A dual vulnerability hypothesis for seasonal depression is supported by the seasonal pattern assessment questionnaire in relation to the temperament and character inventory of personality in a general population

BACKGROUND: Personality structure obtained from the psychobiological Temperament and Character Inventory (TCI) was studied in relation to self-reported seasonal variations in mood and behavior measured by the Seasonal Pattern Assessment Questionnaire (SPAQ). METHODS: The subjects comprised 1761 adults (57.6% women) in the age range 35-85 years, enrolled in the Betula prospective random cohort study of Umea, Sweden. RESULTS: Personality profiles of subjects who reported the occurrence of a high degree of seasonal variation as such were associated with a combination of high self-transcendence (ST) and high persistence (PS), irrespective of the level of harm avoidance (HA). Subjects who reported feeling worst in winter were associated with high HA, irrespective of the levels of ST and PS. Also, subjects feeling worst in summer or experiencing overall problems with seasonal variation were associated with high HA in their personality profiles. Using the SPAQ criteria to define seasonal affective disorder (SAD) or subsyndromal SAD (S-SAD), subjects with these disorders often had combinations of high self-transcendence (ST) and high persistence (PS), but with different associations with HA. LIMITATIONS: No evaluations were made for SAD or subsyndromal SAD according to the DSM-IV or ICD 10 criteria. CONCLUSIONS: Our results relating SPAQ with TCI give support for a dual vulnerability hypothesis for seasonal depression proposed in the literature, where it is attributed to a combination of a seasonal factor and a depression factor. Examining the literature regarding the relationships between the different TCI scales and monoamine neurotransmitter functions, those relationships suggest that these two vulnerability factors for seasonal depression may be modulated by different neurotransmitter systems.     

A rapid, PCR based test for differential molecular diagnosis of Prader-Willi and Angelman syndromes.

Approximately 98% of Prader-Willi syndrome (PWS) and 80% of Angelman syndrome (AS) cases have deletions at a common region in chromosome 15q11-13, uniparental disomy for chromosomes 15 (UPD15), or mutations affecting gene expression in this region. The resulting clinical phenotype (PWS or AS) in each class of mutation depends upon the parent of origin. Both disorders are characterised at the molecular level by abnormal methylation of imprinted genes at 15q11-q13 including the small nuclear ribonucleoprotein N gene (SNRPN). Current diagnostic strategies include high resolution cytogenetics, fluorescence in situ hybridisation (FISH), Southern blot hybridisation, or microsatellite typing. We have developed a novel and rapid diagnostic test for PWS and AS based on differential digestion of expressed (paternally imprinted) SNRPN sequences by the methylation sensitive endonuclease NotI or repressed (maternally imprinted) SNRPN sequences by the methylation requiring nuclease McrBC, followed by PCR amplification of the SNRPN promoter. We have evaluated this test by blinded analysis of 60 characterised DNA samples (20 PWS, 20 AS, and 20 unaffected controls). SNRPN sequences could not be amplified from PWS patient DNA which had been digested with McrBC, nor from AS patient DNA which had been digested with NotI. We were able to make a correct diagnosis of PWS, AS, or unaffected in all 60 samples tested. This novel test is rapid and has a high specificity and sensitivity for deletion and UPD15 cases. These features make this new test suitable as the initial step in a molecular diagnostic strategy for PWS/AS.     

A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.     

Optic nerve surface temperature during intradural anterior clinoidectomy: a comparison between high-speed diamond burr and ultrasonic bone curette

Ultrasonic bone curettes are increasingly used in cranial base surgery. The heat generated by these devices during anterior clinoidectomy has not been evaluated. The purpose of this study was to compare the optic nerve surface temperature during intradural anterior clinoidectomy using the drill and ultrasonic bone curette. Ten fresh cadaver heads were used. During intradural clinoidectomy and optic nerve unroofing with either a 2-mm diamond burr drill or ultrasonic bone curette, temperature was measured along the medial cisternal and proximal intracanalicular segments of the optic nerve. Additional experiments were performed to determine optimal ultrasonic bone curette settings for anterior clinoidectomy. At the lateral cisternal segment, peak and mean temperature were significantly higher with the ultrasonic bone curette (peak 38.8 vs 29.3 °C, p?=?0.03, mean 29.5 vs 22.6 °C, p?=?0.003). At the proximal intracanalicular segment, only peak temperature was significantly higher with the ultrasonic bone curette (peak 32.0 vs 23.5 °C, p?=?0.02, mean 26.9 vs 22.4 °C, p?=?0.07). Using standard company settings, room temperature irrigation fluid was heated by the oscillating tip to peak temperature 36.1 °C without drilling. In order to maintain emitted irrigation fluid at room temperature, optimal settings were power 70 %, cool irrigation (5 °C) at 40 mL/min. Using these settings, the ultrasonic bone curette generated optic nerve surface temperature measurements similar to the drill. Further work is necessary to translate these findings into the operating room.     

Massive expansile ossifying fibroma of the mandible with osteomyelitis

An ossifying fibroma is a benign odontogenic tumor of mesenchymal origin that belongs to the spectrum of fibro-osseous lesions afflicting the craniofacial complex. Although benign, it can be potentially aggressive, reaching very large sizes. The authors report a rare case of an aggressive ossifying fibroma in the mandible of a 30-year-old male patient that reached gigantic proportions with superimposed osteomyelitis, mimicking a malignancy. Differentiation of ossifying fibroma from other fibro-osseous lesions and benign and malignant neoplasms is important for the correct management of this lesion. Proper radiological evaluation and interpretation aids for arriving at a definitive diagnosis are required. The paper also highlights the radiological features of this entity.     

Season of birth variations in suicide methods in relation to any history of psychiatric contacts support an independent suicidality trait

BACKGROUND: Due to reports on season of birth variations in suicidal behaviour as well as in cerebrospinal fluid levels of monoamine metabolites, we investigated season of birth variations in suicide methods for completed suicides in relation to any history of psychiatric contacts. Relationships with the psychiatric diagnoses for those with psychiatric contacts were also studied. METHODS: Sociodemographic variables and suicide methods were examined for all the 693 suicide victims during 1961-1980 in V?sterbotten, Sweden. Information on any history of psychiatric contacts was obtained from psychiatric in-patient and out-patient records. RESULTS: Gender differences in the choice of suicide method were found in the group without any history of psychiatric contacts, but not in those with such a history. Only those without a history of psychiatric contacts showed season of birth variations for suicide methods -- those born during February to April were significantly more likely, and those born during October to January significantly less likely, to have preferred hanging rather than poisoning or petrol gases. These associations were stronger for the determined suicides, for males, and for urban residence. Suicide victims with a history of psychiatric contacts were significantly younger than those without. LIMITATIONS: No psychological autopsies for those without psychiatric contacts. No information on eventual contacts with general practitioners. No measures of monoamine neurotransmitters were available. CONCLUSIONS: Season of birth association for suicide methods is likely to be mediated by a suicidality trait independently of specific major psychiatric disorders. Monoamine neurotransmitters, particularly serotonin, are likely to underlie such a trait.     

A retrospective review comparing two-year patient-reported outcomes,costs, and healthcare resource utilization for TLIF vs. PLF for single-level degenerative spondylolisthesis

Purpose

The purpose of this study was to compare patient-reported outcomes (PROs), morbidity, and costs of TLIF vs PLF to determine whether one treatment was superior in the setting of single-level degenerative spondylolisthesis.

Methods

Patients undergoing TLIF or PLF for single-level spondylolisthesis were included for retrospective analysis. EQ-5D, ODI, SF-12 MCS/PCS, NRS-BP/LP scores were collected at baseline and 24 months after surgery. 90-day post-operative complications, revision surgery rates, and satisfaction scores were also collected. Two-year resource use was multiplied by unit costs based on Medicare payment amounts (direct cost). Patient and caregiver workday losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). Total cost was used to assess mean total 2-year cost per QALYs gained after surgery.

Results

62 and 37 patients underwent TLIF and PLF, respectively. Patients in the PLF group were older (p < 0.01). No significant differences were seen in baseline or 24-month PROs between the two groups. There was a significant improvement in all PROs from baseline to 24 months after surgery (p < 0.001). Both groups had similar rates of 90-day complications, revision surgery, satisfaction, and similar gain in QALYs and cost per QALYs gained. There was no significant difference in 24-month direct, indirect, and total cost.

Conclusions

Overall costs and health care utilization were similar in both the groups. Both TLIF and PLF for single-level degenerative spondylolisthesis provide improvement in disability, pain, quality of life, and general health.