Vertebral artery dissection in term pregnancy after cervical spine manipulation: a case report and review the literature

Background: Vertebral artery dissection is an uncommon, but potentially fatal, vascular event. This case aimed to describe the pathogenesis and clinical presentation of vertebral artery dissection in a term pregnant patient. Moreover, we focused on the differential diagnosis, reviewing the available evidence. Case presentation: A 39-year-old Caucasian woman presented at 38 + 4 weeks of gestation with a short-term history of vertigo, nausea, and vomiting. Symptoms appeared a few days after cervical spine manipulation by an osteopathic specialist. Urgent magnetic resonance imaging of the head was obtained and revealed an ischemic lesion of the right posterolateral portion of the brain bulb. A subsequent computed tomography angiographic scan of the head and neck showed a right vertebral artery dissection. Based on the correlation of the neurological manifestations and imaging findings, a diagnosis of vertebral artery dissection was established. The patient started low-dose acetylsalicylic acid and prophylactic enoxaparin following an urgent cesarean section. Conclusion: Vertebral artery dissection is a rare but potential cause of neurologic impairments in pregnancy and during the postpartum period. It should be considered in the differential diagnosis for women who present with headache and/or vertigo. Women with a history of migraines, hypertension, or autoimmune disorders in pregnancy are at higher risk, as well as following cervical spine manipulations. Prompt diagnosis and management of vertebral artery dissection are essential to ensure favorable outcomes

Synergism through WEE1 and CHK1 inhibition in acute lymphoblastic leukemia

Introduction: Screening for synthetic lethality markers has demonstrated that the inhibition of the cell cycle checkpoint kinases WEE1 together with CHK1 drastically affects stability of the cell cycle and induces cell death in rapidly proliferating cells. Exploiting this finding for a possible therapeutic approach has showed efficacy in various solid and hematologic tumors, though not specifically tested in acute lymphoblastic leukemia. Methods: The efficacy of the combination between WEE1 and CHK1 inhibitors in B and T cell precursor acute lymphoblastic leukemia (B/T-ALL) was evaluated in vitro and ex vivo studies. The efficacy of the therapeutic strategy was tested in terms of cytotoxicity, induction of apoptosis, and changes in cell cycle profile and protein expression using B/T-ALL cell lines. In addition, the efficacy of the drug combination was studied in primary B-ALL blasts using clonogenic assays. Results: This study reports, for the first time, the efficacy of the concomitant inhibition of CHK1/CHK2 and WEE1 in ALL cell lines and primary leukemic B-ALL cells using two selective inhibitors: PF-0047736 (CHK1/CHK2 inhibitor) and AZD-1775 (WEE1 inhibitor). We showed strong synergism in the reduction of cell viability, proliferation and induction of apoptosis. The efficacy of the combination was related to the induction of early S-phase arrest and to the induction of DNA damage, ultimately triggering cell death. We reported evidence that the efficacy of the combination treatment is independent from the activation of the p53-p21 pathway. Moreover, gene expression analysis on B-ALL primary samples showed that Chek1 and Wee1 are significantly co-expressed in samples at diagnosis (Pearson r = 0.5770, p = 0.0001) and relapse (Pearson r= 0.8919; p = 0.0001). Finally, the efficacy of the combination was confirmed by the reduction in clonogenic survival of primary leukemic B-ALL cells. Conclusion: Our findings suggest that the combination of CHK1 and WEE1 inhibitors may be a promising therapeutic strategy to be tested in clinical trials for adult ALL

Probing the nature of the low state in the extreme ultraluminous X-ray pulsar NGC 5907 ULX1

NGC 5907 ULX1 is the most luminous ultra-luminous X-ray pulsar (ULXP) known to date, reaching luminosities in excess of 1e41 erg/s. The pulsar is known for its fast spin-up during the on-state. Here, we present a long-term monitoring of the X-ray flux and the pulse period between 2003-2022. We find that the source was in an off- or low-state between mid-2017 to mid-2020. During this state, our pulse period monitoring shows that the source had spun down considerably. We interpret this spin-down as likely being due to the propeller effect, whereby accretion onto the neutron star surface is inhibited. Using state-of-the-art accretion and torque models, we use the spin-up and spin-down episodes to constrain the magnetic field. For the spin-up episode, we find solutions for magnetic field strengths of either around 1e12G or 1e13G, however, the strong spin-down during the off-state seems only to be consistent with a very high magnetic field, namely, >1e13G. This is the first time a strong spin-down is seen during a low flux state in a ULXP. Based on the assumption that the source entered the propeller regime, this gives us the best estimate so far for the magnetic field of NGC 5907 ULX1.Comment: 10 pages, 1 figure, accepted for publication in A&

Discovery of a magnetar candidate X-ray pulsar in the Large Magellanic Cloud

During a systematic search for new X-ray pulsators in the XMM-Newton archive, we discovered a high amplitude ($PF\simeq86\%$) periodic ($P\simeq7.25\,\mathrm{s}$) modulation in the X-ray flux of 4XMM J045626.3-694723 (J0456 hereafter), a previously unclassified source in the Large Magellanic Cloud (LMC). The period of the modulation is strongly suggestive of a spinning neutron star (NS). The source was detected only during one out of six observations in 2018-2022. Based on an absorbed power-law spectral model with photon slope of $\Gamma\simeq 1.9$, we derive a 0.3-10 keV luminosity of $L_\mathrm{X}\simeq2.7\times10^{34}$ erg cm$^{-2}$ s$^{-1}$ for a distance of 50 kpc. The X-ray properties of J0456 are at variance with those of variable LMC X-ray pulsars hosted in high-mass X-ray binary systems with a Be-star companion. Based on SALT spectroscopic observations of the only optical object that matches the X-ray uncertainty region, we cannot completely rule out that J0456 is a NS accreting from a late-type (G8-K3) star, an as-yet-unobserved binary evolutionary outcome in the MCs. We show that the source properties are in better agreement with those of magnetars. J0456 may thus be second known magnetar in the LMC after SGR 0526-66.Comment: 9 pages, 6 figures, 1 table. Accepted for publication in MNRA

A soft and transient ultraluminous X-ray source with 6-h modulation in the NGC 300 galaxy

We investigate the nature of CXOU J005440.5-374320 (J0054), a peculiar bright ($\sim$$4\times10^{39}$ erg/s) and soft X-ray transient in the spiral galaxy NGC 300 with a 6-hour periodic flux modulation that was detected in a 2014 Chandra observation. Subsequent observations with Chandra and XMM-Newton, as well as a large observational campaign of NGC 300 and its sources performed with the Swift Neil Gehrels Observatory, showed that this source exhibits recurrent flaring activity: four other outbursts were detected across $\sim$8 years of monitoring. Using data from the Swift/UVOT archive and from the XMM-Newton/OM and Gaia catalogues, we noted the source is likely associated with a bright blue optical/ultraviolet counterpart. This prompted us to perform follow-up observations with the Southern African Large Telescope in December 2019. With the multi-wavelength information at hand, we discuss several possibilities for the nature of J0054. Although none is able to account for the full range of the observed peculiar features, we found that the two most promising scenarios are a stellar-mass compact object in a binary system with a Wolf$-$Rayet star companion, or the recurrent tidal stripping of a stellar object trapped in a system with an intermediate-mass ($\sim1000$ $M_\odot$) black hole.Comment: 13 pages, 11 Figures, 3 Tables (the Table in appendix A will be available in the published version). Accepted for publication in A&

Plasma concentrations of angiogenetic factors and angiogenetic inhibitors in patients with ductal pancreatic neoplasms. A pilot study

The aim of the study was to evaluate the circulating concentrations of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), vascular endothelial growth factor-D (VEGF-D) and endostatin in patients with intraductal papillary mucinous neoplasm (IPMN), and in those with ductal adenocarcinomas. METHODS: Sixty patients (32 males, 28 females, mean age 69.3\ub111.3 years) were enrolled: 31 (51.7%) had IPMNs and 29 (48.3%) had histologically confirmed pancreatic adenocarcinomas. Thirty blood donors were also studied as controls. In all study subjects, the concentrations of VEGF, VEGF-D, VEGFR-2, and endostatin were determined using enzyme-linked immunosorbent assays. RESULTS: Serum concentrations of VEGF, VEGF-D, and VEGFR-2 were significantly higher in patients with pancreatic ductal adenocarcinoma and those with IPMNs compared with healthy subjects, while endostatin was significantly higher only in patients with pancreatic ductal adenocarcinoma compared with healthy subjects. Within the group of patients, VEGFR-2 was significantly higher in patients with ductal adenocarcinoma compared to those with IPMNs. The sensitivity and the specificity of VEGFR-2 in differentiating patients with ductal adenocarcinomas from those with IPMN at a cut-off range of 4003-4034 pg/mL was 86.2% and 54.8%, respectively. CONCLUSIONS: IPMNs have serum VEGFR-2 concentrations different from those in patients with ductal adenocarcinomas. However, serum VEGFR-2 cannot be routinely utilized to differentiate IPMNs from pancreatic ductal adenocarcinoma

Effects of aircraft noise on annoyance, sleep disorders, and blood pressure among adult residents near the Orio al Serio International Airport (BGY), Italy

Introduzione: Il rumore aeroportuale pu\uf2 causare effetti extra-uditivi quali annoyance, disturbi del sonno, ipertensione, patologie cardiovascolari e alterazioni delle abilit\ue0 cognitive nei bambini. Obiettivi: Condurre un\u2019indagine trasversale tra gli adulti residenti in prossimit\ue0 dell\u2019Aeroporto Internazionale di Orio al Serio (BGY), per studiare l\u2019associazione tra rumore aeroportuale, annoyance, disturbi del sonno, pressione arteriosa e ipertensione. Metodi: Soggetti di et\ue0 45-70 anni sono stati suddivisi, sulla base della residenza, in tre zone acustiche di rumore aeroportuale: <60 (Riferimento), 60-65 (Zona A) e 65-75 dBA (Zona B). Un campione di soggetti \ue8 stato invitato a sottoporsi a intervista e misurazioni della pressione arteriosa. Per analizzare variabili quantitative e categoriche, sono stati utilizzati modelli di regressione lineare multipla e di Poisson robusta, rispettivamente. Risultati: Tra giugno e settembre 2013 sono stati reclutati 400 soggetti (166 nella Zona di Riferimento, 164 nella Zona A e 70 nella Zona B). Rispetto al riferimento, sono stati rilevati elevati punteggi di annoyance (diurni e notturni) nelle Zone A (+2,7) e B (+4,0) (p<0,001) e circa il doppio di soggetti fortemente infastiditi in entrambe le zone (p<0,001). Anche i disturbi del sonno riferiti nel mese precedente erano pi\uf9 frequenti nelle Zone A e B. I disturbi del sonno considerati complessivamente corrispondevano a 19,9% nella Zona di Riferimento, 29,9% nella Zona A e 35,7% nella Zona B (p<0,001). Conclusioni: \uc8 stata evidenziata una forte associazione tra rumore aeroportuale, annoyance e disturbi del sonno. Non \ue8 stata riscontrata alcuna relazione con i livelli di pressione arteriosa e la prevalenza di ipertensione.Background: Aircraft noise may cause several non-auditory health effects, including annoyance, sleep disorders, hypertension, cardiovascular diseases, and impaired cognitive skills in children. Objectives: To perform a cross-sectional study among adult residents near the Orio al Serio International Airport (BGY), Italy to investigate the association between aircraft noise, annoyance, sleep disorders, blood pressure levels, and prevalence of hypertension. Methods: Residential addresses of subjects aged 45-70 years were geocoded and classified in three groups according to noise levels: <60 (Reference), 60-65 (Zone A), and 65-75 dBA (Zone B). A sample of subjects was invited to undergo a personal interview and blood pressure measurements. Multiple linear and robust Poisson regression models were used to analyze quantitative and categorical variables, respectively. Results: Between June and September 2013, we enrolled 400 subjects (166 in the Reference Zone, 164 in Zone A, and 70 in Zone B). Compared to the Reference Zone, we found elevated adjusted annoyance scores (day and night) in Zone A (+2.7) and Zone B (+4.0) (p<0.001) and about doubled proportions of severely annoyed subjects (p<0.001). Reported sleep disorders in the previous month were also more frequent in Zones A and B. Sleep disorders in general were 19.9% in the Reference Zone, 29.9% in Zone A, and 35.7% in Zone B (p<0.001). Conclusions: We found a strong association between aircraft noise levels, annoyance, and sleep disorders among adult residents near the Orio al Serio International Airport. We found no relationship with blood pressure levels and prevalence of hypertension

Is the pancreas affected in patients with septic shock? A prospective study

Hyperamylasemia can be observed anecdotally during the course of severe sepsis or septic shock. This study aimed to investigate the possibility of pancreatic involvement in patients with septic shock using serum pancreatic enzyme determinations and imaging techniques in 21 consecutive patients with septic shock and 21 healthy subjects as controls. METHODS: The serum activity of pancreatic amylase and lipase was assayed initially in all subjects and 24 and 48 hours after the initial observation in the 21 patients with septic shock. All patients also underwent radiological examination to detect pancreatic abnormalities. RESULTS: The serum activity of pancreatic amylase was significantly higher in the 21 patients with septic shock than in the 21 control subjects during the study period, while the serum activity of lipase was similar to that of the control subjects. Amylase and lipase serum activity did not significantly changed throughout the study period in the 21 patients with septic shock. None of the patients with pancreatic hyperenzymemia had clinical signs or morphological alterations compatible with acute pancreatitis. CONCLUSION: The presence of pancreatic hyperenzymemia in septic shock patients is not a biochemical manifestation of acute pancreatic damage, and the management of these patients should be dependent on the clinical situation and not merely the biochemical result

T-shaped uterus: What has been done, what should be done

T-shaped uterus is a uterine malformation which has been suggested to be associated with poor reproductive performance. Over the years, different diagnostic methods have been used to determine the anatomical status of the female genital tract and to recognize any anomalies and the 3D-ultrasound is now considered the gold standard in diagnosing uterine anomalies. The importance of a correct diagnosis of the T-shaped uterus relates to the impact that such malformation has on female fertility. Although, to date, the prevalence does not seem to be so high, the fertility of the woman is reported to be somehow compromised by this uterine dysmorphism. Correcting the abnormal uterine morphology could be the main goal in order to optimize reproductive outcomes. To date, hysteroscopic correction of T-shaped uterus may be considered in patients with infertility, recurrent miscarriages or recurrent IVF failure. However, the absence of randomized controlled trials, multicentric data and the difficulty to state that metroplasty was the reason for improved outcome, make the data available inconclusive. More studies, led by an objective diagnosis, are urgently needed to understand the real impact of T-shaped uterus on the reproductive life of women and its effective prevalence in the population of infertile women