Dysfunctional uterine bleeding: medical therapies

About a third of all gynecological consultations are carried out for abnormal uterine bleeding and this ratio rises to 70% in women in peri- and postmenopause. The diagnosis of dysfunctional uterine bleeding (DUB) which is generally due to a chronic anovulatory condition, is only arrived at after objective examination has excluded transvaginal echography, sonohysterography, hysteroscopy and if necessary biopsy to check for the presence of organic pathology. The drugs commonly used in DUB are methylergometrine, the antifibrinolytics, the FANS, estrogens, progesterone and its derivaties, the estroprogestinics, danazol and the superagonist analogues of GnRH. Following these simple guidelines, all derived from evidence-based medicine, medical treatments for DUB are certainly together with patient satisfaction but there is also a marked reduction in costs linked above all to the diminution in the number of hysterectomy operations.     

Diagnostic and prognostic value of 18F-DOPA PET and 1H-MR spectroscopy in pediatric supratentorial infiltrative gliomas: a comparative study

Background¹H-MR spectroscopy (MRS) and ¹⁸F-dihydroxyphenylalanine (DOPA) PET are noninvasive imaging techniques able to assess metabolic features of brain tumors. The aim of this study was to compare diagnostic and prognostic information gathered by ¹⁸F-DOPA PET and ¹H-MRS in children with supratentorial infiltrative gliomas or nonneoplastic brain lesions suspected to be gliomas.MethodsWe retrospectively analyzed 27 pediatric patients with supratentorial infiltrative brain lesions on conventional MRI (21 gliomas and 6 nonneoplastic lesions) who underwent ¹⁸F-DOPA PET and ¹H-MRS within 2 weeks of each other. ¹H-MRS data (choline/N-acetylaspartate, choline-to-creatine ratios, and presence of lactate) and ¹⁸F-DOPA uptake parameters (lesion-to-normal tissue and lesion-to-striatum ratios) were compared and correlated with histology, WHO tumor grade, and patient outcome.Results¹H-MRS and ¹⁸F-DOPA PET data were positively correlated. Sensitivity, specificity, and accuracy in distinguishing gliomas from nonneoplastic lesions were 95%, 83%, and 93% for ¹H-MRS and 76%, 83%, and 78% for ¹⁸F-DOPA PET, respectively. No statistically significant differences were found between the 2 techniques (P > .05). Significant differences regarding ¹⁸F-DOPA uptake and ¹H-MRS ratios were found between low-grade and high-grade gliomas (P≤.001 and P≤.04, respectively). On multivariate analysis, ¹⁸F-DOPA uptake independently correlated with progression-free survival (P≤.05) and overall survival (P = .04), whereas ¹H-MRS did not show significant association with outcome.Conclusions¹H-MRS and ¹⁸F-DOPA PET provide useful complementary information for evaluating the metabolism of pediatric brain lesions. ¹H-MRS represents the method of first choice for differentiating brain gliomas from nonneoplastic lesions.¹⁸F-DOPA uptake better discriminates low-grade from high-grade gliomas and is an independent predictor of outcome.     

Croatia is a safe tourist destination – study of foreign citizen mortality in Splitsko-dalmatinska and Primorsko-goranska County during the period 2001-2010

Aim

To investigate the mortality rate of foreign citizens in Croatia.

Methods

Data were collected from the Departments for Forensic Pathology in Split and Rijeka, which are the autopsy centers of the counties with approximately 35% of total foreign visitors, as well as from the Croatian Central Bureau for Statistics for the period 2001-2010. The mortality rate (number of deaths of members of each nationality per 100 000 entrances ratio) and standardized mortality ratio (ratio between the observed and expected number of deaths) were calculated, and χ² goodness of fit test was used for statistical analyses.

Results

There were 447 deaths (325 men, 72.7%) of foreign citizens (mortality rate of 0.0015%). A total of 207 deaths (46.3%) were by natural causes, more often among older people, and 240 deaths (53.7%) were injury deaths, more often among younger people, mostly by drowning or traffic-related (22.2% and 18.6% of all deaths, respectively). Most represented were citizens of German, Austrian, Czech, and Italian nationality, with 115 (25.7%), 59 (13.2%), 58 (13.0%), and 52 deaths (11.6%), respectively. Mortality rate by nationality showed no significant difference (P < 0.05). The standardized mortality ratio was lowest in Hungarian and Czech citizens (0.17) and highest in US citizens (0.35).

Conclusions

Croatia has low foreign citizens’ mortality rate and could be considered a safe tourist destination.In the period 2001-2010, the number of foreign citizens who visited Croatia rose from 6 544 217 to 10 604 116, twice the Croatian population every year. As it is impossible to distinguish tourists from visitors who come to Croatia for business-related reasons, the term “foreign citizens” was used through the article. In the 10-year period, the number of entries in Croatia was 84 595 522, and 35.9% (30 357 901) entered Splitsko-dalmatinska and Primorsko-goranska Counties (1). Tourism amounts to 13.6% of Croatian GDP (2010) (2), so health and safety of foreign citizens are an important issue. Croatia has been chosen for the top tourist destination in the world several times (by Lonely Planet for 2005, by National Geographic Adventure Magazine for 2006, by New York Times for 2012). The country has very high hygienic standards, good health care, excellent drinking tap water, virtually no dangerous infectious diseases, and a small number of dangerous species.Nearly 50% of travelers worldwide suffer from some kind of illness (3-6), and commonly these conditions are nothing more than gastrointestinal problems (like travelers’ diarrhea), which are not dangerous and are rarely reported as a cause of death (3,7). However, some foreign citizens arrive with more serious conditions, mostly cardiovascular in nature, and they are usually unaware of them. Cardiovascular diseases are the single most common cause of death among this population, while the majority of unintentional deaths are ascribed to traffic related deaths and drowning (4,8,9). The aim of this study was to investigate the mortality rate of foreign citizens in Splitsko-dalmatinska and Primorsko-goranska Counties.     

18F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. ¹²³I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established.¹⁸F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with ¹²³I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of ¹⁸F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of ¹²³I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed.     

Even stressed cells are individuals: second messengers of free radicals in pathophysiology of cancer

Pathophysiological processes associated with disturbances in cell and tissue oxidative homeostasis, are associated with self-catalyzed process of lipid peroxidation. The end products of lipid peroxidation are reactive aldehydes such as 4-hydroxy-2-nonenal (HNE), acting as "second messengers of free radicals." Although reactive aldehydes were first recognized only as cytotoxic, new evidence has come to light, related to their cell growth regulatory functions achieved through cell signaling. The variable appearance of HNE in several organs indicates that its mode of action might be related to an individual cell stress adaptation. The underlying mechanism could be that specific mutations and epigenetic changes on one hand interfere with hormesis on the other. The precise role of oxidative stress and lipid peroxidation in these processes still needs more clarification at molecular level. Finally, an individual approach to each patient, based on the individual cell response to stress, opens a new possibility of integrative medicine in cancer treatment and strongly supports modern concepts of personalized medicine.     

Design of Three Residues Peptides against SARS-CoV-2 Infection

The continuous and rapid spread of the COVID-19 pandemic has emphasized the need to seek new therapeutic and prophylactic treatments. Peptide inhibitors are a valid alternative approach for the treatment of emerging viral infections, mainly due to their low toxicity and high efficiency. Recently, two small nucleotide signatures were identified in the genome of some members of the Coronaviridae family and many other human pathogens. In this study, we investigated whether the corresponding amino acid sequences of such nucleotide sequences could have effects on the viral infection of two representative human coronaviruses: HCoV-OC43 and SARS-CoV-2. Our results showed that the synthetic peptides analyzed inhibit the infection of both coronaviruses in a dose-dependent manner by binding the RBD of the Spike protein, as suggested by molecular docking and validated by biochemical studies. The peptides tested do not provide toxicity on cultured cells or human erythrocytes and are resistant to human serum proteases, indicating that they may be very promising antiviral peptides.