Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span

Children conceived by assisted reproductive technologies (ART) display a level of vascular dysfunction similar to that seen in children of mothers with preeclamspia. The long-term consequences of ART-associated vascular disorders are unknown and difficult to investigate in healthy children. Here, we found that vasculature from mice generated by ART display endothelial dysfunction and increased stiffness, which translated into arterial hypertension in vivo. Progeny of male ART mice also exhibited vascular dysfunction, suggesting underlying epigenetic modifications. ART mice had altered methylation at the promoter of the gene encoding eNOS in the aorta, which correlated with decreased vascular eNOS expression and NO synthesis. Administration of a deacetylase inhibitor to ART mice normalized vascular gene methylation and function and resulted in progeny without vascular dysfunction. The induction of ART-associated vascular and epigenetic alterations appeared to be related to the embryo environment; these alterations were possibly facilitated by the hormonally stimulated ovulation accompanying ART. Finally, ART mice challenged with a high-fat diet had roughly a 25% shorter life span compared with control animals. This study highlights the potential of ART to induce vascular dysfunction and shorten life span and suggests that epigenetic alterations contribute to these problems.     

Survivors of war in the Northern Kosovo (II): baseline clinical and functional assessment and lasting effects on the health of a vulnerable population

Background

This study documents torture and injury experience and investigates emotional well-being of victims of massive violence identified during a household survey in Mitrovicë district in Kosovo. Their physical health indicators such as body mass index (BMI), handgrip strength and standing balance were also measured. A further aim is to suggest approaches for developing and monitoring rehabilitation programmes.

Methods

A detailed assessment was carried out on 63 male and 62 female victims. Interviews and physical examination provided information about traumatic exposure, injuries, and intensity and frequency of pain. Emotional well-being was assessed using the "WHO-5 Well-Being" score. Height, weight, handgrip strength and standing balance performance were measured.

Results

Around 50% of victims had experienced at least two types of torture methods and reported at least two injury locations; 70% had moderate or severe pain and 92% reported constant or periodic pain within the previous two weeks. Only 10% of the victims were in paid employment. Nearly 90% of victims had experienced at least four types of emotional disturbances within the previous two weeks, and many had low scores for emotional well-being. This was found to be associated with severe pain, higher exposure to violence and human rights violations and with a low educational level, unemployment and the absence of political or social involvement.Over two thirds of victims were overweight or obese. They showed marked decline in handgrip strength and only 19 victims managed to maintain standing balance. Those who were employed or had a higher education level, who did not take anti-depressant or anxiety drugs and had better emotional well-being or no pain complaints showed better handgrip strength and standing balance.

Conclusions

The victims reported a high prevalence of severe pain and emotional disturbance. They showed high BMI and a reduced level of physical fitness. Education, employment, political and social participation were associated with emotional well-being. Interventions to promote physical activity and social participation are recommended. The results indicate that the rapid assessment procedure used here offers an adequate tool for collecting data for the monitoring of health interventions among the most vulnerable groups of a population exposed to violence.

     

Outcomes of primary thyroid non-Hodgkin’s Lymphoma

Primary non-Hodgkin’s lymphoma (NHL) of the thyroid gland is a rare disease with an incidence of 0.5 per 100,000 population. Stages IE and IIE thyroid NHL have been traditionally treated by surgical resection; however, modern treatment consists of chemotherapy and local radiotherapy, and surgery is often reserved for tissue diagnosis and relief of airway compression. We retrospectively reviewed the management and outcomes of nine consecutive patients with thyroid NHL, eight females and one male (median age 63 yr, range 34-71 yr) treated between 1994 and 1999. Five patients had disease stage IE and 4 stage IIE. Median follow-up was 72 mo. Pathohistology and immunohistochemistry identified two patients with mucosa-associated lymphoid tissue (MALT), three follicular center cell lymphoma (FCC), two patients large B-cell lymphoma (BLCL), one a marginal zone lymphoma (MZL), and one patient a peripheral T-cell lymphoma (PTCL). Total thyroidectomy was performed in three patients and subtotal thyroidectomy in four. One (MALT) patient underwent surgery alone; three patients surgery, radiotherapy, and chemotherapy (two FCC, one PTCL); three patients surgery and chemotherapy (one MALT, one FCC, one LBCL); and two chemotherapy alone (one LBCL, one MZL). Median survival was 79 mo (range 13–124 mo). The PTCL patient, a 34-yr-old man, died from disseminated disease at 13 mo despite secondary chemotherapy, and one LBCL patient with extensively invasive local disease died from stroke 17 mo after diagnosis. The remaining seven patients remain in remission with no local or systemic relapse at a mean of 86 mo. With appropriate therapy primary thyroid NHL has a favorable course; however, prognosis depends on the histology, local spread, and the stage of the disease at presentation, as well as the patient’s performance status. Surgery in combination with chemotherapy and/or radiotherapy is still warranted for intermediate and high-grade thyroid NHLs, with over 77% of patients achieving long-term remission. Peripheral T-cell lymphoma carries a poor prognosis.