The usability of daytime and night-time heart rate dynamics as digital biomarkers of depression severity.

BACKGROUND: Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity. METHODS: Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions. RESULTS: Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms. CONCLUSIONS: Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.

Remote assessment of disease and relapse in major depressive disorder (RADAR-MDD): a multi-centre prospective cohort study protocol.

BACKGROUND: There is a growing body of literature highlighting the role that wearable and mobile remote measurement technology (RMT) can play in measuring symptoms of major depressive disorder (MDD). Outcomes assessment typically relies on self-report, which can be biased by dysfunctional perceptions and current symptom severity. Predictors of depressive relapse include disrupted sleep, reduced sociability, physical activity, changes in mood, prosody and cognitive function, which are all amenable to measurement via RMT. This study aims to: 1) determine the usability, feasibility and acceptability of RMT; 2) improve and refine clinical outcome measurement using RMT to identify current clinical state; 3) determine whether RMT can provide information predictive of depressive relapse and other critical outcomes. METHODS: RADAR-MDD is a multi-site prospective cohort study, aiming to recruit 600 participants with a history of depressive disorder across three sites: London, Amsterdam and Barcelona. Participants will be asked to wear a wrist-worn activity tracker and download several apps onto their smartphones. These apps will be used to either collect data passively from existing smartphone sensors, or to deliver questionnaires, cognitive tasks, and speech assessments. The wearable device, smartphone sensors and questionnaires will collect data for up to 2-years about participants' sleep, physical activity, stress, mood, sociability, speech patterns, and cognitive function. The primary outcome of interest is MDD relapse, defined via the Inventory of Depressive Symptomatology- Self-Report questionnaire (IDS-SR) and the World Health Organisation's self-reported Composite International Diagnostic Interview (CIDI-SF). DISCUSSION: This study aims to provide insight into the early predictors of major depressive relapse, measured unobtrusively via RMT. If found to be acceptable to patients and other key stakeholders and able to provide clinically useful information predictive of future deterioration, RMT has potential to change the way in which depression and other long-term conditions are measured and managed.

Mobile health applications for improving physical function, physical activity, and quality of life in stroke survivors: a systematic review.

PURPOSE: To evaluate the effectiveness of mobile health applications (mHealth apps) containing a physical training component on physical function and physical activity in stroke rehabilitation. MATERIALS AND METHODS: A systematic literature search was conducted in three databases for studies published from inception to 12 July 2022. Clinical trials including mHealth apps with a physical training component were included using outcomes of physical function and physical activity. Quality of life was extracted as a secondary outcome. RESULTS: Five RCTs, two non-RCTs, and four uncontrolled clinical trials were included with a total of 264 stroke survivors. Eleven apps were identified with a physical training component using features of gamification (six apps), exercise prescription (three apps), and physical activity (two apps). Six out of seven studies reported statistically significant improvements in physical function in favor of the experimental group, with the most robust findings for upper extremity function. For physical activity, statistically significant improvements were seen in the experimental groups. Only one study showed significant improvement in quality of life. Overall study quality was fair. CONCLUSIONS: mHealth apps containing a physical training component are promising for physical function and physical activity in stroke rehabilitation. Further research is warranted to confirm these conclusions.Implications for rehabilitationDesign content of mobile apps with a physical training component were focused on gamification, exercise prescription, and physical activityUsing mobile app-delivered therapy seem promising for improving upper extremity function in stroke rehabilitationUsing mobile apps also supported an increase of physical activity in people with strokeStudies using mobile apps should report more specifically the dosage of physical training and adherenceUsing mobile apps seems promising as an additional tool for clinical work, however, more studies are required to understand their effectiveness in stroke rehabilitation.

Emotional outcomes in clinically isolated syndrome and early phase multiple sclerosis: a systematic review and meta-analysis.

OBJECTIVE: To study depression, anxiety, suicide risk, and emotional health-related quality of life (HRQoL) in people with clinically isolated syndrome (CIS) and in early phase multiple sclerosis (MS). METHODS: A systematic literature review was conducted with inclusion criteria of observational studies on outcomes of depression, anxiety, suicide risk, and emotional HRQoL in CIS and within five years since diagnosis of MS. Studies were screened using the Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, and study quality was determined for included studies. Meta-analysis and meta-regression were performed if applicable. RESULTS: Fifty-one studies were included in the systematic review. In early phase MS, meta-analyses of the Hospital Anxiety Depression Scale (HADS) indicated prevalence levels of 17% (95% confidence interval (CI): 9 to 25%; p < .001) for depressive and 35% (95% CI: 28 to 41%; p < .001) for anxiety symptoms. Meta-regression analyses revealed an increase in mean HADS-D and HADS-A associated with larger sample size, and higher HADS-D mean with increased study quality. Similar depressive and anxiety symptoms were observed in CIS, and increased suicide risk and low emotional HRQoL was associated with depressive symptoms in early phase MS. The methodological quality of the studies was considered fair. CONCLUSIONS: Findings suggest that mild-to-moderate symptoms of depression and anxiety might be prevalent in CIS and in early phase MS. Future research on both clinical populations are needed, especially longitudinal monitoring of emotional outcomes.

Collagen gene expression in keloids: analysis of collagen metabolism and type I, III, IV, and V procollagen mRNAs in keloid tissue and keloid fibroblast cultures.

Regulation of collagen gene expression was studied in keloids and fibroblast cultures established from keloid biopsies from 9 patients. The collagen concentration in keloid tissue was not different from that in normal skin. The activities of 2 enzymes catalyzing intracellular collagen biosynthesis, prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyltransferase (GGT) were significantly elevated in the keloids, the mean increase in the former enzyme being 5-fold and in the latter 3-fold with respect to the controls. The mean procollagen production rate in the keloid fibroblasts was at the control level, with only 1 keloid cell line showing a procollagen synthesis rate higher than the mean value + 2 SD of the controls. The mean PH and GGT activities of the keloid fibroblasts were not elevated, but PH activity in 2 cell lines and GGT activity in 1 cell line were higher than the mean + 2 SD for the controls. Cellular type I, III, IV, and V procollagen mRNAs were measured by slot blot hybridization using specific human cDNA clones for the various collagen types. The amounts of type I, III, and V procollagen mRNAs corresponded to the ratios in which these collagen types are produced by fibroblasts. No synthesis of type IV procollagen mRNA by keloid fibroblasts was observed. The total amount of type I and III procollagen mRNAs correlated significantly (p less than 0.01) with the procollagen synthesis rate measured after radioactive labeling of the cells in the keloid and control fibroblasts, indicating that collagen production in these cells is mainly controlled by regulating the final steady state levels of collagen mRNA. The results suggest that fibroblasts isolated from keloids often synthesize normal amounts of collagen.

Fluorescence produced by transfection reagents can be confused with green fluorescent proteins in mammalian cells.

The Aequorea victoria green fluorescent protein (GFP) reporter system is a convenient way to monitor gene expression and other cellular functions in mammalian cells. To study gene expression, a GFP-fusion plasmid construct is often transfected into mammalian cells using a variety of methods including calcium phosphate- and liposome-based DNA transfer. Subsequently, the expression of GFP-fusion protein is monitored by fluorescence microscopy or flow cytometry. Here, we report that certain transfection reagents can produce fluorescence that can be detected in a wide range of wavelengths, which can be confused with GFP-fusion protein. The fluorescence false positives can be a problem, particularly when the GFP expression levels are low. To improve the GFP-based detection or screening methods, it is imperative to include an appropriate negative control and to detect GFP using a narrow-wavelength emission filter corresponding to the emission spectrum around the GFP peak.

The generation and characterization of a radiation-resistant model system to study radioresistance in human breast cancer cells.

To systematically study the selection of radioresistant cells in clinically advanced breast cancer, a model system was generated by treating MDA-MB231 breast cancer cells with fractionated gamma radiation. A clonogenic assay of the surviving cell populations showed that 2-6 Gy per fraction resulted in a rapid selection of radioresistant populations, within three to five fractions. Irradiation with additional fractions after this initial increase did not increase the radioresistance of the surviving population significantly. Doses of 0.5 and 8 Gy per fraction were not effective in selecting radioresistant cells. To further determine the cause of the changes in radiosensitivity, 15 clones were isolated from the cell populations treated with 40 or 60 Gy with 2 or 4 Gy per fraction, respectively, and were analyzed for radiosensitivity. The average D(10) for these clones was 6.75 +/- 0.36 Gy, which was higher than that for the parental cell population (D(10) = 6.0 +/- 0.2 Gy). The operation of cell cycle checkpoints and the doubling time were similar for both the nonirradiated parental population and the isolated radioresistant subclones. In contrast, a decrease in the apoptotic potential was correlated (r = 0.7, P < 0.01) with increased survival after irradiation, suggesting that apoptosis is an important factor in determining radioresistance under our experimental conditions. We also isolated several subclones from the nonirradiated parental cell population and analyzed them to determine their radiosensitivity after fractionated irradiation. Ten fractions of 4 Gy (40 Gy in total) did not result in a significant increase in the radioresistance of these subclones compared to the irradiated cell populations. The possible mechanisms of the increased radioresistance after fractionated irradiation are discussed.

Periosteal flaps and grafts in primary cleft repair: a follow-up study.

A long-term follow-up study of maxillary clefts operated on primarily with the maxillary periosteal flap (67 patients) and the free tibial periosteal graft (23 patients) showed a definite bone bridge in 64 versus 85 percent of the patients. Still, secondary bone grafting was indicated in both in over 70 percent. Lateral crossbite was observed in all and anterior crossbite (mostly dental) was seen in over 80 percent of both groups. There were no statistically significant differences in the cephalometric angular measurements between the groups. Inside the maxillary periosteal flap group the maxillary growth was more retarded in unilateral and especially bilateral complete clefts than in alveolar clefts only. The maxillary growth seemed to be on average better than in primarily bone-grafted materials. The primary use of periosteum had been abandoned in our unit already in 1974, because it did not fulfill the expectations of prevention of maxillary collapse, lesser need for secondary bone grafting, and better midfacial growth.

Soft tissue profile changes after Le Fort I osteotomy in UCLP patients.

The changes in soft tissue profile after Le Fort I osteotomy were evaluated cephalometrically in 38 consecutive UCLP patients (25 males, 13 females) operated on between 1987 and 1995. Mean age at operation was 23.5 years. The one-piece Le Fort I osteotomy was fixed with titanium plates and the osteotomy site was bone grafted. Neither intermaxillary fixation nor occlusal splints were used postoperatively. Soft tissue changes were analyzed both horizontally and vertically by cephalograms taken shortly before surgery, 6 months and 1 year postoperatively. The mean maxillary skeletal advancement (point A) during surgery was 3.8 mm and mean vertical lengthening 4.4 mm. One year postoperatively the horizontal change in the upper lip profile (point a) was 80% of the skeletal change. Vertically, the soft tissue change in the upper lip was smaller 40%, but increased significantly (to 58%) if V-Y plasty was used. The V-Y plasty also increased the anteroposterior thickness of the upper lip. No significant soft tissue changes were observed between 6 months and 1 year postoperatively.

Accelerated tissue expansion with the "overfilling" technique.

Temporary overexpansion of the tissues at each filling session increased the actual inflation volume by about 59 percent. This shortened the process of tissue expansion considerably. "Overexpansion" means that the pressure in the expander is increased to a point where the dermal capillary flow is zero or the patient experiences so much discomfort that inflation cannot be carried out any further. The pressure in the expander is thereafter gradually decreased by taking out saline until both the capillary refill and all other clinical criteria are sufficient for safe dermal circulation. Comparison of the expander volume at the final pressure to the initial filling volume at the same pressure before the "overfilling" confirmed an average gain of about 59 percent in 14 patients.

Tissue expander injection dome leakage.

Injection dome leakage was found to be the cause for partial disappearance of the saline solution injected into some tissue expanders. When the injection domes of 22 consecutively removed tissue expanders were checked, we found that the average leakage pressure of these was 32 mmHg, with a range of 8 to 110 mmHg. When the patients were lying on their expanders, the weight of the corresponding body part caused intraluminal pressures of up to 90 mmHg in their expanders. Following removal of the expanders, the total leakage was calculated quantitatively and found to be maximally over 50 percent of the injected volume in some instances. The leakage flow through the injection dome in seven consecutively removed expanders was checked at pressures of 25, 50, and 75 mmHg over 30 minutes and was found to be slow. The possibility of injection dome leakage should be kept in mind, however, as a potential complication under unfavorable conditions. At the same time, we want to emphasize that in most instances tissue expanders function quite well and in predictable ways.

Oblique lateral oro-ocular facial cleft. Case report.

2 patients are presented, and the oblique lateral oro-ocular clefts discussed with emphasis on classification, dentition and microforms. A review of the literature revealed 10 patients with oblique lateral oro-ocular facial cleft (no. 5 in Tessier's classification), 3 bilateral and 7 unilateral. 5 unilateral cases had a median oblique facial cleft (no. 4) on the other side. 3 cases had a cleft lip and palate. The site of the alveolar cleft was in the region of the first and second premolar in 2 and slightly posterior to the canine tooth in 3 of 5 reliably documented cases. The dentition was documented only in 1 child with a lateral and median oblique facial cleft, resulting in full permanent dentition. The author's 2 cases had a bilateral oblique lateral oro-ocular facial cleft with the alveolar defect in the region of the first and second premolar. An isolated cleft (no. 6 in Tessier's classification) has to our knowledge not been reported at all. Furthermore, there are transitional forms between Tessier's clefts 5-8. Based upon our observations, it is also evident that variations inside one type occur as well. More attention should be paid to the exact location of the cleft and especially to the skeletal deformity, alveolar site and dentition. This would facilitate both classification and diagnosis of microforms.

Skeletal stability of Le Fort I osteotomy in patients with isolated cleft palate and bilateral cleft lip and palate.

The skeletal stability of Le Fort I osteotomy was evaluated retrospectively in 14 patients with isolated cleft palate (CP, mean age 27.2 years) and 11 patients with bilateral cleft lip and palate (BCLP, mean age 23.7 years). The osteotomy was fixed with titanium plates and the osteotomy gap was grafted with autologous bone. Neither intermaxillary fixation nor occlusal splints were used postoperatively. Skeletal stability was analysed both horizontally and vertically by cephalograms taken shortly before operation, immediately afterwards, and at six months and at one year postoperatively. In the CP group the mean maxillary horizontal advancement (point A) was 4.7 mm (range 0.3-7.8) and the mean vertical lengthening 3.6 mm (range 0.7-6.1). One year postoperatively the mean relapse was 8.5% (0.4 mm) horizontally and 16.7% (0.6 mm) vertically. In the BCLP group the mean horizontal advancement was 5.3 mm (range 0.2-10.7) and the mean vertical lengthening 7.3 mm (range 0.6-11.8). The mean postoperative relapse was 9.4% (0.5 mm) horizontally and 17.8% (1.3 mm) vertically. The skeletal stability and relapse were similar in both cleft types although BCLP patients had more residual cleft problems and their mean surgical advancement was greater. There was great individual variation.

The correlation between training and skill of the surgeon and reoperation rate for persistent cleft palate speech.

The correlation between the surgeons training and skill and the speech after primary repair was tested using the reoperation rate as a measure for success in 439 cleft palate/cleft lip and palate (CP/CLP) patients operated at the average age of 22 months by 4 specialists and 4 residents. The reoperation rate for residents was 11-60% (av. 36) and for specialists 13-31% (av. 19). The relative reoperation rates in CP/CLP were 20/19% for specialists but 35/38% residents. In groups consisting of the four with the best (A) and the four with the worst results (B) the reoperations rate in group A was 16% for CP and 13% for CLP, but in group B 37/44%. As the residents became specialists, the degree of their improvement varied greatly. Thus both the training and skill are important for the patients speech, but they are not necessarily synonymous terms.

One-stage closure of isolated cleft palate with the Veau-Wardill-Kilner V to Y pushback procedure or the Cronin modification. I. Comparison of operative results.

The long term operative results of one-stage closure of isolated cleft palate with either the Veau-Wardill-Kilner V to Y pushback procedure or the Cronin modification were evaluated and compared retrospectively. A total of 116 consecutive patients with isolated cleft palate who had been operated on at the age of 18-24 months were followed up until 17-20 years of age. Twenty-four of the patients needed one or more additional operations on the palate, mainly pharyngeal flaps (20%) and repair of fistulas (10%). There was no significant difference in the number of patients who needed further operations, either between the two different operations or between the sexes, but the patients who presented with the most extensive clefts required the most operations.

Spontaneous narrowing of the palatal cleft during the first year of life: a quantitative study.

In 44 clefts of the hard palate the relative size of the cleft, as a percentage of the total palatal area, decreased by an average of 7% between the ages of 3 and 17 months. The relative size of the cleft at the second examination was only 52% of that at the first evaluation. The length of the cleft (per cent of the palatoalveolar length) shortened by 7%. The palatal height increased by 2.2 mm in this group and by 2.4 mm in a control group (23) with only minor posterior clefts. The spontaneous narrowing, most evident in wide anterior clefts, seems to be primarily due to actual growth, and not to bending or collapse. This phenomenon should be taken into consideration in the choice of the optimum age for surgery, which, in selected cases, should not take place before the age of one year.

Comparison of quality of speech after Veau-Wardill-Kilner pushback operation and the Cronin modification in the primary treatment of cleft palate.

The quality of speech was compared in 124 young adults with isolated cleft palate. Forty-seven subjects were excluded because of the presence of factors that might have biased the evaluation of the success rate of the two operations studied, leaving 77 subjects who had undergone primary palatoplasty for analysis. One stage closure of the soft and hard palate was done for 43 patients by the mucoperiosteal palatal V to Y pushback technique (Veau-Wardill-Kilner, group V), and 34 underwent the Cronin modification (group C). Their speech was tape recorded, analysed by three qualified listeners, and hypernasality assessed by four published hypernasality indexes. More subjects in group C achieved normal resonance than in group V, who had higher hypernasality index scores than group C. The groups managed pressure consonants similarly. Only a few patients had weak plosives, audible nasal air emission, or compensatory articulation. Similar numbers of secondary operations were done for both groups. However, group V would have actually required secondary surgery more frequently than group C.

Treatment of severe developmental asymmetry of the female breast.

In a material of 49 female patients with severe developmental breast asymmetry, Poland's syndrome and isolated unilateral hypoplasia were the most frequent etiological factors (69%). Prosthetic augmentation alone, transfer of the de-epithelialized latissimus dorsi musculocutaneous flap to fill up the infraclavicular hollow, combined with an expander prosthesis for the breast, or augmentation with tissue from the contralateral "healthy" hypertrophic breast were found to be the methods of choice in selected cases. In order to achieve optimum symmetry the contralateral ptotic/hypertrophic breast should be corrected in most patients.

Skeletal stability of Le Fort I osteotomy in patients with unilateral cleft lip and palate.

The skeletal stability of Le Fort I osteotomy was evaluated cephalometrically in 40 consecutive patients with unilateral cleft lip and palate (UCLP) (27 male and 13 female) who were operated on between 1987-1995. Their mean age at the time of operation was 23.7 years (range 16.3-40.4). The one-piece Le Fort I osteotomy was fixed with titanium plates and the osteotomy line was bone-grafted. Neither intermaxillary fixation nor occlusal splints were used postoperatively. Skeletal stability was analysed both horizontally and vertically on cephalograms taken shortly before operation, immediately afterwards, and at six months and at one year postoperatively. The mean maxillary advancement (point A) during the Le Fort I was 3.9 mm (range 0-8.9) and mean vertical lengthening 4.5 mm (range -0.6-10.5). One year postoperatively the mean maxillary horizontal relapse was 20.5% (0.8 mm, range 0-3.7) whereas the mean vertical relapse was 22.2% (1 mm, range 0-5.7). The vertical relapse reduced from 38% to 8.3% between 1987 and 1995, and there was a positive correlation between the amount of maxillary advancement and relapse both horizontally and vertically.

Primary hereditary systemic amyloidosis (Meretoja's syndrome): clinical features and treatment by plastic surgery.

The characteristic, bloodhound-like appearance, which degenerates gradually, of patients with primary hereditary systemic amyloidosis, also called Meretoja's syndrome (MS), is attributable to amyloid degeneration of the craniofacial skin and peripheral facial nerves, but apparently also to amyloid deposits in the muscles; a finding not previously described. A material of five patients treated with plastic surgery is presented, and the peculiarities and differences of this rare disease in comparison with other peripheral neuropathies is discussed from a reconstructive viewpoint.