A two-year longitudinal evaluation of the impact of the COVID-19 pandemic on pre-existing mental health service attenders.

BACKGROUND: To examine if the COVID-19 pandemic was associated with a differential effect longitudinally in relation to its psychological and functional impact on patients with bipolar disorder and Emotionally Unstable Personality Disorder (EUPD). METHODS: Semi-structured interviews were conducted with 29 individuals attending the Galway-Roscommon Mental Health Services with an ICD-10 diagnosis of either bipolar disorder (n = 18) or EUPD (n = 11). The impact of the COVID-19 pandemic was assessed in relation to anxiety and mood symptoms, social and occupational functioning, and quality of life utilising psychometric instruments and Likert scale data, with qualitative data assessing participants' subjective experiences. RESULTS: Individuals with EUPD exhibited significant anxiety and depressive symptoms and increased hopelessness compared to individuals with bipolar disorder. Repeated measures data demonstrated no significant change in symptomatology for either the EUPD or bipolar disorder group over time, but demonstrated an improvement in social (t = 4.40, p < 0.001) and occupational functioning (t = 3.65, p = 0.03), and in quality of life (t = 4.03, p < 0.001) for both participant groups. Themes attained from qualitative data included the positive impact of the discontinuation of COVID-19 mandated restrictions (n = 19), and difficulties experienced secondary to reductions in the provision of mental health services during the COVID-19 pandemic (n = 17). CONCLUSION: Individuals with EUPD demonstrated increased symptomatology over a two-year period compared to those with bipolar disorder. The importance of face-to-face mental health supports for this cohort are indicated, particularly if future pandemics impact the delivery of mental health services.

Y2K: effects on pacemaker and implantable defibrillator programmers.

All permanent pacemakers and implantable defibrillators (PPM/ICDs) will continue to function as programmed without regard to the date in the year 2000 (Y2K). All manufacturers contacted reassured us that some of these devices incorporate a day/year clock in the circuitry; however, these are not involved in sensing or delivering programmed therapy. Some manufacturers' device programmers will roll over to the year 2000 without any problems at all, whereas others may have difficulty with date and time stamping on printed reports. We tested 14 different types of PPM/ICD programmers for Y2K compliance using 8 tests. Five of the 14 models passed each test and were labeled at our institution with a green "Y2K" sticker to identify them as Y2K compatible and needing no special attention after December 31, 1999. The most common test failed was the ability to roll the date forward from December 31, 1999, with the programmer power off. Organizations should consider testing and replacing noncompliant device programmers or placing a red sticker with "Y2K" crossed out on noncompliant pieces. The red sticker alerts the advanced practice nurse or physician to the need to confirm the appropriate date and time in the programmer after startup in the year 2000 and before interrogating or programming any PPM/ICD, to avoid inappropriate date and time stamping on printed reports from that programmer.

Stimulation of mitochondrial gene expression and proliferation of mitochondria following impairment of cellular energy transfer by inhibition of the phosphocreatine circuit in rat hearts.

Mitochondria proliferate when cellular energy demand increases. However, the pathways leading to enhanced expression of mitochondrial genes are largely unknown. We tested the hypothesis that an altered flux through energy metabolism is the key regulatory event by decreasing mitochondrial energy supply to rat heart cells by creatine depletion. Electron microscopy showed that the density of mitochondria increased by 75% in such hearts (p < 0.01). Levels of representative mRNAs encoded on mitochondrial DNA (mtDNA) or on nuclear chromosomes were elevated 1.5 to 2-fold (p < 0.05), while the mtDNA content was unchanged. The mRNA for the nuclear encoded mitochondrial transcription factor A (mtTFA) was increased after GPA feeding (p < 0.05). Thus, we have shown that an impairment of mitochondrial energy supply causes stimulation of gene expression resulting in mitochondrial proliferation, probably as a compensatory mechanism. The observed activation of the mtTFA gene corroborates the important function of this protein in nuclear-mitochondrial communication.

Brain ATP metabolism in hypoxia resistant mice fed guanidinopropionic acid.

Feeding beta-guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, decreases mortality and increases brain ATP stability in hypoxic mice. To study brain ATP metabolism in GPA-fed animals, respiratory rates were measured in grey matter and white matter slices as well as cerebral hemisphere mitochondria from GPA-fed mice and rats. Creatine kinase and adenylate kinase activities were measured in rat cerebral grey matter and white matter. Respiratory rates and oxidative phosphorylation were the same in GPA-fed mice and control mice. The adenylate kinase activity increased 50% and creatine kinase showed a small decrease in grey matter. In white matter, creatine kinase increased 50% while adenylate kinase decreased. Thus, GPA produces opposite adaptive changes in adenylate kinase and creatine kinase in grey matter and in white matter. These results suggest that the creatine kinase reaction in grey matter acts to regulate cellular ADP and ATP concentrations.

Some new aspects of creatine kinase (CK): compartmentation, structure, function and regulation for cellular and mitochondrial bioenergetics and physiology.

Creatine kinase (CK) isoenzymes, specifically located at places of energy demand and energy production, are linked by a phosphocreatine/creatine (PCr/Cr) circuit, found in cells with intermittently high energy demands. Cytosolic CKs, in close conjunction with Ca(2+)-pumps, play a crucial role for the energetics of Ca(2+)-homeostasis. Mitochondrial Mi-CK, a cuboidal-shaped octamer with a central channel, binds and crosslinks mitochondrial membranes and forms a functionally coupled microcompartment with porin and adenine nucleotide translocase for vectorial export of PCr into the cytosol. The CK system is regulated by AMP-activated protein kinase via PCr/Cr and ATP/AMP ratios. Mi-CK stabilizes and cross-links cristae- or inner/outer membranes to form parallel membrane stacks and, if overexpressed due to creatine depletion or cellular energy stress, forms those crystalline intramitochondrial inclusions seen in some mitochondrial cytopathy patients. Mi-CK is a prime target for free radical damage by peroxynitrite. Mi-CK octamers, together with CK substrates have a marked stabilizing and protective effect against mitochondrial permeability transition pore opening, thus providing a rationale for creatine supplementation of patients with neuromuscular and neurodegenerative diseases.

Mitochondrial intermembrane inclusion bodies: the common denominator between human mitochondrial myopathies and creatine depletion, due to impairment of cellular energetics.

Mitochondrial inclusion bodies are often described in skeletal muscle of patients suffering diseases termed mitochondrial myopathies. A major component of these structures was discovered as being mitochondrial creatine kinase. Similar creatine kinase enriched inclusion bodies in the mitochondria of creatine depleted adult rat cardiomyocytes have been demonstrated. Structurally similar inclusion bodies are observed in mitochondria of ischemic and creatine depleted rat skeletal muscle. This paper describes the various methods for inducing mitochondrial inclusion bodies in rodent skeletal muscle, and compares their effects on muscle metabolism to the metabolic defects of mitochondrial myopathy muscle. We fed rats with a creatine analogue guanidino propionic acid and checked their solei for mitochondrial inclusion bodies, with the electron microscope. The activity of creatine kinase was analysed by measuring creatine stimulated oxidative phosphorylation in soleus skinned fibres using an oxygen electrode. The guanidino propionic acid-rat soleus mitochondria displayed no creatine stimulation, whereas control soleus did, even though the GPA solei had a five fold increase in creatine kinase protein per mitochondrial protein. The significance of these results in light of their relevance to human mitochondrial myopathies and the importance of altered cell energetics and metabolism in the formation of these crystalline structures are discussed.

The role of creatine kinase in inhibition of mitochondrial permeability transition.

Cyclosporin A sensitive swelling of mitochondria isolated from control mouse livers and from the livers of transgenic mice expressing human ubiquitous mitochondrial creatine kinase occurred in the presence of both 40 microM calcium and 5 microM atractyloside which was accompanied by a 2.5-fold increase over state 4 respiration rates. Creatine and cyclocreatine inhibited the latter only in transgenic liver mitochondria. Protein complexes isolated from detergent solubilised rat brain extracts, containing octameric mitochondrial creatine kinase, porin and the adenine nucleotide translocator, were reconstituted into malate loaded lipid vesicles. Dimerisation of creatine kinase in the complexes and exposure of the reconstituted complexes to >200 microM calcium induced a cyclosporin A sensitive malate release. No malate release occurred with complexes containing octameric creatine kinase under the same conditions.

Crystalline mitochondrial inclusion bodies isolated from creatine depleted rat soleus muscle.

Rats were fed a 2% guanidino propionic acid diet for up to 18 weeks to induce cellular creatine depletion by inhibition of creatine uptake by this creatine analogue. Ultrastructural analysis of creatine depleted tissues showed that mitochondrial intermembrane inclusion bodies appeared in all skeletal muscles analysed, after 11 weeks of feeding. Heart had relatively few even after 18 weeks of analogue feeding and none were evident in kidney, brain or liver. These structures were strongly immuno-positive for sarcomeric mitochondrial creatine kinase and upon removal from mitochondria, the inclusion bodies were shown to diffract to a resolution of 2.5 nm. Two-dimensional image analysis and three-dimensional reconstruction revealed arrays of creatine kinase octamers with additional components between the octameric structures. The same mitochondria had a 3-fold higher extractable specific creatine kinase activity than controls. Molecular mass gel filtration of inclusion body containing mitochondrial extracts from analogue fed rat solei revealed mitochondrial creatine kinase eluting as an aggregate of an apparent molecular mass > or = 2,000 kDa. Mitochondrial creatine kinase of control soleus mitochondrial extract eluted as an octamer, with a molecular mass of 340 kDa. Respiration measurements of control solei mitochondria displayed creatine mediated stimulation of oxidative phosphorylation that was absent in analogue-fed rat solei mitochondria. The latter also had 19% and 14% slower rates of state 4 and maximal state 3 respiration, respectively, than control mitochondria. These results indicate that mitochondrial creatine kinase co-crystallises with another component within the inter membrane space of select mitochondria in creatine depleted skeletal muscle, and is inactive in situ.

In vivo brain phosphocreatine and ATP regulation in mice fed a creatine analog.

Mitochondrial and cytosolic creatine kinase (CK) isozymes are active in cells with high and variable ATP metabolic rates. beta-Guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, was used to study the hypothesis that the creatine-CK-phosphocreatine (PCr) system is important in regulating brain ATP metabolism. The CK-catalyzed reaction rate and reactant concentrations were measured in vivo with 31P nuclear magnetic resonance spectroscopy during energy deficit (hypoxia) or high-energy turnover (seizures) states in urethane-anesthetized mice fed GPA, creatine, or standard chow (controls). Brain phosphagen (i.e., cellular energy reserves) or PCr plus phosphorylated GPA (GPAP) concentrations were equal. The phosphagen-to-NTP ratio was lower than in controls. In vivo CK reaction rate decreased fourfold, whereas ex vivo CK activity that was biochemically measured was doubled. During seizures, CK-catalyzed fluxes increased only in GPA-fed mice. Phosphagen increased in GPA-fed mice, whereas PCr decreased in controls. Survival was higher and brain phosphagen and ATP losses were less for hypoxic GPA-fed mice than for controls. In contrast to mice fed GPA, hypoxic survival and CK reactant concentrations during hypoxia and seizures were the same in creatine-fed mice and controls. Thus GPA, GPAP, or adaptive changes in ATP metabolism stabilize brain ATP and enhance survival during hypoxia in mice.

Differential effects of creatine depletion on the regulation of enzyme activities and on creatine-stimulated mitochondrial respiration in skeletal muscle, heart, and brain.

Guanidinopropionic acid (GPA), an analogue of creatine (Cr), is known to inhibit Cr uptake by cells. The metabolic effects of chronic Cr depletion on brain, heart and soleus muscle of rats were studied. In GPA hearts and soleus muscle, total specific creatine kinase (CK) activity was decreased by approx. 40% compared to controls, whereas in brain this same activity was elevated by a factor of two. Immunoblot analysis of soleus mitochondria from GPA rats showed an approximate 4-fold increase in Mi-CK protein and a concomitant 3-fold increase in adenine nucleotide translocator (ANT) protein, when compared to control. In GPA-fed rats, the specific activities of adenylate kinase (ADK) and succinate dehydrogenase were significantly higher in brain and soleus (2-fold), but heart remained the same. However, hexokinase (HK) decreased by approx. 50% both in heart and soleus, indicating that muscle and brain follow different strategies to compensate the energy deficit caused by creatine depletion. Skinned muscle fibres from Cr-depleted soleus attained approx. only 70% maximum state 3 respiration with 0.1 M ADP in the presence of 10 mM Cr compared to 100% in control fibres. This defect in Cr stimulated respiration was also seen in isolated heart mitochondria, but was normal in those from brain. The observed deficit of Cr-stimulated respiration, the significant accumulation of Mib-CK and ANT, concomitant with the formation of Mib-CK rich intra-mitochondrial inclusions shown by electron microscopy, indicate that Mib-CK function and coupling to oxidative phosphorylation (OXPHOS), is impaired in these abnormal mitochondria. In addition, our results show tissue-specific metabolic compensations to Cr depletion.

Lung capillary albumin leak in oxygen toxicity. A quantitative immunocytochemical study.

The study is based on the hypothesis that lung endothelial cell permeability increases in 100% oxygen and predates the appearance of microscopically visible interstitial edema. Rats were exposed to either 100% oxygen or air in a chamber. Endogenous albumin was used as an index of permeability and measured by electron microscopic colloidal gold linked immunocytochemistry, quantified by systematic random methods. Albumin staining was expressed as relative albumin concentration (RAC), the ratio of gold particles (x 100) per point counted (gp.10(2)/pt) relating to each component. The RAC in lung perivascular/peribronchial interstitial ground substance after 24 h of hyperoxia was five times more than that of rats exposed to air for the same interval. The median value (interquartile ranges) for the oxygen-exposed group was 92.4 (39.5, 149.6) gp. 10(2)/pt compared with 14.7 (6.6, 25.9) gp. 10(2)/pt for the air-exposed group. After 60 h of 100% oxygen, the RAC was 103.4 (65.5, 148.9) gp. 10(2)/pt (60-h air exposed RAC was 11.6 (8.7, 60.4) gp. 10(2)/pt), no different from 24-h exposures. These results suggest that there was a significant leak of albumin to the perivascular/peribronchial interstitium by 24 h of exposure to 100% oxygen, which would indicate endothelial cell permeability to albumin increases earlier than has previously been reported.

Assailants' sexual dysfunction during rape reported by their victims.

Sexual dysfunction is known to occur in a proportion of rapists during the assault. The most common dysfunctions are erectile insufficiency and absent or retarded ejaculation. The study assessed the incidence and characteristics of assailants' sexual dysfunction reported by 50 victims of rape. 20% of victims reported that their assailant experienced erectile insufficiency at some point during the assault, and a further 12% reported retarded ejaculation or failure to ejaculate by their attacker. In attacks where sexual dysfunction occurred, there was a higher incidence both of intra-rape violence and commissioning of degrading sexual activity and this behaviour was related to the onset of the dysfunction. It was felt that the pattern of behaviour reported in those attacks where rapists' sexual dysfunction occurred might reflect a typologically distinct subgroup of offender. This finding has implications both for the safety of the victim during the attack and subsequent offender assessment.

Rape--a comparison of stranger and acquaintance assaults.

One of the variables that influences victim trauma in rape attacks is the relationship between assailant and victim (Ellis, 1981). Rapes by strangers have been shown to involve more violence and trauma (Katz and Mazur, 1979). Rapes by acquaintances may involve a betrayal of trust. The study compares 21 rape attacks where the assailant was known to the victim with 30 attacks where the assailant was a stranger. Three main elements of each assault are described: the contextual nature of the rape encounter, the assault characteristics (force, injuries, nature of sexual activity) and the post-rape behaviour. Significant differences were found between the two groups in each of these respects. Contact between rapist and victim took place in a social setting immediately prior to the assault in significantly more of the acquaintance rapes. Significantly more of the stranger rapes involved the display of a weapon. Coercive reciprocation of sexual activity occurred in proportionately more of stranger rapes. The role of verbal aggression was more prominent in acquaintance rapes. Significantly more of the acquaintance rapists (95% as opposed to 17%) interacted with the victim after the overtly sexual part of the attack. Two types of behaviour were displayed in almost equal proportions. Conciliatory/non-threatening behaviour consistent with a distorted affirmation of a person-orientated relationship with the victim was displayed by 43% of these assailants; 48% displayed threatening behaviour. We believe that stranger and acquaintance rapes can be clearly differentiated in terms of the behavioural dimensions of the assault. An understanding of such differences has implications for professionals involved in the assessment and treatment of sexual offenders and their victims.

Assault characteristics and posttraumatic stress disorder in rape victims.

A diagnosis of posttraumatic stress disorder (PTSD) encompasses several of the symptoms associated with the response to rape. The object of this study was to determine the incidence of PTSD among 51 rape victims and to compare the groups with and without PTSD with respect to the characteristics of the assaults. The results showed that 70% of the victims had PTSD and further suggested that PTSD was likely to be a long-term problem for these women. The results supported the view that psychological treatment approaches to rape victims should take into account the posttraumatic nature of the response. The incidence of rapes by strangers, of physical force being used, of weapons being displayed and of injuries being sustained by the victim were all higher in the group of women who had PTSD. These are all features that can be readily identified in the initial assessment of the rape victim and may help to identify the victims at risk of developing long-term psychological sequelae after rape. Appropriate therapeutic action taken early may influence the prognosis for a significant proportion of rape victims.

Sexual anxiety in sexual dysfunction.

Sexual anxiety was examined in 98 patients presenting with sexual dysfunction and 68 of their partners at a psychosexual clinic using the SOMA questionnaire. All patients had raised values for heterosexual anxiety. Female partners had raised values while male partners did not. This provides further evidence for the role of heterosexual anxiety in the aetiology and treatment of sexual dysfunction.

Sexual problems and their management: a survey of general practice in Northern Ireland.

This survey suggests a similar prevalence of sexual problems in general practice in Northern Ireland compared with England and Wales. Of the respondents, 9.6% reported a much higher prevalence which may indicate a greater ability in detecting sexual problems and therefore implies that many cases are being missed. The majority of problems appear to be dealt with in general practice, although referral is often considered, with the Psychosexual Clinic being the preferred option. Difficulties encountered with referral are highlighted by the survey. It is suggested that provision of more information about the clinic, visits by therapists to practices and further training opportunities would help general practitioners in managing sexual problems.

The SOMA--a questionnaire measure of sexual anxiety.

SOMA, a questionnaire designed by J. T. Quinn to measure sexual anxiety in patients presenting at a psychosexual clinic, has been used extensively as a clinical and research tool. Its construction and scoring are described, and data are presented for internal consistency, test-retest reliability, principal components analysis, and validity. Practical applications for diagnosis, prognosis, and research are discussed.

A review of referrals to the psychosexual clinic at the Belfast City Hospital.

The number of patients seen at the psychosexual clinic has more than doubled in eight years. The diagnostic categories of the patients referred have also changed, especially in the area of homosexuality, and now show greater similarity to figures obtained in two reports from Great Britain, apart from a lower referral rate for orgasmic dysfunction. There is also an overall lower rate of referral in Northern Ireland. This raises the question as to whether or not there is a real difference in the prevalence of these disorders in the Province, compared with Great Britain.

A new spinal brace for use in Duchenne muscular dystrophy.

Nine boys with Duchenne muscular dystrophy, chairbound but without scoliosis, were fitted with a recently developed brace of metal and moulded medium-density polyethylene, the modified Calot brace. Each was also fitted with a wrap-around, moulded leather jacket. Each brace held the relaxed lumbar spine in an angle of lordosis similar to that achieved by a brief active effort to sit erect without a brace. Over-all, they proved equally acceptable to patients and carers. The modified Calot brace caused substantially less restriction of pulmonary function and so may be preferable to the moulded leather jacket.

Assessment of clinical psychiatric skills in final-year medical students: the use of videotape.

Sixty final-year medical students had their clinical performance in psychiatry assessed by the following three methods: a multiple choice questionnaire based on a series of short videotaped interviews with psychiatric patients; the examination of a traditional long 'case' with presentation of the history, mental state findings and formulation about diagnosis and management to a panel of three examiners; and a conventional oral examination about the principles and practice of psychiatry with a different trio of examiners. The total mark on the videotape session correlated significantly with the combined clinical and oral marks. There was also a significant positive correlation between the total video marks and the individual clinical marks, but none between the marks obtained during the video and oral components of the examination. However, the significant positive correlations between the video marks and those of the clinical examination were modest and only accounted for not more than 14% of the variance. Inspection of the distribution of correct answers to the videotape questions shows that students do best in identifying mental state symptoms and signs and in choosing the correct diagnosis. They do less well in the areas of aetiology and treatment. Indeed, optimal performance in the latter distinguishes those who do well in the clinical/oral examination from those whose performance is mediocre. The significance of these findings to the teaching and assessment of psychiatric skills in medical students is discussed.