The Historical Significance of Titicut Follies in Psychiatric Treatment: An Anti-Censorship Perspective.

Works of art and information judged as obscene can be censored or banned. This brief review evaluates the costs and benefits of censorship and the banning of artwork and information. In the history of psychology, Frederick Wiseman's film Titicut Follies epitomizes the disadvantages of concealing art content. Despite protecting the privacy of patients, the ban of Titicut Follies delayed the reform of psychiatric treatment practices and hospitals. The decision to censor or ban artistic and scientific information can result in the loss of knowledge and potential improvements to social, political, and economic institution practices.

Prisoner exposure to nature: Benefits for wellbeing and citizenship.

The direct or indirect experience of crime can cause individuals to feel vengeful against the perpetrator(s). The prison system reflects this sentiment by creating austere environments that are dehumanizing, punitive, and hopeless. Prisons are, therefore, environments in which retribution and punishment take priority over rehabilitation. Frequently, prisoners are believed to be untreatable because of their antisocial orientation. However, several factors influence an antisocial orientation such as socioeconomic status, family of origin, and mental health. The ubiquitous nothing works misbelief has resulted in prisoner marginalization and increased recidivism because of insufficient treatment. In 2015, 10 million individuals were incarcerated worldwide with around 30 million circulating through prisons each year. The prison environment decreases prisoner life expectancy and overall health. Sadly, prisoner benefits from treatment post-incarceration dissipate after 3-6 months and many prisoners die by suicide or drug overdose. Prison overpopulation, as well as poor outcome post-incarceration, requires more effective treatment. We hypothesize that Prisoner Exposure to Nature (PEN) can transform prisons into environments that are conducive to maintaining and improving physical and mental health. In prior work we proposed the continuum Nature Exposure Sufficiency (NES) versus Nature Exposure Insufficiency (NEI). Prisons are impoverished environments that limit Nature Exposure (NE) which results in NEI. Individuals experience fluctuations in mental and physical health as a result of NEI. Numerous studies have shown that direct and indirect NE can improve mood, physical health, and facilitate connectivity with self and society. It is necessary to consider ways in which we can incorporate NE for prisoner wellbeing. Additionally, it is crucial that prison personnel and prisoners develop a therapeutic/helping relationship (i.e., alliance) that is facilitated by friendliness and warmth to foster social change and citizenship. Many prisoners experience isolation and disconnection with society upon reentry. Given that most prisoners are eventually released into the community, we are obligated not to make them worse. Hence, it is important that prisons create programs that develop citizenship to engender prisoner volition to become positive and active citizens. We focus on the prison and prisoners, however our work is relevant to all total institutions (e.g., mental hospitals, nursing homes, schools, etc.). The prison system favors punishment and mass incarceration over treatment and decarceration. The deleterious effects of incarceration are clear and it is time to implement treatments based on the principles of PEN to improve prisoner wellbeing and citizenship.

High coherence plane breaking packaging for superconducting qubits.

We demonstrate a pogo pin package for a superconducting quantum processor specifically designed with a nontrivial layout topology (e.g., a center qubit that cannot be accessed from the sides of the chip). Two experiments on two nominally identical superconducting quantum processors in pogo packages, which use commercially available parts and require modest machining tolerances, are performed at low temperature (10 mK) in a dilution refrigerator and both found to behave comparably to processors in standard planar packages with wirebonds where control and readout signals come in from the edges. Single- and two-qubit gate errors are also characterized via randomized benchmarking, exhibiting similar error rates as in standard packages, opening the possibility of integrating pogo pin packaging with extensible qubit architectures.

Nature exposure sufficiency and insufficiency: The benefits of environmental preservation.

Increasing industrialization, urbanization, and a failure of many world leaders to appreciate the consequences of climate change are deleteriously impacting quality of life as well as diminishing the prospects for long term survival. Economic competitiveness and corporate profitability often pre-empt environmental concerns. The calving of an iceberg in Antarctica and the hurricane activity in the Caribbean during 2017 are unfortunate illustrations of the continuing escalation of environmental issues. We provide historical and current evidence for the importance of Nature Exposure (NE) and introduce the continuum Nature Exposure Sufficiency (NES) and Insufficiency (NEI). Insufficiency includes impoverished environments (e.g., slums and prisons) where nature exposure is very limited. Nature Exposure Sufficiency (NES) is an optimal amount of exposure to nature where many benefits such as reinvigoration can be obtained by everyone. NES also has several benefits for individuals with various health conditions such as arthritis, dementia, or depression. The benefits of NE are not just derivable from parks, forests, and other natural settings. Interiors of buildings and homes can be enhanced with plants and even pictures or objects from nature. Additionally, there is abundant evidence indicating that virtual and artificial environments depicting nature can provide substantial NE and therefore contribute to general wellbeing. Besides the difficulty in achieving cooperation amongst nations, corporations, and other collectives in developing and implementing long range plans to deal with climate change, there is also sometimes an aversion at the individual level whereby people are unwilling to experience nature due to insects and other discomforts. Such individuals are often averse to supplanting the comforts of home, even temporarily, with inadequate facilities that are seemingly less pleasant than their typical dwellings. We propose using the term Nature Exposure Aversion (NEA) to describe such behavior and propose that the aversion is largely due to conditioning. Such behavior may be addressed through desensitization in virtual environments which in turn may contribute to an endorsement of the view that climate change is occurring and must be dealt with. The issues of Nature Exposure Sufficiency and Insufficiency are intertwined with the sustainability of the planet and future planning and efforts to deal with the environment. If the outcome is unfavorable, the descent of civilization will be more rapid than the ascent.

Is 2-deoxy-2-[(18)F]fluoro-D-glucose PET/CT acquisition from the upper thigh to the vertex of skull useful in oncological patients?

AIM: To assess whether performing routinely 2-deoxy-2-[(18)F]fluoro-D-glucose PET/CT ((18)FDG PET/CT) scan from the upper thigh to the vertex of skull is clinically relevant. MATERIALS AND METHODS: 3502 (1634 female; mean-age 60+16) consecutive patients undergoing (18)FDG PET/CT were retrospectively analyzed. Patients were divided in 10 groups according to primary malignancy. Chi-square analysis was used to assess differences among proportions. A p value < 0.05 was considered significant. RESULTS: (18)FDG PET/CT was positive in head district in 130/3502 (3,7%) patients. In all patients lesions were unknown before PET/CT examination. PET/CT showed 158 positive brain/head uptake in the 130 patients. The 158 lesions were localized in: brain (43/158; 27%), bone (52/158; 33%), lymph node (1/158; 0,6%), soft tissue (55/158; 35%) and other sites (7/158; 4,4%). According to each group, patients were positive in the head district in 1.0% for Gastrointestinal Cancer (7/690), 3.0 % for Genitourinary Cancer (3/101), 3.7 % for Haemathologic Cancer (59/1590), 2.7 % for Gynaecologic Cancer (3/112), 7.8% for Head-Neck-Thyroid and Parathyroid Cancer (26/331), 3.5% for Breast Cancer (7/200), 2.6% for Lung Cancer (7/271), 3.4% for Melanoma (2/59), 7.4% for Sarcoma (2/27), 11.6% for Unknown Primary Tumour (14/121). CONCLUSION: Our data show a relatively high incidence of brain/head lesion in patients with Unknown Primary Tumour.

Valproic acid synergistically enhances the cytotoxicity of clofarabine in pediatric acute myeloid leukemia cells.

BACKGROUND: Acute myeloid leukemia (AML) remains a major therapeutic challenge in pediatric oncology even with intensified cytarabine (ara-C)-based chemotherapy. Therefore, new therapies are urgently needed to improve treatment outcome of this deadly disease. In this study, we evaluated antileukemic interactions between clofarabine (a second-generation purine nucleoside analog) and valproic acid (VPA, a FDA-approved agent for treating epilepsy in both children and adult and a histone deacetylase inhibitor), in pediatric AML. METHODOLOGY: In vitro clofarabine and VPA cytotoxicities of the pediatric AML cell lines and diagnostic blasts were measured by using MTT assays. The effects of clofarabine and VPA on apoptosis and DNA double strand breaks (DSBs) were determined by flow cytometry analysis and Western blotting, respectively. Active form of Bax was measured by Western blotting post-immunoprecipitation. RESULTS: We demonstrated synergistic antileukemic activities between clofarabine and VPA in both pediatric AML cell lines and diagnostic blasts sensitive to VPA. In contrast, antagonism between the two agents could be detected in AML cells resistant to VPA. Clofarabine and VPA cooperate in inducing DNA DSBs, accompanied by Bax activation and apoptosis in pediatric AML cells. CONCLUSION: Our results document synergistic antileukemic activities of combined VPA and clofarabine in pediatric AML and suggest that this combination could be an alternative treatment option for the disease.

18F-FDG PET and PET/CT in the Localization and Characterization of Lesions in Patients with Ovarian Cancer.

AIM: The aim was to compare the imaging findings of (18)F-fluorodeoxyglucose ((18)F-FDG) PET and integrated PET/CT in patients with primary, recurrent or metastatic ovarian cancer. MATERIALS AND METHODS: 21 women with ovarian cancer were evaluated. All patients had a integrated PET/CT scan. Localization, infiltration and uptake intensity of [(18)F]FDG were evaluated on PET and PET/CT. The certainty of localisation and characterisation was scored on a 3 point scale (L1 definite localisation; L2 probable localisation; L3 uncertain localisation; C1 benign; C2 equivocal; C3 malignant). RESULTS: PET scored as L1 54 lesions (44%), as L2 51 (42%), and as L3 17 (14%). On the other hand, PET/CT scored as L1 120 lesions (98%), as L2 2 (2%), and none as L3. Thus PET/CT allowed a better localization in 54% of lesions. Moreover, PET scored as C1 25 lesions (20%), as C2 62 (51%), and as C3 35 (29%). On the other hand, PET/CT scored as C1 57 lesions (47%), as C2 13 (11%), and as C3 52 (42%). Thus PET/CT allowed a sensible reduction in the number of equivocal lesions (40%). Even when patients were subgrouped on the basis of clinical stage of the disease, PET/CT was capable of better definition of the lesions either for localization and for characterization. CONCLUSIONS: In patients with ovarian cancer, PET/CT allows better anatomical localisation of pathologic uptake providing high accuracy for staging and restaging of ovarian cancer when compared with PET alone.

A long-lasting response to sorafenib treatment in an advanced hepatocellular carcinoma patient.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. No effective systemic treatment has been established, except for sorafenib chemotherapy. In fact, sorafenib has proved to provide a statistically significant survival extension of about two months in two phase III trials in the North America-Europe area and in the Asia-Pacific area, which respectively reported a median survival after treatment of 10.7 and 6.5 months, respectively. We report the case of an HCC patient, who received a four-month therapy with sorafenib with a clinical, biochemical and radiographic response, but had to interrupt treatment because of a myocardial infarction. Surprisingly, despite no antitumor treatment having been administered for about a year, the patient has shown no tumor progression and is currently on a close follow-up. Should other similar cases be presented, a subset of patients with long-lasting response to sorafenib might be identified.

Postsurgical diagnostic evaluation of patients with differentiated thyroid carcinoma: comparison of ultrasound, iodine-131 scintigraphy and PET with fluorine-18 fluorodeoxyglucose.

PURPOSE: The aim of this study was to compare the results of ultrasound (US), whole-body scintigraphy with iodine-131 (I-131 WBS) and positron emission tomography with fluorine-18 deoxyglucose (FDG-PET) in the follow-up of patients after thyroidectomy for differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: Thirteen patients (3 men, 10 women) were evaluated by neck US, I-131 WBS and FDG-PET. In each patient six anatomical regions (right and left thyroid bed, right and left cervical region, right and left supraclavicular region) were investigated, for a total of 78 regions. Distant metastases were investigated by I-131 WBS and FDG-PET and considered separately in the analysis. Imaging findings were compared with the reference standards, such as fine-needle aspiration cytology (2), biopsy (4) or clinical-radiological studies (7). RESULTS: US, FDG-PET and I-131 WBS showed concordant negative results in most (70, 90%) of the anatomical sites considered. In one patient with left cervical lymph node metastasis, the imaging techniques showed concordant positive results (1%). In the remaining 7 regions (9%), the imaging results were discordant; in particular, tumour lesions, nodal metastases (4) and thyroid bed recurrences (3) were detected by US only (3), by US and I-131 WBS (1) and by FDG-PET only (3). With regard to distant metastases, FDG-PET and I-131 WBS yielded concordant negative results in the majority (77%) of patients (9); in one patient only were the two imaging techniques concordant in their positive result. In the last three patients, the results were discordant; in particular, distant metastases were detected by I-131 WBS only in two patients and by FDG-PET only in one patient. CONCLUSIONS: Our work indicates a fundamental role for US in evaluation of the neck after surgery for DTC. WBS is useful to determine differentiation of tumour lesions, to identify thyroid remnants and to look for distant metastases. FDG-PET has an important role in cases of dedifferentiated thyroid carcinoma in which WBS and thyroglobulin measurements are unable to detect tumour lesions.

Fluorodeoxyglucose PET/CT in patients with differentiated thyroid cancer and elevated thyroglobulin after total thyroidectomy and (131)I ablation.

AIM: The aim of this study was to evaluate the role of 18F fluorodeoxyglucose-positron emission tomography (FDG-PET), differentiated thyroid carcinoma (DTC) treated with therapeutic (131)I because of elevated thyroglobulin (Tg) levels during follow up. The results of FDG-PET/CT were compared with post-therapy (131)I whole body scan (131I-t-WBS) and Tg at short term follow up. METHODS: Forty-five patients with DTC underwent a new therapeutic (131I) administration based upon Tg values >1.5 ng/mL. All patients underwent (131I-t-WBS) 5-7 days after 131I therapy. A few days before 131I administration, a FDG-PET scan was performed in all patients. FDG-PET/CT was considered positive (PET+) when at least one abnormal focus of FDG uptake was found; likewise, 131I-t-WBS was considered positive(WBS+) when at least on abnormal focus of uptake was found. Assessment of short-term response to radioiodine was performed by measuring Tg values. RESULTS: FDG-PET/CT was positive in 32 patients, 23 of which had positive 131I-t-WBS and negative in 13, 8 of which had a negative 131I-t-WBS. Overall agreement was 69%. Tg values were significantly higher in FDG-PET/CT positive (502+/-1 027 ng/mL) than in FDG-PET/CT negative patients (57+/-94 ng/mL). A significant difference emerged between 131I-t-WBS positive (561 +/- 1 086 ng/mL) and 131I-t-WBS negative (65+/- 120 ng/mL) findings. In these 45 patients Tg normalized in 36%, was reduced by at least 50% in 24% and remained unchanged in the remaining 40%. Overall, at short-term follow-up, Tg values normalized in 77% of the 13 patients with negative FDG-PET/CT and in 19% of the 32 patients with positive FDG-PET/CT. CONCLUSION: FDG-PET/CT is a powerful and useful tool for assessing patients with DTC. it can provide additional information in those patients with high Tg at follow-up and eligible for 131I therapy. A negative FDG-PET/CT could also represent a prognostic tool combined with serum Tg testing a short term follow-up.

Washout of [99mTc] sestamibi in predicting response to chemotherapy in patients with multiple myeloma.

AIM: Technetium-99m 2-methoxy-isobutyl-isonitrile ([99mTc] MIBI) has been successfully used to study patients with multiple myeloma (MM). This tracer is also a substrate for P-glycoprotein (Pgp). Since Pgp overexpression is one of the primary mechanisms of multidrug resistance in MM, the aim of this study was to test whether [99mTc] MIBI could be an index of Pgp overexpression and function in MM and therefore predicts response to chemotherapy. METHODS: Forty patients with MM (12 in stage I, 15 in stage II, and 13 in stage III) showing diffuse bone marrow [99mTc] MIBI uptake were included in the study. All patients underwent whole body scintigraphy at 10 and 60 minutes after i.v. injection of 555 MBq of [99mTc] MIBI. [99mTc] MIBI washout was measured, after decay correction, as: (10 minute counts/pixel minus 60 minute counts/pixel) divided by 10 minute counts/pixel, computed on a region of interest drawn on the thoracic spine (posterior projection), taking care of avoiding heart and splanchnic organs. Disease restaging was performed at a mean time of 32+/-20 months, and patients were considered to be in remission (complete or partial) or to show disease progression on the basis of a complete clinical and hematological evaluation. RESULTS: Patients showing disease progression at restaging (n=26) had higher washout (19.3+/-9.8% vs 12.8+/-6.9%, p<0.05) than patients in remission (n=14). Disease free survival was significantly better in patients with lower washout of [99mTc] MIBI. No differences in therapeutic regimen and stage of disease at admission were found between the 2 groups. When patients treated with melphalan were excluded from the analysis, 87.5% of patients in remission had low washout. CONCLUSIONS: The present study suggests a potential role of [99mTc] MIBI washout in predicting response to chemotherapy in patients with MM.

Vitamin E analogues as inducers of apoptosis: structure-function relation.

Recent results show that alpha-tocopheryl succinate (alpha-TOS) is a proapoptotic agent with antineoplastic activity. As modifications of the vitamin E (VE) molecule may affect its apoptogenic activity, we tested a number of newly synthesised VE analogues using malignant cell lines. Analogues of alpha-TOS with lower number of methyl substitutions on the aromatic ring were less active than alpha-TOS. Replacement of the succinyl group with a maleyl group greatly enhanced the activity, while it was lower for the glutaryl esters. Methylation of the free succinyl carboxyl group on alpha-TOS and delta-TOS completely prevented the apoptogenic activity of the parent compounds. Both Trolox and its succinylated derivative were inactive. alpha-tocotrienol (alpha-T3 H) failed to induce apoptosis, while gamma-T3 H was apoptogenic, and more so when succinylated. Shortening the aliphatic side chain of gamma-T3 by one isoprenyl unit increased its activity. Neither phytyl nor oleyl succinate caused apoptosis. These findings show that modifications of different functional moieties of the VE molecule can enhance apoptogenic activity. It is hoped that these observations will lead to the synthesis of analogues with even higher apoptogenic and, consequently, antineoplastic efficacy.

Multiple sclerosis recurrence risk for siblings in an isolated population of Central Sardinia, Italy.

Studies of twins, adoptees, half siblings, and familial recurrence risk have shown that genetic and non-genetic factors are involved in multiple sclerosis (MS) etiology. Age at onset, gender, and parental MS status seem to influence sibling risk. We studied the recurrence risk in siblings of MS patients in an isolated population of Sardinia, Italy, which is genetically homogeneous, inbred, and very stable, with a high MS frequency. The Aalen-Nelson estimate of the recurrence risk in siblings is 4.7%, and the risk ratio compared with the general population is 31. Proportional hazards models were used to investigate the effect of sibling sex, sex, and age at onset of the proband, and number of affected relatives on a sibling's predicted MS risk. Sib's risk is influenced by age at onset (P = 0.02), and possibly by sex of the proband (P = 0.08). There is also a borderline significant interaction (P = 0.05) between the sex and age at onset of the proband: early age at onset influences sib's risk only if the proband is female. The number of affected relatives in the family is not found to influence sibling risk, but the power is lacking (95% CI 0.50-2.62). This result is consistent with a single dominant gene with an extremely low penetrance, a model that has not yet been disproved as a possible inheritance model for MS.

A new therapeutic strategy for electrical cardioversion of atrial fibrillation.

BACKGROUND: The conventional approach to cardioversion of atrial fibrillation includes a period of anticoagulation with oral anticoagulant therapy (OAT) extending from 3 weeks precardioversion to 4 weeks postcardioversion. The protocol of rapid anticoagulation (such as that of the ACUTE study) consists of a precardioversion transesophageal echocardiography (TEE) followed by OAT for 4 weeks. In the last few years low-molecular-weight heparins have established themselves as a safe and efficacious alternative to traditional antithrombotic therapies. The aim of this study was to demonstrate that the exclusion of thrombi by precardioversion TEE together with the exclusion of atrial stunning by a second TEE performed after 1 week, to date not suggested in the literature, could reduce to 7 days the period of pericardioversion anticoagulation. This therapy would be carried out using low-molecular-weight heparins with no need for biological monitoring and with the possibility of self-administration. METHODS: We have studied 57 consecutive patients who had atrial fibrillation or flutter with a history of atrial fibrillation lasting > 48 hours. All patients received enoxaparin at a dosage of 100 IU antiXa/kg twice daily before undergoing multiplane TEE. Previous informed consent and ethical committee authorization had been obtained. Twenty-four hours following TEE, in the absence of thrombi and/or spontaneous moderate/severe echocontrast in the atrial chambers, the patients underwent electrical cardioversion and were discharged within 24 hours of sinus rhythm restoration. These patients were prescribed enoxaparin at the indicated dosage twice daily until TEE, performed in an outpatients setting 7 days following cardioversion. In the absence of thrombi and/or atrial and/or left atrial appendage stunning, OAT was terminated. Enoxaparin was associated with OAT for the following 3 weeks if any of the following signs of stunning were present: A wave inferior to the normal value for age at transmitral Doppler; a left atrial appendage emptying velocity < 40 cm/s; the appearance or increase in the severity of spontaneous echocontrast. For all patients, clinical and electrocardiographic follow-up was carried out at 1 month. RESULTS: In one patient TEE was not tolerated and one refused it. In 7 patients cardioversion was not performed: 4 because of the presence of thrombi, 1 because of moderate/severe spontaneous echocontrast and 2 owing to spontaneous cardioversion. Of the remaining 48 patients, cardioversion proved to be efficacious in 38, with sustained sinus rhythm at 1 week in 33 patients. One of these refused the second TEE and of the remaining 32 patients, 24 (75%) showed no signs of stunning at the second TEE and so anticoagulation was terminated. Thus, after 1 week, 75% (24/33) of patients in sinus rhythm could benefit from a shortened anticoagulation therapy which lasted for a mean of only 8.5 days. No patients showed signs of a thromboembolic accident at 1 and 2 months of follow-up. CONCLUSIONS: Most patients undergoing electrical cardioversion for atrial fibrillation could benefit from a shorter period of anticoagulation with low-molecular-weight heparins for 1 week if TEE precardioversion and 7 days postcardioversion excludes thrombi and atrial stunning. The management of patients with atrial fibrillation would be greatly simplified.

[The effect of S-adenosyl-L-methionine (SAM) on membrane permeability in the perfused rat liver]. / Studi sull'effetto dell'S-adenosil-L-metionina (SAMe) sulla permeabilita' di membrana in fegato di ratto in perfusione.

S-adenosilmethionine is present in most human tissues and is an important factor for transmethylation, transulphuration and aminopropylation reactions. The compound improves the biological, morphological and histochemical aspects of rat liver following CCl4 intossication. At the same time has been successfully used during chronic liver disease in man. With the aim to better clarify the action mechanism of SAMe some aspects concerning its effects on cell permeability in rat liver, by using the perfusion technique, have been investigated. In particular the capacity of this compound to prevent the enzymatic loss (GPT and GOT) during liver perfusion has been studied. 30 perfusions without SAMe, as control, and 6 by infusing 2 mg of compound during the perfusion time have been accomplished. Varing the perfusion time from 0 to 120 min it has been observed that at any time the presence of the SAMe reduced by about 50% the loss of GOT. Similarly the activity of GPT ranging from 2 to 6 mU/ml indicate that no appreciable enzyme output occurs in presence of SAMe.