen consumption, and synthesis of ATP, a molecule that is critical in energy conversions. These results indicate that alterations in neuronal development and mitochondrial function occur early in this model, which we think is suitable for answering further questions. Abstract Background: The presence of mitochondrial alterations in Down syndrome suggests that it might affect neuronal differentiation. We established a model of trisomic iPSCs, differentiating into neural precursor cells (NPCs) to monitor the occurrence of differentiation defects and mitochondrial dysfunction. Methods: Isogenic trisomic and euploid iPSCs were differentiated into NPCs in monolayer cultures using the dual-SMAD inhibition protocol. Expression of pluripotency and neural differentiation genes was assessed by qRT-PCR and immunofluorescence. Meta-analysis of expression data was performed on iPSCs. Mitochondrial Ca2+, reactive oxygen species (ROS) and ATP production were investigated using fluorescent probes. Oxygen consumption rate (OCR) was determined by Seahorse Analyzer. Results: NPCs at day 7 of induction uniformly expressed the differentiation markers PAX6, SOX2 and NESTIN but not the stemness marker OCT4. At day 21, trisomic NPCs expressed higher levels of typical glial differentiation genes. Expression profiles indicated that mitochondrial genes were dysregulated in trisomic iPSCs. Trisomic NPCs showed altered mitochondrial Ca2+, reduced OCR and ATP synthesis, and elevated ROS production. Conclusions: Human trisomic iPSCs can be rapidly and efficiently differentiated into NPC monolayers. The trisomic NPCs obtained exhibit greater glial-like differentiation potential than their euploid counterparts and manifest mitochondrial dysfunction as early as day 7 of neuronal differentiation.

Background The clinical benefit of galcanezumab, demonstrated in randomized clinical trials (RCTs), remains to be quantified in real life. This study aimed at evaluating the effectiveness, safety and tolerability of galcanezumab in the prevention of high-frequency episodic migraine (HFEM) and chronic migraine (CM) in a real-life setting. Methods This multicenter prospective observational cohort study was conducted between November 2019 and January 2021 at 13 Italian headache centers. Consecutive adult HFEM and CM patients clinically eligible were enrolled and treated with galcanezumab subcutaneous injection 120 mg monthly with the first loading dose of 240 mg. The primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients after 6 months of therapy (V6). Secondary endpoints were the Numerical Rating Scale (NRS), monthly painkiller intake (MPI), HIT-6 and MIDAS scores changes, ≥50% responder rates (RR), the conversion rate from CM to episodic migraine (EM) and Medication Overuse (MO) discontinuation. Results One hundred sixty-three patients (80.5% female, 47.1 ± 11.7 years, 79.8% CM) were included. At V6, MMDs reduced by 8 days in HFEM and MHDs by 13 days in CM patients (both p p p = .018) and had failed a lower number of preventive treatments (p = .013) than non-responders. At V6, 77.2% of CM patients converted to EM, and 82.0% ceased MO. Adverse events, none serious, were reported in up to 10.3% of patients during evaluation times. Conclusions Galcanezumab in real life was safe, well tolerated and seemed more effective than in RCTs. Normal weight and a low number of failed preventives were positively associated with galcanezumab effectiveness in CM patients. Trial registration ClinicalTrials.govNCT04803513.

Background Monoclonal antibodies acting on the calcitonin gene-related peptide (CGRP) or its receptor have changed migraine preventive treatment. Those treatments have led to reconsidering the outcomes of migraine prevention. Available data mostly considered benefits in terms of relative efficacy (percent or absolute decrease in monthly migraine days [MMDs] or headache days compared with baseline). However, not enough attention has been paid to residual MMDs and/or migraine-related disability in treated patients. In the present study, we aimed at comparing the relative and absolute efficacy of erenumab. Methods ESTEEMen was a collaborative project among 16 European headache centers which already performed real-life data collections on patients treated with erenumab for at least 12 weeks. For the present study, we performed a subgroup analysis on patients with complete data on MMDs at baseline and at weeks 9-12 of treatment. Starting from efficacy thresholds proposed by previous literature, we classified patients into 0-29%, 30-49%, 50-74%, and ≥75% responders according to MMD decrease from baseline to weeks 9-12 of treatment. For each response category, we reported the median MMDs and Headache Impact test-6 (HIT-6) scores at baseline and at weeks 9-12. We categorized the number of residual MMDs at weeks 9-12 as follows: 0-3, 4-7, 8-14, ≥15. We classified HIT-6 score into four categories: ≤49, 50-55, 56-59, and ≥60. To keep in line with the original scope of the ESTEEMen study, calculations were performed in men and women. Results Out of 1215 patients, at weeks 9-12, 381 (31.4%) had a 0-29% response, 186 (15.3%) a 30-49% response, 396 (32.6%) a 50-74% response, and 252 (20.7%) a ≥75% response; 246 patients (20.2%) had 0-3 residual MMDs, 443 (36.5%) had 4-7 MMDs, 299 (24.6%) had 8-14 MMDs, and 227 (18.7%) had ≥15 MMDs. Among patients with 50-74% response, 246 (62.1%) had 4-7 and 94 (23.7%) 8-14 residual MMDs, while among patients with ≥75% response 187 (74.2%) had 0-3 and 65 (25.8%) had 4-7 residual MMDs. Conclusions The present study shows that even patients with good relative response to erenumab may have a clinically non-negligible residual migraine burden. Relative measures of efficacy cannot be enough to thoroughly consider the efficacy of migraine prevention.

Background Mechanical ventilation is still needed in most preterm newborns, even in the non-invasive ventilation era. Ventilator-induced lung injury is one of the known pathogenetic factors of bronchopulmonary dysplasia (BPD) in preterm newborns. Lung injury has several patterns including surfactant dysfunction. Some recent trials have showed that a late surfactant administration can improve respiratory outcome in preterm babies still on invasive ventilation after the first week of life. Unfortunately, these results are still not conclusive. Moreover, giving surfactant after a recruitment manoeuvre in High Frequency Oscillatory Ventilation (HFOV) was shown to be safe and to reduce mortality in extremely preterm infants in a recent RCT. Our aim is to test the hypothesis that endotracheal administration of poractant-alfa preceded by a recruitment manoeuvre in HFOV in preterm infants still requiring mechanical ventilation at 7-10 days of life could facilitate extubation. Methods/Design: This will be an unblinded monocentric pilot trial that will be conducted in a III level Neonatal Intensive Care Unit at Fondazione Policlinico Agostino Gemelli IRCCS in Rome - Italy. Preterm newborns with a gestational age < 28 weeks still requiring invasive mechanical ventilation at 7-10 days of life with a fraction of inspired oxygen (FiO2) of more than 0.30 and/or an oxygenation index of 8 or more for at least 6 hours will be eligible for the study. Patients will be randomly assigned to intervention or to standard care. Intervention group infants will receive up to 4 doses of Poractant-alfa every 12 hours, each dose preceded by a recruitment manoeuvre in HFOV, until extubation. Primary endpoint will be the first successful extubation. Discussion Surfactant therapy is nowadays recommended in case of RDS in the first days of life but little is known about its effects in ventilator-dependant preterm newborns. Late administration of surfactant could help healing the lung of preterm babies in which RDS is evolving in a chronic pulmonary insufficiency of prematurity. The findings of this pilot trial will permit evaluation of the study design for a full-scale RCT. Trial registration: Clinicaltrials.gov – ID NCT04825197. Registered 12 April 2021, https://clinicaltrials.gov/ct2/home

Kabupaten Kuningan Jawa Barat memiliki target menumbuhkan 25 desa wisata, dan salah satu yang sedang dirintis adalah desa wisata Cikaso Desa Kramatmulya. Dalam pembentukan desa wisata membutuhkan organisasi kelembagaan yang akan mengelola pariwisata di desa tersebut. Meskipun pemerintah telah menetapkan kelembagaan Kelompok Sadar Wisata (Pokdarwis) di desa wisata namun dalam perjalanannya pengelola masih memiliki ketidakmampuan dalam mengelola. Masalah lain adalah tidak adanya hubungan harmonis dan tumpang tindih tupoksi antara Badan Usaha Milik Desa (Bumdes) dengan Pokdarwis dalam pengelolaan rintisan desa wisata. Pokdarwis membutuhkan pendampingan bagaimana tata organisasi dapat berjalan, tupoksi masing-masing, apa saja permasalahan yang ada dalam pengembangan destinasi dan bagaimana mendapatkan dukungan dari masyarakat. Tujuan dari kegiatan pengabdian masyarakat ini adalah memperkuat kerjasama antara Bumdes dan Pokdarwis dalam rintisan suatu desa wisata. Metode yang digunakan dalam kegiatan ini meliputi ceramah, Focus Group Discussion , simulasi, dan role play lapangan.

Additional file 1: Table S1. Change in monthly migraine days (MMDs), monthly headache days (MHDs), monthly analgesic intake, Numerical Rating Scale (NRS) score, Headache Impact Test-6 (HIT-6) score, and Migraine Disability Assessment Scale (MIDAS) score from baseline to week 12. Table S2. Univariate analysis of independent determinant of ≥50% response in patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM).

Additional file 1.

Classically, a secosteroid hormone, vitamin D, has been implicated in calcium and phosphate homeostasis and has been associated with the pathogenesis of rickets and osteomalacia in patients with severe nutritional vitamin D deficiency. The spectrum of known vitamin D-mediated effects has been expanded in recent years. However, the mechanisms of how exactly this hormone elicits its biological function are still not fully understood. The interaction of this metabolite with the vitamin D receptor (VDR) and, subsequently, with the vitamin D-responsive element in the region of specific target genes leading to the transcription of genes whose protein products are involved in the traditional function of calcitriol (known as genomic actions). Moreover, in addition to these transcription-dependent mechanisms, it has been recognized that the biologically active form of vitamin D3, as well as its immediate precursor metabolite, calcifediol, initiate rapid, non-genomic actions through the membrane receptors that are bound as described for other steroid hormones. So far, among the best candidates responsible for mediating rapid membrane response to vitamin D metabolites are membrane-associated VDR (VDRm) and protein disulfide isomerase family A member 3 (Pdia3). The purpose of this paper is to provide an overview of the rapid, non-genomic effects of calcifediol and calcitriol, whose elucidation could improve the understanding of the vitamin D3 endocrine system. This will contribute to a better recognition of the physiological acute functions of vitamin D3, and it could lead to the identification of novel therapeutic targets able to modulate these actions.

Penelitian ini bertujuan untuk membahas alasan mengapa rumus matematika menjadi momok bagi siswa serta cara agar rumus matematika tidak lagi menjadi hal yang menakutkan untuk siswa. Metode yang digunakan dalam penelitian ini adalah metode kualitaatif dengan kajian pustaka. Dari penelitian ini dapat diketahui bahwa alasan siswa menganggap rumus matemtika sebagai momok atau hal yang menakutkan adalah karena adanya faktor internal dan eksternal. Faktor internal seperti konsentrasi belajar siswa dan faktor eksternal adalah guru sebagi pembimbing siswa dalam belajar. Anggapan rumus matematika sebagai momok ini pada akhirnya akan mendatangkan kecemasan matematika. Kecemasan matematika adalah sebuah rasa takut dan tertekan saat menyelesaikan permasalahan matematika. Kecemasan matematika ini tidak boleh dibiarkan karena akan mengakibatkan tidak pahamnya siswa terhadap materi yang diajarakan. Untuk mengatasi kecemasan matematika ini, guru perlu menerapakan metode belajar yang menyenagkan. Salah satu metode yang dapat digunakan adalah metode HARUMPALA, yaitu sebuah metode belajar rumus matematika dengan menggunakn lagu. Dengan bernyanyi siswa akan lebih mudah untuk menghafal rumus matematika, dan rumus tersebut akan mampu diingat siswa dalam jangka panjang.

Background Fremanezumab has demonstrated to be effective, safe, and tolerated in the prevention of episodic or chronic migraine (CM) in randomized, placebo-controlled trials (RCTs). Real-life studies are needed to explore drug effects in unselected patients in routine circumstances and to provide higher generalizability results. This study explores the effectiveness, safety, and tolerability of fremanezumab in a real-life population of individuals affected by high-frequency episodic (HFEM: 8-14 days/month) or CM. Methods This is a 12-week multicenter, prospective, cohort, real-life study. We considered all consecutive patients affected by HFEM or CM visited at 9 Italian headache centers from 28/07/2020 to 11/11/2020. Eligible patients were given subcutaneous fremanezumab at the doses of 225 mg monthly or 675 mg quarterly, according to their preference. Primary study endpoints were the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM patients at weeks 9-12 compared to baseline. Secondary endpoints encompassed variation in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), HIT-6 and MIDAS scores, and ≥50%, ≥75% and 100% responder rates at the same time intervals. Results 67 migraine patients had received ≥1 subcutaneous fremanezumab dose and were considered for safety analysis, while 53 patients completed 12 weeks of treatment and were included also in the effectiveness analysis. Fremanezumab was effective in both HFEM and CM, inducing at week 12 a significant reduction in MMDs (-4.6, p