Recent advances in the application of stable isotope ratio analysis in forensic chemistry

This review paper updates the previous literature in relation to the continued and developing use of stable isotope ratio analysis in samples which are relevant to forensic science. Recent advances in the analysis of drug samples, explosive materials, and samples derived from human and animal samples are discussed. The paper also aims to put the use of isotope ratio mass spectrometry into a forensic context and discuss its evidential potential

A várandósság alatti emlőrák kezelése = Treatment of pregnancy associated breast cancer

Terhességi emlőráknak a várandósság ideje alatt, illetve a szülést követő egy éven belül kialakuló rosszindulatú emlődaganatot nevezzük. Háromezer várandós nőből körülbelül 1-ben alakul ki. A tumor incidenciája növekedő tendenciát mutat, amelyben elsősorban a gyermekvállalás egyre későbbi életkorra való kitolódása játszhat szerepet. A várandós állapot késlekedést okozhat mind a diagnózis felállításában, mind a megfelelő kezelés elindításában. Közleményünkben egy 30 éves nőbeteg esetét ismertetjük, aki első terhességének 21. hetében önvizsgálat során észlelte a jobb emlő bőrének gyulladásos elváltozását, és a hónaljárokban levő megnagyobbodott nyirokcsomókat. Az antibiotikus kezelésre a páciens panaszai nem javultak, ezért az axillaris képlet vékonytű-aspirációs citológiai vizsgálatát végezték el, amelynek során metasztatikus emlőrák igazolódott. A klinikánkon végzett vizsgálat során cT4 cN3 lokoregionális kiterjedésű daganatot véleményeztünk. Az emlő bőrének elváltozása gyulladásos emlőrákra utalt, emellett axillaris, valamint supraclavicularis nyirokcsomó-konglomerátumot is tapintottunk. A core-bioptátum értékelése során hormonreceptor-negatív, Her-2-pozitív, grade III differenciáltságú invazív carcinoma igazolódott. Neonatológiai és onkológiai konzíliumot követően a beteg úgy döntött, hogy a várandósság alatt elzárkózik a kemoterápiás kezeléstől, ezért a 30. gesztációs héten elektív császármetszést végeztünk. A további vizsgálatok távoli áttétet nem igazoltak, így primer szisztémás kemoterápiát kezdtünk, majd ezt követően mastectomia és axillaris blokkdisszekció történt. Az eltávolított emlőállományban visszamaradt tumort a kórszövettani vizsgálat során már nem azonosítottunk, a szöveti kép alapján komplett patológiai remissziót véleményeztünk. A sugárkezelés befejezése után trastuzumabkezelést indítottunk. Az ellenőrző vizsgálatok a páciensnél eddig sem helyi kiújulást, sem távoli áttétet nem igazoltak. Az újszülött generalizált izomtónus-eloszlási zavarok miatt jelenleg is fejlődésneurológiai gondozás alatt áll. | Pregnancy-associated breast cancer (PABC) is defined as cancer of the breast diagnosed during pregnancy and up to 1 year postpartum. The crude incidence is 1/3000 pregnant women. As women delay childbearing the incidence of PABC increases with age. Young patients with PABC do not have worse prognosis compared with those with non-PABC; however, pregnancy can contribute to a delay in breast cancer diagnosis, evaluation, and treatment. Primary care physicians and gynecologists should be careful in the thorough workup of breast symptoms in the pregnant population to expedite diagnosis and allow multidisciplinary treatment as early as possible following the established diagnosis. Authors report a case of a 30-year-old pregnant woman, who detected inflammatory signs of her right breast and a palpable axillary mass at the 21st week of gestation. Her symptoms did not improve with administration of antibiotics. Therefore fine needle aspiration biopsy of the axillary lump was performed, with the result of unequivocal diagnosis of metastatic invasive carcinoma. The patient was referred to the multidisciplinary tumor board of our Department at the 27st week of gestation with the symptoms of inflammatory breast cancer, palpable right axillary and supraclavicular lymph nodes. Core biopsy showed an ER and PR negative, Her-2 positive, grade 3, infiltrating ductal carcinoma of the breast. After multidisciplinary team consultation the patient declined any kind of therapy during her pregnancy. On the 30th week of gestation caesarean section was performed. The premature baby girl was treated in the Neonatal Intensive Care Unit. Imaging modalities revealed no evidence of distant metastases short after the delivery. After 6 cycles of chemotherapy (docetaxel-doxorubicin-cycclophosphamid) the patient underwent right mastectomy and axillary lymph node dissection. Complete pathological response was diagnosed, since no residual tumor was found in the surgical resection specimen. After radiotherapy, trastuzumab medication was initiated. To date, there is no evidence of local recurrence or distant metastases during her 24 months follow-up. The newborn is on close neurohabilitation folow-up due to the evidence of generalized muscle dystonia. Had the patient accepted chemotherapy, the damage of the newborn baby would have been avoidable

The Gifted and Gifted Education in Hungary

The real challenge is to see value that is not yet in its true form. Becoming gifted is a process, during which characteristics of giftedness are present throughout, but not necessarily in a form perceptible or acceptable to the environment. Giftedness does not hide itself, only to the extent that the environment believes it hidden. Perception defines the pattern that manifests itself. The beginning of the 20th century is a success story of Hungarian gifted education. Outstanding teachers and their students have reached outstanding achievements through gifted education linked to everyday education. Their methods and ideas are durable, and are therefore worth recalling

MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival

MarvelD3 is a transmembrane component of tight junctions, but there is little evidence for a direct involvement in the junctional permeability barrier. Tight junctions also regulate signaling mechanisms that guide cell proliferation; however, the transmembrane components that link the junction to such signaling pathways are not well understood. In this paper, we show that MarvelD3 is a dynamic junctional regulator of the MEKK1-c-Jun NH2-terminal kinase (JNK) pathway. Loss of MarvelD3 expression in differentiating Caco-2 cells resulted in increased cell migration and proliferation, whereas reexpression in a metastatic tumor cell line inhibited migration, proliferation, and in vivo tumor formation. Expression levels of MarvelD3 inversely correlated with JNK activity, as MarvelD3 recruited MEKK1 to junctions, leading to down-regulation of JNK phosphorylation and inhibition of JNK-regulated transcriptional mechanisms. Interplay between MarvelD3 internalization and JNK activation tuned activation of MEKK1 during osmotic stress, leading to junction dissociation and cell death in MarvelD3-depleted cells. MarvelD3 thus couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival

Supported liquid-liquid extraction of the active ingredient (3,4-methylenedioxymethylamphetamine) from ecstasy tablets for isotopic analysis

A method was developed for the isolation of 3,4-methylenedioxymethylamphetamine (MDMA) and other active ingredients from illicit ecstasy tablets. The method employed supported liquid extraction (SLE) with cartridges containing a modified form of diatomaceous earth. The method developed was simple and robust and the extract could be analysed directly, by GC-MS, to identify ingredients and reduced in volume for isotope ratio MS analysis of both δ13C and δ15N. The technique was shown to be highly reproducible, independent of the tablet matrix and considerably faster than existing liquid-liquid extraction methods. Crucially, no significant isotopic fractionation was observed as a result of the extraction process

The acceptability, safety, and tolerability of methadone/naloxone in a 50:1 ratio

Methadone is an effective therapy for heroin addiction, but the public health benefits are compromised by diversion and injection of prescribed methadone. Combination with naloxone is one way to reduce the risk of diversion and injection. Two studies were conducted. The first ascertained the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral methadone-naloxone in a 50:1 ratio compared with methadone. The second study investigated the effectiveness of intramuscularly injected methadone-naloxone in precipitating withdrawal in methadone-maintained subjects. The first double-blind, crossover study randomized 10 stable methadone-maintained subjects equally to receive either methadone-naloxone or methadone over two alternate 14 day periods. In the second study, 5 subjects received intramuscular injections of methadone-naloxone before their scheduled methadone dose. Oral methadone-naloxone in a 50:1 ratio appeared to be well tolerated, although a taste difference between the preparations may have compromised blinding. There were no significant differences between methadone and methadone-naloxone in objective and subjective opioid withdrawal signs, and trough and peak plasma concentrations. Methadone-naloxone in a 50:1 ratio intramuscularly precipitated mild to moderate signs of opioid withdrawal in 4 out of 5 subjects whereas a 5th subject who did not experience withdrawal at a lower dose refused higher dose challenges. Withdrawal symptoms peaked 15 to 30 minutes postchallenge and returned to baseline levels at 60 minutes. Methadone-naloxone in 50:1 ratio has the pharmacological properties to be a useful combination product for treatment of heroin addiction with reduced risk of injection