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Current models for the study of neuroendocrine tumours (NETs) are severely limited. While in vitro (e.g. cell lines), ex vivo (e.g. organoids) and in vivo (e.g. mice) models all exist, each has limitations. To address these limitations and collectively identify strategies to move the NET models field forward, we held an inaugural NET models meeting, hosted by our founding group: Dr Lines (Oxford), Prof. Quelle (Iowa), Dr Dayton (Barcelona), Dr Ear (Iowa), Dr Marinoni (Bern) and Dr Guenter (Alabama). This two-day meeting in Oxford (UK) was organised and supported by Bioscientifica Ltd and was solely dedicated to the discussion of NET models. The meeting was attended by ∼30 international researchers (from the UK, EU, Israel, USA and Canada). Plenary talks were given by Prof. Thakker, who summarised NET research over the past few decades, and Dr Schrader, who described the process and pitfalls of generating new cell lines. Eight researchers also presented their work on topics ranging from human cell 3D bioprinting to zebrafish models and included novel ideas and improvements on current concepts. This was followed by an interactive workshop, where discussion topics included a summary of currently available NET models, limitations of these models, barriers to developing new models, and how we can address these issues going forward. This white paper summarises the key points raised in these discussions and the future aspirations of the NET Models Consortium. The next meeting will take place in Oxford (UK) in 2025; contact contact@netcancerfoundation.com for more information.

Latar Belakang: Pengetahuan, keterlibatan, dan kepercayaan diri tenaga gizi sangat dibutuhkan dalam penerapan pelayanan gizi berbasis gen. Sedikitnya tenaga gizi yang menerapkan pelayanan gizi berbasis gen ini adalah tantangan tersendiri dalam proses perkembangan pelayanan gizi berbasis gen di Indonesia. Tujuan: Untuk mengetahui hubungan pengetahuan, keterlibatan dan kepercayaan diri tenaga gizi terhadap pelayanan gizi berbasis gen di Indonesia. Metode: Desain penelitian ini adalah cross-sectional yang dilaksanakan pada Mei-Juni 2023. Responden adalah tenaga gizi di lima provinsi di Indonesia. Kuesioner penelitian meliputi data sosio-demografis, pengetahuan, keterlibatan, dan kepercayaan diri tenaga gizi yang disebarkan secara daring demgam Qualtrics Survey. Analisis data penelitian ini menggunakan uji chi square dengan SPSS versi 25.0. Hasil: Sebanyak 423 responden diperoleh menunjukkan bahwa 53,4% tenaga gizi memiliki pengetahuan rendah, 60,0% tidak terlibat, dan 51,8% memiliki kepercayaan diri rendah terhadap pelayanan gizi berbasis gen. Terdapat hubungan yang signifikan antara pengetahuan dengan kepercayaan diri tenaga gizi terhadap pelayanan gizi berbasis gen (p= 0,001; OR 2,0; CI= 1,35-2,94). Kemudian ditemukan hubungan yang signifikan antara pengetahuan dengan keterlibatan tenaga gizi terhadap pelayanan gizi berbasis gen (p= 0,001; OR 1,99; CI= 1,34-2,96). Kesimpulan: Terdapat hubungan pengetahuan tenaga gizi dengan keterlibatan diri dan kepercayaan diri tenaga gizi terhadap pelayanan gizi berbasis gen di Indonesia. Diharapkan tenaga gizi untuk meningkatkan pengetahuan terkait genetik dan hubungannya dengan gizi melalui pelatihan, seminar, dan pendidikan lanjut.

Latar Belakang: Ilmu genetik berkembang sangat pesat memberikan dampak signifikan teradap suatu penyakit yang dapat dicegah dan dikelola oleh tenaga kesehatan professional, tetapi di Indonesia sendiri pengaplikasian dietetik masih belum banyak diketahui oleh karena itu ahli gizi perlu berperan dalam pengaplikasian nutritional genomics ini di dalam praktik kerja dietetik. Peran ahli gizi penting dalam memberikan informasi mengenai bagaimana gizi dan genetik berinteraksi dalam mempengaruhi Kesehatan dan memberikan alternatif intervensi gizi yang lebih dini. Tujuan: Mengetahui peran ahli gizi dalam memberikan pelayanan gizi berbasis gen di indonesia. Metode: Penelitian ini merupakan penelitian kualitatif dengan pendekatan fenomenologi, yang dilakukan di lima provinsi di Indonesia. Data informan di dapatkan dari penelitian kuantitatif, dengan teknik pengambilan informan yaitu purposive sampling dengan jumlah informan sebanyak enam orang. Pengumpulan data menggunakan structured interview dilaksanakan secara online dengan menggunakan Zoom Meeting. Analisis data yang digunakan yaitu analisis tematik dengan software NVIVO v.12. Hasil: Tenaga gizi yang sudah dan yang belum menerapkan pelayanan gizi berbasis gen ini sebagian besar sudah mengetahui terkait pelayanan gizi berbasis gen. Namun, sebagian dari mereka tidak mengetahui terkait definisi nutrigenetik dan nutrigenomik. sebagiannya mengetahui terkait peran tenaga gizi yaitu sebagai konselor untuk memberikan konseling, memberikan saran terkait pola makan yang sesuai dengan kebutuhan pasien, memberikan motivasi kepada pasien untuk menjalankan diet sesuai dengan kebutuhan pasien. Kesimpulan: Peran tenaga gizi dalam memberikan pelayanan gizi berbasis gen yaitu sebagai konselor untuk memberikan konseling, memberikan saran terkait pola makan yang sesuai dengan kebutuhan pasien, dan memberikan motivasi kepada pasien untuk menjalankan diet sesuai dengan kebutuhan pasien.

Latar Belakang: Penyakit kardiometabolik adalah penyebab utama kematian, morbiditas dan pengeluaran perawatan kesehatan polimorfisme nukleotida tunggal berhubungan dengan penyakit dan karakteristik kardiometabolik. Pandangan ahli gizi terhadap pelayanan gizi berbasis genetik memegang peranan penting dalam proses pencegahan dan penanganan dari penyakit-penyakit yang tidak menular tersebut (PTM). Tujuan: Mengetahui gambaran pandangan ahli gizi terhadap pelayanan gizi berbasis gen di Indonesia. Metode: Penelitian ini menggunakan metode penelitian kualitatif dengan pendekatan fenomenologi. Informan dalam penelitian ini adalah ahli gizi Indonesia yang berdomisili di lima provinsi besar yaitu DKI Jakarta, Jawa Barat, Jawa Tengah, Jawa Timur dan D.I Yogyakarta. Wawancara mendalam dilakukan terhadap enam informan. Teknik sampling yang digunakan purposive sampling tema penelitian adalah pandangan ahli gizi tentang pelayanan gizi berbasis gen sebagai pencegah PTM, pengetahuan ilmu genetik dan tes genetik. Analisis tematik dilakukan dalam menggunakan Nvivo v.12. Hasil: Pengetahuan ahli gizi terkait genetika dan pelayanan gizi berbasis gen sudah cukup baik, kemudian ahli gizi mengeluhkan biaya tes yang mahal untuk saat ini. Pengetahuan ahli gizi tentang pelayanan gizi berbasis gen sebagai pencegahan PTM sudah baik. Ahli gizi memahami apa itu PTM dan mereka mengaggap tes ini penting sebagai pencegahan PTM. Kesimpulan: Ahli gizi memiliki pandangan bahwa pelayanan gizi berbasis gen itu penting untuk pencegahan PTM dan ahli gizi sudah cukup baik mengenai ilmu genetik. Ahli gizi perlu melaksanakan sosialisasi ke masyarakat tentang pentingnya keuntungan tes genetik untuk mencegah PTM agar banyak masyarakat yang berminat untuk melakukan pelayanan gizi berbasis gen.

Latar Belakang: Setiap individu memiliki jenis gen yang berbeda dan berpengaruh terhadap perbedaan risiko penyakit dan respon individu terhadap diet. Perkembangan ilmu nutritional genomics berakibat pada diketahuinya kerentanan penyakit dan dapat dicegah melalui pelayanan gizi berbasis gen. Pengetahuan pelayanan gizi berbasis gen penting bagi ahli gizi karena dapat memberikan informasi terkait gen dan diet. Tujuan: Untuk mengetahui gambaran pengetahuan ahli gizi tentang pelayanan gizi berbasis gen di Indonesia. Metode: Penelitian ini menggunakan desain penelitian kualitatif dengan pendekatan fenomenologi yang dilakukan di DKI Jakarta, Jawa Barat, Jawa Tengah, Jawa Timur, dan DI Yogyakarta. Teknik pengambilan sampel menggunakan purposive sampling dengan jumlah subjek sebanyak tujuh Ahli Gizi. Pengambilan data melalui wawancara mendalam secara offline dan online menggunakan Zoom Meeting. Hasil wawancara direkam dan dianalisis dengan teknik analisis tematik menggunakan software Nvivo 12.0. Hasil: Pengetahuan ahli gizi tentang ilmu nutritional genomics masih kurang. Ahli gizi bisa menjelaskan konsep dasar akan tetapi tidak mengetahui pengetahuan ini secara mendalam. Pengetahuan ahli gizi tentang pelayanan gizi berbasis gen juga masih terbatas, sehingga mereka masih meragukan peran mereka dalam pelayanan ini. Sedangkan pandangan ahli gizi terhadap pelayanan gizi berbasis gen umumnya positif dan menganggap pelayanan ini penting dan berharap instansi mereka bekerja dapat menyediakannya. Ahli gizi tertarik untuk memberikan pelayanan gizi berbasis gen dan bersemangat untuk belajar lebih lanjut mengenai ilmu nutritional genomics. Kesimpulan: Pengetahuan ahli gizi tentang pelayanan gizi berbasis gen masih kurang. Harapannya ahli gizi mendapat pelatihan, seminar, dan pemerataan pendidikan tentang ilmu nutritional genomics di perguruan tinggi untuk memenuhi kompetensi ahli gizi di masa depan.

Background: The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. Objective: This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. Methods: We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Results: Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. Conclusions: Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology.

Abstract Background Migraine is the second world’s cause of disability. Among non-pharmacological treatments, nutritional intervention, particularly ketogenic diet, represents one of the most promising approaches. Methods This a prospective, single center, randomized, controlled study aimed at evaluating the efficacy of a very low-calorie ketogenic diet (VLCKD) compared to a hypocaloric balanced diet (HBD) in migraine prophylaxis in patients affected by high-frequency episodic migraine (HFEM) with a Body Mass Index (BMI) > 27 kg/m2. Fifty-seven patients were randomly assigned to a VLCKD (group 1) or HBD (group 2). Group 1 patients followed a VLCKD for 8 weeks, followed by a low calorie diet (LCD, weeks 9–12), and a HBD (weeks 13–24), whereas group 2 patients followed a HBD from week 0 to 24. Anthropometric indexes, urine and blood chemistry were assessed at enrollment, baseline, weeks 4, 8, 12, and 24. Migraine characteristics were evaluated at baseline, weeks 8, 12 and 24. Change in monthly migraine days (MMDs) at weeks 5–8 compared to baseline was the primary endpoint. Secondary endpoints encompassed changes in visual analogue scale (VAS), Headache Impact Test-6 (HIT-6) and Short Form Health Survey-36 (SF-36) scores. We also studied effects on circulating lymphocytes and markers of inflammation, changes in plasma aldosterone and renin levels before and after VLCKD or HBD treatment. Results Reduction from baseline in MMDs was greater in VLCKD compared to HBD group at week 8 (p = 0.008), at week 12 (p = 0.007), when ketosis had been interrupted by carbohydrates reintroduction, and at week 24 (p = 0.042), when all patients were following the same dietary regimen. Quality of life scores (SF-36) were improved in VLCKD group at week 8 and 12, and were also improved in HBD group, but only at week 12. Weight-loss was significantly higher in VLCKD group at week 8 (p = 0.002) and week 12 (p = 0.020). At the end of the study weight loss was maintained in VLCKD group whereas a slight weight regain was observed in HBD group. Inflammatory indexes, namely C reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and total white blood cell count (WBC) were significantly reduced (p

We conducted a multicenter, prospective study (EMBRACE) evaluating the real-life effectiveness, safety, and tolerability of eptinezumab (100 mg/300 mg)—a monoclonal antibody targeting the calcitonin-gene-related peptide (anti-CGRP mAb)—in high-frequency episodic migraine (HFEM) or chronic migraine (CM). The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at weeks 9–12 compared to baseline. The secondary endpoints included changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates. The safety analysis involved 44 subjects; the effectiveness analysis included 26 individuals. Eptinezumab was well-tolerated. In CM patients, eptinezumab significantly reduced MHD (−16.1 ± 9.9, p < 0.001), MAI, NRS, HIT-6, MIDAS, and MIBS-4. In HFEM patients, it significantly reduced NRS, HIT-6, MIDAS, and MIBS-4, though reductions in MMD (−3.3 ± 4.5) and MAI were not statistically significant. Overall, ≥50% and ≥75% response rates were 61.5% and 30.8%, respectively (60% and 30% in non-responders to subcutaneous anti-CGRP mAbs). The clinical change was rated as much or very much improved by 61.0% of the patients. Eptinezumab demonstrated high effectiveness, safety, and tolerability in real-life among hard-to-treat migraine patients with multiple treatment failures, including anti-CGRP mAbs.

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.

Abstract 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.

Menopause, an extremely delicate phase in a woman’s life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles. In recent years, research has focused on the field of myokines, cytokines, or peptides secreted by skeletal muscle fibers following exercise. Among these, irisin has attracted great interest as it possesses myogenic properties but at the same time exerts anabolic effects on bone and could therefore represent the link between muscle and bone. Therefore, irisin could represent a new therapeutic strategy for the treatment of osteoporosis and also serve as a new biomarker of sarcopenia, thus facilitating diagnosis and pharmacological intervention. The purpose of this review is to provide an updated summary of what we know about the role of irisin in postmenopausal osteoporosis and sarcopenia.

In the age of globalization where the midst of increasingly fierce competition, human ability as a resource for mastery of technology, adaptation and responsiveness to change is needed. This research is done to explore and analyze the impact of job satisfaction and competency on employee performance. Besides that organizational citizenship behavior is a mediating variable. Respondents used in this study were employees of the Garment Company factory in Semarang Regency as many as 105 people. The questionnaire method is used to collect the primary data needed. The AMOS SEM program is used for analytical tools. The results of the study found that: 1). Employee competency variables and job satisfaction variables have a positive influence on OCB. 2). Employee competency variables and job satisfaction variables have a positive influence on employee performance. 3). OCB has a positive influence on employee performance. 4). Employee competency variables and job satisfaction variables have a positive influence through OCB on employee performance.

Abstract 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 Sixty-seventh number 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

Abstract 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.

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.

Background: Tactile stimulation manoeuvres stimulate spontaneous breathing in preterm newborns. The aim of this study is to evaluate the effect of early respiratory physiotherapy on the need for mechanical ventilation during the first week of life in preterm infants with respiratory failure. Methods: This is a monocentric, randomised controlled trial. Preterm infants (gestational age ≤ 30 weeks) not intubated in the delivery room and requiring non-invasive respiratory support at birth were eligible for the study. The intervention group received early respiratory physiotherapy, while the control group received only a daily physiotherapy program (i.e., modifying the infant’s posture in accordance with the patient’s needs). Results: between October 2019 and March 2021, 133 preterm infants were studied, 68 infants in the study group and 65 in routine care. The study group showed a reduction in the need for mechanical ventilation (not statistically significant) and a statistically significant reduction in hemodynamically significant patent ductus arteriosus with respect to the control group (19/68 (28%) vs. 35/65 (54%), respectively, p = 0.03). Conclusions: early respiratory physiotherapy in preterm infants requiring non-invasive respiratory support at birth is safe and has proven to be protective against haemodynamically significant PDA.

Abstract Background Tactile maneuvers stimulating spontaneous respiratory activity in preterm infants are recommended since birth, but data on how and how often these maneuvers are applied in clinical practice are unknown. In the last years, most preterm newborns with respiratory failure are preferentially managed with non-invasive respiratory support and by stimulating spontaneous respiratory activity from the delivery room and in neonatal intensive care unit (NICU), in order to avoid the risks of intubation and prolonged mechanical ventilation. Methods Preterm infants with gestational age

Abstract: Wastewater from gold treatment by amalgamation has a high TSS value and heavy metal content in the form of Cu and Hg. This content can endanger the surrounding environment. Therefore, wastewater must be treated until it shows results below the permitted quality standards. Wastewater treatment is carried out using the batch reactor electrocoagulation method. The purpose of this study was to determine the efficiency value and optimal conditions by reducing the TSS, Cu, and Hg content in wastewater based on the effect of time (10 minutes) and voltage (4.5 volts, 6 volts, and 7.5 volts). This calculation of the efficiency and analysis showed that the optimal conditions occurred at a voltage of 6 volts from the three parameters, there are TSS = 97.49%, Cu = 95.71%, and Hg = 98.95%. Based on the test results after treatment, the wastewater still needs to be treated until it is below the safe quality standard according to Government Regulation of Indonesia Republic No. 82 of 2001 class 4. Abstrak: Air limbah pencucian emas dengan metode amalgamasi memiliki nilai TSS yang tinggi dan kandungan logam berat berupa Cu dan Hg. Kandungan tersebut dapat membahayakan lingkungan sekitar. Oleh karena itu, air limbah harus diolah hingga menunjukkan hasil di bawah baku mutu yang diizinkan. Pengolahan air limbah dilakukan dengan metode elektrokoagulasi reaktor batch. Tujuan penelitian ini adalah untuk mengetahui nilai efisiensi dan kondisi optimal dengan mereduksi kandungan TSS, Cu, dan Hg pada limbah cair berdasarkan pengaruh waktu (10 menit) dan tegangan (4,5 volt, 6 volt, dan 7,5 volt). Hasil perhitungan efisiensi dan analisis ini menunjukkan bahwa kondisi optimal terjadi pada tegangan 6 volt dari ketiga parameter yaitu TSS = 97,49%, Cu = 95,71%, dan Hg = 98,95%. Berdasarkan hasil pengujian setelah diolah, air limbah masih perlu diolah hingga berada di bawah baku mutu aman sesuai dengan PP RI No. 82 Tahun 2001 pada kelas 4.

Abstract 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

Background: The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. Objective: This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. Methods: We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Results: Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. Conclusions: Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology. [ABSTRACT FROM AUTHOR]

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.

ObjectiveTo evaluate the effect of volume guarantee (VG) combined with high-frequency oscillatory ventilation (HFOV) on respiratory and other physiological parameters immediately after lung recruitment and surfactant administration in HFOV elective ventilated extremely low gestational age newborns (ELGAN) with respiratory distress syndrome (RDS).DesignObservational study.SettingTertiary neonatal intensive care unit.PatientsTwenty-two ELGANs of 25.5 ± 1.1 weeks of gestational age requiring invasive mechanical ventilation and surfactant administration for RDS during the first 6 h of life.InterventionsAll infants intubated in delivery room, were managed with elective HFOV and received surfactant after a lung recruitment manoeuver. Eleven infants received HFOV + VG and were compared with a control group of 11 infants receiving HFOV alone. HFOV was delivered in both groups by Dräger Babylog VN500 ventilator (Dräger, Lubeck, Germany).Main Outcome MeasuresVariations and fluctuations of delivered high-frequency tidal volume (VThf), fluctuation of pressure amplitude (ΔP) and partial pressure of CO2 (pCO2) levels after recruitment manoeuver and immediately after surfactant administration, in HFOV + VG vs. HFOV ventilated infants.ResultsThere were no significant differences in the two groups at starting ventilation with or without VG. The mean applied VThf per kg was 1.7 ± 0.3 ml/kg in the HFOV group and 1.7 ± 0.1 ml/kg in the HFOV + VG group. Thirty minutes after surfactant administration, HFOV group had a significant higher VThf/Kg than HFOV + VG (2.1 ± 0.3 vs. 1.6 ± 0.1 ml/kg, p < 0.0001) with significantly lower pCO2 levels (43.1 ± 3.8 vs. 46.8 ± 1.5 mmHg, p = 0.01), 54.4% of patients having pCO2 below 45 mmHg. Measured post-surfactant ΔP values were higher in HFOV group (17 ± 3 cmH2O) than in HFOV + VG group (13 ± 3 cmH2O, p = 0.01).ConclusionHFOV + VG maintains pCO2 levels within target range and reduces VThf delivered variations more consistently than HFOV alone after surfactant administration.

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.

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.

Objective: We reported gender-specific data on the efficacy and safety of erenumab, a monoclonal antibody antagonizing the calcitonin gene-related peptide (CGRP) receptor.Methods: Our pooled patient-level analysis of real-world data included patients treated with erenumab and followed up for 12 weeks. We considered the following outcomes at weeks 9–12 of treatment compared with baseline: 0–29%, 30–49%, 50–75%, and ≥75% responder rates, according to the decrease in monthly headache days (MHDs), rate of treatment stopping, change in MHDs, monthly migraine days (MMDs), monthly days of acute medication and triptan use, and Headache Impact Test-6 (HIT-6) score from baseline to weeks 9–12. Outcomes were compared between men and women by the chi-squared test or t-test, as appropriate. An analysis of covariance (ANCOVA) was performed to identify factors influencing the efficacy outcomes.Results: We included 1,410 patients from 16 centers, of which 256 (18.2%) were men. Men were older than women and had a lower number of MHDs at baseline. At weeks 9–12, compared with baseline, 46 (18.0%) men had a ≥75% response, 75 (29.3%) had a 50–74% response, 35 (13.7%) had a 30–49% response, and 86 (33.6%) had a 0–29% response, while 14 (5.5%) stopped the treatment. The corresponding numbers for women were 220 (19.1%), 314 (27.2%), 139 (12.0%), 402 (34.8%), and 79 (6.8%). No gender difference was found in any of the outcomes. The ANCOVA showed that gender did not influence the efficacy of outcomes.Conclusion: We found that erenumab is equally safe and effective in men compared with women after 12 weeks.

Pancreatic cancer (PC) is a malignancy accounting for only 3% of total cancers, but with a low 5-year relative survival rate. Approximately 80% of PC patients are diagnosed at a late stage when the disease has already spread from the primary site. Despite advances in PC treatment, there is an urgently needed for the identification of novel therapeutic strategies for PC, particularly for patients who cannot undergo classical surgery. Autophagy is an evolutionarily conserved process used by cells to adapt to metabolic stress via the degrading or recycling of damaged or unnecessary organelles and cellular components. This process is elevated in PC and, thus, it contributes to the onset, progression, and cancer cell resistance to chemotherapy in pancreatic tumors. Autophagy inhibition has been shown to lead to cancer regression and to increase the sensitivity of pancreatic cells to radiation and chemotherapy. Emerging studies have focused on the roles of non-coding RNAs (ncRNAs), such as miRNAs, long non-coding RNAs, and circular RNAs, in PC development and progression. Furthermore, ncRNAs have been reported as crucial regulators of many biological processes, including autophagy, suggesting that ncRNA-based autophagy targeting methods could be promising novel molecular approaches for specifically reducing autophagic flux, thus improving the management of PC patients. In this review, we briefly summarize the existing studies regarding the role and the regulatory mechanisms of autophagy-related ncRNAs in the context of this cancer.

We conducted a multicenter, prospective study (EMBRACE) evaluating the real-life effectiveness, safety, and tolerability of eptinezumab (100 mg/300 mg)—a monoclonal antibody targeting the calcitonin-gene-related peptide (anti-CGRP mAb)—in high-frequency episodic migraine (HFEM) or chronic migraine (CM). The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at weeks 9–12 compared to baseline. The secondary endpoints included changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates. The safety analysis involved 44 subjects; the effectiveness analysis included 26 individuals. Eptinezumab was well-tolerated. In CM patients, eptinezumab significantly reduced MHD (−16.1 ± 9.9, p < 0.001), MAI, NRS, HIT-6, MIDAS, and MIBS-4. In HFEM patients, it significantly reduced NRS, HIT-6, MIDAS, and MIBS-4, though reductions in MMD (−3.3 ± 4.5) and MAI were not statistically significant. Overall, ≥50% and ≥75% response rates were 61.5% and 30.8%, respectively (60% and 30% in non-responders to subcutaneous anti-CGRP mAbs). The clinical change was rated as much or very much improved by 61.0% of the patients. Eptinezumab demonstrated high effectiveness, safety, and tolerability in real-life among hard-to-treat migraine patients with multiple treatment failures, including anti-CGRP mAbs. [ABSTRACT FROM AUTHOR]

Penelitian ini menguji pengaruh kepribadian proaktif terhadap intensi kewirausahaan mahasiswa dengan pendidikan kewirausahaan sebagai variabel moderasi. Menggunakan teknik quota sampling, diambil sampel penelitian sejumlah 200 mahasiswa pada sepuluh perguruan tinggi di Semarang. Hasil menunjukkan kepribadian proaktif secara positif dan signifikan berpengaruh terhadap intensi kewirausahaan mahasiswa. Pendidikan kewirausahaan secara signifikan juga berpengaruh terhadap intensi kewirausahaan mahasiswa, sekaligus memoderasi hubungan kepribadian proaktif dan intensi kewirausahaan mahasiswa. Temuan ini konsisten dengan teori kepribadian kewirausahaan. Implikasi dari penelitian ini dapat digunakan bagi penyelenggara pendidikan tinggi dalam mendesain pola pendidikan kewirausahaan yang tepat dalam menumbuhkan intensi berwirausaha pada mahasiswanya.

The study investigates the role of the oxidative and proteolytic inactivation of alpha-1 antitrypsin (AAT) in the pathogenesis of bronchopulmonary dysplasia (BPD) in premature infants. Bronchoalveolar lavage fluid (BALF) samples were collected on the 3rd day of life from mechanically ventilated neonates with gestational age ≤ 30 weeks and analyzed without previous treatment (top-down proteomics) by reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry. AAT fragments were identified by high-resolution LTQ Orbitrap XL experiments and the relative abundances determined by considering the extracted ion current (XIC) peak area. Forty preterm neonates were studied: 20 (50%) did not develop BPD (no-BPD group), 17 (42.5%) developed mild or moderate new-BPD (mild + moderate BPD group), and 3 (7.5%) developed severe new-BPD (severe BPD group). Eighteen fragments of AAT and a fragment of AAT oxidized at a methionine residue were identified: significantly higher values of AAT fragments 25–57, 375–418, 397–418, 144–171, and 397–418 with oxidized methionine were found in the severe BPD group. The significantly higher levels of several AAT fragments and of the fragment 397–418, oxidized in BALF of preterm infants developing BPD, underlie the central role of an imbalance between proteases and protease inhibitors in exacerbating lung injury and inducing most severe forms of BPD. The study has some limitations, and between them, the small sample size implies the need for further confirmation by larger studies.

Abstract Background A physiologic test for estimating BPD rate has been developed by Walsh and collaborators. Actually there are not standard criteria for weaning from CPAP and/or oxygen therapy the premature babies. Aim of this study was to verify if a physiologic test, modified respect to that developed by Walsh and collaborators for estimating BPD rate, can be used as a clinical tool for weaning the premature babies from CPAP and/or oxygen therapy. Methods Neonates with BW 500–1250 g and GA ≤ 32 weeks, receiving FiO2 ≤ 0.30 by hood or CPAP, were prospectively studied at 28 days of life and at 36 weeks of postmestrual age. The test was performed in 3 steps: baseline, challenge (FiO2 and CPAP reduction to room air) and post test (room air). Monitoring of transcutaneous CO2 was added to SpO2 and the newborns passing the test were left in room air. Results Six of 23 tested babies (26%) passed the challenge at 28 days of life, 4 of 10 tested babies (40%) passed the challenge at 36 weeks. Median values of SpO2 were significantly higher in the neonates passing the test, respect to the failing patients. At the same time median values of TcPCO2 were significantly higher in the latter babies. Conclusion TcPCO2 monitoring appeared to be a new useful parameter for failure prediction of weaning. The test represented a clinical guide because the newborns passing it were left in room air.

Abstract Background The degree to which work-related difficulties are recognized in headache research is poor and often carried out with inadequate information such as “reduced ability to work as usual”, which do not capture at all the variety of difficulties and the factors that impact over them. The aim of this paper is to present the validation of the HEADWORK questionnaire, which addresses the amount and severity of difficulties in work-related tasks and the factors that impact over them. Methods We developed a set of items based on a previous literature review and patients’ focus groups and tested it on a wide set of patients with episodic and chronic migraine attending eight different Italian headache centers. HEADWORK factor structure was assessed with exploratory and confirmatory factor analysis; internal consistency and construct validity were addressed as well. Results The validation sample (N = 373) was mostly composed of patients with episodic migraine without aura (64.3%) and of females (81%). Factor analysis retrieved two different scales: “Work-related difficulties”, composed of eleven items which explain 67.1% of the total variance, and “Factors contributing to work difficulties”, composed of six items which explain 52.1% of the total variance. Both HEADWORK subscales have good measurement properties, with higher scores being associated to higher disability, lower quality of life, lower productivity, higher headache frequency and pain intensity. Conclusions HEADWORK is a 17-item, two-scale questionnaire addressing the impact of migraine on work-related difficulties in terms of difficulties in general or specific skills, and the factors contributing to these difficulties, defined as negative impact on work tasks. It can be used to address disability weights for the purpose of calculating the burden of migraine, and to assess the balance between therapeutic and side effects of medication on productivity.

Menopause, an extremely delicate phase in a woman's life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles. In recent years, research has focused on the field of myokines, cytokines, or peptides secreted by skeletal muscle fibers following exercise. Among these, irisin has attracted great interest as it possesses myogenic properties but at the same time exerts anabolic effects on bone and could therefore represent the link between muscle and bone. Therefore, irisin could represent a new therapeutic strategy for the treatment of osteoporosis and also serve as a new biomarker of sarcopenia, thus facilitating diagnosis and pharmacological intervention. The purpose of this review is to provide an updated summary of what we know about the role of irisin in postmenopausal osteoporosis and sarcopenia. [ABSTRACT FROM AUTHOR]

Background: The knowledge, involvement, and self-confidence of nutrition professionals are highly required in the implementation of gene-based nutrition services. The limited number of nutrition professionals applying gene-based nutrition services poses a unique challenge in the developmental process of gene-based nutrition services in Indonesia. Objectives: This study aims to identify the association between the knowledge, engagement, and confidence levels of nutrition workers with gene-based nutrition services in Indonesia. Methods: This cross-sectional study was conducted in May-June 2023. The participants consisted of nutrition workers from five provinces in Indonesia. The instrument of this study used structured questionnaires encompassing socio-demographic information, knowledge, engagement, and confidence levels of nutrition workers distributed using the Qualtrics Survey platform. Data analysis employed the chi-square test with the help of Statistical Package for the Social Sciences (SPSS) version 25.0. Results: This study involved a total of 423 respondents. Findings indicated that 53.4% of nutrition workers possessed limited knowledge, 60.0% exhibited minimal engagement, and 51.8% held low confidence levels in gene-based nutrition services. Notably, a significant correlation was identified between knowledge and confidence in gene-based nutrition services (p=0.001; PR=2.0; CI=1.35-2.94). Additionally, a significant association was present between knowledge and engagement in gene-based nutrition services (p=0.001; PR=2.00; CI=1.34-2.96). Conclusions: This study highlights the association of low nutritionists' knowledge with low personal involvement and confidence levels to gene-based nutrition services in Indonesia. Nutrition professionals are encouraged to enhance their grasp of genetics and its relevance to nutrition through dedicated training, participation in seminars, and ongoing education initiatives. [ABSTRACT FROM AUTHOR]

Pituitary adenomas (PAs) are one of the most common lesions of intracranial neoplasms, occurring in approximately 15% of the general population. They are typically benign, although some adenomas show aggressive behavior, exhibiting rapid growth, drug resistance, and invasion of surrounding tissues. Despite ongoing improvements in diagnostic and therapeutic strategies, late first diagnosis is common, and patients with PAs are prone to relapse. Therefore, earlier diagnosis and prevention of recurrence are of importance to improve patient care. MicroRNAs (miRNAs) are short non-coding single stranded RNAs that regulate gene expression at the post-transcriptional level. An increasing number of studies indicate that a deregulation of their expression patterns is related with pituitary tumorigenesis, suggesting that these small molecules could play a critical role in contributing to tumorigenesis and the onset of these tumors by acting either as oncosuppressors or as oncogenes, depending on the biological context. This paper provides an overview of miRNAs involved in PA tumorigenesis, which might serve as novel potential diagnostic and prognostic non-invasive biomarkers, and for the future development of miRNA-based therapeutic strategies for PAs.

Abstract Background Despite an increased use of non-invasive ventilatory strategies and gentle ventilation, pneumothorax remains a common complication in preterm infants. The ventilator management of infants with air leaks remains challenging in terms of both prevention and treatment. Recently the safety and efficacy of expectant management avoiding chest tube drainage to treat large air leak in preterm infants hemodynamically stable has been reported. Case presentation In the present study, we report five cases of preterm infants with birth weight ≤ 1250 g affected by respiratory distress syndrome and treated with nasal continuous positive airway pressure as first intention. They were intubated for worsening of respiratory distress with increasing oxygen requirement and concomitant increase of respiratory rate and PCO2 values due to occurrence of pneumothorax, and they were successfully treated using high-frequency oscillatory ventilation without chest tube insertion. Conclusion In our experience high-frequency oscillatory ventilation provided a conservative management of a significant pneumothorax in preterm newborns hemodynamically stable and requiring mechanical ventilation. This approach allowed us to avoid the increasing of air leak and the insertion of chest tube drainage and all the subsequent associated risks.