Abstract Vitamin deficiencies are a common problem worldwide, and vitamin B12 deficiency has been identified as a health concern for nearly a century. People all over the world are frequently deficient in vitamin B12. A number of 30–50% of patients with cobalamin deficiency a kind of neurological involvement, for example neuropathy, myelopathy, dementia or optic neuropathy. We present the case of a 56 years old female patient, who suddenly developed gait difficulty due to motor deficit in the lower limbs. After hospitalization in the neurology ward and specialized investigations, thoracic myelitis and axonal sensorimotor polyneuropathy due to vitamin B12 deficiency are diagnosed. The patient underwent functional evaluation at Techirghiol Rehabilitation Sanatorium, where she received individualized treatment for her motor deficit. Despite longstanding recognition of vitamin B12 deficiency, accurately diagnosing the condition and determining the most appropriate management strategy remain challenging.
Abstract Cervical carcinoma remains a critical public health issue, especially in developing regions despite advances in HPV vaccination and screening programs. This study evaluates the prognostic significance of Ki-67 and p53 immunohistochemical markers in cervical carcinoma and explores their correlation with FIGO stage, histological grade, and lymphovascular space invasion (LVSI). Fifty cases of cervical carcinoma were analyzed retrospectively using WHO 2020 classification and FIGO 2018 staging. The expression patterns of both Ki-67 and p53 were assessed for all cases and significant associations were found between high Ki-67 index and older age, poor differentiated tumors and LVSI. Similarly, mutated p53 patterns correlated strongly with advanced clinical stage, poor differentiation andlympho-vascular positivity. The presence of a high proliferation rate of expression of Ki-67 alongside a mutated pattern or p53 immunostaining indicated a synergistic molecular phenotype linked with aggressive disease biology. These findings support the integration of Ki-67 and p53 biomarkers into diagnostic workflows and highlight their potential role for guiding personalized treatment strategies. Future large-scale studies with follow-up data are needed to substantiate their utility as routine prognostic biomarkers.
Abstract HIV infection is associated with an increased risk for the development of hematological malignancies, especially non-Hodgkin lymphoma (NHL), which continues to present aggressive forms despite therapeutic advances. We present the case of a 49-year-old patient, originally from Ukraine, diagnosed in January 2023 with HIV infection stage A3 according to the Centers for Disease Control and Prevention (CDC) classification. Clinical, paraclinical and histopathological data were retrospectively analyzed to highlight evolutionary and therapeutic peculiarities. Although the patient promptly initiated antiretroviral therapy (ART), the oncological risk associated with persistent immunosuppression remains significant, according to data in the literature. Eleven months after the diagnosis of HIV infection, he developed systemic symptoms, and investigations confirmed the presence of an aggressive NHL, an entity described as being among the most common HIV-associated malignancies. Despite the rapid institution of specific treatment, the evolution was fulminant, with progressive deterioration and death, a scenario also documented in other cases of aggressive NHL associated with immunosuppression. This case reflects the severe evolutionary potential of NHL in HIV patients, even in early stages of infection. Early identification of symptoms, prompt evaluation and multidisciplinary management are crucial to improve prognosis, according to international recommendations.
Abstract Introduction: With multiple indications in both cardiovascular and non-cardiovascular diseases, beta-blockers exert complex effects on the cardiovascular system and energy metabolism, potentially impacting functional performance in medical rehabilitation programs. While their efficacy in controlling cardiac function is well-documented, the literature reports inconsistent results regarding the effects of this drug class on metabolic parameters and exercise tolerance. In the context of medical rehabilitation, these aspects justify the evaluation of the potential impact of beta-blockers on functional response. Materials and Methods: The study had a prospective design and included 320 patients hospitalized between January and December 2025 at the Techirghiol Balneary and Rehabilitation Sanatorium. The antihypertensive medication used was analyzed, with patients grouped based on the administration of beta-blockers or other classes of antihypertensive drugs. Clinical observations regarding exercise tolerance were noted according to the timing of beta-blocker medication administration. Body Mass Index (BMI) was calculated to compare the weight status between groups. Functional evaluation was performed at the beginning and at the end of the rehabilitation program using the Visual Analog Scale (VAS) and the Six-Minute Walk Test (6MWT). Results: Of the included patients, 179 were under treatment with beta-blockers, with metoprolol being the predominantly used active substance. In this group, 72% had BMI values above 25 kg/m², with a gender distribution of 59.7% females and 40.3% males. Comparative analysis revealed higher average BMI values in women treated with beta-blockers compared to those receiving other classes of antihypertensive drugs. Dynamic evaluation indicated a more limited functional improvement in the group of patients treated with beta-blockers. Conclusion: Differences were observed between patients treated with beta-blockers and those treated with other classes of antihypertensive drugs regarding metabolic and functional parameters. These findings highlight the importance of considering antihypertensive therapy and monitoring exercise tolerance in the context of medical rehabilitation programs.
Abstract The recognition of human papillomavirus (HPV) as the main cause for cervical cancer transformed prevention and management, leading to widespread HPV vaccination and a change from Pap smear to HPV-based screening. Therapeutic progress includes advances in image-guided radiotherapy, concurrent chemoradiation, and the integration of targeted biologic agents such as anti-angiogenics and immune checkpoint inhibitors. Emerging technologies, including digital pathology, artificial intelligence–assisted diagnostics, and immunohistochemistry-based profiling, are improving accuracy and enabling personalized treatment. New immunotherapeutic approaches, including tumor-infiltrating lymphocyte therapy, offer new options for advanced or recurrent disease. Despite these advances, global disparities persist in access to vaccination, early detection, and comprehensive care. Achieving the World Health Organization’s elimination targets will require coordinated efforts to expand preventive strategies and ensure timely, equitable treatment.
Background: Postoperative nosocomial infections (NIs) increase morbidity, hospitalisation, and mortality. The emergence of multidrug-resistant organisms (MDROs) complicate care and require strict infection control and antibiotic therapy. This study examined postoperative NIs’ clinical, microbiological, treatment profiles and identified risk factors. Methods: This retrospective observational study included 56 adult surgical patients from two tertiary centers in Constanta, Romania. We analysed demographics, comorbidities, operation type, microbiology, inflammatory indicators, ICU admission, mortality, and antibiotic resistance/sensitivity. Results: Patients had a mean age of 53.21 ± 22.61 years, with a slightly male predominance. The ICU had 26.4% admission and 9.4% death. The most common comorbidities were dementia, obesity, diabetes, and atrial fibrillation. Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus epidermidis dominated the pathogens spectrum. In particular, 40% of cultures were resistant to tetracycline, ceftriaxone, and erythromycin, while vancomycin and linezolid were effective. Klebsiella pneumoniae, Serratia marcescens, and Bacteroides fragilis polymicrobial infections increased ICU utilisation and hospitalisation. Conclusion: Host, procedural, and microbiological variables affect postoperative NIs. Antimicrobial medicines must be tailored to multidrug resistance patterns, and surveillance and stewardship programs are essential. Early detection of high-risk infections may enhance results with focused therapy.
Background: Temporomandibular disorders (TMD) are prevalent musculoskeletal conditions that impair function and quality of life. Intra-articular therapies such as hyaluronic acid (HA) and platelet-rich plasma (PRP) have emerged as minimally invasive options, yet comparative real-world evidence remains limited. Methods: A total of 100 patients with TMD were analyzed in two parallel cohorts: 50 treated with HA and 50 with PRP. Baseline characteristics, treatment protocols, and outcomes were extracted from clinical databases. Primary outcomes included changes in mouth opening (mm) and pain intensity (VAS, 0–10). Secondary outcomes included imaging findings and patient-reported improvement. Statistical analysis was performed using SPSS version 29.0. Results: Patients in the HA group were older on average (47.3 ± 17.9 years) compared with PRP patients (38.6 ± 10.8 years). HA-treated patients more frequently presented with degenerative or structural etiologies, whereas PRP was preferred in cases of parafunctional habits and post-traumatic etiologies. HA was associated with greater improvement in mouth opening (+10.7 mm), while PRP provided superior pain relief (VAS reduction: –4.3 vs. –3.6). Imaging revealed more frequent disc displacement in HA patients (16%), whereas PRP patients more often presented with effusion and degenerative changes (24% and 76%, respectively). Patient-reported outcomes favored PRP, with major improvement or remission more commonly reported. Conclusion: Both HA and PRP provided clinically meaningful improvements in TMD management but with distinct therapeutic profiles. HA appeared most effective in improving function in degenerative disease, whereas PRP offered superior analgesia and higher patient satisfaction. These findings support a patient-tailored approach, with future trials needed to confirm long-term comparative effectiveness and the potential role of combination therapy.
Background: Temporomandibular joint (TMJ) disorders are multifactorial conditions characterized by pain, dysfunction, and reduced quality of life. Minimally invasive biologic therapies such as hyaluronic acid (HA) and platelet-rich plasma (PRP) infiltrations have emerged as promising alternatives to conventional management. Methods: Fifty patients treated with HA and fifty patients treated with PRP were analyzed retrospectively. Baseline demographics, etiology, imaging profiles, and adjunctive therapies were recorded. Clinical outcomes were assessed using maximal mouth opening, visual analog scale (VAS) for pain, and patient-reported results. Results: HA patients were older (mean 47.3 years) with predominantly degenerative imaging findings, while PRP patients were younger (mean 38.6 years) with parafunctional or inflammatory etiologies. HA infiltrations improved oral opening by more than 10 mm on average, whereas PRP achieved comparable functional recovery but significantly greater pain reduction (VAS decrease from 5.6 to 1.4). Patient-reported remission was more frequent in the PRP group, while HA provided consistent moderate improvement. Conclusion: Both HA and PRP represent effective therapeutic pathways in TMJ management, with complementary benefits. HA is best suited for degenerative cases requiring improved mobility, while PRP provides superior pain relief in inflammatory and parafunctional disorders.
One of the most common respiratory conditions in infants and young children is bronchiolitis, which, in addition to the medical problems it causes, can have a serious emotional impact on parents. To highlight the psychosocial demands associated with this medical experience, this research examines the emotional and administrative difficulties faced by parents of children with bronchiolitis. The study was conducted on a sample of approximately 2,650 pediatric cases, of which 350 were diagnosed with bronchiolitis. The parents of these children completed a standardized questionnaire on emotional experiences, difficulties in understanding medical information, stress levels, perceived social support, and ability to manage critical situations. To further explore the quantitative data, a subgroup of 50 parents participated in semi-structured interviews, which provided a detailed perspective on the difficulties experienced on a personal and family level. The results showed high levels of stress (82%), anxiety (78%), and feelings of helplessness (65%) among parents. Challenges related to communication with medical staff, lack of social support, and financial difficulties were also identified. Qualitative analysis highlighted recurring themes such as fear of the child’s condition worsening, lack of clarity in medical information, and the emotional impact on family balance. The study emphasizes the importance of a family-centered approach in the care of children with bronchiolitis and highlights the need to integrate psychological support into pediatric medical practice.
Esophagogastric junction cancer is a boundary oncological pathology characterized by tumors located at the interface between the esophagus and stomach, with proximal and distal limits established according to the Siewert classification, which describes three types (I, II, and III) depending on the position of the tumor center relative to the esophagogastric junction. The surgical approach is determined both by this classification and by the surgeon’s experience and the level of expertise of the center where the procedure is performed. Radical surgery is based on preoperative TNM staging. The types of surgery performed and agreed upon by most centers are: transthoracic esophagectomy (Ivor Lewis), transhiatal esophagectomy (Orrienger), abdominal esophagogastrectomy (Hill), McKeown esophagectomy (triple approach), and total gastrectomy. Restoring digestive continuity usually involves the use of the stomach and jejunum, but when the situation requires it, the colon can also be used. As for lymph node dissection, it is performed either by dissection or by en bloc excision, both approaches being accepted. For the most accurate postoperative staging, at least 15 lymph nodes must be harvested. Splenectomy has a limited indication and is justified only when imaging or intraoperative findings reveal invasion of lymph nodes located along the splenic artery or at the splenic hilum. Neoadjuvant chemoradiotherapy is indicated for patients with locally advanced esophagogastric junction adenocarcinoma (Siewert type I-III), with the aim of reducing tumor volume and increasing the probability of achieving complete resection (R0). In situations where radical surgery is not possible, treatment options include endoscopic esophageal stenting, feeding gastrostomy (PEG or classic), and palliative chemotherapy. In conclusion, the surgical management of esophagogastric junction cancer is complex, guided by the Siewert classification and preoperative staging according to the TNM system -fundamental landmarks in establishing the therapeutic approach.
Pretty privilege” refers to the social and professional advantages enjoyed by physically attractive individuals, regardless of their actual competence. This study examined the phenomenon through an international online survey completed by over 100 participants from diverse cultural and social contexts. The main objectives were to identify which social relationships are most influenced by attractiveness bias and to explore the dynamics that increase this vulnerability. Findings indicated that professional relationships, especially employer–employee interactions, were perceived as most affected, followed by friendships and client–server relationships. Demographic analyses revealed variations by nationality, gender, work experience, and relationship status, showing that perceptions of attractiveness are culturally and contextually shaped. Furthermore, 71.4% of respondents admitted using attractiveness as a basis for assumptions, linked to the halo effect and self-fulfilling prophecy. Social comparison emerged as an ambivalent factor: it facilitates relationship initiation for attractive individuals but also generates intimidation and jealousy, undermining authenticity. The conclusions highlight two directions: targeted awareness campaigns in different social domains and early educational interventions to equalize expectations toward children regardless of appearance. Addressing pretty privilege therefore requires both immediate measures and long-term strategies to promote equity and ensure that merit, rather than appearance, drives social progress.
As Parkinson’s disease (PD) progresses to advanced stages, treatment optimization becomes imperative for managing refractory motor fluctuations and non-motor symptoms. Conventional oral and transdermal therapies demonstrate limited efficacy in >70% of patients after 5-7 years of treatment. Device-aided therapies (DATs) providing continuous dopaminergic stimulation represent an established approach, reducing OFF-time by 4-6 hours/day in clinical trials. The novel levodopa-entacapone-carbidopa intestinal gel (LECIG) formulation, approved in 202X, uniquely combines continuous duodenal levodopa delivery with peripheral COMT inhibition, enhancing bioavailability while reducing dose requirements. This article has two primary aims: firstly to review LECIG’s pharmacokinetic profile and synthesize clinical evidence from real-world experience, including patient-reported outcomes from early adopters (e.g., Swedish cohorts); and secondly to offer practical guidance for clinicians initiating LECIG, covering transitions from oral therapies or other DATs (e.g., LCIG), stepwise dosing titration, and adverse event management. Notably, LECIG demonstrates motor improvements comparable to standard levodopa–carbidopa intestinal gel (LCIG) but achieves therapeutic plasma concentrations at lower doses due to entacapone’s enhancement of levodopa bioavailability. These features position LECIG as a valuable option for personalized advanced PD care.
Background: Postoperative nosocomial infections are a major cause of morbidity and mortality in surgical patients, increasing ICU admissions, prolonging hospitalization, and driving healthcare costs. The emergence of multidrug-resistant organisms further complicates management. Materials and Methods: We conducted a retrospective observational single-center study at Municipal Hospital Mangalia (January 2019–December 2024). Data collected comprised demographics, comorbidities, surgical site, laboratory values, bacterial cultures, and antibiotic resistance patterns. Outcomes analyzed included ICU admission, in-hospital mortality, and prolonged hospitalization. Results: 56 patients met the inclusion criteria. Gram-negative bacteria predominated, with Pseudomonas aeruginosa (25.0%) most common. Antibiotic resistance was present in 60.7% of isolates, most frequently to tetracycline (19.6%) and erythromycin (16.1%). ICU admission occurred in 14 patients (25.0%), and in-hospital mortality was 10.7%. Median hospital stay was 23.5 days (IQR 15.0–33.25), significantly longer than in non-infected patients (p < 0.05). Multivariate analysis identified SOFA score as an independent predictor of ICU admission (OR 8.29, 95% CI 1.13–60.90, p = 0.038) and qSOFA score as a predictor of mortality (OR 8.67, 95% CI 1.41–53.29, p = 0.020). Conclusions: Postoperative nosocomial infections in this cohort were associated with high ICU admission rates, increased mortality, and prolonged hospitalization. Severity scores were strong prognostic markers, underscoring their utility for early risk stratification in surgical patients.
Acquired cystic disease associated renal cell carcinoma is an entity first described in 2006 and recognized in the WHO (World Health Organization) guidelines of 2016, also present in the current edition, which develops in the context of chronic kidney disease. We present the case of a 61 years old patient with significant comorbidities, on hemodialysis for 15 years, who was admitted to the hospital’s Emergency Department for a retroperitoneal hematoma. The histopathological examination of the left nephrectomy specimen revealed polycystic kidney disease, chronic pyelonephritis, and a malignant neoplastic proliferation. Immunohistochemical tests established the diagnosis of acquired cystic disease associated renal cell carcinoma. The particularity of this case consisted in its clinical presentation, the incidental finding of the malignant renal tumor in the context of polycystic kidney disease, and the variable immunoexpression of the CK7 marker within the tumor tissue.
Esophagogastric junction cancer is a distinct anatomical and oncological entity with specific clinical and therapeutic characteristics. It is a pathology located at the interface between the esophagus and the stomach. It is classified according to the system proposed by Siewert into three types (I, II, III), depending on the location of the tumor center relative to the esophagogastric junction. From an anatomopathological point of view, esophagogastric junction cancer is an adenocarcinoma. The incidence of this type of neoplasm has been increasing in recent decades, especially in developed countries, and is associated with risk factors such as chronic gastroesophageal reflux, obesity, and Helicobacter pylori infection. The clinical diagnosis is based on the appearance of swallowing disorders, which at onset are represented by a feeling of retrosternal discomfort or a foreign body sensation, and in advanced stages by obstructive phenomena, manifested by dysphagia, which also associates general signs: asthenia, fatigue, weight loss. Occult or obvious bleeding may also occur, with secondary anemia. Paraclinically, upper digestive endoscopy assesses the tumor level and degree of obstruction, and biopsy sampling allows for histopathological typing, grading, and immunohistochemical and genetic testing. Computed tomography is still the most widely used investigation for diagnosis, pre-treatment TNM staging, assessment of neoadjuvant treatment efficacy, and detection of recurrence. In conclusion, the diagnosis of esophagogastric junction cancer involves a multimodal approach, which is essential for accurate staging and choice of therapeutic strategy.
Our study on 51 cases was performed by dissection and injection of plastic mass followed by corrosion with NaOH, on formalinized human cadavers and on organic blocks aorta-inferior vena cava-right and left kidneys. The trajectory of the gonadal veins was in all cases rectilinear, in 47.06% of cases being oriented supero-medially, and in 52.04% of cases being vertical. At the termination the gonadal vein made with the corresponding renal vein an open lateral angle ranging between 37-900. The termination of the gonadal vein in the renal vein was most frequently on its postero-inferior surface, an aspect encountered in 54.90% of cases. The gonadal vein ended in the renal vein closer to the aorta (56.86% of cases). Compared to the termination of the left inferior adrenal vein, the gonadal vein ended laterally from it in 58.82% of cases, in 33.33% of cases ending at the same level as it, and in 4 cases (7.84% of cases) it ended laterally from the inferior adrenal vein. The caliber of the gonadal vein at the termination in the renal vein was found to be between 1.3-3.2 mm, the average being 2.04 mm. The present study examines the morphological features of the left gonadal veins, providing insights into the increased prevalence of varicocele on the left side. Anatomical knowledge of testicular vein variations and their spatial relationships with neighboring vessels is crucial for urologists and vascular surgeons, as it aids in the accurate diagnosis of urogenital conditions and helps prevent complications during retroperitoneal surgeries and imaging procedures.
Diabetes mellitus is a major public health issue, with the number of cases continuously increasing. This results in significant direct and indirect costs, representing a massive economic burden on the healthcare system. In Romania, costs are covered through the National Diabetes Program, so analyzing the cost trends can help better allocate funds, potentially improving program efficiency in the long term. Using a retrospective descriptive study with data on medication and monitoring costs for diabetes patients in Constanța County from 2018-2022, provided by the National Health Insurance House, it was found that the total number of patients reimbursed for antidiabetic medications steadily increased, with costs in 2022 almost doubling compared to the start of the study period. Non-insulin medication generated the most significant costs, being 4-6 times higher than those for insulin. The results highlight the growing economic challenges associated with proper diabetes management, emphasizing the need for more efficient solutions to reduce costs.
In upper limb orthopedic surgeries, two main anesthetic techniques are used: regional anesthesia (RA), more precisely brachial plexus block, and general anesthesia (GA). The objective of this study was to compare the two techniques by assessing postoperative pain using the NRS (Numerical Rating Scale), opioid consumption, and antiemetic consumption, to identify the differences and advantages of each method. This retrospective observational study was conducted in the Orthopedics and Traumatology Clinic of SCJU Constanța. 82 patients with ASA I-III classification were included in the study, of which 43 received general anesthesia (GA) and 39 regional anesthesia (RA) via brachial plexus block, axillary approach. The GA group was treated according to a uniform general anesthesia protocol, while the RA group followed the same postoperative analgesia scheme. All included patients underwent surgical interventions in the distal arm, elbow, forearm, and hand RAea. The NRS pain scores assessed at 2, 4, 6, and 12 hours postoperatively were significantly lower in the RA group compared to the GA group. Regarding opioid use, 66% of patients in the GA group required administration, while only 2.3% of patients in the RA group required them. No patients in the RA group received antiemetics, while 30% of patients in the GA group required this type of medication. Regional anesthesia through brachial plexus block demonstrated superior benefits compared to general anesthesia, both in terms of reducing postoperative pain scores and in reducing the need for opioids and antiemetics.
Abstract Objectives: Pregnancy has a profound impact on maternal thyroid morpho-functionality; thus, thyroid dysfunction can cause multiple perinatal risks and complications. The aim of the study is to determine the incidence of maternal thyroid autoimmunity and dysfunction, their influence on some gestational and perinatal parameters of the newborn, and the impact of iodine status on thyroid autoimmunity in a region with sufficient iodine intake. Material and method: Retrospective study conducted on a number of 74 full-term pregnancies with singletons, pregnant women originating from the perimarine area of Romania. The participants were divided into 2 groups: group 1 - pregnant with chronic autoimmune thyroiditis and subclinical/clinical manifest hypothyroidism; group 2 - pregnant without thyroid pathology considered as a control group. Maternal variables studied: dosage of thyroid hormone and antithyroid autoantibodies, median urinary iodine concentration; and for the newborns: birth weight, APGAR score, gestational age, incidence of perinatal events. The administration of iodine supplements during pregnancy was monitored. Results: The incidence of chronic autoimmune thyroiditis was 36.4%. Maternal thyroid autoimmunity is associated with low birth weight and premature birth compared to the control group. The predominant perinatal pathology among pregnant women with thyroid autoimmunity was represented by spontaneous abortion, presenting a 2.8x higher risk compared to the control group. Median urinary iodine concentration was under 150 mcg/L in both studied groups of pregnant women. Iodine nutritional deficiency, but also excess iodine intake, were positively correlated with maternal thyroid autoimmunity. Consumption of iodine supplements and iodized salt was reduced in the category of pregnant women with thyroid autoimmunity. Conclusions: Thyroid autoimmunity during pregnancy presents significant challenges even in iodine-sufficient geographical areas. Maternal autoimmune thyroiditis represents a risk factor with effects on fetal development and repercussions in the perinatal period. Evaluation of thyroid function parameters before conception or in the first weeks of pregnancy is recommended as a diagnostic and prophylactic measure.
The study was performed on 116 kidneys, using dissection and injection of plastic mass (followed by dissection or corrosion) as study methods. We found 6 cases of double renal veins (5.17% of cases), 5 cases being straight veins (9.62% of right veins) and 1 single case on the left being left veins (1.56% of left veins). In the formation of the venous trunk, both at the level of the superior veins and at the level of the inferior veins, two branches of origin participated in all cases, which most frequently were of different caliber. The trajectory of the superior renal vein in 4 cases was obliquely supero-medially, and in one case it was obliquely infero-medially, respectively horizontal. The trajectory of the inferior renal vein in 4 cases was obliquely supero-medially, and in 2 cases it was horizontal. The termination of the superior renal vein in the inferior vena cava is was done in 3 cases on the lateral side, respectively on the postero-lateral side. The termination of the inferior renal vein in the inferior vena cava was done in 3 cases on the postero-lateral side, in 2 cases on the antero-lateral side, and in only one case) on the lateral side. The caliber of the superior renal vein at the level of its termination in the vena cava, we found to be between 2.72-8.50 mm, the caliber of the inferior renal vein being between 2.10-3.60 mm. Significant morphological variations, particularly in venous morphometry, were observed compared to existing literature. These differences may be explained by methodological diversity, sample characteristics, and anatomical variability related to geographical area, sex, and age.
